Good morning. My name is Jenny, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics call to discuss top-line results from the phase III SENTRY trial. There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the conference call over to Brendan Strong, Senior Vice President, Investor Relations. Good morning, and thank you for joining us on today's conference call to discuss the results from our phase III SENTRY trial, evaluating Selinexor in combination with Ruxolitinib in Myelofibrosis. Today's news is many years in the making, and we're delighted that you're able to join our call today. We issued a press release this morning with top-line efficacy and safety data from SENTRY. We also issued a press release to announce a financing that provides us with $30 million at closing, with additional funding if the associated warrants are exercised. These releases, along with a slide presentation that we'll reference during our call today, are available on our website. For today's call, as seen on slide two, I'm joined by Richard and Reshma, who will be presenting, and Sohanya and Lori, who are also joining for Q&A. We're also joined today by 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. Dr. Mascarenhas is one of the world's leading experts on Myelofibrosis and the principal investigator of our phase III SENTRY trial. We're very pleased that you will hear directly from him on the importance of our results and the potential benefit to patients. 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 three. 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-K on file with the SEC and in other filings that 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 five. Good morning, and thank you for joining us today. Today, we are excited to share top-line results from our phase III SENTRY trial evaluating Selinexor in combination with Ruxolitinib in patients with JAK inhibitor-naive Myelofibrosis. These data represent an important milestone for Karyopharm and, more importantly, for patients living with this serious disease. Myelofibrosis remains a disease with significant unmet need. Current therapies deliver modest spleen responses, limited evidence of disease modification, and JAK inhibitors remain the only approved class of therapies. There's a clear need for new treatment options that can improve outcomes for patients, particularly overall survival. From an efficacy perspective, the study met the first of its two co-primary endpoints. Selinexor plus Ruxolitinib delivered a statistically significant improvement in spleen volume reduction. In addition, the combination showed rapid, deep, and sustained spleen volume response rates compared to Ruxolitinib alone. As many of you know, spleen reduction is a critical clinical outcome in Myelofibrosis and one that physicians focus on closely in practice. While the difference on the absolute TSS endpoint was not statistically significant, patients in both arms experienced important and similar symptom improvement from baseline. Additionally, the combination showed a promising overall survival signal as well as evidence of potential disease modification reflected by greater reduction in variant allele frequency in the combination arm. Taken together, we believe these findings represent an important and encouraging clinical profile. In addition, no new safety signals were identified in the study. The safety and tolerability profile was consistent with the known profiles of Selinexor and Ruxolitinib individually. Importantly, Selinexor's differentiated XPO1 inhibition targets broader disease biology in a way that we believe is complementary to JAK inhibition. Taken together, we believe these results support the potential of Selinexor as a meaningful new option for patients with Myelofibrosis and mark an important step forward for Karyopharm. With that, I'd like to turn the call over to Reshma, who will review the top-line results from SENTRY in greater detail, and then Dr. Mascarenhas will share his perspective on why he believes these results are important. Reshma? Thank you, Richard. Before getting into the data, I'd like to remind you of the contribution that XPO1 inhibition may offer in Myelofibrosis, as seen on slide seven. XPO1 inhibition simultaneously targets multiple biologically relevant pathways in Myelofibrosis that may be additive, if not synergistic, with JAK inhibitors. These include inhibition of NF-κB, activation of the p53 pathway, and decreases in clonal cell division via inhibition of oncoproteins. Together, these effects may contribute to spleen volume reduction, reductions in variant allele frequency, a measure of mutational burden, and potential improvement in long-term outcomes, including overall survival. Turning to slide eight, I will briefly review the key elements of the phase III SENTRY trial design. SENTRY enrolled JAK-naive or frontline Myelofibrosis patients, all of whom had baseline platelet counts of greater than 100,000. Patients were randomized in a 2-to-1 ratio to Selinexor 60 mg in combination with Ruxolitinib dosed per label or Ruxolitinib in combination with