Good morning. My name is Ryan. I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics first quarter 2023 financial results conference call. There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Elhan Webb, Senior Vice President, Investor Relations. Thank you. Over to you. Thank you, operator. Thank you all for joining us on today's conference call to discuss Karyopharm's first quarter 2023 financial results and recent company progress. We issued a press release this morning detailing our financial results for the first quarter 2023. This release, along with a slide presentation that we will reference during our call today, are available on our website. For today's call, as seen on slide two, I'm joined by Richard, Sohanya, Reshma, and Mike, who will provide an update on our Q1 results and recent clinical developments. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on slide three. Actual results may differ materially from those indicated by these forward-looking statements, FLS, as a result of various important factors, including those discussed in the Risk Factors section of our most recent Form 10-K, which is on file with the SEC, and in other filings that we may make with the SEC in the future. Any FLS represent our views as of today only. While we may elect to update these FLS 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 FLS as representing our views as of any later date. I will now turn the call over to Richard. Please turn to slide four. Thank you, Elhan, and thank you all for joining us today for Karyopharm's Q1 2023 earnings call. As we turn to slide five, we are making strong progress as we execute on Karyopharm's next stage of growth by deploying our novel mechanism of action, selective inhibition of nuclear export, to expand our existing multiple myeloma franchise, currently centered around our commercial drug, XPOVIO, which is now approved in over 40 countries and continues to move into earlier lines of therapy in multiple myeloma. As Sohanya will discuss further, year-over-year total demand for XPOVIO continues to grow. However, this is not translating into growth in net product revenue due to increased distribution of free product through our Kary Forward Patient Assistance Program, PAP, and higher gross to net discounts. These factors have caused us to revise our total revenue guidance for 2023 to a new range of $145 million-$160 million. We have accelerated our closure of non-priority programs, thus lowering our spend in 2023, and we are maintaining our guidance for cash runway through late 2025. We believe the factors resulting in the significant increased use of our PFAP programs are expected to be mostly limited to 2023. While we are not specifically commenting on our revenue expectations for 2024, we believe we will see a decreased impact of this challenge next year, given the IRA-related Medicare Part D redesign. We have a focused pipeline and are rapidly advancing our mid- and late-stage clinical development programs that can help patients who suffer from cancers with high unmet need demonstrate efficacy at lower doses with improved tolerability and where we believe we'll have the highest probability of success. We are conducting pivotal Phase III studies in both multiple myeloma and endometrial cancer, with a third pivotal Phase III study of myelofibrosis, which we expect to start in the first half of 2023. Collectively, we believe we have the potential to achieve multiple product approvals over the next two to four years as we deliver our next phase of growth, leveraging our proven and established commercialization and mid- to late-stage development capabilities as we work to generate value for patients and shareholders. We look at our first quarter highlights on slide six, we achieved $28.3 million in XPOVIO next product revenue for the quarter, which is consistent with the first quarter last year. Total demand for XPOVIO grew year-over-year in a very competitive multiple myeloma marketplace. We are encouraged by the continued growth in the community setting. Shifting to Selinexor position internationally, our continued global expansion provides further opportunities to treat patients in need with the additions of new licensed territories with Menarini in the Middle East and Africa, as well as full marketing authorization for NEXPOVIO in the U.K., broadening our international footprint. We continue to advance a streamlined clinical pipeline focused on our four core programs. I wanna highlight our recent data presented at AACR in treatment-naive myelofibrosis, where Selinexor 60 milligram in combination with ruxolitinib demonstrated rapid, deep, and sustained spleen response. Based on this, we are planning to initiate a pivotal phase III study this quarter, as we believe Selinexor 60 mg plus ruxolitinib has the potential to transform standard of care for frontline myelofibrosis. Additionally, earlier this week, we announced encouraging interim efficacy data from the phase II study of eltanexor, our second novel SINE compound, in 30 patients with hard to treat higher risk relapsed or refractory MDS, which Reshma will discuss. With that, I would now like to turn the call over to Sohanya on slide seven for her review of the commercial performance for the quarter and perspectives on our updated guidance for 2023. Sohanya? Thank you, Richard. Good morning, everyone. On slide eight, I will be discussing first quarter of XPOVIO performance within an evolving and competitive multiple myeloma landscape. In the first quarter, XPOVIO continued to show growth year-over-year in total demand and new patient starts despite facing a competitive landscape that intensified over the past year. Net product revenue was consistent with the same period last year