KPTI

Image source: The Motley Fool. Thursday, Aug. 13, 2026 at 8:00 a.m. ET Senior Vice President, Investor Relations - Brendan Strong President and Chief Executive Officer - Richard Paulson Chief Medical Officer - Reshma Rangwala Chief Commercial Officer - Sohanya Cheng Chief Financial Officer - Lori Macomber 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. 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. Before you buy stock in Karyopharm Therapeutics, consider this: The Motley Fool Stock Advisor analyst team just identified what they believe are the 10 best stocks for investors to buy now… and Karyopharm Therapeutics wasn’t one of them. The 10 stocks that made the cut could produce monster returns in the coming years. Consider when Netflix made this list on December 17, 2004... if you invested $1,000 at the time of our recommendation, you’d have $432,621!* Or when Nvidia made this list on April 15, 2005... if you invested $1,000 at the time of our recommendation, you’d have $1,335,314!* Now, it’s worth noting Stock Advisor’s total average return is 976% — a market-crushing outperformance compared to 214% for the S&P 500. Don't miss the latest top 10 list, available with Stock Advisor, and join an investing community built by individual investors for individual investors. See the 10 stocks » *Stock Advisor returns as of August 20, 2026. This article is a transcript of this conference call produced for The Motley Fool. While we strive for our Foolish Best, there may be errors, omissions, or inaccuracies in this transcript. As with all our articles, The Motley Fool does not assume any responsibility for your use of this content, and we strongly encourage you to do your own research, including listening to the call yourself and reading the company's SEC filings. Please see our Terms and Conditions for additional details, including our Obligatory Capitalized Disclaimers of Liability. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy. Karyopharm (KPTI) Q2 2026 Earnings Call Transcript was originally published by The Motley Fool

Our analysts just identified a stock with the potential to be the next Nvidia. Tell us how you invest and we'll show you why it's our #1 pick. Tap here. Management is executing a strategic pivot to sharpen focus exclusively on hematology (myelofibrosis and multiple myeloma) following the Phase III XPORT-EC-042 study's failure to meet statistical significance in endometrial cancer. The myelofibrosis program is transitioning to a regulatory phase, supported by SENTRY trial data demonstrating statistically significant, rapid, and sustained spleen responses (SVR35) when combining selinexor with ruxolitinib. Management attributes the strength of the myelofibrosis case to a 'first-of-a-kind' prospective correlation between SVR35 and overall survival, which they believe establishes SVR35 as a reasonably likely surrogate endpoint for accelerated approval. Operational efficiency is being prioritized by leveraging the existing XPOVIO commercial infrastructure, which management claims will allow for a rapid launch without building a new organization from the ground up. Performance in multiple myeloma remains resilient despite a competitive landscape, serving as a foundational cash-generating business that supports the broader hematology platform. The company is aggressively reducing investment in the endometrial cancer program to reallocate capital toward the myelofibrosis launch and debt obligations. The company plans to submit a supplemental New Drug Application (sNDA) for selinexor in myelofibrosis in August 2026, targeting a potential launch as early as the first quarter of 2027. Management expects top-line data from the 60-milligram cohort of the Phase II SENTRY-2 study in the second half of 2026 to further define selinexor's role as a monotherapy and in combination with other JAK inhibitors. Financial guidance assumes a cash runway into September 2026, with a critical $15.8 million principal payment due on September 10, 2026, that requires additional financing or a lender waiver to avoid a covenant default. The regulatory strategy for traditional approval relies on using mature overall survival data from the ongoing SENTRY trial as the required confirmatory evidence following a potential accelerated approval. Management is actively evaluating strategic alternatives and financing opportunities to address the upcoming debt maturity and extend the liquidity runway through the myelofibrosis approval milestone. A $15.8 million principal payment due in September 2026 poses a significant liquidity risk; failure to secure financing or a waiver would cause cash to fall below the $10 million minimum liquidity covenant. The discontinuation of the endometrial cancer program will result in one-time costs in 2026, with the primary financial benefit of reduced R&D spending not fully realized until 2027. Revenue comparisons were impacted by the conclusion of a reimbursement agreement with Menarini at the end of 2025, which reduced year-over-year revenue by approximately $6.5 million. Management flagged that third-quarter 2026 expenses may be modestly higher due to the 'unique transition period' of implementing organizational changes and evaluating strategic alternatives. One stock. Nvidia-level potential. 30M+ investors trust Moby to find it first. Get the pick. Tap here. Management is currently aligning and finalizing details with the FDA to use mature overall survival (OS) data from the ongoing SENTRY trial as the confirmatory data set. The sNDA submission will focus on week 24 SVR35 data, while the OS data will mature over the next few years to support the conversion to traditional approval. Management noted that NCCN inclusion is expected in the second half of 2026 and Inclusion in the NCCN compendia could potentially drive up to 50% of peak revenue in scenarios where NCCN listing is the only milestone achieved. While NCCN is a key milestone, the company remains focused on the full regulatory pathway to ensure the broadest possible patient access. Richard Paulson stated that lenders have been 'consistently supportive' and the company is in direct dialogue regarding the September payment and liquidity options. Management declined to provide specific details on waiver terms but emphasized they are working toward a solution to enhance liquidity ahead of the myelofibrosis launch. The company will request priority review at the time of filing; the FDA will have 60 days from submission to respond to that request. The filing will primarily rely on week 24 data, though some week 48 data will be included; Management plans to submit an sNDA based primarily on week 24 data, including SVR35 and pre-specified OS confirmatory analysis, while also providing available 48-week data.

This article first appeared on GuruFocus. Total Revenue: $33.4 million in Q2 2026, compared to $37.9 million in the prior year period. XPOVIO U.S. Net Product Revenue: $30.8 million, compared to $29.7 million in the prior year period. Gross-to-Net Rate: 26.6%, comparable to the second quarter of 2025. R&D Expenses: $29 million, down 12% year over year. SG&A Expenses: $25.9 million, down 9% year over year. Net Loss: $67 million for the quarter, compared to $37.3 million in the prior year period. Cash Position: Ended the quarter with $65.4 million in cash, cash equivalents, restricted cash, and investments. Full Year 2026 Revenue Guidance: Reaffirmed total revenue in the range of $130 million to $150 million. Full Year 2026 XPOVIO Revenue Guidance: U.S. XPOVIO net product revenue of $115 million to $130 million. Full Year 2026 Expense Guidance: Combined R&D and SG&A expenses of $230 million to $245 million. Warning! GuruFocus has detected 6 Warning Signs with KPTI. Is KPTI fairly valued? Test your thesis with our free DCF calculator. Release Date: August 13, 2026 For the complete transcript of the earnings call, please refer to the full earnings call transcript. SENTRY trial demonstrated statistically significant, rapid, deep, and sustained spleen responses, with a nearly double SVR35 rate at week 24 for selinexor plus ruxolitinib versus ruxolitinib alone. Promising overall survival signal with a hazard ratio of 0.43, and a post hoc landmark analysis showing SVR35 at week 24 predicts overall survival, supporting SVR35 as a surrogate endpoint. FDA feedback indicates SVR35 appears to qualify as a reasonably likely surrogate endpoint for overall survival, enabling a planned sNDA submission under the Accelerated Approval Pathway. Established commercial hematology platform with existing relationships in community and academic settings, plus the KaryoForward patient support program, positions for a rapid and efficient launch if approved. Multiple myeloma franchise remains resilient with Q2 XPOVIO net product revenue of $30.8 million, providing a stable commercial foundation. SENTRY data published in the Journal of Clinical Oncology and presented at ASCO and EHA, generating strong interest and scientific engagement in the hematology community. Potential for up to $1 billion in peak annual US revenue in myelofibrosis, with no approved combination therapy in frontline setting. Phase 3 XPORT-EC-042 study in endometrial cancer failed to meet its primary endpoint, leading to a decision to reduce investment in that program. Cash position is tight, with $65.4 million in cash expected to fund operations only into September 2026, and a $15.8 million debt payment due on September 10, 2026, which could trigger a liquidity covenant breach. The company is actively evaluating financing opportunities and strategic alternatives, indicating potential dilution or restructuring risk. Accelerated approval is not guaranteed, and the confirmatory overall survival data from SENTRY will take years to mature, creating uncertainty for full approval. The sNDA submission is still