placebo. In total, 353 patients were randomized. The trial had two co-primary endpoints, SVR35 and absolute TSS, both evaluated at week 24. The endpoints were evaluated at a one-sided alpha of 0.025 and were tested sequentially. The trial also included multiple secondary and exploratory endpoints, including overall survival as a secondary endpoint and variant allele frequency or VAF reduction as an exploratory endpoint. Moving to the data on slide nine, the first co-primary endpoint of SVR35 at week 24 was met. The benefit was highly significant, with an almost doubling in SVR35 rates observed with the combination versus Ruxolitinib alone at 50% versus 28% respectively, translating to a p value of less than 0.0001. The kinetics of these response rates were as important. Turning to slide 10, at week 12, the SVR35 rates were already 49% versus only 20% observed with Ruxolitinib alone. Furthermore, the response rates were sustained at week 36, with SVR35 rates of 47% for the combination versus only 23% for Ruxolitinib alone. Taken together, these results speak to the rapid and sustained benefit of the combination on SVR35 rates. On slide 11, in addition to this rapidity of response, we see that the spleen volume reduction was deeper with the combination compared to Ruxolitinib. Over time, the combination arm led to greater reductions in spleen size. Turning to symptoms as seen on slide 12, the mean change in total symptom score at week 24 was similar across the two arms, with an approximate 10-point improvement observed with the combination and an 11-point improvement observed with Ruxolitinib. Importantly for patients, the combination led to very similar symptom improvement relative to baseline. One of the most encouraging findings in our study is the promising overall survival signal observed, which is shown on slide 13. Overall survival is arguably the most important endpoint in any clinical trial. The combination demonstrated a greater than 50% reduction in the risk of death compared to Ruxolitinib. At a median follow-up of approximately 12 months, the rate of overall survival events observed with the combination was less than half the rate observed with Ruxolitinib alone at 4.7% and 10.2% respectively, corresponding to a hazard ratio of 0.43 and a nominal P- value of 0.0222. We believe the magnitude and early emergence of this signal is particularly notable, and this may be one of the only trials to show a signal of overall survival benefit compared to Ruxolitinib alone. We will continue to follow this very promising signal to maturity. Furthermore, a post-hoc analysis suggests that SVR 35 as early as week 12 may predict overall survival. These data are consistent with the multiple analyses done with JAK inhibitors, which show a similar correlation, potentially validating spleen volume reduction as a surrogate for overall survival and highlighting the importance of achieving a rapid SVR. As seen on slide 14, variant allele frequency or VAF in Myelofibrosis measures the percentage of blood cells carrying a specific driver mutation, including JAK2, CALR or MPL, and reflects the malignant clonal burden. VAF reduction of the relevant driver mutations in Myelofibrosis, again including JAK2, MPL and CALR, is evidence of potential disease modification. VAF reductions greater or equal to 20% at week 24 was observed in 32% of the evaluable combination-treated patients versus 24% of Ruxolitinib-treated patients. Notably, these reductions occurred early and may reflect the rapidity of the spleen volume reduction and the promising signal observed in overall survival. We believe these differentiating findings highlight the relevance of the XPO1 inhibition in Myelofibrosis. The safety profile of the combination was manageable, as seen on slide 15. The safety and tolerability profile was consistent with the known safety profiles of Selinexor and Ruxolitinib individually, both of which are marketed drugs and have been used to treat tens of thousands of patients. No new safety signals have been observed. The five most common treatment-emergent adverse events observed with the combination were either hematologic or GI in nature, including thrombocytopenia at 59%, anemia at 57%, nausea at 57%, constipation at 32%, and neutropenia at 27%. I do like that when combining both drugs, we do not see an increase in anemia, and in fact, we see a slightly lower rate of all-grade anemia in the combination versus Ruxolitinib. Notably, the nausea rates, a known side effect of Selinexor, was lower than what was reported in the phase I of SENTRY due to incorporation of prophylactic antiemetics. Grade three plus treatment-emergent adverse events were observed in approximately 70% of patients treated with the combination versus 50% treated with Ruxolitinib. Treatment-emergent adverse events leading to discontinuation were 14.5% versus 8.6%. These rates are very consistent with other combination therapies commonly used in the treatment of cancer indications. Finally, confirmed leukemic transformations were the same at 1.7% in each arm. In conclusion, on slide 16, the combination of