Good morning. My name is Sarah, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics fourth quarter and full year 2021 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 Sarah Connors, Vice President of Corporate Communications. Please go ahead. Thank you, Sarah, and thank you all for joining us on today's conference call to discuss the top-line results from the phase III SIENDO study, as well as Karyopharm's fourth quarter and full year 2021 financial results. Today, I am joined by Mr. Richard Paulson, President and Chief Executive Officer, Ms. Sohanya Cheng, Chief Commercial Officer, Dr. Jatin Shah, Chief Medical Officer, Mr. Mike Mason, Chief Financial Officer, Mr. Stephen Mitchener, Chief Business Officer, and Sharon Shacham, Chief Scientific Officer. Earlier this morning, we issued two press releases, one announcing top-line results from the phase III SIENDO study in endometrial cancer, and one detailing Karyopharm's financial results for the fourth quarter and full year 2021. These releases, along with the slide presentation that we plan to reference during today's call, are available under the Events and Presentations section of our website at karyopharm.com. 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 two. These include statements about our future expectations, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, including our expectations relating to the commercialization of XPOVIO and NEXPOVIO, financial projections, and our plans and prospects. 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 quarterly report on Form 10-Q, which is 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 date subsequent to today. If you turn to slide three, you can see our agenda for today. I will now turn the call over to Richard. Please turn to slide four. Thank you, Sarah, and good morning, everyone. As we work to defeat cancer and improve patients' lives, I'm very pleased to report that the phase III SIENDO study met its primary endpoint of a statistically significant improvement in median progression-free survival compared to placebo. Selinexor-treated patients had a median PFS of 5.7 months compared to 3.8 months for patients on placebo, representing an improvement of 50% with a hazard ratio of 0.70 and a P value of 0.0486. Additionally, selinexor demonstrated sustained and long-term improvement in progression-free survival. At 12 months, there was an improvement in patients in remission from 25.8% to 35.3%, representing a 37% increase in probability that selinexor-treated patients will be in remission compared to patients on no treatment or today's standard of watch and wait. In this study, selinexor was well-tolerated, with no new safety signals identified and a low discontinuation rate of 10.5% due to adverse events. Karyopharm will work with investigators and the FDA to complete a full evaluation of the SIENDO data. Importantly, the preliminary data also identified a pre-specified subgroup, biotype P53, known as the guardian of the genome, which achieved a statistically significant reduction in the risk of disease progression or death. In this pre-specified subgroup, currently consisting of 103 patients, the data showed an almost four-fold improvement in progression-free survival for selinexor-treated patients with a median progression-free survival of 13.7 months compared to 3.7 months for patients on placebo, with a hazard ratio of 0.38 and a P-value of 0.0006. We plan to submit a supplemental new drug application to the FDA during the first half of 2022, and also plan to submit the detailed results from the study for presentation at upcoming medical meetings in the first half of 2022. I would like to acknowledge the exceptional work done by a lot of very dedicated individuals at both Karyopharm and at the SIENDO clinical trial site. I wish to express our sincerest gratitude for everyone involved, especially the patients and their families. On slide five, I will present an overview of our five key pillars that drive our underlying value and will provide opportunity for what we believe will be substantial future growth. First, we are successfully building upon our existing U.S. multiple myeloma foundation as our lead oncology asset, XPOVIO, generated $29.8 million in net product revenue in the fourth quarter of 2021, representing growth of 47% year-over-year. For the full year 2021, we generated net product revenue of $98.4 million, representing growth of 29% compared to the prior full year. We expect to continue growing sales in 2022 through strong execution and proven commercial capabilities, creating value for both patients and shareholders. We are striving to become the standard of care in second-line plus post anti-CD38 and establish XPOVIO as a novel, effective modality in the multiple myeloma treatment landscape. Globally, I am very pleased we have brought on board a new commercialization partner for Europe, Latin America, and other key territories with our Menarini partnership that was finalized in December. In the near term, we are expecting the European CHMP to complete its review of the selinexor MAA in second line plus and issue an opinion during the first half of 2022. With Menarini and our other global partners, we will increasingly bring XPOVIO to patients worldwide. Second, as just outlined, our near-term opportunity in solid tumors took a huge step forward as SIENDO met its primary endpoint with a statistically significant 50% improvement in median progression-free survival versus placebo. Third, we are advancing a clinical pipeline that is being purposefully built and strategically focused on targeting cancers with high unmet need, where our science enables us to make the biggest difference in the lives of patients and in areas with high probability of success. To that end, we have rapidly initiated new phase II trials in myelodysplastic syndromes