Ladies, good morning, and welcome to the Karyopharm Therapeutics Q2 2022 earnings conference call. All participants will be in the listen-only mode. Should you need assistance, please signal a conference specialist by pressing star then zero on your telephone keypad. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad. To withdraw your questions, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Ms. Elhan Webb, Senior Vice President, Investor Relations. Please go ahead. Thank you, operator, and thank you all for joining us on today's conference call to discuss Karyopharm's second quarter 2022 financial results and recent company progress. Today I'm joined by Mr. Richard Paulson, President and Chief Executive Officer, Ms. Sohanya Cheng, Chief Commercial Officer, Dr. Reshma Rangwala, Chief Medical Officer, and Mr. Mike Mason, Chief Financial Officer. Earlier this morning, we issued a press release detailing Karyopharm's financial results for the second quarter 2022. This release, along with a slide presentation that we will reference during today's call, are available under the Events and Presentation section of our website at Karyopharm.com. Closing remarks before opening the call up for questions. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on slide three. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent 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 day subsequent to today. In addition, we will also be providing on this call outlook for non-GAAP, R&D, and SG&A expenses for 2022. We are not providing reconciliations of these forward-looking non-GAAP measures because projections of stock compensation expense, which is required for such reconciliations, are not available without unreasonable efforts. I will now turn the call over to Richard. Please turn to slide four. Thank you, Elhan, and good morning to everyone joining us on the call and webcast today. This morning, I am excited to provide an update on our plan as we continue to execute on our growth strategy through our focused pipeline targeting life-threatening cancers. In Q2, we saw a significant increase in total revenues compared to Q2 of 2021 of approximately $40 million, which includes the benefit of licensing and milestone revenue as we continue to receive new or expanded regulatory approvals globally. With growing patient access for selinexor across the world, we expect revenues in ex-U.S. territories to have an increasing contribution to total selinexor revenues in the future. In addition, we are pleased to have delivered 44% net product revenue growth year-over-year despite an increasingly competitive multiple myeloma market and some continuation of COVID-19 related challenges. I am pleased with our team's ongoing commitment to successfully execute against key priorities. As a global leader in the inhibition of nuclear export, everything we do is driven by our mission to positively impact patient lives and defeat cancer. On slide five, we have an overview of the key pillars that drive our underlying value and provide opportunity for what we believe will be substantial future growth. First, we continue to successfully build upon our existing multiple myeloma franchise. Second, we continue to advance our focused clinical pipeline comprised of mid- and late-stage clinical development programs 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 where we believe we'll have the highest probability of success. To that end, based on compelling data signals, we are pursuing opportunities in endometrial cancer, myelofibrosis, and myelodysplastic syndromes. Collectively, we believe we have the potential to achieve multiple product approvals over the next two to four years. Our third pillar is our people. We strengthened the leadership team during the second quarter, including the appointment of Dr. Reshma Rangwala as the company's Chief Medical Officer, and the recent promotion of Stuart Poulton to Executive Vice President and Chief Development Officer. Stuart has more than 25 years of experience in the global biotech and pharmaceutical space, including both clinical operations and portfolio leadership roles at AbbVie, Amgen, and Eli Lilly. With Stuart's promotion, we consolidated the leadership structure of our R&D organization, driving increased accountability and focus. We believe we have the right people in place who have exceptional abilities to achieve both scientific and commercial excellence while executing on our key corporate objectives. Fourth and finally, we believe we are well funded into early 2024, and Mike will highlight our reduced expense guidance as we initiated cost reduction initiatives in line with the evolution of our focus pipeline. With these pillars in place, we believe we have a solid foundation allowing us to execute this year and beyond. Let's now turn to the second quarter of 2022, which was marked by several meaningful achievements, as outlined on slide six, including continued healthy commercial performance and significant progress across our pipeline. First, we grew total revenues to $39.7 million. As outlined in our press release this morning, we introduced guidance for total revenues of $155 million-$165 million, reflecting our growing global footprint and increased visibility into license and other revenues, which is becoming an increasingly important financial driver for us. Second, XPOVIO delivered strong year-over-year