the XPO1 inhibitor Selinexor and Ruxolitinib demonstrates an encouraging product profile that has the potential to improve outcomes for patients. Importantly, we see rapid near doubling in sustained SVR35 rates, similar improvement in symptoms relative to Ruxolitinib from baseline, and a promising signal in overall survival. The early and notable reductions in VAS levels greater or equal to 20% relative to baseline highlight a potential mechanism driving these key efficacy outcomes. I would now like to turn the call over to Dr. John Mascarenhas to talk about the importance of these results and the potential implications in the treatment of Myelofibrosis. I will start on slide 18 by level setting the discussion around SENTRY by highlighting the clinical hallmarks of Myelofibrosis, which define both disease burden and treatment goals. The four key features of MF are first and foremost splenomegaly, which is a function of extramedullary hematopoiesis due to aberrant MF stem cell trafficking and represents a fundamental complication of this chronic and progressive neoplasm. This contributes to frank discomfort in the abdomen and also can lead to early satiety and contribute to weight loss. Second, Cytopenias include anemia and thrombocytopenia, which are a function of the bone marrow failure aspect of MF and worsen with time and limit treatment options and have been shown to associate with poor prognosis. Third, progressive bone marrow fibrosis, the underlying histopathologic driver of the disease attributed to activated MF Megakaryocytes and the consequence of highly inflamed bone marrow microenvironment. The fourth feature, a substantial symptom burden, including fatigue, night sweats, and weight loss, which reduce quality of life and negatively impact functioning. With that context, I would like to comment on the top-line results from the SENTRY study reported on this call, which I believe are compelling and promising. We observed rapid and sustained spleen volume reductions with the combination of Seli and Rux, with faster, deeper, and more sustained SVR rates compared to placebo in Rux in this randomized study. This was clearly superior to Rux alone, as anticipated by the phase I data and as credentialed by the mechanism of action of Seli in hitting multiple disease-relevant pathways, such as p53 activation, that preclinical data suggests would synergize with Rux. The spleen is a clinical biomarker of disease burden, and SVR is an important outcome measure initially set forth by the COMFORT studies and one in which JAK inhibitors have been focused on achieving in clinical trials. Here we can see that a rational combination strategy delivers greater SVR than Rux alone. In addition, we are seeing an encouraging signal in overall survival, favoring the combination, which is ultimately the endpoint that matters most to patients, caregivers, clinicians, and regulatory agencies. The correlation of SVR with overall survival reinforces both the importance of it delivering an on-target activity and attaining spleen response for immediate benefit to the patient, but with added potential benefit of disease course modification. What is also notable is the greater reduction in variant allele frequency of driver mutation, which, still early, suggests we may be impacting the underlying biology of the disease, not simply managing symptoms. This also aligns nicely with the clinical outcome of greater SVR35 with the combination. These results highlight clinically meaningful endpoints. The trial achieved strong spleen responses and promising overall survival outcomes. While total symptom score was not statistically different between the two arms, we importantly see no detriment with the combination, and there was a meaningful improvement in symptoms relative to baseline. From a clinical perspective, maintaining or improving symptom control while enhancing spleen response and disease modification with potential overall survival benefit is what we seek to accomplish with combination therapy in the frontline MF setting. Finally, I want to emphasize the rationale behind the combination approach. By adding Selinexor, an approved agent in multiple Myeloma with a well-established safety profile to Ruxolitinib, we're introducing a novel and relevant mechanism of action. This combination has the potential to go beyond what JAK inhibition alone can achieve, which is well established over many trials of four approved JAK inhibitors and may meaningfully improve survival outcomes for patients, which are only modestly achieved with single agent JAK inhibitors. Taken together, these findings support the potential for Selinexor and Ruxolitinib as first-line combination approach to the treatment of Myelofibrosis. Turning to slide 19, we can look back at other studies for reference of the importance of spleen reduction. Most notably is the 2023 MYNERVA real-world retrospective study in Italy of 154 patients with Myelofibrosis treated with Ruxolitinib. Spleen responses were achieved in a substantial proportion of patients, approximately 68%, typically within the first 24 weeks of