and was adversely impacted by multiple external factors. When you look at what is positively driving our total demand, the community business continued to grow, contributing to about 70% of XPOVIO's revenues in the first quarter. In the community setting, XPOVIO continues to be viewed increasingly favorably as an effective, convenient, oral and manageable therapy with a novel mechanism of action in second to fourth line. In the academic setting, we saw sustained demand year-over-year despite increasing uptake of the novel bispecifics and CAR Ts. The positioning of Xpovio is actively evolving in the academic study with the emergence of theotherapy. We have an opportunity to serve key patient segments with an increasing body of evidence for Xpovio that Reshma will expand upon shortly. Now, let's take a look at some of the key headwinds we faced that adversely impacted our net product revenues year-over-year. First, there was an impact from a higher gross to net discount, five points higher in Q1 2023 versus Q1 2022, driven by increased 340B discounts and Medicare and Medicaid rebates. Second, there was a significant increase in utilization of our Kary Forward Patient Assistance Program or PAP, where we provide free drugs to patients who qualify and who are unable to afford the cost of their medication. Many patients rely on financial assistance from independent nonprofit foundations dedicated to improving access to important medications by providing financial support including programs supporting Medicare Part D patients who need copay assistance for their multiple myeloma oral therapy. Medicare patients constitute about 60% of our total patient mix for Xpovio. These foundations did not have sufficient funding and were unable to provide financial support to patients in Q1 of 2023 and continuing through the end of April. We faced an unprecedented increase in the use of our patient assistance program in this period. Historically, our PAP program attributed to approximately 5% of total demand and has steadily increased since February of this year, approaching 20% in April. Patients entering PAP remain in the program through the year and course of treatment. There is a cumulative effect over subsequent quarters due to the refills associated with these new starts. Moving forward in 2024, IRA related changes in the design of Medicare Part D will eliminate the patient burden of the 5% beneficiary coinsurance requirement, and we expect significantly less need for Medicare Part D patients to utilize carry forward for co-pay assistance. While there are several external factors that can shift in the marketplace, the primary driver for revising our net product revenue guidance to $110 million-$125 million is higher year-to-date usage of PAP and their associated refill impact, as well as our uncertainty around whether foundations supporting multiple myeloma patients will be able to provide financial support for new eligible patients throughout 2023. We recognize the important role that Xpovio can play in patients that are battling multiple myeloma. We are dedicated to continuing to provide free access to Xpovio for patients that qualify for our carry forward program. We look to key drivers of growth for 2023 and beyond. We're pleased with the continued positive momentum across our leading indicators. Importantly, we continue to make strong progress in shifting into earlier lines. In Q1 2023, XPOVIO new patient share approached 60% in the second to fourth line compared to 45% in Q1 of last year. This is encouraging as it allows patients to potentially have a more optimal experience in the early lines and extend time on therapy. This is supported by our intent to prescribe data which showed an improvement in tolerability perception in the second to fourth line. Let's now turn to slide nine. Amidst the crowded and evolving landscape, we believe we're strongly positioned as a novel class of therapy in the second to fourth line, in between the three major classes used in the first and second lines and T-cell therapies in later lines. I remain confident in our potential for mid to long-term growth. We are positioning XPOVIO in three targeted patient populations. First, in the community setting where early line patients tend to be treated, Xpovio is an optimal therapy in the 2nd to 4th line post-anti-CD38 treatments as a novel class of therapy that is an effective, manageable, easily combinable, and a convenient oral therapy. Second, as T-cell therapies emerge and are used increasingly in the academic setting, Xpovio may be an optimal, potentially T-cell sparing therapy that can be used at any stage of a patient's treatment journey. Reshma will expand on the building body of evidence that suggests XPO1 inhibition may be associated with preserving T-cell health. Finally, in the academic setting, a third segment of patients is the elderly patients that constitute about 2/3 of all myeloma patients, and they typically are not able to access a T-cell therapy due to age and frailty. As we think about the mid to long-term growth potential of XPOVIO in multiple myeloma, we're encouraged by our XPd study, the triple combination of selinexor with pomalidomide and dexamethasone, and find our investment could lead to the only all-oral, potentially T-cell sparing regimen in the marketplace if approved. Pomalidomide and IMiD has shown no potential negative impact on T-cell function, unlike alkylating agents such as cyclophosphamide that have shown to impact T-cells at one year post-exposure. Additionally, pomalidomide is over a $2 billion drug and a critical backbone in 2nd to 4th line, with potential for increasing utilization accelerated by the need for T-cell sparing therapies in the future. In summary, despite the