growth in the U.S. during the second quarter, achieving $29 million in net product revenue compared to $20.2 million in second quarter of 2021. We achieved these results through continued increasing uptake in second through fourth line setting despite the ongoing impacts from the pandemic and intensified competition in late line settings. However, driven by these challenges in the first half of the year, we are updating our XPOVIO net revenue guidance to $120 million-$130 million, representing 27% year-over-year growth at the midpoint. Karyopharm and our European partner, Menarini, were recently granted full approval for NEXPOVIO in combination with bortezomib and dexamethasone for the treatment of adults who have received one prior therapy. This new approval dramatically expands NEXPOVIO's potential use in Europe. Selinexor is now approved in 39 countries, including the recent launches in mainland China, Australia, and South Korea through our partner Antengene, and in Canada through our partner Forus. We continued to advance our clinical pipeline in core indications in the second quarter. For the treatment of myelofibrosis, the FDA granted orphan drug designation for selinexor in May. In addition, we presented encouraging initial data observed in our phase I-II frontline study of selinexor in combination with ruxolitinib at ASCO 2022 and expect to provide further myelofibrosis data in the second half of this year. For MDS, eltanexor was recently granted Fast Track designation by the FDA as a monotherapy to treat patients with relapsed or refractory intermediate, high, or very high risk MDS. In addition, the European Commission granted orphan medicinal product designation to eltanexor to treat patients with MDS in the E.U. Finally, we completed enrollment for the interim analysis of our relapsed or refractory phase II study in MDS, with the data expected to be shared in the second half of this year. As shown on slide seven, as the global leader in the inhibition of nuclear export, our drive, vision, and innovation, along with the scope and range of data generated to date, have led us to focus on our four core programs shown here: multiple myeloma, endometrial cancer, myelofibrosis, and myelodysplastic syndromes. In addition to all of these being areas of high unmet need for patients, each has a significant addressable market. As we turn now to slide eight, I would like to turn the call over to Sohanya for her review of the commercial performance for the quarter. Sohanya? Thank you, Richard, and good morning, everyone. Since our launch, we continue to focus on expanding the potential of XPOVIO and its benefit to patients in earlier lines. Turning now to slide nine on our commercial highlights for the second quarter of 2022, we grew net product revenue by 44% versus the same period last year and continued to make progress across key indicators since our second line plus launch at the beginning of 2021. This growth was achieved despite two key challenges, namely the COVID impact on new starts in January and February of 2022, which resulted in a decline in refills in the second quarter and an intensifying competitive landscape in the later lines. Our team executed with strength to access and educate our physician community, improving in-person engagements with healthcare providers from 60% last quarter to 75% in the second quarter, resulting in a recovery of new patient starts. We continue to make progress with our primary growth driver and what we believe is most important to patients, which is the continued shift of XPOVIO into earlier lines and the community setting, with over half of our patients in the second to fourth line. As we track duration of therapy, which takes time to mature, we expect to see the benefit of this earlier line shift and continued education to improve tolerability, resulting in more patients staying on therapy longer as we approach the end of the year. Although we have seen increasing competition in the late line setting at academic centers with new approvals and ongoing trials, our focus remains on expanding the use of XPOVIO in the community setting, where a majority of earlier line patients are treated. We drove growth in the community setting and increased our penetration from 64% to 67% versus the prior quarter in the top 20% of myeloma accounts, which represents about 80% of myeloma patient volume in the U.S. We continue to see a positive shift in perception of XPOVIO in the second to fourth line per the intent to prescribe data due to the growing confidence among our physicians in using the lower dose once weekly XPOVIO-based triplet regimen, with over 90% of patients now starting on a 100 mg weekly dose or less. The evolution from higher to lower dose and from late to earlier line use is one that we have seen with many myeloma therapies over several years since the original launches, and XPOVIO continues to make steady progress along this same journey. As we look to the future potential of XPOVIO within a rapidly evolving multiple myeloma landscape, it is clear there continues to be a high unmet need, both in the near and long term. Over the next several years, while new therapies may emerge in the fifth line plus setting, and while the anti-CD38 class shifts to the front line, there remains a wide space in that middle section of the treatment journey where no standard of care is established. Setting up patients