therapy. Importantly, achieving a spleen response by palpation was strongly associated with improved overall survival. This was independent of baseline risk as measured by DIPSS. As important as attaining spleen response at a landmark analysis of 24 weeks is those patients who maintain spleen response had the most favorable survival outcomes, whereas those who lost response experienced outcomes comparable to non-responders. It is not sufficient to simply attain the endpoint of 24 weeks, but the real benefit is in maintaining it over time. These findings underscore spleen reduction is not only a marker of clinical benefit, but also a meaningful prognostic indicator, linking durable spleen responses with longer survival in real-world practice. The landmark analysis of the SENTRY study at 12 and 24 weeks reinforces the potential to rapidly achieve SVR and maintain this clinical outcome, which in the ad hoc analysis of SENTRY data, irrespective of treatment arm, would support a relationship between SVR and overall survival. I believe that this prospective data from a phase III study not only validates the Italian retrospective data set, but also has the potential to support credentialing SVR as a surrogate for overall survival in MF therapeutic development. Obviously, following this data out further is paramount to confirm the validity of this exciting finding. Finally, slide 20 shows the current NCCN guidelines for the treatment of MF with low risk on the left and higher risk on the right. What I want to point out is that the subcategory of platelets greater than 50,000, in addition to the availability of four JAK inhibitors in which Ruxolitinib is most frequently used, it would be possible to imagine that a combination approach such as Ruxolitinib and Selinexor would be commercially available and NCCN endorsed, giving the provider and patient the option to choose an active initial treatment regimen with the highest probability of optimizing disease response and attaining SVR while not compromising symptom benefit in order to maximize potential for overall survival benefit. I believe the combination should be available to all patients, although this may not be the preferred treatment selection for every patient. I look forward to presenting the greater data set from the pivotal trial at upcoming meetings, and thank you. Now I will turn it back to Richard. Thank you, Dr. Mascarenhas. In closing, as outlined on slide 22, we believe the SENTRY top-line results represent an important milestone for Karyopharm and an encouraging step forward for patients living with Myelofibrosis. These results suggest the potential to improve on key dimensions of treatment benefit in a disease where patients and physicians continue to need better options. We observed rapid near doubling and sustained spleen responses, similar symptom improvement relative to Ruxolitinib, a promising overall survival signal and evidence of potential disease modification reflected by reductions in VAF. Taken together, we believe these findings represent an important and encouraging clinical profile. From here, we plan to meet with the FDA to discuss the totality of the SENTRY data and our potential sNDA filing plan. We also intend to present phase III SENTRY data at an upcoming medical meeting and submit a manuscript to a peer-reviewed journal. Beyond SENTRY, we remain focused on advancing XPORT-EC-042 in endometrial cancer, which remains on track for top-line data in mid-2026 and represents a significant opportunity for Karyopharm. Importantly, the financing that we announced this morning extends our cash runway into late Q3, enabling us to deliver on a second major inflection point with our top-line XPORT-EC-042 results while continuing to execute in each of these areas. Before we start Q&A, I want to recognize and thank the patients, families, caregivers, investigators, and the broader clinical trial teams whose participation made this study possible. We are deeply grateful for their commitment. I would also like to thank Dr. John Mascarenhas for his leadership in this study and for sharing his perspective that these results represent an important advance for the Myelofibrosis community and one that should be available to patients and physicians. Thank you again for joining us today. We'll now open the call for questions. Thank you. Ladies and gentlemen, we will now begin the question and answer session. To ask a question, you may press star one on your telephone keypad. To withdraw your question, you may press star two. Please be advised that you may only ask one question and one follow-up. Once again, that is star one should you wish to ask a question. Your first question is from Ted Tenthoff from Piper Sandler. Your line is now open. Great. Thank you very much, and congratulations on the impressive data. I know a lot of work's gone into getting here, and pleased to see the emerging OS signal. I'm curious about absolute total symptom score, and I know this is still just top line. I'm wondering if you have a concept of what maybe was the difference? that sort of left those measures