headwinds in 2023, we continue to advance our mission for XPOVIO that every eligible patient with multiple myeloma should receive selinexor during their patient journey. Please advance now to slide 10, and I'll turn the call over to Reshma to review our clinical pipeline progress. Thank you, Sohanya. Starting off with an overview of our clinical pipeline on slide 11, we are rapidly advancing our pipeline, which is evaluating two complementary novel SINE compounds, selinexor and eltanexor, across multiple cancers of high unmet need, including myelofibrosis, myelodysplastic neoplasms, endometrial cancer, and multiple myeloma. Turning now to slide 12, we continue to optimize the dose of selinexor across our clinical programs. The lower doses of 40 or 60 milligrams weekly that are incorporated in all of our current selinexor clinical trials are a quarter to less than half of the original approved dose of 80 milligrams twice weekly. These substantially lower doses optimize the patient benefit by improving its tolerability, ultimately enabling patients to stay on therapy longer and improving their overall benefit. I'm going to spend most of my time today talking about our recent data in myelofibrosis and myelodysplastic neoplasms. First, on slide 14, it is worth reviewing some of the evidence about the potential benefit of selinexor in T-cell fitness. There are a number of published studies which have shown that selinexor maintains T-cell function in mice and can help maintain the effectiveness of CAR T therapies in mice pre-treated with selinexor. To further expand on these data, we are collaborating with academic institutions on additional preclinical research studies to further explore the impact of SINE mechanisms on T-cell fitness. In addition, we are leveraging real-world evidence data to determine whether patients who were treated with selinexor prior to receiving CAR T therapy benefit from improved outcomes with CAR T. Lastly, we are evaluating multiple clinical studies that will evaluate the benefit of selinexor when used before or after BCMA or CAR T therapy in patients with multiple myeloma. This body of evidence will enhance our understanding of the role of XPO1 inhibition has in maintaining the T-cell environment, which may potentially augment the benefit achieved with subsequent T-cell therapies. Now, let's discuss the data that we presented a few weeks ago at AACR on the efficacy and safety of selinexor plus ruxolitinib in first-line myelofibrosis patients. Since we already discussed these data at the event we hosted on April 18th, I will cover these slides quickly. For anyone looking for additional details, I would encourage you to listen to a replay of our webcast from April 18th, which is available in the Events and Presentation section of our website. Turning to slide 16, the only approved class of therapy in myelofibrosis is the JAK inhibitors. Less than 50% of patients achieve an SVR35 and TSS50. There are notable subgroups, including men and those who start on low dose of ruxolitinib, where fewer than 25% achieve an SVR35 at week 24. First, let's turn to slide 17, which shows the trial design for our phase 1034 study, from which the efficacy and safety data for the selinexor plus ruxolitinib combination have been observed. On slide 18 are the SVR35 and TSS50 results broken down by dose. In the efficacy evaluable in ITT populations, the SVR35 rates at week 24 achieved in the 60 milligram dose cohort were 92% and 79% respectively, which is almost double compared to the rates achieved at 40 milligrams. Furthermore, these reductions occurred rapidly, with the 71% SVR35 rates observed at week 12 in the 60 milligram ITT patient population. Consistent with the SVR35 data, treatment with the 60 milligram dose showed greater symptom improvement compared to patients treated with the 40 milligram dose. At week 24, for patients who received a 60 milligram dose of selinexor, TSS50 was observed in 78% of the efficacy evaluable population and 58% of the ITT population. Here as well, you see rapid improvement in symptoms with approximately 67% of the ITT population who received selinexor 60 milligrams achieve a TSS50 as early as week 12. The waterfall on slide 19 shows the spleen volume response in the efficacy evaluable patients. As you can see, 100% of the evaluable patients treated with selinexor 60 milligrams achieved a spleen volume response of 35% or more at any time. Moving to slide 20, we have the subgroup data in patients treated with selinexor 60 milligrams. In general, efficacy was similar across all of the subgroups that were evaluated. Highlighted in orange are two important subgroups, specifically the response rates for men and women in the ITT population, which were similar at 78% and 80% respectively. Similar efficacy was also observed by ruxolitinib starting dose with patients who were treated at starting doses of 15 or 20 milligrams of ruxolitinib, achieving an SVR35 of 75% as compared to 83% amongst patients treated with five or 10 milligrams of ruxolitinib. On slide 21, we show a unique subgroup analysis from patients that had their ruxolitinib dose reduced to 5 milligrams as early as cycle two and remained on that dose for the remaining duration of their therapy. Even with the subtherapeutic dose of ruxolitinib, all patients evaluable at week 24 achieved a spleen volume reduction of 35% or more. Similarly, symptom score improvement was observed in all patients with five out of six patients achieving a 50% or greater improvement in their total symptoms. These data suggest that XPO1 is a fundamental mechanism in myelofibrosis. Slide 22 presents a breakdown of adverse events. The most common adverse events were nausea, anemia, fatigue, and thrombocytopenia. The most