for success in that middle section of the treatment plan may allow them to access subsequent therapies in later lines as we see improved patient outcomes with multiple classes and lines of therapy over an ever-increasing number of years. As a new class of therapy, XPOVIO is a convenient oral regimen that is manageable and easily combinable for second to fourth line patients. In the long term, as the treatment paradigm evolves, we continue to build a body of evidence to further demonstrate the value of XPOVIO and further entrench our positioning in the second to fourth line, and Reshma will discuss this in further detail. For the second half of this year, my team and I remain laser-focused on continuing to drive the shift into earlier lines and expanding our growth in the community with an unwavering passion to improve the lives of these patients. With that, please advance to slide 10, and I'll turn the call over to Reshma to review our clinical pipeline progress. Thank you, Sohanya. We have strategically partnered selinexor in key ex-U.S. territories. As we look to the future on slide 11, one of our top priorities is to expand our footprint in multiple myeloma across the globe. As touched on by Richard, Karyopharm and our partners, Menarini, just recently obtained approval in Europe for NEXPOVIO in combination with bortezomib and dexamethasone in patients with multiple myeloma following at least one prior therapy. The approval follows a positive opinion granted in May 2022 by the CHMP based upon results from the phase III BOSTON study. In addition, selinexor was recently launched in mainland China, Hong Kong, and in Canada through our strategic partners. Turning now to slide 12, I will be reviewing our focused developmental pipeline, which has the potential to deliver a consistent and steady stream of new approvals over the next two to four years. As you turn to slide 13, the unmet need remains strong for new modalities like selinexor to treat multiple myeloma because physicians' ability to class switch with multiple combinations has driven significantly better patient outcomes. The majority of patients treated in the first to second line are given an anti-CD38 based treatment regimen. Unfortunately, multiple myeloma is still considered an incurable disease due to inevitable relapse and acquired drug resistance, and therefore many of these patients' disease will become refractory to or relapse from an anti-CD38 PI and IMID treatment. Our clinical data support the use of selinexor in the post anti-CD38 setting. We believe this is the setting in which selinexor has the strongest fit. Selinexor has an increasingly understood and manageable safety profile. While we only promote FDA-approved regimens, physicians have the option to combine with several different backbones per the NCCN guidelines. Additionally, with the emergence of new multiple myeloma treatments, including T-cell engaging therapies, immunotherapies, and cellular therapies, we are actively investigating the role XPO1 inhibition plays in preserving and maintaining T-cell fitness, which is needed for optimal stem cell collection for patients considering cellular therapies and a robust immune environment. We believe these data will underscore the role of XPO1 inhibition in this evolving landscape and further anchor selinexor as an earlier line treatment. If you would now turn to slide 14, I would like to highlight our rapidly advancing myelofibrosis program and the current treatment landscape. Ruxolitinib is the current standard of care for newly diagnosed myelofibrosis, with only approximately 40% of patients achieving a spleen volume reduction of 35% as a first-line treatment. No other drug classes other than JAK inhibitors have been approved in the last 10 years. Our first-line myelofibrosis study outlined on this slide is a phase I-II study evaluating the combination of selinexor and ruxolitinib in patients with treatment-naive myelofibrosis. Our goals for this study are to evaluate the efficacy and safety of selinexor and ruxolitinib in this first-line myelofibrosis patient population, building on the single-agent activity of both compounds. Given the potential synergism between these two drugs, we believe that the combination of selinexor plus ruxolitinib has the potential to improve upon multiple efficacy parameters, including maintaining or improving symptom burden. Turning to slide 15, this study, which began in mid-2021, has shown encouraging results thus far, with preliminary phase I data recently presented at ASCO 2022 and the European Hematology Association 2022 Congress. These results included favorable tolerability, with no dose-limiting toxicities and 75% of evaluable patients demonstrating a greater or equal to 35% spleen volume reduction at week 12. 