pending, and the FDA's decision on priority review is unknown, which could delay potential approval beyond the first quarter of 2027. Net loss widened to $67 million in Q2 2026, partly due to non-cash mark-to-market adjustments, reflecting financial pressure. The company is reducing investment in endometrial cancer, which may limit future growth opportunities in that indication. Q: What remains to be completed for the sNDA submission, and will the ongoing SENTRY trial's overall survival data serve as the confirmatory data set for accelerated approval?A: Reshma Rangwala, EVP and Chief Medical Officer, stated that the vast majority of the sNDA is already compiled and ready. The key remaining piece is finalizing the statistical analysis plans and aligning with the FDA on the confirmatory data requirements. She confirmed that the mature overall survival data from the ongoing SENTRY trial will serve as the confirmatory data set to verify clinical benefit, a requirement for converting accelerated approval to traditional approval in the future. Q: Can you provide an update on the company's liquidity, the upcoming September 2026 debt payment, and the status of financing negotiations?A: Richard Paulson, President and CEO, acknowledged the company's immediate priority is to address its financial position. He noted that lenders have been consistently supportive in the past and that the company is in direct dialogue with them, working on a range of financing opportunities and strategic alternatives to enhance liquidity and extend the runway through the important milestones in the second half of 2026. Q: What is the company's strategy regarding NCCN compendia listing, and what is the potential impact on revenue if only that is achieved?A: Richard Paulson, President and CEO, stated that NCCN inclusion is a very important near-term milestone. He noted that in similar situations, if NCCN is all that is achieved, products typically reach about 50% of their peak revenue potential. However, the company's goal is to enable broad access by also advancing the regulatory pathway, which would be very positive for funding operations and patient access. Q: What is the company's plan for patients from the clinical studies to access the drug if only an NCCN compendial listing is achieved?A: Richard Paulson, President and CEO, explained that the SENTRY study will continue with patients and clinicians remaining blinded. The company's focus is on working with sites, investigators, and patients to continue the Phase 3 program, as this data is intended to serve as the confirmatory evidence for accelerated approval. Q: Will the sNDA submission include week 48 data, and will the pre-specified overall survival confirmatory analysis be part of the package?A: Reshma Rangwala, EVP and Chief Medical Officer, clarified that the sNDA will primarily focus on the week 24 data, which is the primary analysis time point. While some patients have been followed for 48 weeks and that data will be provided, the primary focus is on week 24. She confirmed that the pre-specified OS data will be included as it is a critical part of the differentiating package, forming the basis for the post-hoc analysis showing the relationship between SVR35 and OS. Q: What insights has the company received from the FDA regarding the potential for priority review of the sNDA?A: Reshma Rangwala, EVP and Chief Medical Officer, stated that priority review is a formal request made at the time of submission, and the FDA has 60 days to review it. While no specific insight was provided, she believes the strong package, differentiating profile, and unmet need for a combination therapy will support the request, potentially expediting the PDUFA date for an approval early next year. Q: What is the company's view on the feasibility of future operations, and is accelerated approval absolutely necessary for financial viability?A: Richard Paulson, President and CEO, responded that several milestones are happening in the near term. He emphasized that NCCN is very important and that physicians utilize it heavily. While NCCN alone could achieve about 50% of peak revenue, the company's goal is to enable broad access by advancing the regulatory pathway. Both NCCN and regulatory progress would be positive for funding operations and enabling patient access. Q: Can you provide more detail on the term loan negotiations and what updated obligations might look like if a waiver is granted?A: Richard Paulson, President and CEO, declined to provide specific details on the negotiations but reiterated that lenders have been consistently supportive. He expressed confidence that they will continue to be supportive and that the company is working to achieve a rapid solution to strengthen its financial position. For the complete transcript of the earnings call, please refer to the full earnings call transcript.

– Planned August sNDA Submission for Selinexor in Combination with Ruxolitinib in Myelofibrosis under the Accelerated Approval Pathway Remains on Track – – Planned sNDA for Selinexor plus Ruxolitinib Supported by Phase 3 SENTRY Results Presented at ASCO and EHA and Published in the Journal of Clinical Oncology; Potential to Become the First Approved Combination Therapy for Patients with Myelofibrosis – – Total Revenue was $33.4 Million, and U.S. XPOVIO® (selinexor) Net Product Revenue was $30.8 Million for the Second Quarter of 2026 – – Company Reaffirms Full-Year 2026 Total Revenue Guidance of $130 Million to $150 Million Including U.S. XPOVIO Net Product Revenue Guidance of $115 Million to $130 Million – – Conference Call Scheduled for Today at 8:00 a.m. ET – NEWTON, Mass., Aug. 13, 2026 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported financial results for the second quarter of 2026 and provided an update on the Company's myelofibrosis program. Following continued constructive engagement with the U.S. Food and Drug Administration (FDA), the Company remains on track to submit its planned supplemental New Drug Application (sNDA) in August under the Accelerated Approval pathway for selinexor in combination with ruxolitinib for patients with myelofibrosis. Karyopharm intends to request Priority Review at the time of submission. "Our planned submission under the Accelerated Approval pathway represents the beginning of an important new chapter for Karyopharm and an important milestone for the myelofibrosis community," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "If approved, selinexor plus ruxolitinib would become the first approved combination therapy for patients with myelofibrosis, introducing a novel therapeutic mechanism for the treatment of this disease within the multi-billion-dollar U.S. marketplace. Our planned submission follows productive engagements with the FDA and reflects the speed, focus, urgency and extraordinary commitment of our teams. We look forward to continuing to work closely with the FDA." "Together with the continued scientific engagement we are seeing across the myelofibrosis community, we believe the strength and consistency of the SENTRY data reinforce the potential of selinexor to fundamentally change the treatment of patients with myelofibrosis," added Mr. Paulson. Second Quarter 2026 and Recent Company Highlights XPOVIO Commercial Performance U.S. net product revenue was $30.8 million for the quarter ended June 30, 2026 compared to $29.7 million for the quarter ended June 30, 2025. Demand for XPOVIO was relatively consistent in the second quarter of 2026 compared to the second quarter of 2025, amidst a highly competitive commercial landscape. The community setting continued to represent approximately 60% of net product revenue. Expanded global patient access for selinexor is translating into growth in royalty revenue from Menarini, Antengene and other international partners. Royalty revenue increased to $2.5 million in the second quarter of 2026 compared to $1.6 million in the second quarter of 2025, with selinexor approved in more than 50 ex-U.S. countries and territories. Research and Development (R&D) Highlights Myelofibrosis Planned sNDA submission under the Accelerated Approval pathway following multiple, productive engagements with the FDA, including Type B and Type C meetings, and received written feedback from the FDA that spleen volume reduction ≥ 35% (SVR35) appears to qualify as a reasonably likely surrogate endpoint (RLSE) to predict overall survival and can be used to support an sNDA submission. Results from the Phase 3 SENTRY trial (NCT04562389) in myelofibrosis were presented in a Late-Breaking Oral Presentation at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the peer-reviewed Journal of Clinical Oncology demonstrating rapid, deep and sustained spleen responses, promising overall survival findings and evidence consistent with potential disease modification. Additional analyses presented during a Late-Breaking Oral Presentation at the European Hematology Association (EHA) Congress—where the abstract was selected as one of the six best abstracts presented at the meeting—provided additional evidence supporting SVR35 as a potential predictor of overall survival. The Company continues active scientific exchange with investigators and treating physicians following the ASCO and EHA presentations and publication of the SENTRY results in the Journal of Clinical Oncology. Continue enrolling patients into the 40 mg cohort of the Phase 2 SENTRY-2 trial (NCT05980806), following completion of enrollment of the 60 mg cohort (n=29) earlier this year. Endometrial Cancer Announced topline results from the Phase 3 XPORT-EC-042 trial (NCT05611931), evaluating selinexor as a maintenance-only therapy compared to placebo in adult patients with TP53 wild-type advanced or recurrent endometrial cancer. The trial did not meet its primary endpoint of progression-free survival. A