comparable between the two arms at a, you know, individual line level, w as there anything that really stood out? Thank you. Yeah. Thanks, Ted. Maybe I'll turn to Reshma to touch on that. Yeah. Thank you, Ted. Great question. I do wanna emphasize, I think the really important aspect of this trial demonstrated very meaningful benefit in terms of TSS for the combination arm relative to baseline. It was a 10-point improvement. Really indicating that these patients at week 24 do feel substantially better relative to baseline. Now, as I mentioned on the call, you know, while we're disappointed that it did not show superiority relative to the placebo arm, I think it really highlights the variability that you see in the TSS. it potentially may not be the best marker of improvement, you know, in a trial such as Myelofibrosis. We are certainly looking into the individual domains and trying to understand whether there was a specific contribution from one of the domains, you know, for the overall results a gain, I'm just very encouraged by the improvement relative to baseline. Dr. Mascarenhas, anything you would add to that? No. I mean, I would agree with Reshma i think it's really a reflection of what to expect in this setting of a phase III randomized study where the control arm is active. We have numerous studies that demonstrate that Ruxolitinib and other JAK inhibitors are quite potent in reducing symptom burden, likely by reducing inflammatory cues. I think the real question for people like myself that are investigators across the board in these trials is it realistic to expect improvement upon symptom burden in this setting? From my perspective, if you're not worsening symptom burden but delivering improvements to that individual in terms of their symptom burden relative to Ruxolitinib, that's a win. It is in some ways it shouldn't be shocking that we see this phenomena over and over again i think it's a reflection of the disease and the fact that it's really probably not realistic to improve upon symptom burden in this setting from baseline to Ruxolitinib at 24 weeks. The real question is, can you deliver other meaningful endpoints like spleen reduction and other biomarkers that would suggest disease modification? You know, my attention is more focused these days on those outcomes. The spleen as we see that spleen is meaningful, that spleen reduction is not simply a regulatory endpoint but is probably a clinical outcome measure that is associated with survival. In my mind, you know, rapid deeper spleen responses is really the endpoint of interest, and we want to make sure we're not adding symptomatology or detracting from quality of life, but at least, you know, matching what Ruxolitinib can deliver. I'm not sure I'm disappointed by this result in the sense that I think it's a hard bar to overcome and i think, you know, it's like any other study. It's hard when you go from a phase I study to a phase III study, broad study across multiple countries, different investigators, you know, different reporting structures t here's always going to be that potential to not hit in a measurable way here. Not surprising in some ways, but still reassuring that the most important primary endpoint was met. Great. Thank you so much. Thanks, Dr. Mascarenhas. Thank you. Your next question is from Colleen Kusy from Baird. Your line is now open. Great, good morning. Congrats on the updates, and thanks for taking our questions. If you could just speak to the level of confidence that the FDA would approve this given the historical precedent of needing to hit on both SVR35 and TSS. Then just kind of can you talk about what the NCCN guidelines next steps would look like? If Dr. Mascarenhas could chime in on how he thinks physicians might view not approved but included on NCCN guidelines and use expectations there. Thank you. Yeah. Thanks, Colleen. Maybe I'll start with Reshma on the first part, and then I'll turn to Dr. Mascarenhas. Yeah. Thanks, Colleen. I think overall, you know, once again, we are very encouraged by the profile that has been demonstrated from this trial y ou know, as John mentioned, as I reported in the prepared remarks, you know, the early, the sustained, the substantial proportion of patients that achieve that SVR really demonstrates that meaningful benefit layer on top of this very promising early overall survival signal and a manageable safety and tolerability profile really suggests, you know, a positive benefit risk w e look forward to engaging with the FDA on the totality of that data. We plan on finalizing our steps with the FDA and the sNDA path forward, hopefully in the next six months. In the meantime, we look forward to presenting the data in upcoming medical congress and publishing the data that hopefully will enable NCCN guidelines a lthough that is an independent body that ultimately, you know, determines whether they want to incorporate in the guidelines. Hand it over to Richard. Yeah. Dr. Mascarenhas, your thoughts from a NCCN perspective? Well, I think, you know, I'll first say that as an investigator in this field, I find it a little bit