50% of transfusion-independent patients who had at least eight weeks of treatment maintained stable hemoglobin or improved hemoglobin levels at last follow-up. In addition, all of the evaluable seven patients who had been on treatment for at least 12 weeks and had complete data experienced rapid reductions in their symptom scores, with three of seven patients having greater or equal to 50% reduction at week 12. Turning to slide 16, you can see that the combination of selinexor and ruxolitinib was generally well-tolerated and manageable. In the phase I-A portion of the study, no dose-limiting toxicities were reported at either dose level of selinexor, with the most common reported grade three to four adverse events being thrombocytopenia, anemia, and neutropenia. The hematologic adverse events were reversible, with dose interruptions and reductions that occurred with both ruxolitinib and selinexor. On slide 17, you can see detailed SVR 35 and TSS 50 scores of all evaluable patients in this study. Currently, patients are being enrolled in the phase I-B portion of the study, with the last patient expected to be dosed this month. We expect to present updated clinical data from this study in the second half of 2022. Additionally, we continue to enroll in our previously treated myelofibrosis XPORT-MF-035 study, and we look forward to report our top-line results in the second half of 2023 as we deliver a robust development program in myelofibrosis with this novel mechanism of action. Now as we turn to slide 18, I would like to discuss the unmet need in endometrial cancer and why we find our upcoming opportunities so exciting for patients. First, endometrial cancer is the most common form of gynecologic cancer in the United States, with approximately 50% of tumors classified as p53 wild-type. Next, the current treatment landscape for advanced or recurrent endometrial cancer consists of first-line chemotherapy. Upon completion of chemotherapy, the NCCN guidelines recommend a watch-and-wait approach until disease progression. This approach clearly needs improvement, given that the five-year survival rate in this patient population is only 17%. As selinexor is administered orally and maintenance therapy is well established with physicians that treat multiple types of solid tumors, including breast and ovarian cancer, we believe selinexor has the potential to offer a maintenance option that could sustain the response from chemotherapy and improve the overall clinical benefit for these patients. Presented at ASCO 2022 were the subgroup analyses and molecular classification data from the SIENDO study evaluating selinexor in endometrial cancer. A preliminary analysis of exploratory subgroups of the SIENDO study assessed four distinct molecular subtypes in endometrial cancer using The Cancer Genome Atlas, one of the accepted gynecologic oncology algorithms that is used to calculate prognostic risk scores. As previously disclosed, this analysis indicated that patients whose tumors were p53 wild-type treated with selinexor demonstrated a median progression-free survival of 13.7 months, compared to 3.7 months for patients treated with placebo. In contrast, patients whose tumors were either p53 mutant or aberrant and treated with selinexor demonstrated a median progression-free survival of 3.7 months, compared to 5.6 months for patients treated with placebo. These data suggests that p53 wild-type has the potential to be a robust biomarker, and selinexor may provide meaningful benefit to patients with p53 wild-type endometrial cancer. Based upon productive dialogue we have had with the FDA, we have selected companion diagnostic partner and are in the process of finalizing an agreement with them. We are excited with the ongoing close collaboration with both GOG and NRG Oncology, and remain on track to initiate this phase III registration enabling trial in the fourth quarter of this year. With that, I'll now advance to slide 19 and turn the call over to Mike to review the second quarter financial highlights. Mike. Thank you, Reshma. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which begin on slide 20. Total revenue for the second quarter of 2022 was $39.7 million, compared to $22.6 million for the second quarter of 2021. With increasing approvals and commercial launches for selinexor globally, we expect milestone and royalty payments by our partners to deliver a larger contribution to our total revenues in the future. Net product revenue from U.S. commercial sales of XPOVIO for the second quarter of 2022 was $29 million, compared to $20.2 million for the second quarter of 2021, representing a 44% increase year-over-year. The gross to net discount for XPOVIO in the second quarter was 17%. We expect gross to net discount to be in the 15%-20% range for the full year 2022. We recognized $10.7 million of license and milestone revenue in the second quarter of 2022, which includes $6.5 million earned in reimbursement of development expenses from the Menarini Group and $1.5 million related to milestones earned from our partner, FORUS Therapeutics. R&D expenses for the second quarter of 2022 were $44.3 million, compared to $34 million for the second quarter of 2021. Our results this quarter included a one-time $3.8 million severance related stock compensation charge. We expect our 2022 non-GAAP R&D expense to decrease by approximately 10% compared to 2021, with the majority of the decrease expected in the second half of 2022. SG&A expenses for the second quarter of 2022 were $37.3 million, compared to $36.5 million for the second quarter of 2021. The increase in SG&A expenses was due to a one-time $3.5 million severance related stock compensation charge in the second quarter. Cash, cash equivalents, restricted cash, and investments as of June 30, 2022 totaled $172.6 million, compared to $235.6 million as of December 31st, 2021. Based on our current operating plans, Karyopharm's guidance for full year 2022 is as follows. Total revenue in the range of $155 million-$165 