trend favoring the selinexor arm was observed in the modified intent to treat (mITT) population (n=236), with a median PFS of 12.75 months in the selinexor arm compared to 7.43 months in the placebo arm (hazard ratio=0.76 [95% CI: 0.51, 1.12]; one-sided p-value=0.0791). The safety and tolerability profile of selinexor was consistent with its established safety profile, with no new safety signals observed. Following the Phase 3 topline results, the Company has prioritized future investment toward its myelofibrosis and multiple myeloma programs while continuing long-term follow-up of patients enrolled in XPORT-EC-042. Multiple Myeloma Patients enrolled in the Phase 3 XPORT-MM-031 trial (EMN29; NCT05028348) continue to be followed for progression-free survival events contributing towards the primary endpoint. The trial is being conducted in collaboration with the European Myeloma Network and is evaluating the all-oral combination of selinexor 40 mg, pomalidomide and dexamethasone (SPd40) in patients with previously treated multiple myeloma who received an anti-CD38 as their immediate prior line of therapy. Anticipated Catalysts and Operational Objectives Myelofibrosis FDA acceptance of the Company's planned August sNDA submission for selinexor in myelofibrosis, including potential Priority Review designation. Planned advancement of global regulatory activities with the Company's partners to support potential regulatory submissions outside the United States. Potential inclusion of selinexor plus ruxolitinib in relevant compendia in the second half of 2026. Topline data from the Phase 2 SENTRY-2 60 mg cohort expected in the second half of 2026. Multiple Myeloma Maintain the Company's commercial foundation in the increasingly competitive multiple myeloma marketplace and drive increased XPOVIO revenues. Support global launches by the Company's partners following regulatory and reimbursement approvals for selinexor in ex-U.S. countries and territories. Announce topline data from the event-driven Phase 3 XPORT-MM-031 (EMN29) trial expected in the second half of 2026. 2026 Financial Outlook Based on its current operating plans, Karyopharm expects the following for full year 2026: Total revenue to be in the range of $130 million to $150 million. Total revenue consists of U.S. XPOVIO net product revenue and license, royalty and milestone revenue earned from partners. U.S. XPOVIO net product revenue to be in the range of $115 million to $130 million. R&D and selling, general and administrative (SG&A) expenses to be in the range of $230 million to $245 million, excluding certain one-time costs that the Company may incur associated with its endometrial cancer program and evaluating financing opportunities and/or strategic transactions. The Company, together with its financial advisor Centerview Partners and other advisors, is actively evaluating a range of financing opportunities and strategic alternatives with the objective of maximizing both near- and long-term value for stakeholders while preserving strategic flexibility as it advances its myelofibrosis program. The Company expects its existing liquidity, including cash, cash equivalents and investments, together with anticipated cash flow from net product revenue and license and other revenue, to fund its current operating plans into September 2026. As discussed above, the Company is actively evaluating a range of financing opportunities and strategic alternatives with the objective of extending its cash runway, preserving strategic flexibility and maximizing long-term shareholder value as it advances its myelofibrosis program. On September 10, 2026, a $15.8 million principal payment is due under the Company's senior secured term loan facility. If that payment is made without additional financing or a waiver from the Company's lenders, the Company expects its cash, cash equivalents and investments would fall below its $10.0 million minimum liquidity covenant, which would constitute an event of default under the term loan. Second Quarter 2026 Financial Results Total revenue: Total revenue for the second quarter of 2026 was $33.4 million, compared to $37.9 million for the second quarter of 2025. Net product revenue: Net product revenue was $30.8 million for the second quarter of 2026, compared to $29.7 million for the second quarter of 2025. Net product revenue for the three months ended June 30, 2026, reflects relatively consistent demand for XPOVIO in an increasingly competitive multiple myeloma marketplace. License and other revenue: License and other revenue was $2.6 million for the second quarter of 2026, compared to $8.2 million for the second quarter of 2025. The decrease was primarily attributable to a $6.5 million reduction in development-related reimbursement revenue from Menarini following the expiration, on December 31, 2025, of Menarini's annual $15.0 million research and development obligation. Cost of sales: Cost of sales was $1.1 million for both the second quarter of 2026 and 2025. R&D expenses: R&D expenses were $29.0 million for the second quarter of 2026, compared to $32.8 million for the second quarter of 2025. The decrease was driven by our continued prioritization, focus, and efficient spending while advancing our late-stage programs, with our Phase 3 trials having completed full enrollment. SG&A expenses: SG&A expenses were $25.9 million for the second quarter of 2026, compared to $28.5 million for the second quarter of 2025. The decrease was primarily driven by proactive cost containment while maintaining disciplined alignment of pre-launch investments with clinical and regulatory milestones. Loss from operations: Loss from operations was $22.5 million for the second quarter of 2026, compared to $24.4 million for the second quarter of 2025. The improvement reflects the benefit of cost reduction initiatives implemented over the past several years. Interest income: Interest income was $0.7 million for the second quarter of 2026, compared to $0.6 million for the second quarter of 2025. Interest expense: Interest expense was $13.1 million for the second quarter of 2026, compared to $11.2 million for the second quarter of 2025. The increase reflects higher outstanding debt and higher interest rates following the Company's financing transactions executed in October 2025. Other expense, net: Other expense, net was $32.1 million in the second quarter of 2026, compared to $2.2 million in the second quarter of 2025. This expense is primarily non-operational and non-cash due to fair value of embedded derivatives and liability-classified common stock warrants related to the refinancing transactions completed in the second quarter of 2024 and the fourth quarter of 2025. The fair value of these instruments is remeasured each reporting period and is impacted by various inputs, including changes in the Company's share price. Net loss: Net loss was $67.0 million, or $2.32 per basic and diluted share, for the second quarter of 2026, compared to $37.3 million, or $4.32 per basic and diluted share, for the second quarter of 2025. Net loss for the second quarter of 2026 reflects an operating loss of $22.5 million and $44.5 million in non-operating expense comprised of $13.1 million of interest expense and $32.1 million of other expense partially offset by $0.7 million of interest income. Cash position: Cash, cash equivalents, restricted cash and investments as of June 30, 2026, totaled $65.4 million. Conference Call Information Karyopharm will host a conference call today, August 13, 2026, at 8:00 a.m. Eastern Time, to discuss the second quarter 2026 financial results, the financial outlook for 2026 and to provide other business updates. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company's website. An archived webcast will be available on the Company's website approximately two hours after the event. About the Phase 3 SENTRY Trial SENTRY (XPORT-MF-034; NCT04562389) is a Phase 3 clinical trial evaluating a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib in JAKi-naïve myelofibrosis patients with platelet counts >100 x 109/L (N=353). Patients were randomized 2-to-1 to the selinexor arm. The co-primary endpoints for this trial are spleen volume reduction ≥ 35% (SVR35) at week 24 and the average change in absolute total symptom score (Abs-TSS) over 24 weeks relative to baseline. The results from the Phase 3 SENTRY trial were presented at the 2026 American Society of Clinical Oncology Annual Meeting and were simultaneously published in the peer-reviewed Journal of Clinical Oncology. In addition, the results were presented at the 2026 European Hematology Association Congress, where the presentation was recognized as one of the six best abstracts at the meeting. About Myelofibrosis Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 17,000 patients in the European Union1. The disease causes bone marrow fibrosis (scarring in the bone marrow), which makes it difficult for the bone marrow to make healthy blood cells, splenomegaly (enlarged spleen), progressive anemia which often leads to symptoms like fatigue and weakness, and other disease associated symptoms including abdominal discomfort, pain under the left ribs, early satiety, night sweats and bone pain. The only approved class of therapies to treat myelofibrosis are JAK inhibitors, including ruxolitinib. About the Phase 3 XPORT-EC-042 Trial EC-042 (XPORT-EC-042; ENGOT-EN20; GOG-3083; NCT05611931) is a global, Phase 3, randomized, double-blind, placebo-controlled clinical trial evaluating selinexor as a maintenance-only therapy following chemotherapy or chemotherapy plus a checkpoint inhibitor in patients with TP53 wild-type advanced or recurrent endometrial cancer (N=257). Patients were randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The trial includes two patient populations, for which the primary endpoint of