and myelofibrosis, where we believe we have the potential to achieve approvals over the next three-four years. Our fourth pillar is our people, and we have the right people in place, along with a strong leadership team with an exceptional ability to achieve both scientific and commercial excellence in executing on our key corporate objectives. Most recently, we bolstered our team even further with the promotion of Sohanya Cheng to Chief Commercial Officer and the addition of Peter Honig to the Board of Directors. Fifth, and finally, to support our strategic and focused growth plan, we are well-capitalized to fund our operations into early 2024. At Karyopharm, everything we do is driven by our mission to positively impact patients' lives and defeat cancer. Our foundation is in our science, and we are the global leader with our first-in-class science technology. Against this backdrop, we believe we have a strong organization which allows us to begin 2022 primed to support patients and deliver for shareholders this year and beyond. Turning now to slide six. Driven by our vision, our innovation, as well as our scope and range of data, we are focused on our core programs, multiple myeloma, endometrial cancer, myelofibrosis, and myelodysplastic syndromes. As we now turn to slide seven, I would like to turn the call over to Sohanya for her to review the commercial results for the quarter. Sohanya? Thank you, Richard, and good morning, everyone. As Richard mentioned, we have maintained strong growth in the fourth quarter and continue to make excellent progress across key indicators since our second-line plus launch at the beginning of 2021. Please now turn to slide eight. On this slide, we show how we have rapidly evolved XPOVIO dosing in three important ways over the past two years to improve efficacy and the patient experience. On the left, from a high dose administered at 160 mg per week to lower doses of 60 mg to 100 mg. In the center, from twice-weekly to once-weekly dosing. On the right, evolving from a doublet in later lines to triplets in earlier lines. While XPOVIO in combination with Velcade is the approved indication and the only indication we promote to, XPOVIO in combination with pomalidomide, daratumumab, and carfilzomib are also included as part of the NCCN guidelines for the treatment of second-line plus multiple myeloma. This evolution is an important part of the drug life cycle, and we have worked rapidly to explore different doses and combinations as we continue to expand the breadth and depth of XPOVIO's life cycle. Turning now to slide nine, it is clear that over the last few quarters, we positively changed the growth trajectory and continued to make steady progress across key indicators. We continue to see a positive shift from the pentarefractory setting towards earlier lines, with the most rapid growth this year in the third line, as we continue to focus our messaging on XPOVIO as a new class of therapy in the wide space of second to fourth line in the myeloma treatment journey. We are also expanding in the breadth and depth of use of XPOVIO with strong growth in the community setting. We continue to add more accounts every quarter and increase penetration at top myeloma accounts. In addition, our intent to prescribe data continues to show sustained improvement in the efficacy and safety perception of the product and growing confidence in utilization in earlier lines as physicians have an increasingly positive experience with the lower dose once-weekly XPOVIO-based triplet regimen. While we continue to see the impact of COVID on oncology patient visits compared to pre-COVID baseline, our field team achieved a high level of live engagement with physicians in the fourth quarter. As we've all observed in January, the Omicron variant has added pressure on the healthcare system and our access to providers. We will continue to adapt to this and remain focused on strong execution and positioning XPOVIO as a standard of care in second-line plus. Building on our momentum in 2021 and with a rapidly advancing myeloma pipeline, we expect to continue to drive steady growth in the near, mid, and long term. If you'll advance to slide 10, I will now turn the call to Jatin to discuss the positive update from our phase III SIENDO study evaluating selinexor in patients with endometrial cancer. Jatin. Thank you, Sohanya. First, I would like to send a thank you to our teams, the SIENDO investigators, our lead global investigator and steering committee chair, Dr. Vergote from the University of Leuven Cancer Institute in Belgium, and the lead U.S. principal investigator, Dr. Vicky Makker from Memorial Sloan Kettering. As well as our partners, the European Network of Gynaecological Oncological Trial groups and the GOG Foundation, and of course, the patients who participated in the SIENDO trial and their families. Now please turn to slide 11, where I'll recap the positive SIENDO results covered by Richard. I am very pleased to report the phase III SIENDO results demonstrate selinexor significantly extends remission in patients with advanced or recurrent endometrial cancer. Selinexor-treated patients had a median progression-free survival of 5.7 months compared to 3.8 months for patients on placebo, representing an improvement of 50%. A hazard ratio of 0.7 with a P value of 0.0486, representing a 30% reduction in the risk of death, disease progression, or death. In addition, selinexor demonstrated sustained and long-term benefit in progression-free survival, as seen at 12 months, with a 37% increase in the probability that a selinexor treated patient will be in remission compared to a patient on no treatment for today's current standard of care of watch and wait. In this study, selinexor was well-tolerated with no safety signal, no new safety signals identified, and a low discontinuation rate