challenging to necessarily predict what the FDA, you know, will evaluate and assess data results i think the FDA will be interested in the survival benefit here, because I think that's obviously important, and the relationship between SVR. I think that will translate into the community and likely be reflected in NCCN- -endorsement that would then at least give providers the opportunity to combine it with Rux in the real-world commercial setting, even if it's not approved off-label, as can be seen already with drugs like Luspatercept, which is approved in MDS for transfusion-dependent lower-risk MDS but has phase II data in MF, and soon to be released full data set in MF in a phase III setting, but is already used in the commercial setting based on NCCN endorsement. Selinexor is an approved drug i t's already out there. Many people in the community have some, you know, some use and some understanding of the drug from Myeloma i t's not impossible to imagine the utilization of Selinexor in the community setting even with Rux to deepen the spleen response based on the data we've seen here at SENTRY. I could see a path forward in this way. Great. Super helpful. Thank you. Thanks, Colleen. Thank you. Your next question is from Brian Abrahams from RBC Capital Markets. Your line is now open. Hey, good morning, guys t hanks for taking my question. Just wondering if you could comment on the causes of deaths here in the study, any patterns or timing there. Maybe for Dr. Mascarenhas, do you think 36 weeks is long enough for spleen benefits of this degree to translate to the overall survival signal of this magnitude? Thanks. Sure, Brian. The causes of deaths, we've looked into it, and they're very consistent with what you would expect with Myelofibrosis, especially across the two arms. There's no pattern that we see, either amongst the deaths or any kind of, I would say, discrepancies across the two arms. The other aspect that I just wanna highlight is that when we look at the Ruxolitinib arm, especially the 18-month overall survival landmarks, they're very consistent with what's been published, especially with Ruxolitinib and their overall survival data. You know, nothing out of the blue. We don't see that Ruxolitinib over or underperforms. Those data, again, really suggest that this could be a very promising signal in overall survival. Dr. Mascarenhas for the second part of the question. I'm encouraged by the fact that you see not simply this rapid reduction in spleen volume, which I think speaks to the fact that there's true synergy between Selinexor and Ruxolitinib, as the preclinical modeling would show and the phase I data would demonstrate so t hat was reassuring to see. It was also reassuring to see that it predicted response at 12 weeks also predicted response at 24. It maintained at 24, and then you continue to see that response at 36. Obviously, it's always nice to continue to see the response beyond 36 weeks, but you know, you don't see the same degree of rapidity, depth, and maintenance of response with Ruxolitinib. You start to lose that over time. I do think that that's important. I'm happy that Karyopharm is committed to following this out longer to demonstrate the continued maintenance of that SVR and to observe you know differences in survival, which at this early time point I think is very encouraging to see already. I think the totality of the spleen data would suggest that there is in fact a relationship. Not necessarily that a smaller spleen lets people live longer, but it is a biomarker i t's a clinical readout for on-target you know disease modulation that likely you know over time is gonna read out as an improvement in outcomes. Super helpful. Thanks so much. Thank you, Dr. Mascarenhas. Brian. Thank you. Your next question is from Ioannis Souroudzidis from Cantor. Your line is now open. Hey, folks. Congrats on the data again. Just had a question on the OS signal. Obviously, it's only 23 events, and so I think that's roughly 93% of the patients are still censored. I guess, could you walk us through how you expect to kind of communicate updates there on how those survival curves might mature? Speak to, you know, how these patients are getting therapy subsequent to this study as well, just to understand kind of the follow-through there and how that might affect overall survival in the long term. Yeah, absolutely, Ioannis. We absolutely need to continue to follow the OS signal out to maturity. You know, there is no crossover in the study, so that hopefully will allow us to better detect a meaningful overall survival as the patients continue on therapy. We haven't communicated, you know, sort of like how we're gonna follow or when we're gonna communicate out those OS events, but, we'll continue to look at it and find an appropriate venue in which to ultimately publish those more mature overall survival deaths. In terms of the subsequent therapy, this is another marker that we follow very closely w e do collect all of the subsequent therapies. Right now it's relatively small or a small number of patients are getting those subsequent