progression-free survival was tested sequentially: 1) a modified intent to treat population (mITT) that includes patients with either, a) TP53 wild-type tumors with proficient mismatch repair status (pMMR); or, b) TP53 wild-type tumors with deficient mismatch repair status (dMMR), who are medically ineligible to receive checkpoint inhibitors; and, 2) the trial's original intent to treat (ITT) population, which includes all patients enrolled in the trial whose tumors are TP53 wild-type, regardless of MMR status. Overall survival is a key secondary endpoint. The mITT population enrolled 236 patients. As of the data cut-off, 106 progression-free survival events as assessed by the investigator had been observed in the mITT population. In connection with the EC-042 trial, Karyopharm entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOne®CDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 wild-type. The trial is being conducted in collaboration with the European Network of Gynaecological Oncological Trial groups (ENGOT) and the GOG Foundation, Inc. About Endometrial Cancer Endometrial cancer (EC) is the most common gynecologic malignancy in the U.S.1 In 2026, approximately 68,000 uterine cancers (predominantly endometrial) are expected to be diagnosed, with approximately 14,000 deaths.1 Worldwide there were about 420,368 cases with 97,723 deaths in 2022.2 Both incidence and mortality have continued to rise.3,4  Key risk factors include obesity, type 2 diabetes, high-fat diets, tamoxifen or oral estrogen use, and delayed menopause.5 TP53 is a well-recognized prognostic marker for EC; >50% of advanced or recurrent EC tumors are TP53wt (gene for tumor protein P53; wild-type), and ~40%-55% are both TP53wt and mismatch repair-proficient (pMMR).6-8 While immune checkpoint inhibitors have shown benefit in patients with mismatch repair–deficient (dMMR) and pMMR, the magnitude of benefit is greater for patients with dMMR tumors versus pMMR tumors.9-10  There remains an unmet need for targeted therapies for patients with pMMR EC.11 About XPOVIO® (selinexor) XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor compound for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved and marketed by Karyopharm in the U.S. in multiple oncology indications, including: (i) in combination with VELCADE® (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma after at least one prior therapy; and (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma. XPOVIO® (also known as NEXPOVIO® in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO®/NEXPOVIO® is marketed in these respective ex-U.S. territories by Karyopharm's partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high-unmet need cancer indications. For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected] XPOVIO® (selinexor) is a prescription medicine approved: In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd). In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd). SELECT IMPORTANT SAFETY INFORMATION Warnings and Precautions Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.Serious Infection: Monitor for infection and treat promptly.Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract. Adverse Reactions The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia, and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%. The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%. Use In Specific PopulationsLactation: Advise not to breastfeed. For additional product information, including full prescribing information, please visit www.XPOVIO.com.To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch. About Karyopharm Therapeutics Karyopharm Therapeutics is a commercial-stage pharmaceutical company pioneering the science of nuclear export inhibition to develop differentiated therapies for patients with cancer. The Company's lead therapy, XPOVIO® (selinexor), is a first-in-class inhibitor of exportin 1 (XPO1). XPOVIO is marketed by the Company in the U.S. for adults with relapsed or refractory multiple myeloma and is approved as XPOVIO or NEXPOVIO® in more than 50 ex-U.S. countries and territories. Building on its leadership in XPO1 biology, Karyopharm is advancing selinexor's potential in hematological cancers, including in myelofibrosis. The Company is also exploring opportunities to evaluate XPO1 inhibition across myeloproliferative neoplasms using next-generation compounds, including eltanexor. Headquartered in Newton, Massachusetts, Karyopharm has an established, efficient, and scalable commercial infrastructure to bring novel therapeutic options to patients with cancer. For more information, visit www.karyopharm.com and follow Karyopharm on LinkedIn and on X at @Karyopharm. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's guidance on its 2026 total revenue, 2026 U.S. net product revenue and 2026 R&D and SG&A expenses; expected cash runway and liquidity, including its ability to make scheduled debt service payments and maintain compliance with its minimum liquidity covenant; Karyopharm's expectations with respect to the timing and submission of a potential sNDA for selinexor in combination with ruxolitinib in myelofibrosis; Karyopharm's ongoing engagement with the FDA; the potential availability of the accelerated approval pathway; whether long-term overall survival data from the SENTRY trial will verify clinical benefit; the potential availability of priority review of the sNDA; expectations with respect to commercialization efforts; expectations regarding the timing of reporting topline data from ongoing clinical trials; the ability of selinexor and eltanexor to treat patients with multiple myeloma, myelofibrosis, and other diseases; expectations with respect to the clinical development plans and potential regulatory submissions of selinexor; and the potential inclusion of the combination of selinexor plus ruxolitinib in relevant compendia. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical trials, including subsequent analysis of existing data and new data received from ongoing and future trials; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical trials; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; substantial doubt exists regarding Karyopharm's ability to continue as a going concern; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, which was filed with the Securities and Exchange Commission (SEC) on May 14, 2026, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. CONTACTS: Investors: Brendan StrongSenior Vice President, Investor [email protected] Media: Mary Ann OndishHead of Corporate [email protected] View original content to download multimedia:https://www.prnewswire.com/news-releases/karyopharm-reports-second-quarter-2026-financial-results-and-highlights-continued-progress-toward-myelofibrosis-snda-submission-302850269.html

-- Conference Call Scheduled for Thursday, August 13, 2026, at 8:00 a.m. ET -- NEWTON, Mass., Aug. 10, 2026 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced it will report second quarter 2026 financial results on Thursday, August 13, 2026. Karyopharm's management team will host a conference call and audio webcast at 8:00 a.m. ET on Thursday, August 13, 2026, to discuss the financial results and other company updates. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company's website approximately two hours after the event. About Karyopharm Therapeutics Karyopharm Therapeutics is a commercial-stage pharmaceutical company pioneering the science of nuclear export inhibition to develop differentiated therapies for patients with cancer. The Company's lead therapy, XPOVIO® (selinexor), is a first-in-class inhibitor of exportin 1 (XPO1). XPOVIO is marketed by the Company in the U.S. for adults with relapsed or refractory multiple myeloma and is approved as XPOVIO or NEXPOVIO® in more than 50 ex-U.S. countries and territories. Building on its leadership in XPO1 biology, Karyopharm is advancing selinexor's potential in hematological cancers, including in myelofibrosis. The Company is also exploring opportunities to evaluate XPO1 inhibition across myeloproliferative neoplasms using next-generation compounds, including eltanexor. Headquartered in Newton, Massachusetts, Karyopharm has an established, efficient, and scalable commercial infrastructure to bring novel therapeutic options to patients with cancer. For more information about our people, science and pipeline, please visit www.karyopharm.com, and follow us on LinkedIn and on X at @Karyopharm. XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. View original content to download multimedia:https://www.prnewswire.com/news-releases/karyopharm-to-report-second-quarter-2026-financial-results-on-august-13-2026-302845213.html