of 10.5% due to adverse events. Additionally, the preliminary data also identified in a pre-specified subgroup, wild-type P53, again known as a guardian of the genome, where we achieved a statistically significant reduction in the risk of disease progression or death. In this pre-specified subgroup of patients with wild type P53, currently consisting of 103 patients, the data showed an almost four-fold improvement in progression-free survival for selinexor-treated patients with a median progression-free survival of 13.7 months, compared to 3.7 months for patients on placebo. With a hazard ratio of 0.38 and a P value of 0.0006. Inhibition of XPO1 by selinexor leads to the nuclear accumulation of P53, which is a well-established tumor suppressor protein, which we believe allows P53 to carry out its function, again because selinexor inhibits XPO1. Why is this top-line data so significant? Because there is no current treatment to extend their time in remission for patients in the maintenance setting, which is simply unacceptable. As you can see on slide 12, endometrial cancer is the most common gynecologic cancer with significant unmet need for patients with advanced disease. It is projected there will be nearly 66,000 new cases in the U.S. and more than 130,000 new cases in Europe in 2022. The current treatment landscape consists of first-line treatment with chemotherapy, typically a taxane plus a platinum, where response rates can be as high as 67%. However, following a response from chemotherapy with no available treatments, the NCCN guidelines recommends a watch and wait approach until disease progresses. The prognosis is poor with this approach, with progression typically within four months for those who have responded to chemotherapy. Now let me turn the call back to Sohanya to talk in more detail about the market opportunity and patients selinexor can benefit if approved. Thank you, Jatin. We have a meaningful market opportunity in front of us. Turning to slide 13, while most of the 66,000 cases in the U.S. are diagnosed with early stage disease and have a good prognosis after surgery alone, approximately 14,000 patients each year in the U.S. will present with advanced or recurrent disease. Of those patients, up to 67% of those treated with chemotherapy will respond, translating to approximately 9,000 patients being eligible to benefit from selinexor in a maintenance therapy in the front line. Further driving and enhancing that opportunity are several factors. First, maintenance therapy is already well established with physicians that treat multiple solid tumors, including breast and ovarian cancer. Second, progression-free survival of 5.7 months demonstrated by selinexor in SIENDO is superior to the watch-and-wait approach used today. Third, patients are treated until progression in the maintenance setting. Fourth, selinexor is an oral medicine that is well-positioned to be the first and only treatment post-chemotherapy in the maintenance setting that has the potential to extend time in response and remission. Finally, Karyopharm has an established and strong commercial and medical affairs footprint, which is rapidly engaging in preparing for a potential launch. In summary, as we turn to slide 14, we believe selinexor has the potential to become an exciting new standard of care for women with advanced or recurrent endometrial cancer. This belief is driven by powerful phase III results, a dire unmet need in the maintenance setting, and a significant market opportunity. In short, a paradigm shift for patients living with advanced endometrial cancer. Turning to slide 15, I'd like to now turn the call back to Jatin Shah to discuss highlights from some of our other core programs. Thank you, Sohanya. Turning to slide 16, we'll now turn to our other core programs which are focused on blood cancers. We are confident in our programs with a proven track record with robust clinical data. Selinexor has demonstrated strong response rates, both as a single agent and in combination in many hematologic indications. First in myeloma and diffuse large B-cell lymphoma, and more recently in myelofibrosis and myelodysplastic syndromes. Single-agent activity is one of the key factors in predicting positive phase III results and regulatory approvals, and selinexor has been no exception. In multiple myeloma, there's an increasing use at least 80% and growing in the first two lines of an anti-CD38-based therapy. There's limited data in one to four lines of therapy from trials of how to manage patients whose disease progresses after an anti-CD38-based treatment. This is where we have focused and generated data with selinexor-based combinations that include pomalidomide, carfilzomib, and bortezomib, with a goal of solving that data gap. As you can see on slide 17, the design of our phase III SPD study continues to fill this data gap and further evaluates and entrenches selinexor-based combinations post an anti-CD38. This study will compare the triplet regimen of elotuzumab, pomalidomide, and dexamethasone, or EPD, versus SPD. This will be our global study that's expected to recruit up to 280 patients who received one to four prior lines of therapy. We expect to dose the first patient during the first quarter of 2022, and top-line data is expected in 2024. If approved, the SPD triplet will be the second all-oral triplet combination approved in relapsed refractory multiple myeloma. Turning now to the XPOVIO regulatory expansion beyond the U.S. on slide 18. We continue to see increased access to selinexor worldwide through regulatory filings made by both Karyopharm and our global strategic partners. In Europe, the marketing authorization application based on clinical data from the phase III BOSTON study has been validated and is currently under review by the CHMP. We expect this review to be completed during the