common grade 3-4 AEs were anemia, thrombocytopenia, and neutropenia. While 75% of patients experienced nausea, the vast majority of these events were grade 1 and transient, with the majority of these events resolving within two cycles. Amongst the patients who received one prophylactic antiemetic, nausea rates both decreased and occurred at only a grade one severity. We anticipate that these rates will further decrease in the phase III study, which will incorporate mandatory dual antiemetics for the first two cycles. On slide 23, even though some patients experienced nausea and vomiting, there was a median absolute weight gain of 2.5 kilograms observed at week 24 in patients treated with selinexor 60 milligrams. As shown on slide 24, we highlight the potential findings for disease modification, given that the median hemoglobin levels return to baseline and there's a rapid normalization of platelet levels. Contrast this with findings from patients who have received ruxolitinib as a single agent, where hemoglobin levels drop after treatment initiation and stay low. The increase in hemoglobin over time, coupled with the rapid normalization of platelet levels between cycles two to three, may be evidence of disease modification, a critical finding for patients given that thrombocytopenia is the leading cause for ruxolitinib discontinuation. In summary, as we turn to slide 25, we believe selinexor 60 milligrams in combination with ruxolitinib has the potential to transform frontline myelofibrosis treatment paradigms. The combination is generally well-tolerated and manageable, allowing most patients to remain on therapy. Rapid, deep, and sustained spleen response and robust symptom improvement were found in patients treated with selinexor 60 milligrams in combination with ruxolitinib, appearing to work together synergistically. As seen on slide 26, the planned phase III trial will enroll JAK inhibitor-naive patients with intermediate and high risk myelofibrosis. 306 patients will be randomized two to one to ruxolitinib plus selinexor or ruxolitinib plus placebo. We are eagerly looking forward to initiating the phase III trial this quarter. Let's turn our attention to our research in patients with myelodysplastic neoplasms, or MDS, starting on slide 28. Between 12,000- 20,000 people in the United States are expected to have been diagnosed with higher-risk MDS in 2022. Hypomethylating agents are the current standard of care for newly diagnosed higher-risk MDS patients. Only approximately 50% of patients respond. Prognosis and higher-risk relapse/refractory disease is poor, with an expected overall survival of only four to six months. There are currently no approved therapies for HMA refractory MDS. Given the importance of XPO1 inhibition in MDS, eltanexor has the potential to meaningfully improve survival and provide benefit to patients who are in need of effective therapies. Turning to slide 29, you can see the design of our phase II study of eltanexor in relapsed/refractory higher-risk MDS. The data that we will be discussing today is from the 30 patients enrolled as part of the phase II interim analysis. All patients were treated with the recommended phase II dose of eltanexor identified in the phase I, which was 10 milligrams daily for five days of each week. As shown on slide 30, the objective response rate observed in the ITT population was 27%. All of the responses were mCRs, with two of these patients also achieving hematologic improvement. Noteworthy was the transfusion independence rate observed in 29% of the patients who were transfusion-dependent on red blood cells or platelets at baseline. The median overall survival was 8.7 months, which is encouraging given the median overall survival for patients with higher risk relapse or refractory MDS is typically only four-six months. Finally, on slide 31, side effects were generally tolerable and manageable. The most common AEs were asthenia, diarrhea, and nausea. The most common grade 3+ AEs were neutropenia, thrombocytopenia, and asthenia. There were no treatment-related adverse events leading to death, and three patients discontinued due to a treatment-related adverse event. Overall, the data from our interim analysis points to the potential importance of XPO1 inhibition in MDS. We plan to study these data further and determine the optimal development plan for eltanexor in MDS in the second half of this year. With that, please turn to slide 32, and I will now hand it over to Mike. I hope everyone is having a great morning, and thank you, Reshma. Turning to our financials, since we issued a press release earlier today with the full financial results, I will just focus on the highlights which begin on slide 33. Total revenue for the first quarter of 2023 was $38.7 million, compared to $47.7 million for the first quarter of 2022. Net product revenue from U.S. commercial sales of XPOVIO for the first quarter of 2023 was $28.3 million, compared to $28.3 million for the first quarter of 2022. As Sohanya discussed, net product revenue was adversely affected by more patients using our patient assistance program as well as higher gross to net discounts, which were 24% for the quarter. We now expect our gross to net discounts will be near the higher end of our range of 20%-25% this year. Turning to costs, with our continued discipline execution, we are pleased to be delivering a combined 16% year-over-year reduction in our R&D and SG&A expenses this quarter. As we have discussed in the past, we have a focused pipeline and you are seeing this in our R&D spend. R&D expenses for the first quarter of 2023 were $32.3 million, down 23% compared to $42.1 million for the first quarter of 2022. Likewise, SG&A expenses for the first quarter of 2023 were $35.9 million, down 7% compared to $38.8 million for the first quarter of 2022. We are achieving this through purposeful and comprehensive spend discipline, which includes the accelerated closure of our non-core programs while simultaneously rapidly advancing three pivotal phase III programs. Cash, cash equivalents, restricted cash and investments as of March 31, 2023 totaled $261.9 million, compared to $279.7 million as of December 31, 2022. As Sohanya outlined, we are lowering both our total revenue and XPOVIO net product revenue ranges by $15 million, primarily due to the higher than anticipated use of our patient assistance programs and associated free drug. In 2024, we expect this to improve with fewer patients utilizing our PFAP for co-pay assistance due to IRA-related redesign of Part D benefits. With these changes, we are now guiding to total revenue of $145 million-$160 million for 2023 and U.S. XPOVIO net product revenue of $110 million-$125 million. On the cost side, as we've accelerated our closure of non-party programs and disciplined expense management, we are also lowering our expense guidance by $15 million. We now anticipate non-GAAP R&D and SG&A expenses, which excludes stock-based compensation expense to be in the range of $245 million-$260 million for the full year of 2023. Finally, that our existing cash equivalents, and investments as well as the revenue we expect to generate from XPOVIO product sales and other licensed revenues will be sufficient to fund our planned operations into late 2025. I'll now flip to slide 34 and turn the call over to Richard for some final thoughts. Richard? Thank you, Mike. Turning to slide 35. As we have discussed today, we are rapidly advancing our pipeline with three phase III programs to potentially expand our commercial indications as we demonstrate the benefit that XPO1 inhibition can deliver to patients in areas with high unmet need. We continue to expand on our foundation in multiple myeloma and believe that every eligible patient should receive selinexor during their patient journey. I would like to thank our teams that continue to execute in a disciplined manner and who strive each day for patients with high unmet needs as we work to generate value for patients and shareholders. Thank you again for joining us today. I would now like to ask the operator to open the call up to the Q&A portion of today's call. Operator? Thank you. We will now begin the question and answer session. To ask a question, you may press star then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. Our first question comes from Peter Lawson from Barclays. Please go ahead. Peter, your line is unmuted. You could please go ahead with your questions. Perfect. Thank you so much. Thanks for all the detail this morning around the quarter. I wonder if you could just add to it. On free drug and PAP program, is that still increasing, and where do you think that could be as you kind of exit 2Q? For Mike, kind of, what do you think the revenue impact on the quarter was from that PAP free drug program and gross to net? Sure, Peter. Thanks for the question. I mean, I think broadly, you know, as you heard from Sohanya, you know, there was a real unprecedented increase in the use of the PAP programs during the period. Historically it's been about 5%, now in April approached about 20%. Obviously, we've built that range into our guidance with our guidance coming at the higher end, you know, if there's less patients having to access our patient assistance program versus more towards the mid to lower end, you know, if it continues at the same rates as it is. Maybe I'll turn to Mike to talk about the impact with regards to gross to net. I think, Peter, your question was on impact on PAP for the quarter? Yes, gross to net. If there's if you can break out the revenue impact or- Yeah. Our gross to net for the quarter was 24%, which is about five points higher year-over-year. We're guiding on the call today. We're keeping our range of 20%-25%, but we're guiding that it'll be on the higher end of that range for the rest of the year. As far as PAP direct impact on the quarter, it was a hair over $1 million or so in Q1. The impact is more forward-looking, as, you know, Sohanya mentioned in her script on, you know, where these foundations or when these foundations would open for the year. It's not a massive impact on Q1, but it's more forward-looking. Perfect. Thank you. Then just on the foundations, is there any change there going forward? I mean, is that spend being more focused around BCMA versus other therapies, do you think? Yeah, Peter, we don't really obviously have insight into what kind of patients are accessing the foundations programs. I think as we touched on, you know, obviously the foundations play a really important role, you know, supporting patients with financial assistance that need access to that assistance, and especially in the Medicare Part D patients who need co-pay assistance, especially with regards to looking at, you know, what's happening to patients as they transition into the 5% extra cost moving forward. As we talked about, you know, looking at 2024 moving forward, kind of this catastrophic coverage of the 5% co-pay, you know, with the change driven through the IRA changes that, you know, we expect will require less patients to access patient assistance programs. Gotcha. Okay. I guess just a final question just for Mike around the cost savings, whether that impacts SG&A or R&D and kind of how that kind of filters through to programs in the second half? Yes. The big part of it is really acceleration of closing our non-prioritized programs. That's really the focus in order to bring down the R&D side of expense. Of course, we, you know, we have our two