– The Trial Did Not Meet the Primary Endpoint of Progression-Free Survival (PFS) – – A Trend Favoring the Selinexor Arm was Observed with a 5.3 Month Improvement in Median PFS Relative to the Placebo Arm in the mITT Population; Company Plans to Continue to Follow Patients for Longer-Term Outcomes – – The Safety and Tolerability Profile was Consistent with the Known Profile of Selinexor; No New Safety Signals Were Observed – – Company Prioritizing its Resources on its Myelofibrosis and Multiple Myeloma Programs; Company to Reduce Planned Investment in Endometrial Cancer – NEWTON, Mass., July 30, 2026 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced topline results from its Phase 3 XPORT-EC-042 trial evaluating selinexor as a maintenance-only therapy compared to placebo in adult patients with TP53 wild-type advanced or recurrent endometrial cancer. The trial did not meet its primary endpoint of progression free survival. A trend favoring the selinexor arm was observed in the modified intent to treat (mITT) population (n=236), with a median PFS of 12.75 months in the selinexor arm compared to 7.43 months in the placebo arm (hazard ratio=0.76 [95% CI: 0.51, 1.12]; one-sided p-value=0.0791). The safety and tolerability profile of selinexor was consistent with its established safety profile, with no new safety signals observed. Karyopharm intends to complete a full evaluation of the data from the XPORT-EC-042 trial and plans to present the data at a future medical meeting. The results of the XPORT-EC-042 trial do not affect ongoing trials of selinexor in other potential indications. "These results are meaningful for a patient population lacking effective maintenance therapies that can delay disease progression," said Professor Ignace Vergote, MD, gynecologic oncologist at the Catholic University Leuven in Belgium, European Network for Gynaecological Oncological Trial groups (ENGOT) and global lead principal investigator. "The trend for a longer progression-free survival observed in the mITT population of the selinexor arm continues to highlight the potential of XPO1 inhibition in patients with TP53 wild-type/pMMR endometrial cancer." "Delaying the progression of cancer by five months at the median is a meaningful and encouraging outcome," said Dr. Robert Coleman, M.D., FACOG, FACS, of Texas Oncology and the Gynecologic Oncology Group (GOG) and lead principal investigator in the United States. "Although I am disappointed that the PFS improvement was not statistically significant, I look forward to continuing to follow these results over time and presenting the data from this important trial at an upcoming medical meeting. This patient population who have TP53 wild-type/pMMR advanced or recurrent endometrial cancer remains in need of new treatment options." "While disappointed by these unexpected results, we believe they advance the scientific understanding of XPO1 inhibition for tens of thousands of endometrial cancer patients worldwide. We are deeply committed to further investigating these data," said Reshma Rangwala, MD, PhD, Chief Medical Officer and Head of Research at Karyopharm. "I would like to thank all of the patients, their families and the clinical trial investigators and their staff, as well as ENGOT and GOG, for participating in this trial." "While the results we are announcing today fell short of our expectations, they do not diminish our confidence in the broader potential of selinexor and benefit of XPO1 inhibition," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "We remain focused on maximizing our opportunity in myelofibrosis and continuing to build on our profitable multiple myeloma business. Looking ahead, we expect several important milestones in our myelofibrosis program over the next year, including the submission of our sNDA, the potential addition of selinexor to relevant compendia guidelines and topline data from the 60 mg cohort of the Phase 2 SENTRY-2 trial, each anticipated in the second half of 2026." About the Phase 3 XPORT-EC-042 Trial EC-042 (XPORT-EC-042; ENGOT-EN20; GOG-3083; NCT05611931) is a global, Phase 3, randomized, double-blind, placebo-controlled clinical trial evaluating selinexor as a maintenance-only therapy following chemotherapy or chemotherapy plus a checkpoint inhibitor in patients with TP53 wild-type advanced or recurrent endometrial cancer (N=257). Patients were randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The trial includes two patient populations, for which the primary endpoint of progression free survival was tested sequentially: 1) a modified intent to treat population (mITT) that includes patients with either, a) TP53 wild-type tumors with proficient mismatch repair status (pMMR); or, b) TP53 wild-type tumors with deficient mismatch repair status (dMMR), who are medically ineligible to receive checkpoint inhibitors; and, 2) the trial's original intent to treat (ITT) population, which includes all patients enrolled in the trial whose tumors are TP53 wild-type, regardless of MMR status. Overall survival is a key secondary endpoint. The mITT population enrolled 236 patients. As of the data cut-off, 106 progression free survival events as assessed by the investigator had been observed in the mITT population. In connection with the EC-042 trial, Karyopharm entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOne®CDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 wild-type. The trial is being conducted in collaboration with the European Network of Gynaecological Oncological Trial groups (ENGOT) and the GOG Foundation, Inc. About Endometrial Cancer Endometrial cancer (EC) is the most common gynecologic malignancy in the U.S.1 In 2026, approximately 68,000 uterine cancers (predominantly endometrial) are expected to be diagnosed, with approximately 14,000 deaths.1 Worldwide there were about 420,368 cases with 97,723 deaths in 2022.2 Both incidence and mortality have continued to rise.3,4  Key risk factors include obesity, type 2 diabetes, high-fat diets, tamoxifen or oral estrogen use, and delayed menopause.5 TP53 is a well-recognized prognostic marker for EC; >50% of advanced or recurrent EC tumors are TP53wt (gene for tumor protein P53; wild-type), and ~40%-55% are both TP53wt and mismatch repair-proficient (pMMR).6-8 While immune checkpoint inhibitors have shown benefit in patients with mismatch repair–deficient (dMMR) and pMMR, the magnitude of benefit is greater for patients with dMMR tumors versus pMMR tumors.9-10  There remains an unmet need for targeted therapies for patients with pMMR EC.11 About XPOVIO® (selinexor) XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor compound for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved and marketed by Karyopharm in the U.S. in multiple oncology indications, including: (i) in combination with VELCADE® (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma after at least one prior therapy; and (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma. XPOVIO® (also known as NEXPOVIO® in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO®/NEXPOVIO® is marketed in these respective ex-U.S. territories by Karyopharm's partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high-unmet need cancer indications. For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected] XPOVIO® (selinexor) is a prescription medicine approved: In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd). In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd). SELECT IMPORTANT SAFETY INFORMATION Warnings and Precautions Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.Serious Infection: Monitor for infection and treat promptly.Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract. Adverse Reactions The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia, and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%. The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%. Use In Specific PopulationsLactation: Advise not to breastfeed. For additional product information, including full prescribing information, please visit www.XPOVIO.com. To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch. About Karyopharm Therapeutics Karyopharm Therapeutics is a commercial-stage pharmaceutical company pioneering the science of nuclear export inhibition to develop differentiated therapies for patients with cancer. The Company's lead therapy, XPOVIO® (selinexor), is a first-in-class inhibitor of exportin 1 (XPO1). XPOVIO is marketed by the Company in the U.S. for adults with relapsed or refractory multiple myeloma and is approved as XPOVIO or NEXPOVIO® in more than 50 ex-U.S. countries and territories. Building on its leadership in XPO1 biology, Karyopharm is advancing selinexor's potential in hematological cancers, including in myelofibrosis. The Company is also exploring opportunities to evaluate XPO1 inhibition across myeloproliferative neoplasms using next-generation compounds, including eltanexor. Headquartered in Newton, Massachusetts, Karyopharm has an established, efficient, and scalable commercial infrastructure to bring novel therapeutic options to patients with cancer. For more information, visit www.karyopharm.com and follow Karyopharm on LinkedIn and on X at @Karyopharm. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor and eltanexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, and other diseases; expectations with respect to the clinical development plans, regulatory discussions and potential regulatory submissions for selinexor; and expectations regarding the timing, presentation and publication of topline data, publications or compendia listings related to selinexor. Such statements are subject to numerous important factors, risks, and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical trials, including subsequent analysis of existing data and new data received from ongoing and future trials; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical trials; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; substantial doubt exists regarding Karyopharm's ability to continue as a going concern; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, which was filed with the Securities and Exchange Commission (SEC) on May 14, 2026, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. View original content to download multimedia:https://www.prnewswire.com/news-releases/karyopharm-announces-topline-results-from-phase-3-xport-ec-042-trial-in-endometrial-cancer-302839314.html