first half of 2022. Our partner, Antengene, received conditional approval for XPOVIO for relapsed multiple myeloma in China. There are also new drug submissions or applications for SPD submitted or on file in Canada and multiple Asia-Pacific markets through our strategic partners. We look forward to keeping you updated on those approvals as they happen. Now turning to slide 19, we review myelofibrosis. We believe selinexor has the potential to improve outcomes for patients with JAK inhibitor refractory disease. As seen on slide 20, there are approximately 5,000 patients per year in the U.S. diagnosed with myelofibrosis, a disease that's characterized by significant anemia, weakness, fatigue, and splenic enlargement. The only class of drugs approved in myelofibrosis are JAK inhibitors. Unfortunately, these are not curative, and 60% of patients do not respond. Among the 40% of patients who do respond initially, the response lasts at most four years. There is no other class of drugs approved, and survival is short, typically less than 14 months for those patients once a JAK inhibitor stops working. It is in this setting we have promising data with once-weekly low-dose selinexor. Turning now to slide 21, recent data that were reported at ASH 2021 show that for patients on study for at least 24 weeks. 40% of patients achieved an SVR 35, and 60% of patients achieved an SVR 25. These are very compelling results in this patient population. As you can see on slide 22, the median duration of treatment was 11 months, with a range of 2.8-28.8 months. On slide 23, you can see that among patients with anemia or transfusion dependence at screening, defined as a hemoglobin less than 10 grams per deciliter, 50% of patients achieved either an improvement in their hemoglobin levels or became transfusion independent as of the time of this data readout. Looking at slide 24, based on all these data, we have rapidly moved into a global randomized phase II trial that's recruiting patients with at least six months of prior JAK inhibition and randomized them to once-weekly low-dose selinexor for physician's choice. 112 patients are expected to be enrolled, and the first patient was dosed in late 2021. Top-line data from this trial is expected during the second half of 2023. Turning now to slide 25 with our program in MDS and our second novel compound, we believe eltanexor has the potential to improve outcomes in patients with hypomethylating agent refractory MDS. On slide 26, we show that approximately 15,000 patients are diagnosed each year in the U.S. with intermediate to high-risk MDS who need therapy. Currently the only class of drugs that are approved are hypomethylating agents. Once the disease progresses on HMA, there are no other approved therapies, and survival is very short, along the line of four-six months. There's a clear high unmet need and an opportunity to improve outcomes for patients with MDS that's refractory to HMAs. Turning to slide 27, our phase I study of single-agent eltanexor showed clear activity in patients with MDS refractory to HMAs. In that study, eltanexor demonstrated a 53% overall response rate and a median overall survival of 9.9 months, doubling historical controls of four-six months. In addition, new results presented at ASH 2021 demonstrate that the response rates also correlated to improved overall survival. The median overall survival for patients with a complete response was nearly 12 months, compared to three months for patients with progressive disease, a hazard ratio of 0.23. Based on this promising signal observed in the phase I study on slide 28 shows our ongoing phase II expansion that we've initiated in 2021, with top-line data expected in 2023. Also of note, just a few weeks ago, the FDA granted orphan drug designation for eltanexor for the treatment of MDS. We believe this designation reinforces eltanexor's potential to improve clinical outcomes for patients with HMA-refractory MDS. With that, now I'll advance to slide 29 and turn the call over to Mike Mason to review the strategic partnerships driving our global footprint, as well as our quarterly and full-year financials. Mike? Thank you, Jatin. Turning now to slide 30. Our business development activities continue to focus on leveraging strategic partners to support commercialization outside the United States. As Richard mentioned earlier, in December 2021, we signed an exclusive license agreement with the Menarini Group, whereby Menarini will develop and commercialize XPOVIO in the E.U., the U.K., and Latin America, among other territories. In exchange, Karyopharm receives an upfront payment of $75 million and is eligible to receive an additional $202.5 million in future milestones based on regulatory and sales performance, plus tiered double-digit royalties on net sales. Menarini is a strong E.U.-based partner with over $4 billion in annual revenue. They operate in over 140 countries and have a deep commitment to developing treatments addressing oncologic and hematologic diseases. This deal adds to the growing global footprint, bringing XPOVIO to patients worldwide with partners FORUS in Canada, Neopharm in Israel, and Antengene in Asia Pacific. With Antengene, Karyopharm recorded $19.5 million in milestone revenue from Antengene in the fourth quarter of 2021, with cash payment expected one year from the anniversary of their launch. Turning to our financials, since we issued a press release earlier today with the full financial results, I will just focus on the highlights beginning on slide 31. Total revenue for the fourth quarter of 2021 was $126.3 million, compared to $35.1 million for the fourth quarter of 2020. Net product revenue from U.S. commercial sales of XPOVIO for the fourth quarter of 2021 was $29.8 million, compared to $20.2 million for the fourth quarter of 2020, representing a 47% increase