million. XPOVIO net product revenue of $120 million-$130 million, reflecting a decrease of approximately $15 million versus our prior guidance. non-GAAP R&D and SG&A expenses, which excludes stock-based compensation expense to be in the range of $250 million-$265 million, including approximately $5 million of severance related expenses, reflecting a decrease of approximately $15 million versus our prior guidance. We initiated cost reduction initiatives in the second quarter that will accelerate in the second half of 2022, including stopping certain signal seeking programs such as our lung and colorectal cancer studies. In addition, we are optimizing our R&D and G&A infrastructure by eliminating roles as we continue to align the organization with our prioritized programs. These efforts will reduce overall compensation costs by approximately 10% in the second half of 2022 compared to the first half of the year. Through these enhanced efforts, we expect these savings will build through 2023, sustaining our cash runway. We project that our existing cash equivalents, and investments, as well as the revenue we expect to generate from XPOVIO product sales and license revenues, including a $20 million cash payment from Antengene that we expect to receive near the end of the year related to a milestone that we previously recognized, will be sufficient to fund our planned operations into early 2024. Let's move to slide 21 and turn the call back to Richard for some final thoughts. Thanks, Mike. As you've heard from the team, we continue to maintain momentum with a number of key near-term catalysts and corporate milestones for us to deliver on, as outlined on slide 22, as we continue to strive each day for patients with high unmet needs. In closing, I would like to thank all of our teams at Karyopharm and our investigators as we work every day to positively impact the lives of patients with cancer. 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 questions, please press star then two. At this time, we will pause momentarily to assemble our roster. First question is from the line of Maury Raycroft with Jefferies. Please go ahead. Hi, this is Kevin Strang on for Maury. Thanks for taking my questions. First question for myeloma. Can you say what percentage of second quarter new patient starts were earlier line? Then should we think of this number as shifting higher from the roughly 50% split with increased academic competition? Thanks. Yeah. Thanks, Kevin, for the question. I'll turn to Sohanya for that. Sohanya? Yeah. Hi there, Kevin. Thanks for the question. Yes, we've seen an improvement in that shift into earlier lines, and we're now well over 50% of our patients are now in the second to fourth line. As for the community, as we know, a majority of these patients are treated, the earlier line patients are treated in the community, and we see that over 65% of our business comes from the community, and we continue to increase our breadth and depth in the community. Great. Thank you. Just one on. Sorry. Go ahead, Kevin. Just one on myelofibrosis. Could you just talk more about what we can expect from the totality of data in the second half of next year in terms of number of patients or follow-up for both monotherapy and combo therapy? Then how are you thinking about how that's going to inform your path forward in myelofibrosis? Thanks. I'll turn to, Reshma to talk to that, Kevin. Reshma? Hi, Kevin. Yeah, thanks for the question. We're very excited to present some updated myelofibrosis data in the second half of 2022. We're focusing on the zero three four study. The zero three four study is in the treatment naive population in which we are evaluating the efficacy and safety of selinexor in combination with Jakafi or ruxolitinib. As you likely know, this study is a phase I followed by a randomized phase II, and we anticipate that we will be providing updated efficacy and safety from the phase one portion of the trial. This will include patients that were enrolled as part of the dose escalation, as well as patients that were enrolled as part of the expansion phase. In total, we are anticipating approximately 21 patients to be included in this cohort, and this is gonna be additional follow-up as compared to what we presented at EHA as well as at ASCO 2022. By and large, the datasets that we are going to be providing are gonna be similar to ASCO 2022, with focus on SVR, TSS50, anemia data, and also updated safety and tolerability data as well. Great. Thank you. Thanks, Kevin. Thank you. Next question comes from the line of Peter Lawson with Barclays. Please go ahead. Great. Thanks for the update. With changing guidance, just wonder if you could walk through any changes in how you're thinking about particular growth drivers for this year and next year, Richard? Yeah, sure. Sure, Peter. I'll just kick it off, and then I'll turn it to Sohanya 'cause I think as Sohanya mentioned, you know, we did face some headwinds in Q2. We are confident in our revised guidance moving forward. You know, as we do believe there's very strong opportunity for growth, especially in that second to fourth line in the community setting. Maybe, Sohanya, I'll turn it to you to talk to some of the growth drivers you see moving forward. Yeah. Thanks, Peter. You know, the first half of the year, we recognize that we face headwinds driven by two things. One was the refills were down in the