– Selinexor in Combination with Ruxolitinib Demonstrated a Rapid and Near Doubling of Patients Achieving SVR35 at Week 24, versus Ruxolitinib, with a Consistent SVR35 Benefit Observed Across Prespecified Subgroups – – Similar Symptom Improvement Was Observed Across the Two Arms Relative to Baseline; Reductions in Symptoms Were Consistent Across Each Domain – – Promising Overall Survival Signal with >50% Reduction of Risk of Death versus Ruxolitinib, with Early Separation of the Kaplan-Meier Curves – – Evidence of Potential Disease Modification with More Patients Achieving ≥20% Reductions in VAF as Early as Week 24 versus Ruxolitinib – NEWTON, Mass., June 2, 2026 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, will present the results of its Phase 3 SENTRY trial in a late-breaking oral presentation titled: Selinexor plus ruxolitinib in JAK inhibitor-naïve myelofibrosis: Phase 3 SENTRY trial (LBA6500) at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting today. The presentation will open the Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant session at 9:45 a.m. CT. The SENTRY results were also published this morning in the peer-reviewed Journal of Clinical Oncology (JCO). "The Phase 3 SENTRY results represent a meaningful advance for patients with myelofibrosis and underscore the promise of combining selinexor with ruxolitinib," said Dr. John Mascarenhas, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders. "What is particularly compelling is the rapid, deep and sustained spleen volume reduction observed in the trial, as spleen response remains one of the most clinically relevant treatment goals in myelofibrosis. The OS Kaplan-Meier curves presented at ASCO demonstrate an early and sustained separation between treatment arms, reinforcing the potential of selinexor plus ruxolitinib to meaningfully improve outcomes for patients." Key Highlights: Spleen Volume Reduction: The combination of selinexor plus ruxolitinib demonstrated a statistically significant improvement in the co-primary endpoint of spleen volume reduction of 35% or more (SVR35), with rapid, deep and sustained spleen volume reduction seen in the combination arm and a consistent benefit observed across prespecified subgroups. At week 24, SVR35 was achieved in 49.8% of patients randomized to the selinexor combination versus 28.0% of patients randomized to ruxolitinib alone (odds ratio 2.58; 95% CI [1.60 to 4.17]; p<0.0001). Responses occurred early and were sustained, with SVR35 rates of 49.4% in the selinexor combination arm versus 20.3% for ruxolitinib alone at week 12 and 46.9% versus 23.0% at week 36, respectively. SVR35 was achieved at any time in 67.7% of patients randomized to the selinexor combination versus 44.9% randomized to ruxolitinib alone. The mean percent change in spleen volume at week 24 was a reduction of 40.0% for the selinexor combination versus a reduction of 26.7% for ruxolitinib alone. In the selinexor combination, the median selinexor dose was 51.7 mg/week and the median ruxolitinib dose was 23.0 mg/day. Notably, at week 24, superior spleen volume reduction was achieved by the selinexor combination, regardless of the ruxolitinib dose, including by patients receiving less than 15 mg of ruxolitinib per day. Absolute Total Symptom Score (Abs-TSS): Similar symptom improvement from baseline was observed with the selinexor combination compared to ruxolitinib alone as measured by Abs-TSS at week 24. A mean (95% CI) reduction of 9.9 points (−11.2 to −8.6) was observed in patients randomized to the selinexor combination versus a reduction of 10.9 points (−12.6 to −9.1) in patients randomized to ruxolitinib alone. Symptom reductions were consistent across each of the six domains measured. The adjusted mean difference of 0.97 points (95% CI [-1.07 to 3.02]; p=0.825) in Abs-TSS, a co-primary endpoint, did not meet statistical significance. Overall Survival: A promising overall survival signal, a pre-specified secondary endpoint, was observed with the selinexor combination compared to ruxolitinib alone. As of February 20, 2026, 224 (95.3%) patients randomized to the selinexor combination and 106 (89.8%) randomized to ruxolitinib alone were alive. With a median follow-up of 11.6 and 12.6 months, respectively, overall survival favored the selinexor combination with a hazard ratio of 0.43 (95% CI [0.19 to 1.00]; nominal one-sided p=0.022) with separation of Kaplan–Meier curves occurring around month 9. Variant Allele Frequency (VAF) Reduction: Potential disease modification from a pre-specified exploratory endpoint was observed as early as week 24 from baseline in the combination arm. VAF reduction ≥20% at week 24 occurred in 32.0% of patients receiving the selinexor combination versus 23.9% of patients receiving ruxolitinib alone and correlated with SVR35 response. Circulating Peripheral Blast Counts: Circulating peripheral blasts are a poor prognostic factor and potential marker of disease burden. A post-hoc analysis showed that more patients who received the selinexor combination and who had no detectable circulating peripheral blasts at baseline maintained no detectable blasts through the course of treatment compared to patients who received ruxolitinib alone. For patients with circulating peripheral blasts at baseline, more patients who received the selinexor combination had no detectable blasts through the course of treatment compared to patients who received ruxolitinib alone. Safety and Tolerability: The combination demonstrated a manageable safety and tolerability profile consistent with the known profile of selinexor and ruxolitinib individually. No new safety signals were observed. Treatment emergent adverse events (TEAEs) occurred in 99.1% of patients receiving the selinexor combination and in 97.4% of patients receiving ruxolitinib alone. The five most common all-grade TEAEs in the selinexor combination arm were thrombocytopenia (selinexor plus ruxolitinib arm: 59%; placebo plus ruxolitinib arm: 43%), anemia (57%; 58%), nausea (57%; 17%), constipation (32%; 36%) and neutropenia (27%; 9%) (n=234; n=116). The rate of grade 3+ TEAEs was 70% in the selinexor combination arm compared to 50% in the placebo plus ruxolitinib arm, and were primarily hematologic in nature. The percentage of patients treated with the combination who experienced TEAEs leading to death occurred in 0.9% of patients receiving the combination compared to 2.6% of patients receiving ruxolitinib alone. Confirmed leukemic transformation was 1.7% in each arm. "We believe the results presented at ASCO today highlight selinexor's differentiated mechanism of action and its potential to offer a complementary approach to JAK inhibition," said Reshma Rangwala, MD, PhD, Chief Medical Officer and Head of Research of Karyopharm. "Importantly, these findings reinforce the opportunity to target biological pathways beyond JAK signaling to further advance outcomes for patients with myelofibrosis." The abstract "Selinexor plus ruxolitinib in JAK inhibitor–naïve myelofibrosis: Phase 3 SENTRY trial" (abstract number LBA6500) is available on ASCO's website. A copy of the SENTRY presentation being delivered at ASCO will be available under Publications and Presentations in the Investors & Media section of the Company's website at approximately 11:00 a.m. ET today. Finally, the peer-reviewed publication discussing the results from the Phase 3 SENTRY trial was published this morning in the Journal of Clinical Oncology and is available on JCO's website. About the Phase 3 SENTRY Trial SENTRY (XPORT-MF-034; NCT04562389) is a Phase 3 clinical trial evaluating a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib in JAKi-naïve myelofibrosis patients with platelet counts >100 x 109/L (N=353). Patients were randomized 2-to-1 to the selinexor arm. The co-primary endpoints for this trial are spleen volume reduction ≥ 35% (SVR35) at week 24 and the average change in absolute total symptom score (Abs-TSS) over 24 weeks relative to baseline. About Myelofibrosis Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 17,000 patients in the European Union1. The disease causes bone marrow fibrosis (scarring in the bone marrow), which makes it difficult for the bone marrow to make healthy blood cells, splenomegaly (enlarged spleen), progressive anemia which often leads to symptoms like fatigue and weakness, and other disease associated symptoms including abdominal discomfort, pain under the left ribs, early satiety, night sweats and bone pain. The only approved class of therapies to treat myelofibrosis are JAK inhibitors, including ruxolitinib. 1. Clarivate/DRG (2023) About XPOVIO® (selinexor) XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor compound for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved and marketed by Karyopharm in the U.S. in multiple oncology indications, including: (i) in combination with VELCADE® (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma after at least one prior therapy; and (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma. XPOVIO® (also known as NEXPOVIO® in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO®/NEXPOVIO® is marketed in these respective ex-U.S. territories by Karyopharm's partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in myelofibrosis and endometrial cancer. For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected] XPOVIO® (selinexor) is a prescription medicine approved: In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd). In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd). SELECT IMPORTANT SAFETY INFORMATION Warnings and Precautions Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care. Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors. Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care. Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care. Serious Infection: Monitor for infection and treat promptly. Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes. Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception. Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract. Adverse Reactions The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%. The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%. Use In Specific PopulationsLactation: Advise not to breastfeed. For additional product information, including full prescribing information, please visit www.XPOVIO.com. To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch. About Karyopharm Therapeutics Karyopharm Therapeutics is a commercial-stage pharmaceutical company pioneering the science of nuclear export inhibition to develop differentiated therapies for patients with cancer. The Company's lead therapy, XPOVIO® (selinexor), is a first-in-class inhibitor of exportin 1 (XPO1). XPOVIO is marketed by the Company in the U.S. for adults with relapsed or refractory multiple myeloma and is approved as XPOVIO or NEXPOVIO® in more than 50 ex-U.S. countries and territories. Building on its leadership in XPO1 biology, Karyopharm is advancing selinexor's potential in hematologic and solid tumor cancers, including in myelofibrosis and TP53 wild-type endometrial cancer. The Company is also exploring opportunities to evaluate XPO1 inhibition across myeloproliferative neoplasms and TP53 wild-type driven solid tumors using next-generation compounds, including eltanexor. Headquartered in Newton, Massachusetts, Karyopharm has an established, efficient and scalable commercial infrastructure to bring novel therapeutic options to patients with cancer. For more information, visit www.karyopharm.com and follow Karyopharm on LinkedIn and on X at @Karyopharm. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's beliefs about the market opportunity and annual peak revenue opportunities for selinexor; expectations with respect to commercialization efforts; expectations regarding the timing of reporting topline data, publications or compendia listing related to ongoing clinical trials; the ability of selinexor and eltanexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, and other diseases; expectations with respect to the clinical development plans and potential regulatory submissions of selinexor; and the potential inclusion of the combination of selinexor plus ruxolitinib in relevant compendia. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical trials, including subsequent analysis of existing data and new data received from ongoing and future trials; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical trials; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; substantial doubt exists regarding Karyopharm's ability to continue as a going concern; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, which was filed with the Securities and Exchange Commission (SEC) on May 14, 2026, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. View original content to download multimedia:https://www.prnewswire.com/news-releases/karyopharm-to-present-results-from-phase-3-sentry-trial-of-selinexor-plus-ruxolitinib-in-myelofibrosis-in-late-breaking-oral-presentation-at-asco-2026-with-simultaneous-publication-in-the-journal-of-clinical-oncology-302788575.html

This article first appeared on GuruFocus. Release Date: May 14, 2026 For the complete transcript of the earnings call, please refer to the full earnings call transcript. Karyopharm Therapeutics Inc (NASDAQ:KPTI) reported strong net product revenue growth, driven by favorable gross-to-net dynamics. The Phase III SENTRY trial in myelofibrosis showed a compelling profile for selinexor in combination with ruxolitinib, including rapid, deep, and sustained spleen volume responses. The company completed enrollment in the export EC042 trial for endometrial cancer, with top-line data expected in mid-2026. Karyopharm Therapeutics Inc (NASDAQ:KPTI) strengthened its balance sheet with financing completed in Q1, providing increased liquidity. The company has established strong commercial capabilities and relationships, positioning it well for future potential launches in myelofibrosis and endometrial cancer. Underlying demand for XPOVIO was lower compared to the first quarter of 2025 due to new competitive entrants. The company faces challenges in the evolving and competitive landscape of multiple myeloma treatment. There is uncertainty regarding the timing and outcome of FDA engagements and potential SNDA for myelofibrosis. The company reported a net loss of $22.4 million for the quarter, although this was an improvement from the previous year. The Phase III SENTRY trial did not achieve statistical significance for symptom improvement at week 24, although both arms showed similar improvements from baseline. Warning! GuruFocus has detected 8 Warning Signs with KPTI. Is KPTI fairly valued? Test your thesis with our free DCF calculator. Q: 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 RUX arm relative to the SELI plus RUX arm? A: (Unidentified_4) We are looking at the deaths, specifically the 23 deaths reported at the time of the top-line. They are consistent with what you would expect in MF and other oncology trials, such as deaths due to progression of disease and adverse events. More details will be shared as we continue to evaluate these data. Q: Can you give us more information about the potential timing or preparation for the meeting with the FDA regarding myelofibrosis? A: (Unidentified_4) We are very compelled by the profile we saw at the time of the top-line results. We look forward to engaging with the FDA, who have been strong partners with us from the beginning of the SENTRY trial. We hope to elaborate on our next steps over the next couple of quarters. Q: Could you discuss the gating factors for potential compendia inclusion for Selinexor, and how do you view this opportunity versus an approval? A: (Unidentified_4) NCCN and other compendia are independent bodies that constantly review literature and data for new treatments. We expect them to be aware of the data we present at ASCO and any publications. If included in guidelines, it could achieve approximately 50% of the revenue potential compared to having a label. Q: With 257 patients enrolled in the ITT for endometrial cancer, does that still provide sufficient powering to show significance in the broader ITT population? A: (Unidentified_4) Yes, we are well-powered to show meaningful benefit in both the MITT and ITT populations. The benefit of selinexor is driven by the P53 status, not the MMR status, so we are confident in our ability to demonstrate significant results. Q: What dose is used in the 042 study, and how does it compare to the CNDO study? What gives you confidence in the 042 study dose? A: (Unidentified_4) In the CNDO study, the dose was 80 mg of selinexor weekly, while in the EC042 study, we optimized it to 60 mg weekly with dual antiemetics for the first two cycles. This dose was chosen based on comprehensive data showing improved safety and tolerability, which should enable patients to stay on treatment longer. For the complete transcript of the earnings call, please refer to the full earnings call transcript.

Interested in Karyopharm Therapeutics Inc.? Here are five stocks we like better. Key clinical catalysts are ahead for Karyopharm, including FDA engagement and publication plans for its Phase 3 SENTRY myelofibrosis trial, plus an expected mid-2026 readout from the endometrial cancer study XPORT-EC-042. The SENTRY trial showed a statistically significant spleen volume response benefit for selinexor plus ruxolitinib, along with an encouraging overall survival signal and no new safety concerns, though the symptom endpoint was not statistically significant. First-quarter revenue rose to $35.1 million, and Karyopharm reaffirmed full-year 2026 guidance; however, management said underlying XPOVIO demand was weaker year over year due to increased competition. Karyopharm Therapeutics (NASDAQ:KPTI) said it entered 2026 with several near-term clinical and regulatory catalysts, led by new Phase 3 data in myelofibrosis and an expected midyear readout in endometrial cancer, while reporting higher first-quarter revenue and reaffirming full-year guidance. On the company’s first-quarter earnings call, President and CEO Richard Paulson said Karyopharm has focused its organization on advancing late-stage clinical programs, maintaining its commercial base in multiple myeloma and managing expenses as it approaches “significant value-creating milestones.” → Rocket Lab Just Hit a New All-Time High—Time to Buy or Let It Breathe? Paulson said the company is now focused on regulatory and scientific engagement for its Phase 3 SENTRY trial in myelofibrosis, preparing for top-line results from XPORT-EC-042 in endometrial cancer and maintaining financial discipline. He said Karyopharm’s current operating plan is expected to fund operations into late in the third quarter of 2026. Chief Medical Officer and Head of Research Reshma Rangwala said Karyopharm remains encouraged by top-line results from SENTRY, which evaluated selinexor in combination with ruxolitinib in myelofibrosis. The company said the combination produced rapid and sustained spleen volume reductions, with the co-primary endpoint of SVR35 at week 24 reached by 50% of patients on the combination versus 28% on ruxolitinib alone. Rangwala said that result was statistically significant, with a P value of less than 0.0001. → MP Materials Is Quietly Building a Rare Earth Powerhouse The trial’s second co-primary endpoint, symptom improvement at week 24, was not statistically significant by absolute total symptom score difference, though Rangwala said patients in both arms had “important and similar improvement from baseline.” Karyopharm also highlighted what it described as an “intriguing” overall survival signal. Rangwala said the overall survival hazard ratio was 0.43 at the time of the top-line data, with a nominal P value of 0.0222. She said post hoc analyses showed SVR35 predicts overall survival, consistent with previously published analyses in other myelofibrosis trials. → Micron Investors Face a High-Stakes Moment After the Latest Rally The company also pointed to variant allele frequency reductions as potential evidence of disease modification. Rangwala said 32% of patients receiving selinexor plus ruxolitinib