year-over-year. The estimated gross-to-net discount for XPOVIO in the fourth quarter was 15%. We expect gross-to-net discounts to be in the 15%-20% range for the full year of 2022. We recognized $96.5 million of license and other revenue in the fourth quarter of 2021, including the upfront payment of $75 million from Menarini. R&D expenses for the fourth quarter of 2021 were $44 million, compared to $37.2 million for the fourth quarter of 2020. SG&A expenses for the fourth quarter of 2021 were $34.6 million, compared to $33.9 million for the fourth quarter of 2020. Cash, cash equivalents, restricted cash and investments as of December 31, 2021, totaled $235.6 million, compared to $276.7 million as of December 31, 2020. Based on our current operating plan, we are expecting net product revenue of $135 million-$145 million for 2022, reflecting approximately 40% growth compared to 2021. Non-GAAP R&D and SG&A expenses, which excludes stock-based comp expense, to be in the range of $265 million-$280 million for the full year of 2022. 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 early 2024. I'll now flip to slide 32 and turn the call over to Richard for some final thoughts. Richard? Thanks, Mike. 2021 was a very strong year for Karyopharm, and I'm excited about our future, especially following the positive phase III SIENDO study, plus our progressing and focused pipeline. We are maintaining strong momentum with a number of key near-term catalysts and corporate milestones for us to deliver on as we continue to deliver for patients with high unmet need and strengthen our organization as outlined on slide 33. For the multiple myeloma program, we expect to leverage our commercial capabilities, striving to become the standard of care in second-line plus post-anti-CD38 and increase U.S. XPOVIO sales throughout the year. To dose the first patient in our phase III study evaluating selinexor, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma in the first quarter and receive a decision from the CHMP and EMA on our MAA requesting approval for selinexor, bortezomib, and dexamethasone in patients with multiple myeloma following at least one prior therapy in the first half of 2022. For the endometrial cancer program, we plan to submit the detailed results from the study for presentation at upcoming medical meetings in the first half of 2022. We plan to submit a supplemental new drug application to the FDA during the first half of 2022. Finally, we plan to conduct pre-launch activities in anticipation of a potential approval and launch in the first half of 2023. For the myelofibrosis program, we expect to report top-line phase I data in combination with JAK inhibition in treatment-naive myelofibrosis during the second half of 2022 and report top-line phase II data in previously treated myelofibrosis during the second half of 2023. Finally, for the MDS program, we expect to report preliminary phase I eltanexor data in combination with an HMA in frontline MDS in 2022 and report top-line phase II data in HMA refractory MDS in the first half of 2023. In closing, I would like to give a heartfelt thank you to our teams, especially all the dedicated people who served to move the SIENDO trial forward during COVID and deliver our data rapidly. I look forward to updating the investment community on our continued progress in the months and quarters ahead. With that, I would now like to ask the operator to open the call up to the question and answer 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 Maury Raycroft with Jefferies. Please go ahead. Hi, good morning, everyone, and congrats on the updates today, and thanks for taking my questions. I'll start off with myeloma guidance. Can you tell us what's going into your assumption of $145 million-$155 million and the 40% growth for XPOVIO in 2022? What proportion of earlier line patients are you assuming, and is there anything built into your assumptions on durability? Thanks, Maury. Just to correct that, our guidance is $135 million-$145 million for the year. Maybe I'll let Sohanya talk to what's going into that to get that guidance. Sohanya? Great. Thanks, Maury, for the question. Yeah, we feel very confident about the annual guidance of $135 million-$145 million, which is roughly 40% growth year-over-year, and it's in line with many best-in-class launches in the multiple myeloma space. As far as growth drivers, we look at what drove growth in 2021, and it was strong execution and the new positioning in the white space of second to fourth line, and we'll continue to focus in these areas. There are three key growth drivers. The first is the continued shift into earlier lines, where we anticipate seeing the most continued rapid growth in the third line. In fact, in 2021, XPOVIO was the fastest growing multiple myeloma product in the third line, and we anticipate continuing to see this shift into earlier lines. We are approaching roughly about half of our patients now in that second to fourth line, and then the remaining half in that fifth line plus. The second growth driver is the continued expansion in the breadth and depth of use of the product. We continue to add more accounts as well as increase our penetration at our top myeloma accounts. The third growth driver is to continue to move the needle on our intent to prescribe data and the perception of the product. As the community is building confidence in our use of our new lower dose once weekly XPOVIO-based triplet regimen, that shift will continue to happen. Those are the kind of the key ingredients driving growth and part of the guidance for next year. Got it. That's really helpful. Also wanted to ask a question on SIENDO. If you could talk more about the proportion of endometrial maintenance that is wild-type P53, and how does that population fit into your regulatory and commercial strategy? Yeah, thanks