therapies. In addition to the overall survival data, we'll likely comment on the subsequent therapies and their impact on that overall survival. Thanks, Ioannis. Got it. One quick follow-up, if you don't mind, for Dr. Mascarenhas. I couldn't help but notice that there was a recent study that you kicked off, looking at Selinexor with Pacritinib. Just kinda curious, what was the impetus there and inspiration for doing that? I'm so glad you asked that question. That is an exciting study as well i think it complements very nicely the secondary study and the results. If you think about MF as a disease spectrum and in the NCCN guidelines in particular, it segregates patients by baseline platelet count. This study was focused on the patients that had adequate platelets, which is the majority of patients, of greater than 100,000. There's substantial data that would suggest that the patients with Cytopenias, thrombocytopenia, anemia, have a different clinical course and a poorer outcome and are not able to enjoy the full benefit of Ruxolitinib t hat's where drugs like Pacritinib, which is a multikinase inhibitor, spares JAK1, hits IRAK1, as well as FLT3 and other enzymes that I think are important to the disease process. Also combines very nicely and neatly with Selinexor in preclinical modeling. The idea there is can we capture the spectrum of patients? Rux perhaps with Seli in the patients who have adequate blood counts at baseline, and then Rux Selinexor plus Pacritinib in the patients with lower counts, anemia and thrombocytopenia. I look forward to that study t hat study is a MPN Research Consortium study, so it's an investigator-initiated study which Karyopharm and Sobi have generously provided a drug for. We hope to start that study through multiple centers in the U.S., starting in May. I think it just adds to the volume of data that will help bring attention to, you know, to combination therapies. You know, I will put in that there are other ongoing studies which I think are exciting. For example, Selinexor up front and then adding at a later time point if spleen and symptom is not met, combinations of Ruxolitinib, Pacritinib, or momelotinib r eally trying to explore different ways of combining Seli. Well, or maybe not even combining Seli, maybe Seli up front, but combining Seli to optimize response across the JAK inhibitor spectrum so i think the more data, the better. It also just helps reinforce when a prescriber's seeing patients that might not all look uniform, how best to tailor the therapy t hat for a complex disease, that's really attractive. Understood. Thank you so much. Thank you. Your next question is from Maurice Raycroft from Jefferies. Your line is now open. Hi. Good morning c ongrats on the update, and thanks for taking my question. SVR35 benefit's compelling. I guess if the base case is compendia listing in the U.S., can Dr. Mascarenhas talk more about the relevant patient population? Would it be used for patients with severe splenomegaly at baseline? How big is that population? Based on the combo's overall profile, would treatment be durable or more of an induction type of treatment out to 24 or 36 weeks? I think the answer is we have to look at this data more carefully and i think at upcoming meetings, when we have the opportunity as a community to really go through it, we'll be able to parse out and understand you know whether there are predictors of response to the combination r ight now, the response looks uniform across all different types, subtypes of MF. There's not really one patient profile that I can glean at this point would be the patient profile to use combination. It could be used in any patient upfront. I think what you will likely find, particularly as you know therapies are introduced into practice, is an adoption that will likely start in many cases with the patients who come really advanced b ig spleens, high symptom burden. I think those are sort of the natural patients where you would probably pick a combination upfront. It's not clear to me that there is a profile, whether it's driver mutation, spleen volume, risk score, that would suggest that this is the population for combination. In some cases, it might be comorbidities that might, you know, that might influence treatment decisions. For example, if someone has underlying, you know, severe IBS or IBD, you know, perhaps a combination with Selinexor may not be the optimal choice for that patient. If a patient has a platelet count of 50,000 at baseline, perhaps, you know, Rux and Seli may not be the best choice for that patient t hat's again, to go back to the previous question, that's why exploring combinations with Pacritinib, for example, would allow us for a more broader usage of combination therapy. Oh, and sorry. Thanks, Maurice. Just to finish my thought. No. I don't know that I would necessarily. I think it's an interesting concept to induce a response and then maybe then back off of it i think on an individual basis, we'll have to see how patients respond to the combination, balancing, you know, benefit and toxicity but i think what we've learned in