had at least a 20% reduction in variant allele frequency, which she said may indicate an effect on disease biology. Rangwala said the combination had a generally manageable tolerability profile, consistent with the known profiles of the individual agents, and that no new safety signals were observed. She said use of a lower selinexor dose and dual antiemetics improved tolerability compared with an earlier Phase 1 study. Karyopharm said SENTRY data have been selected for a late-breaking oral presentation at ASCO, and the company expects a manuscript in a peer-reviewed journal in mid-2026. Rangwala said Karyopharm looks forward to discussions with the FDA, though she did not provide a specific timeline for regulatory feedback. The company’s next major catalyst is XPORT-EC-042, a Phase 3 trial in endometrial cancer. Paulson said enrollment is complete and top-line data remain expected in mid-2026. Rangwala said the study is focused on patients with TP53 wild-type endometrial cancer, especially those with mismatch repair-proficient tumors, where Karyopharm sees a significant unmet need and no approved personalized biomarker-driven maintenance-only therapy. She said approximately half of endometrial cancer patients are TP53 wild-type and about 80% have MMR-proficient tumors. Rangwala reviewed prior SIENDO trial results, saying the TP53 wild-type subgroup had median progression-free survival of 13.7 months for selinexor versus 3.7 months for placebo at top line, corresponding to a hazard ratio of 0.41. With longer-term follow-up, she said median PFS in the selinexor arm extended to 28.4 months, with a hazard ratio of 0.44. In TP53 wild-type, MMR-proficient patients, she said median PFS approached 40 months at long-term follow-up, with a hazard ratio of 0.36. In the ongoing XPORT-EC-042 trial, selinexor is being dosed at 60 milligrams once weekly, compared with 80 milligrams in SIENDO. Rangwala said the study also mandates dual antiemetics during the first two cycles, when nausea and vomiting are most likely to occur. She said the adjusted dose and supportive care approach could improve tolerability and help patients remain on treatment longer. The trial enrolled 257 patients in the intent-to-treat population, including approximately 220 patients in the modified intent-to-treat population, which is the primary analysis population. Rangwala said the study will first assess progression-free survival in the mITT population, with alpha passing sequentially to the full ITT population if the first analysis is statistically significant. Chief Commercial Officer and Head of Business Development Sohanya Cheng said first-quarter net product revenue growth was driven primarily by favorable gross-to-net dynamics. However, she said underlying demand for XPOVIO was lower than in the first quarter of 2025, reflecting new competitive entrants. Cheng said Karyopharm continues to position XPOVIO as a flexible oral option in the second- to fourth-line community setting for multiple myeloma, and as a differentiated mechanism in the peri T-cell engaging therapy setting, including use before CAR T therapy or after progression on a T-cell engaging therapy. Looking ahead, Cheng said Karyopharm believes its sales, marketing, market access and medical affairs capabilities could be leveraged for potential launches in myelofibrosis and endometrial cancer with limited incremental investment before approval and modest additional spending after launch. In myelofibrosis, Cheng said the U.S. market includes roughly 20,000 patients living with the disease and about 7,000 newly diagnosed frontline patients annually, around 4,000 of whom Karyopharm considers addressable. She said the company believes selinexor plus ruxolitinib has potential to generate up to approximately $1 billion in U.S. peak annual revenue, if approved. Chief Financial Officer Lori Macomber said total first-quarter revenue was $35.1 million, up from $30 million in the prior-year period. U.S. XPOVIO net product revenue was $29.2 million, compared with $21.1 million a year earlier. Macomber said the increase was driven by a lower gross-to-net rate of 21.8%, compared with 45% in the first quarter of 2025, which had been affected by an atypical product return adjustment. Excluding those adjustments, she said underlying gross-to-net was approximately 26% in the latest quarter. Research and development expenses were $33.8 million, while selling, general and administrative expenses were $26.7 million, both relatively consistent year over year. Net loss was $22.4 million, compared with $23.5 million in the prior-year period. Macomber said loss from operations fell 20%, reflecting higher revenue and expense discipline. Karyopharm ended the quarter with $91.2 million in cash, cash equivalents and restricted cash, including approximately $50 million raised during the quarter. The company reaffirmed 2026 guidance for total revenue of $130 million to $150 million, U.S. XPOVIO net product revenue of $115 million to $130 million and combined R&D and SG&A expenses of $230 million to $245 million. Paulson closed the call by saying Karyopharm is focused on SENTRY next steps, including FDA engagement, ASCO presentation, publication planning and potential compendia inclusion, while preparing for the endometrial cancer readout in mid-2026. Karyopharm Therapeutics (NASDAQ: KPTI) is a clinical-stage biopharmaceutical company focused on discovering and developing novel first-in-class drugs that target the nuclear export protein XPO1. The company's lead product, selinexor (marketed as XPOVIO), is an oral selective inhibitor of nuclear export (SINE) compound approved for treatment of multiple myeloma and diffuse large B-cell lymphoma. In addition to selinexor, Karyopharm's pipeline includes second-generation SINE compounds and combination studies in solid tumors and hematologic malignancies. Founded in 2008 and headquartered in Newton, Massachusetts, Karyopharm has built a research platform around modulation of nuclear export pathways. This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to [email protected]. The article "Karyopharm Therapeutics Q1 Earnings Call Highlights" was originally published by MarketBeat. View MarketBeat's top stocks for May 2026.

Our analysts just identified a stock with the potential to be the next Nvidia. Tell us how you invest and we'll show you why it's our #1 pick. Tap here. Management is pivoting from clinical execution to regulatory and scientific engagement following the Phase III SENTRY trial readout in myelofibrosis. The SENTRY trial demonstrated a differentiated profile for selinexor plus ruxolitinib, showing rapid and sustained spleen volume reduction alongside a promising overall survival signal. Evidence of potential disease modification was highlighted by greater reductions in variant allele frequency as early as week 24, suggesting an impact on underlying disease biology. In endometrial cancer, the strategy focuses on the p53 wild-type biomarker, where approximately 50% of patients currently lack personalized maintenance therapy options. Commercial performance for XPOVIO in multiple myeloma is being managed through a focus on the community setting and positioning as a bridge to or post-T-cell engaging therapies. Operational discipline is centered on optimizing the patient experience through lower dosing (60mg) and mandated dual antiemetics to improve long-term treatment adherence. Top-line data from the Phase III export EC042 trial in endometrial cancer is expected in mid-2026, serving as the next major value-creating catalyst. Management anticipates that the EC042 trial may show improved safety and efficacy over the previous SIENDO study due to optimized 60mg dosing and mandated antiemetics. The company is preparing for potential rapid market adoption in myelofibrosis, targeting a $1 billion U.S. peak annual revenue opportunity. Current liquidity of $91.2 million is projected to fund operations into late Q3 2026, covering the major clinical and regulatory milestones. Regulatory strategy for myelofibrosis includes upcoming FDA engagement and potential NCCN compendia inclusion following the ASCO late-breaking presentation. Q1 net product revenue growth was primarily driven by favorable gross-to-net dynamics (21.8% vs 45% YoY) due to an atypical product return adjustment. Underlying demand for XPOVIO was lower year-over-year, which management attributed to the impact of new competitive entrants in the myeloma space. The company successfully completed a $50 million financing in Q1 to strengthen the balance sheet ahead of Phase III readouts. Management flagged that while the SENTRY trial met spleen volume endpoints, it did not reach statistical significance for the co-primary endpoint of absolute Total Symptom Score (TSS) improvement. One stock. Nvidia-level potential. 30M+ investors trust Moby to find it first. Get the pick. Tap here. Management noted that the FDA has historically shown flexibility in myelofibrosis, citing approvals for drugs that missed primary endpoints but showed other measures of clinical benefit. They emphasized that the totality of data, including survival signals and disease modification, provides a strong basis for regulatory discussions despite the TSS miss. Management explained that NCCN guidelines can drive meaningful revenue even without a formal label, potentially capturing 50% of peak opportunity through physician choice. They expect the ASCO presentation and mid-2026 manuscript publication to be key triggers for independent compendia review. The EC042 trial enrolled 257 patients, slightly below the original 276 target, but management confirmed they remain well-powered for the primary MITT population of 220 patients. The shift in the ITT number was due to a higher-than-expected proportion of the target biomarker population within the enrolled group.