so much for that, Maury. When we look at patients with P53 wild type, that's approximately 50% of patients with advanced endometrial cancer who have this. We look within our study, approximately 50% as well in our study have a wild type P53. Consistent with what we see in the broader patient population. I think the second question comes to the regulatory kind of path forward with that. I think I wanna be very clear to remind folks that we have a positive phase III study for the overall patient population. We have ongoing discussions with the agency, and we'll continue to have that to this part of that discussion for the final label negotiation. Got it. Also for the 103 patients, that number with the wild type P53, is that a 2-to-1 ratio too for this study? Can you say more about how many patients were in the treatment arm versus placebo? Just clarifying, does that number represent the number of events, or is the PFS for the P53 population still maturing? Yeah. Those 103 patients, I would say the final top line results are based on 104 patients and same thing for the subgroup analysis. That itself is fixed. We'll present the full data set at a major medical meeting. Got it. Okay. Congrats again, and thanks for taking my question. Thanks, Maury. Our next question comes from Peter Lawson with Barclays. Please go ahead. Hey, thanks for taking my question, and, congratulations. On the SIENDO study, just as we think about the P53 subgroup, is that something you'd push in the label, or are you going for a broader label for maintenance setting in endometrial cancer? Yeah. Thanks, Peter. I think as we just touched on, you know, the overall study obviously, as we've shared, is positive and has a positive statistically significant improvement in patients in the maintenance setting. When we look at this area right now, there are no other approved therapies for these patients. As we look at that, we need to understand the full data set as we continue to do the analysis on this, and we'll engage with the FDA, over the near term to work on reviewing the data and determining what the final label will be. Will we get a P53 mutant breakout for whether it's PFS or hazard ratio? Yeah, absolutely. We'll provide the full data set, as we present at a major medical meeting. Got you. Okay. Thanks for taking the question. Our next question comes from Michael Ulz with Morgan Stanley. Please go ahead. Hey, guys. Thanks for taking the question. Just to follow up on XPOVIO 2022 guidance and just thinking about the quarterly progression here, should we consider maybe any seasonality in 1Q or continued maybe pressure from Omicron that persists in 1Q? Thanks. Hey, Sohanya, do you wanna take that? Yep. Thanks for the question, Mike. So we are not disclosing quarterly guidance. We've provided the annual guidance of $135 million-$145 million. As far as quarterly seasonality, given the variances we see in the market in the different quarters to your point, we will focus on year-over-year performance moving forward for that quarter. Again, we feel positive about the annual guidance we've given. To answer your question on Omicron variant, in Q4 and 2021, we did see the impact of COVID on oncology patient visits compared to pre-COVID baselines. However, in January, the Omicron variant has now added pressure on the healthcare system and our access to providers. We continue to leverage a very nimble and patient-centric sales force and strong digital and commercial capabilities. We continue to see strong momentum across our key growth drivers. We remain laser focused on strong execution and positioning XPOVIO as a standard of care in the second-line plus. Got it. Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Please go ahead. Hi. This is Steve on for Brian. Congrats on the progress, and thanks for taking our question. We're curious, do you plan to revisit any other indications in the SIENDO study to look for a possible effect of P53, say, in ovarian or cervical cancer? Maybe as a follow-up, were there any differences in the adverse event profile between the wild type P53 population and the overall population? Thank you. Yes, I'm sorry. The first question was on adverse event profile. I think what we can comment is that, we don't expect to see any differences, right, in the biology between those two patient populations, and we'll provide that full data set as we move along. What's key, though, is that what you need is something that's well-tolerated in a maintenance setting, and the biggest indicator is that 10.5% discontinuation rate, which is very low in that setting and really speaks to the tolerability of once-weekly low-dose selinexor in the maintenance setting. Can you repeat your first question for me? It was on looking at other indications than SIENDO. With the SIENDO that were in the SIENDO study. Looking at ovarian cancer and endometrial and cervical cancer. Those are the two other histologies in the SIENDO study, ovarian and endometrial. We're clearly committed to gynecologic malignancies, and we'll have further discussions. But again, our four key programs is gonna be myelofibrosis, MDS, myeloma, and endometrial cancer, and we'll continue to build upon this platform. Great. Thanks. Our next question comes from Eric Joseph with JP Morgan. Please go ahead. Hi, good morning. Thanks for taking the questions. I'm curious as it relates to SIENDO. I'm curious whether you've taken a preliminary look at OS trends, appreciating that it's not a primary. It's gonna be a secondary endpoint here. Just wondering whether it might be a gating factor to an sNDA submission, and whether OS might be part of the overall package that you submit to FDA. And then secondly, as it relates to the primary endpoint analysis of PFS, does the statistical analysis plan make any distinction between intent to treat and a per protocol treatment