this field is you do want to induce a response and maintain a response i think that would require continued therapy with the combination a t least at this time point, that's the way it's been developed and explored. That's probably the best way to continue using it. Got it. Maybe one other follow-up question. If you guys can just provide more perspective into the Grade 3 + AEs and what trends you're seeing across the two arms. Specifically, how do these compare across both arms on anemia and thrombocytopenia? Yes. Good question, Maurice s o, you know, again, the Grade 3+ AEs were observed in 14.5% of the combination versus 8.6% in Ruxolitinib alone. Again, very consistent, as I mentioned, you know, of other combinations, not only in Myelofibrosis but also in other oncology combination therapies. While we haven't specified the actual Grade 3+ plus AEs and the most common Grade 3+ AEs, they're still gonna be GI as well as hematologic in nature. I think the really important aspect for me, and maybe John can comment as well, is that overall, this is a very manageable profile regardless of that 14.5% t he reason I say that is because it's still enabled to this very rapid and sustained SVR that we see with the combination par... Patients, and we also see this very promising overall survival signal a gain, two things that you wouldn't see if toxicity was a challenge for this combination. Dr. Mascarenhas, is there anything you'd add to that? Well, I think we've learned, you know, with time how to optimize the delivery of Selinexor. At 60 milligrams once weekly with adequate prophylaxis and i have to say, you have to tailor that prophylaxis to that patient. I think awareness is really important too, to be aware of that potential toxicity so you can optimize that. That potential toxicity is really important so i t is deliverable. I think if we didn't see these spleen responses and survival benefit, then one could question, you know, the balancing act between toxicity and efficacy here. I think if you look at the full data set, the GI toxicity is overcome by the clear benefit in spleen reduction and that exciting signal for survival. Got it. Thank you for taking my questions. Thank you. Your next question is from Jonathan Chang from Leerink Partners. Your line's now open. Good morning. This is Albert Agustinus on for Jonathan Chang. Congrats on the data, and thanks for taking my questions. Just a small one for me. Based on your prior interactions with FDA and historical precedents, to what extent do you expect the FDA to weigh on this OS signals against the missed TSS endpoint during the review? And how will this translate to the confidence in your upcoming meeting? Thanks. Yeah. I mean, overall, you know, as I mentioned previously, we're encouraged by the profile that has been established with the combination, right? We see these very rapid, sustained SVR. As John Chang mentioned, it is a likely clinical biomarker for long-term outcomes. You layer on that, we see this very promising overall survival signal in the context of a very manageable and tolerable safety profile. We look forward to engaging with the FDA and engaging with next steps. Thanks, Albert. Thank you. Thank you. Our last question is from Michael King from Rodman & Renshaw. Your line is now open. Good morning, guys. Thanks for taking the question, and I'll add my congratulations on the outcome. I'm just wondering if you could just comment a bit more on OS. How are you defining the maturation? of the data? You know, when will that read out? Is there a specific, you know, event number that you're looking to achieve? Will you wait to speak with FDA until you have more maturity on the OS endpoint? Yeah. Overall survival is a pre-specified secondary endpoint. Again, we see this very promising overall survival signal. We're gonna continue to follow OS in this study. We do not have a predefined number of events, but, you know, we'll continue to look at the data and present the data as it continues to mature. Thank you. Thank you. There are no further questions at this time. I will now hand the call back to Richard Paulson for the closing remarks. Thank you, operator, and thank you everyone for joining us today. I think as we all well know and as we heard again today, you know, Myelofibrosis remains a disease with significant unmet needs. The current therapies really deliver modest spleen responses with limited evidence of disease modification. You know, JAK inhibitors really remain the only approved class of therapies. There's a clear need for new treatment options that can improve outcomes for patients, particularly overall survival. I think as we've shown, these data represent an important milestone for Karyopharm and more importantly, for patients and caregivers and physicians living with this very serious Myelofibrosis disease w e're focused on working together, as we work to try to bring Selinexor to patients with Myelofibrosis. Thank you for joining us today. Thank you, ladies and gentlemen t he conference has now ended. Thank you all for joining. You may now disconnect your lines. Goodbye.