ongoing phase IIIs and, you know, one to start. It's a mix across all three areas of R&D, commercial and SG&A. You know, it's a combination of cost discipline and acceleration, the closure of the non-prioritized programs. Gotcha. Okay. Thanks so much. Thanks, Peter. Thank you. Our next question comes from the line of Maury Raycroft from Jefferies. Please go ahead. Hi. Good morning. This is Kevin on for Maury. Thanks for taking my questions. First question I had was on myeloma. You pointed out that almost 60% of the new patient share is from the earlier line setting, versus I believe around 55%, or close to that earlier this year. Could you say what proportion of that is due to volume increase in the earlier line or whether that's primarily due to increased competition in the later line? Thanks. Yeah. Thanks, Kevin. Maybe I'll turn to Sohanya to expand on that. Yeah. Hi, Maury. Thanks for the question. Yeah, we're approaching 60% of XPOVIO new patient starts moving into the earlier lines. That means that, you know, the remainder of the patients are in the fourth line, fiveth line plus. That is driven by primarily in the community where we're seeing an increased use of XPOVIO as well as use in the earlier lines. Okay, great. Thanks. On the dose response relationship that you saw in turning to myelofibrosis in the phase I, in the 60 versus the 40 milligram doses, what would you expect or what do you expect in the ongoing endometrial and myeloma phase IIIs where you're running studies at lower doses than you previously looked at? Yeah. Reshma, do you want to expand on that? Yeah, great question, Kevin. What you can see across all of our programs, myelofibrosis, endometrial, and multiple myeloma, we've incorporated these lower doses of either 40 milligrams or 60 milligrams dose weekly. A lot of that really suggests that regardless of tumor type, you can drive efficacy again with these lower doses of selinexor. Now there are going to be differences, right, given the underlying tumor type, whether it's a monotherapy or in combination. What we are triangulating around is that these, again, lower doses improve the tolerability, enable patients to stay on therapy, and of course, ultimately drive that efficacy. It is nice to see that consistency again in that positive benefit risk around these lower doses of selinexor, you know, regardless of tumor type. Great. Thanks. Just a final quick follow-up for ASCO, you have a myelofibrosis poster there. Should we expect any new data in terms of maybe durability or dose intensity or anything like that? We haven't guided on the actual content of ASCO. You know, again, we did have a recent presentation, as you know, at AACR with the February data cut. You know, but with that said, we're always going to have opportunities to provide additional data, whether it's from an efficacy, safety, or translational from this phase I, given that we follow patients long term and have collected multiple samples. Again, can't comment specifically at what's gonna happen at ASCO. You know, there are gonna be new data, and we hope to be able to present new data over the course of the next six, 12, 18 months from this study. Okay. Thanks, Reshma. Thanks, Kevin. Thank you. Our next question comes from the line of Michael Ulz from Morgan Stanley. Please go ahead. Hi, this is Wenchang on the line for Mike. I just have a question about this PAP program utilization. What do you see the main driving factor of the increasing, like, from 5% to 20% within just two months? Although you said, like, in 2024 you are expecting, like, lowering utilization, what do you see the evolving in the next three quarters and maybe beyond 2024? Thanks. Yeah. Sohanya, do you want to touch on that? Yep. So the main driver in terms of the significant increase in the utilization of PAP was driven by particularly the Medicare Part D patients. Our PAP program provides free drug to qualified uninsured and underinsured patients broadly, but this includes Medicare Part D patients that need financial assistance with their 5% beneficiary co-insurance requirement above the catastrophic coverage threshold. This segment of patients were a particular driver in terms of financial assistance that they needed and the impact that we saw as a result of the foundation closure. Looking into 2024, this is the piece that is eliminated in the redesign of the Part D benefits per the IRA. The 5% beneficiary co-insurance requirement above the catastrophic coverage threshold is eliminated. That segment of patients will lead less financial assistance and less reliance on patients' assistance programs in 2024. As for the remainder of this year, again, as Richard commented earlier, you know, we've incorporated into the guidance range this uncertainty factor on whether foundations can support new patients for the rest of the year as well as the guidance incorporates the year-to-date impact of PAP as well as subsequent refills Okay. Thank you. Thanks, Wenchang. Thank you. Our next question comes from the line of Colleen Casey from Baird. Please go ahead. Great. Good morning. Thanks for taking our questions. On XPOVIO ex-US, can you talk about some of the drivers there and what gives you confidence in hitting the ex-US portion of your guidance? Yeah. Thanks, Colleen. You know, when I look at what's happening, you know, ex-US, I think as we've talked to, really the commercial launches have taken place in Germany and Austria. Menarini's working through the pricing reimbursement process in the EU, you know, this year and over the next kind of 12 months. I think in those markets, you know, obviously they were able to launch in the second-line plus indication to start. I think that enables them to, you know, move forward, I think, with the