second quarter due to the COVID impact on reducing new patient starts in January and February. Secondly, the intensified competition in the academic centers in the later lines due to new approvals as well as clinical trials ramping up post-COVID. Our revised guidance reflects these headwinds. As we think about looking ahead, the midpoint of the updated guidance range is $125 million, which represents 27% growth year over year for 2022, and we believe there continues to be significant opportunity for long-term growth. As we think about the second half of this year and beyond, our team is laser-focused in two areas. Number one, accelerating growth in the second to fourth line to offset erosion in late lines from late line competition. Secondly, to expand further into the community where a majority of the earlier line patients are treated, and these community physicians prefer a convenient oral regimen that's manageable, easily combinable post an anti-CD38. As we think about growth drivers for the second half of the year, there are several we see continued positive momentum in these areas. Number one, new patients start recovery in the second quarter of the year as oncology patient visits are normalizing post-COVID. Secondly, as I mentioned, we're seeing this continued positive shift in use of XPOVIO in the second to fourth line. Over half of our patients are in this setting. We're seeing higher growth in the community. This is a key area of focus for us. Increased penetration in the top 20% of the myeloma accounts, a majority of which are community accounts. We're seeing the continued improvement in the perception and building of confidence in the community. Most importantly, as we think about tailwind for the second half of this year with COVID access restrictions coming down, our live engagements of our field-based representatives with healthcare providers is increasing significantly. We've moved to over 75% of our interactions being live, and this is critical for us in a competitive space to drive education at this early stage of the launch. For these reasons, we feel confident about our growth trajectory for the second half of this year and beyond. Thank you. What percentage of revenues is coming from the academic settings? Yeah. About 65% of our business is coming from the community, and the remainder is coming from the academic setting. Our focus remains on expanding further into the community. Got you. Thank you. I guess a question just for Mike, just thinking about costs for the second half. You said a 10% reduction in costs in the second half. How does that change as we think about 2023 as well? Thanks, Peter. We, you know, we do expect that cost reduction initiatives that we introduced in the second quarter to accelerate in the second half of 2022. You know, the cost savings from certain signal seeking programs such as the studies in lung and colorectal cancer that we terminated in addition to personnel-related reductions, optimizing our R&D and G&A infrastructure by eliminating certain roles, we look to align the organization, you know, with our core program. This overall will reduce compensation costs by approximately 10% in the second half of 2022. You know, we're not necessarily providing guidance for next year, but our cost reduction initiatives in our focus pipeline, we do expect our cost savings will increase not only in the second half of the year, but will build into 2023, sustaining our cash run rate into early 2024. Okay. Thanks so much. Thanks, Peter. Thank you. Next question comes from the line of Mike Ulz with Morgan Stanley. Please go ahead. Hey, guys. Thanks for taking the question. For XPOVIO in terms of physician perception, can you maybe talk about how that's evolved over the past year or two? Just curious, trying to get a sense of, you know, the progress you've made there so far. Looking forward, you know, what's the opportunity to continue to improve that? Thanks. Yeah, thanks, Mike. I'll turn to Sohanya to talk to that. Thanks, Mike. Perception evolves with a product's evolution, and our product has been through an incredible evolution in the past 18 months, from late lines to early lines, high dose to almost half the dose plus with the right supportive care. So we've seen perception shift in a positive direction over time. In the intent to prescribe data as well as anecdotal feedback that we get from physicians on a daily basis, particularly in the community setting, we're seeing an increase in their likelihood to prescribe in the second to fourth line, as well as a positive perception of the product both in efficacy and safety. What our data is also showing that more than 90% of our patients are being started on 100 mg or less. This is great progress as we've seen the evolution of our dosing. As we think about moving forward and improving our perception, the key is to continue to educate our physicians, our nurses, our support staff on the importance of the right dose reductions, and supportive care. Live engagements are critical, both between the field representative and the healthcare provider as well as physician to physician, peer to peer education. As I mentioned earlier, as COVID restrictions are coming down and our live engagements are increasing, this education will be key to continuing to drive an improvement in our perception moving forward. Got it. Thank you. Thanks, Mike. Thank you. Next question