population? And if so, what population is reflected in this top line data set? Yeah, absolutely. Number one, no overall survival is not a gating factor to submission of the sNDA. Number two, it's too early with too few events with overall survival events to make any conclusions. Number three, for the primary PFS per the statistical analysis plan agreed and reviewed by the FDA, it is progression-free survival by investigator on an intent to treat, and that's the data we have presented. Okay, great. Perhaps if I could follow up just one XPOVIO question, commercial question related to the guidance, and also for Q4 performance. Can you just comment on how patients that were new to brand trended in fourth quarter compared to third quarter? As part of the guidance for this year, how should we be thinking about that metric new to brand trending sequentially? Thanks, Eric. Maybe I'll turn that to you, Sohanya. Yeah, thanks, Eric. We continue to show strong new patient starts, and we also showed improvement in our refill rate with patients staying on therapy longer because of the earlier line shift. I think as we move into 2022, those three key growth drivers of the earlier line shift, the increase in the breadth and depth of use, and the improvement in our intent to prescribe data should all contribute towards increased momentum with our new patients as well as our refill rates. Okay. All right. Thanks for taking the questions, guys. Thanks. Our next question comes from Jonathan Chang with Leerink Partners. Please go ahead. Hi, guys. Thanks for taking my questions and congrats on SIENDO. First question, what is your strategy for commercial success in SIENDO? Are there lessons learned from the multiple myeloma and DLBCL experience that are applicable here? Second question, can you provide any color around the duration of treatment that you're seeing in multiple myeloma? Are you seeing a difference in duration between earlier line versus the penta multiple myeloma treatment setting? Thank you. Yeah. Thanks, Jonathan. Maybe I'll take the first question. I think, again, when you look at the SIENDO patient population, obviously we're still gonna be engaging very much with regards to our action and our plans forward. I think this is very different than multiple myeloma, because there are currently no approved therapies in a maintenance setting. We have the potential to be the first and only therapy. We believe, and this by itself is a real significant market opportunity because I think as Sohanya talked to, there's an incidence of 14,000 patients in frontline with about 67% responding to chemotherapy. Those numbers obviously are different than the multiple myeloma markets in the different areas. Now in the maintenance setting, the difference here is you're really treating through progression. A s we have shared, in here, i n the median PFS for the total population, it's 5.7 months. But also in that P53 wild type population, it's 13.7 months. We've shown through that, with a discontinuation rate of 10.5%, that it's really been well tolerated for those 13 months. A s we know in our study, approximately 50% of the wild type P53 patients are in the study, and t he P53 status is a very known and an actionable mutation. It's part of the kinda standard evaluation workup for when people are looking at their patients. As we move forward, we need to continue to do more work on this, but it's a well understood, well documented, well measured, and physicians, I think, and patients are really looking for moving away from the watch and wait and being able to move to treat their cancer and obviously extend their time in remission. You know, very excited about it and also kind of a very different opportunity. Then the last point I would close with on that is in here, we're taking our established teams, which are well established, which are delivering excellent results, and are gonna be able to move forward rapidly, and engage with healthcare practitioners, f ollowing the potential approval in a label. For the second part of the question, maybe I'll turn to Sohanya to talk overall about what we're seeing in terms of e volution for patients being on therapy in m ultiple myeloma. Thanks, Richard. Multiple myeloma duration therapy. Preliminary data is showing more patients are staying on therapy longer, and again, that's driven by a shift into earlier lines and better side effect management. Now, it's important to remember this data is still maturing. We're still in the early stage of our second line plus launch, so we cannot definitively guide to duration at this time, and we're also in that dynamic phase of our transition into earlier lines of use. As we evolve into earlier lines, and we are now approaching that 50-50 split between second to fourth line and fifth line plus in our patient population, with our greatest growth happening in our third line, we will continue to see these patients in earlier lines stay on therapy longer. Got it. Thanks for taking the question. [Audio distortion]. Our next question comes from Ed White with H.C. Wainwright. Please go ahead. Good morning. Thanks for taking my question. Can you discuss perhaps the use, the prescribing under the label with Velcade versus what you're seeing with the other drugs under the NCCN guidelines? How is that breaking out, and how has the growth been under with the NCCN guidelines? Great. Sohanya, do you wanna take that? Yes. XPOVIO-based triplet use as an overall trend, that is rising significantly. To break it down, 60% or so from the data that we see of XPOVIO-based triplets are XPOVIO combination with Velcade and dex. Again, this is our approved indication and the only triplet regimen we promote to. We also know, to your point, there are other combinations with pomalidomide, carfilzomib, and daratumumab on the NCCN guidelines. There is that remaining 