learnings we have here in the US, and a more rapid, you know, uptake. I think when we look at outside of the U.S., also we know in Asia Pac, you know, XPOVIO is commercially available in Mainland China, Australia, South Korea, Singapore and Taiwan. You know, the commercial launch in Mainland China took place in May of 2022. At the same time, you know, they're working through the China NRDL strategy. It's under evaluation depending on label expansion and timing and further discussion with the China authorities. I think our partners across the globe making really good progress with regards to moving forward from the commercial launch perspective. Great. That's helpful. Thank you. Then just based on the MDS data that you put out this week, what are the potential next steps for that program and are any of those next steps currently included in your cash guidance? Hey, Colleen. I'll take that one. Thanks for the question. Yeah, encouraged by the data that we reported from the interim analysis. You know, just to provide background again and to highlight, you know, this is a very hard-to-treat patient population. You know, we enrolled these higher risk relapsed refractory MDS patients. Overall survival is very poor, unfortunately at four to six months. Again, encouraged by those 8.7 median overall survival that we observed from the interim. Also encouraged by the ORR. You know, we're gonna take a look at these data, interrogate them further and define the next steps in the next half of the second year. I'll turn the financial question over to Mike. Hey, Colleen. We do have some eltanexor costs in our, you know, cash guidance. Ultimately, depending what happens with the MDS program is where, you know, those costs will be. For now we have some probabilized placeholders for sure. Understood. Thank you. Last question, just on myelofibrosis and the competitive landscape there. I know we're gonna get some phase III data by the end of this year from the MANIFEST-II study. How do you expect that data would impact your development and regulatory plans in myelofibrosis? Yeah, great question. You know, at a high level, I don't think it really impacts, you know, what we do with our, with our phase III. You know, again, very encouraged by the phase I data. Right now our entire focus is really initiating the phase III, which we anticipate is gonna start, you know, this quarter and being able to enroll the trial. You know, with that said, I think, you know, looking at the data, I think regardless of what the MANIFEST data look like, potential save and transform, we have an opportunity to be best in class and to really transform the first line myelofibrosis space. Not only based upon the numerical SVR and TSS50 data that we've presented at week 24, but also the very important improvement in cytopenias given the underlying disease modification that our current data suggest. Also importantly, the fact that we potentially may have monotherapy activity with Selinexor. Those data are really based upon that suboptimal Rux data in which efficacy is preserved for both SVR and TSS50, even when the Ruxolitinib doses are reduced all the way down to 5 milligrams. That affords physicians a lot of flexibility to potentially discontinue Rux due to, let's say, toxicity, and continue a patient on with Selinexor. Again, I think there's a lot of differentiating factors with Selinexor plus Ruxolitinib that can potentially enable it to be a best in class, really regardless of what happens with some of the other competitors. Great. Thanks for taking the questions. Thanks, Colleen. Thank you. Our next question comes from the line of Chris Raymond from Piper Jaffray. Please go ahead. Good morning. This is Nicole Gabreski on for Chris. Thanks for taking the question. Sorry if I missed this, but just as we think about the rest of the year, in terms of guidance, I guess, is there any certain quarter where most of the impact of these headwinds for XPOVIO might be recognized? Or I guess, how should we be thinking about that? And then just quickly for myelofibrosis. Just, you know, as we look at the other myelofibrosis programs in development, those tend to have a single primary endpoint of SVR35. Can you just maybe talk about the rationale or drivers behind having co-primary endpoints for your phase III study? Yeah. Thanks, Nicole. I'll comment on the first and then turn it over to Reshma. You know, when you look at the evolution over quarters, I think you can expect your kind of consistent differences that you see quarter-over-quarter, you know, in line with our historical patterns. As we talked to, you know, looking at the impact of patient assistance programs. We just need to see how that evolves during the year, and that's obviously something which we have to see what comes in in terms of patients requiring assistance through our programs. As we've said, you know, in our guidance range, you know, with less patients having to access our patient assistance program, that'll move us towards the higher end, you know. If we continue to see high rates of patients accessing our Patient Assistance Program, that moves us towards the middle to lower end. Reshma, do you want to expand on the second part of the question? Yeah, absolutely. Thank you for the question, Nicole. We're really focused on two main endpoints, the SVR 35 and TSS 50. You know, ultimately for the patients, it's really critical that we show significant improvement in both of those endpoints. Of course, the SVR is a potential surrogate for overall survival. That reduction is key in showing a significant improvement, potentially portends, you know, overall long-term improvement for the patient. Of course, that's symptoms. It affects directly how they feel. Again, we're focused