comes from the line of Colleen Kusy with Baird. Please go ahead. Thanks. Good morning, and thanks for taking our questions. Should we be thinking about that the COVID-19 impact from Q1 has now fully cycled through, or should we be expecting some pressures still in the second half of this year? In Europe, can you just talk about how soon you think that could be a meaningful contributor to your top line and remind us what your economics are there, please? Yeah, sure, Colleen. Thanks for the question. Maybe for the first part, you know, I'll turn to Sohanya to talk about the COVID-19 impact from Q1 and how that evolves because it does evolve over time and becomes reduced as we move forward. For the second part, I will turn to Mike to talk kind of about the economics in Europe. Sohanya, maybe kick off the first part. Yeah. The COVID impact we break down into two fronts. One is oncology patient visits and the impact that that has on our new patient starts and refills. And we felt that we went through the peak of it in January and February with Omicron, where we saw patient visits come down by up to 10%, which impacted our new starts and in turn our refills. We feel that is reflected in our lowering of our guidance. I think the second impact of COVID is access to physicians. What we're seeing is a trend to returning to normal, when we are not at 100% of live access, but we are around 70%-75% or so. As we think about moving forward, the signs that we see are continued improving signs. We obviously, you know, don't have a crystal ball to predict any changes in COVID fluctuations over the course of the year. The trends that we're seeing, both on the oncology patient visit side as well as the access to our physicians are both improving. Mike, do you wanna take the second part? We talk about the European launch as kind of as they evolve over the next, you know, 12-24 months. Sure, yeah. Thanks. You know, just a refresher on our Menarini deal. That we announced back in December of 2021 includes about $200 million in future milestones plus tiered double-digit royalties on next, on net sales. Menarini expects first commercial launch in Germany in the second half of this year. They'll, as Richard mentioned, this launch will evolve over the next 12 months as pricing and reimbursement discussions, you know, evolve with each country. Great. Thank you. If I can ask a follow-up on myelofibrosis. We saw some encouraging early data, I believe at 12 weeks at ASCO. The update in the second half, will that include 24-week data? Can you talk about how you expect that data to mature from 12 to 24 weeks for both SVR 35 and TSS 50? Yeah, maybe I'll turn to Reshma to talk about that. Again, as you remember, kind of looking even from our earlier data on deepening over time, I think is an important perspective to look at, Reshma. Yeah, absolutely. Hi, Colleen. Thanks for the question. Yes, we absolutely will provide 24-week data. The data set that we anticipate to provide in the second half of 2022 is going to include more patients, so more patients that were enrolled as part of the phase I-B in addition to the data already presented from the phase I-A, but also more mature data. We'll see the 12-week as well as 24-week in a subgroup of those patients. As Richard just alluded, you know, we keep going back to the essential data. The essential data is an investigator-initiated trial that was evaluating selinexor as a monotherapy, primarily in our relapsed or pretreated patient population. What we saw in those data were quite intriguing in that patients who stayed on therapy over time, we saw that their responses deepened over time. We do anticipate a similar kind of phenomenon as we evaluate selinexor in combination with ruxolitinib now in a first-line population, specifically that their, you know, SVR potentially could deepen over time. We're looking forward to presenting those data soon. Great. Thanks for taking our questions. Thanks, Colleen. Thank you. Next question comes from the line of Brian Abrahams with RBC Capital Markets. Please go ahead. Great, thanks. This is Steve on for Brian. Thanks for taking our question. Can you share any thoughts on how increasing competition in myelofibrosis, including with combo rux studies, might affect trial recruitment moving forward? And any thinking how that might affect your timeline assumptions for the next steps? Thanks. Yeah, thanks, Steve. I'll turn to Reshma for that, but I think as we've been talking to, we do see our overall recruitment moving forward well, but Reshma may want to talk to that. Yeah, absolutely. Again, thank you for the question. You know, there's a lot of interest coming out of ASCO and especially EHA with the XPORT-MF-034 study. That data set was small, as you know. Again, we will have an opportunity to present updated data in the second half of this year. Those initial data again were very encouraging given the fact that we saw some very robust responses in terms of the SVR, as well as intriguing data around TSS50 as well as anemia. This really has, you know, sort of a halo effect, I will say, with the investigators too. It is a competitive space, especially because that myelofibrosis patient population is rare. With that said, I think there is a lot of interest in being able to participate in these clinical trials. We do anticipate enrollment to continue, and we haven't changed. We don't anticipate any