40% or so of that triplet use, from the data that we see where it's those other combinations. An overall rapid rise in that trend from doublets to triplets. Great. Thanks for taking my question. Our next question comes from Arlinda Lee with Canaccord Genuity. Please go ahead. Hi. Thanks for taking my question. I guess I had another one on the duration. Can you comment maybe on the, on the duration of treatment? Is that contributing on the growth in sales? Is it from improved duration versus what proportion can you help us understand, the improved duration versus new patients? And then on the SIENDO side, can you remind us, when you initially started the trial, what were kind of the ongoing regulatory discussions then and maybe what FDA was looking for, and how you came about that? Thank you. Sohanya, do you wanna talk to the first part? Yes. Thanks. Thanks, Arlinda. Again, the earlier line shift, right, it's got two drivers here. One is there's a larger addressable population in the earlier lines, and hence, XPOVIO that remains a focus for us to establish in that second to fourth line setting. In addition, the growth driver is as these patients move into earlier lines, they do stay on therapy longer. A second line patient will stay on therapy longer than a fourth line patient. Preliminary data is showing that more patients are gradually staying on therapy longer, and that's driven primarily by that shift into earlier lines, but also the better side effect management. Again, data is still maturing. We're still a year into our Boston launch, and so we can't definitively guide to mean duration. Also, that we are still in that dynamic phase into the earlier line shift, but we're seeing kind of good progress, as that earlier line shift happens with those patients staying on therapy longer. Jay, maybe you can just address the second part of Arlinda's question. Yeah, absolutely. You know, we're engaged with the agency throughout the entire life cycle of the trial from the beginning and continuously. The one key point from the regulatory discussions is it's clear that the primary endpoint is progression-free survival by investigator and intent to treat, and that has not changed. That's where we report positive phase III results from SIENDO. Okay, great. Thank you. Our next question is a follow-up from Peter Lawson with Barclays. Please go ahead. Hey, thanks for the follow-up. Just on the wild-type P53 population, does that make you rethink in any way the use in endometrial in the sense of potential use in earlier line or combinations, et cetera? Yeah, great question. Thanks for that, Peter. Obviously, we share that same excitement around P53 as well as the entire population. We'll dive more into this with additional data analyses with our investigators and the agency for future trials. Got you. Just maybe a question on the P&L, just what was the stock option expense in 2021? I'm just trying to back out the guidance. Mike, you wanna manage that? Sure. Our stock comp expense was just about $30 million. $30 million. Perfect. Thank you. Just on the P53 mutant population, are you gonna break that out or just wait for a conference? Would you have to break that out on the label as well for the P53 mutant population? Yeah. It'll be broken out at a conference as the data is presented. Then I think, as we said, we have to engage with the FDA and look at the totality of the data and determine the outcome as we look at that in the label. Gotcha. How should we think about pricing in the endometrial population? It's the same. I mean, our product's already on the market, so it's gonna be remaining at the same price. I think the key thing again to look at is in the maintenance setting, patients are really treating themselves through progression. So, with physicians and patients, they want to then extend the time in remission. I think that's where it's really important looking at those median PFS we talked about, but also looking at, [audio distortion], the real importance that over that long tail. When you're seeing that, about 35% of patients are still in remission one year after starting therapy, I think that'll be very important when you look at the duration of therapy. As we've talked to, we see with the discontinuation, that's been very well tolerated for a long period of time and, for instance, the 13 months that we see in the wild-type P53 population. All those factors we'll obviously look at the total value of the market, but from a pricing perspective, we're at the same price we're already in the market. Gotcha. Okay, thank you. Just a final question on the guidance. I know you're not doing quarterly guidance, but are there any headwinds or tailwinds that we should be thinking about year over year, when we're kind of doing the model? Sohanya, do you wanna take that one? Yeah. I think the tailwinds are really the key growth drivers where we continue to sustain our momentum. As far as headwinds, I think the wildcard continues to remain the impact of Omicron variant. As I mentioned earlier, we are adapting to it, and we've got strong commercial digital capabilities. We'll see how that evolves. Our focus remains on strong execution and positioning XPOVIO as a standard of care in second-line plus. Okay. Thanks so much. Thanks for taking all the questions. This concludes our question and answer session. I would like to turn the conference back over to Richard Paulson for any closing remarks. Thank you, operator, and thank you for all of our participants today in the call. With that, again, we look forward to being able to share our ongoing progress as how we're moving forward with our pipeline and how we're working forward to continue to focus on trying to defeat cancer and benefit patients' lives who are fighting cancer. Thank you very much, operator. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.