on both of those endpoints. The data to date in the phase I really suggests that we can maximize benefit for both of these endpoints compared to ruxolitinib. It's gonna be our focus in our phase III trial as well. Great. Thanks. Thanks, Nicole. Thank you. Our next question comes from the line of Eric Joseph from JPMorgan. Please go ahead. Thanks for taking the questions. Just following up on the commercial outlook with XPOVIO in 2024. I get that you anticipate less COP utilization, but outside of that, can you just comment on expectations on net pricing? You know, we typically have seen some price hike. Can you just kind of comment on whether those might actually flow through ultimately on to net price? Then for eltanexor, I know that you're, you know, it sounds like you're just, you're currently evaluating sort of the development path forward there. Is combination therapy part of the consideration there? Can you just talk about the potential combination path with eltanexor? Thanks. Maybe I'll turn to Sohanya for the first part of that and then Reshma on the second part. Yeah. Thanks, Eric, for the question. Again, in terms of 2024, we're, you know, not providing guidance for 2024 revenues. To your point, in 2024, you know, because of that IRA-related change, we do expect to see significantly fewer patients utilizing KaryForward PFAP assistance in that segment that we discussed earlier. Again, we don't comment on future pricing strategy for 2024. As far as growth in 2024, again, growth potential for mid to long term, I remain confident in our growth potential. I can take the next one, Eric. Thank you for the question. Great question. You know, so, yeah, as you noted, like we're not talking about the next steps in the development at this time. You know, with that said, the fact that eltanexor is showing monotherapy activity in this hard to treat patient population just gives us a lot of flexibility in terms of next steps in our development, whether it's continuing to evaluate as a monotherapy, looking at different patient populations, or to your point, potentially even looking at combinations. Again, lots of opportunities, but again, it's built upon the foundation that eltanexor does have monotherapy activity. In addition to myelofibrosis, is now showing in this different tumor type that XPO1 is a fundamental mechanism in this hard to treat cancer. Thanks, Eric. Thank you. Our next question comes from the line of Jonathan Chang from SVB Leerink. Please go ahead. Hey, guys. This is Matt Cowper on for Jonathan. Thanks for taking my questions. just, first one, any updates on the regulatory interactions for the myelofibrosis phase III? Are you able to discuss any of the statistical assumptions, behind the study? Then I have a follow-up. Thanks. Sure, Matt. I'll turn to Reshma for that. Yeah. Thanks, Matt, for the question. We've had productive discussions with the FDA and have incorporated their feedback into our design. We don't talk about any specifics of those FDA interactions. You know, as I mentioned earlier on the call, you know, really our focus at this point is initiating this trial likely this quarter. You know, in terms of the statistical assumptions, there too, we haven't disclosed any of the details. You know, with that said, we're looking very closely not only at the data that we've observed as part of our phase I for both SVR and TSS50, but also looking at the historical data that we know that ruxolitinib has provided again, for both of those endpoints. We really have utilized, those data to ultimately design the most efficient, trial that can enable this, treatment to patients who have myelofibrosis. Great. That's very helpful. Just following up on the eltanexor data that you just released, we noticed there was a high degree of censoring in some of the survival data. I was wondering if you could provide any, you know, color on those patients and you know, what happened with them. Also, if you're able to provide any detail on the patient experience for patients that were post both venetoclax and azacitidine. Thanks. Yeah, great question. We still have quite a few patients who are still in survival follow-up, hence, you know, one of the reasons that they are censored. You know, this trial is ongoing. We continue to follow those patients for survival, and hopefully we'll have an opportunity to present updated survival, you know, over the course of the next few months. In terms of the post-venetoclax azacitidine, great point, and this is a key differentiation from our phase I study in that we had a subgroup of patients who did receive prior venetoclax, which is a BCL-2, a smaller subgroup of patients who received a combination of venetoclax plus HMA inhibitors. Why is this such important point? Largely because there are some preliminary data coming out of MD Anderson that suggests that patients who have received prior BCL-2 may have poor prognosis compared to the already very poor prognosis in relapsed refractory MDS. You know, this is something that we're looking at more closely, but again, gives us opportunity to further develop eltanexor, especially as venetoclax and azacitidine is expected to move as a new potential first-line therapy, leaving a gap, right, to further develop new therapies in this relapsed refractory space. Great. That's, that's it for me. Thanks for taking my questions. Thanks, Matt. Thank you. Ladies and gentlemen, this concludes our question and answer session. I would like to turn the conference back to Mr. Richard Paulson for any closing remarks. Thank you, operator. Thank you again to everyone for joining today's call. We're wishing everyone a great day. Thank you. The conference of Karyopharm has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.