changes in our data availability in terms of readouts. Great. Thanks for that color. Thanks, Steve. Thank you. Next question comes from the line of Eric Joseph, J.P. Morgan. Please go ahead. Hi, good morning. Thanks for taking the questions. First one on XPOVIO commercial. I'm curious to know whether you're seeing any tension with the expansion of anti-CD38 use in earlier lines from the J&J results. You know, we saw impressive growth of Darzalex given the introduction of the sub-Q formulation. I'm just wondering whether you're kind of seeing a competitive dynamic. And also, whether you have a sense of XPOVIO uptake today among patients whose prior therapy was an anti-CD38 to the extent that Darzalex expansion today might, you know, represent a windfall in subsequent years. Also just kind of drilling down a little bit further on the uptake that you're seeing today by line of therapy. Do you have a sense of or could you sort of weigh XPOVIO uptake within that second- to fourth-line setting? It's sort of weighted more towards fourth line versus second line. Thanks. Yeah. Thanks, Eric. Maybe I'll break the question up in a couple parts. I think the first part I'll turn to Sohanya to talk about, you know, as we're seeing increasing use of anti-CD38s in the earlier lines, Darzalex, what that means for us. I think within that, you know, Sohanya, you can probably talk to how we're seeing our evolution between that second to fourth line in terms of lines of therapy, where the greatest growth is. Then I also turn to Reshma to talk to some of our data really, post-anti-CD38 and how, you know, having a novel new class is really positive for patients post anti-CD38. Sohanya, maybe take the first part and then over to Reshma. Great. Thanks, Eric. Yes, we're seeing a continued increase in the use of anti-CD38 in the front line, which in turn continues to leave that unmet need open in that middle section of the treatment journey between second to fourth line, where there is no clear standard of care. XPOVIO has proven data post anti-CD38. We only promote to approved regimen, which is a combination with bortezomib, but the NCCN guidelines also has other triplet regimens of XPOVIO in combination with pomalidomide, carfilzomib, as well as daratumumab. To answer your second question of what about prior therapies that don't include an anti-CD38 backbone? Well, if it included a PI or an IMID backbone, there's optionality to combine with a different backbone and XPOVIO per the NCCN guidelines. Overall, as we take a step back, the continued white space in that second to fourth line is critical for a couple of different reasons. There is no clear standard of care, but also it sets up patients for potentially successful outcome and accessibility to potential late line therapies as they emerge. I just wanna piggyback on what Sohanya said too. I mean, from the R&D perspective, there are growing data to suggest from a clinical perspective that treating patients post CD38 increases their efficacy. The sequence really is an important phenomenon. We also have growing preclinical data that also suggests that treating patients post CD38 with selinexor may improve efficacy as well. This, again, treating with selinexor post CD38 really is very efficacious for these patients. Great. Thanks. Just as a follow-up here on the OpEx guidance. Inclusive of both the lower spend for this year and as you look at 2023, and really just your runway guidance into early 2024, I guess how should we be thinking about any impact to the pace of enrollment of the randomized studies, the phase III in either endometrial cancer or myeloma? Is there any prioritization of enrollment that will need to take place there in order to stay within the runway guidance? Thanks. No. We obviously take assumptions in all our trials of what enrollment will be so that you could see lumpiness in quarters for sure if it has a higher enrollment one quarter versus the next. No, what's in our forecast and our base plan is our prioritized program driving them forward. Okay. Thanks. Take the questions. Thanks, Eric. We're just coming up kind of top of the hour. I think one or two more questions. Thank you. Next question comes from the line of Ed White with H.C. Wainwright. Please go ahead. Good morning. Thanks for taking my questions. I'm just wondering if you have any visibility into the mix of the current regimens being used. In particular, the pomalidomide last combo. You know, while it's not approved, it has the NCCN guidelines. So I'm just wondering what, you know, what the percentage of the oral regimen is right now and how important the combination trial is to the company if you're already penetrating that market. The second question is just on eltanexor. Can you give us an update there? I know the phase II study is ongoing. You're expecting data in the first half of 2023, but if there's anything you can tell us about enrollment or any other updates you can give us. Thank you. Thanks, Ed. For the first part of that question, I'll turn to Sohanya, and the second part we're gonna talk to Reshma, because we have moved up that a little bit. Sohanya? Yep. Thanks, Ed, for the question. From the data that we see, and we don't have full visibility into a hundred percent of our regimen data. But from the data we see, overall triplet use trend is growing over time. About half of that use is XPOVIO. Half of our overall use is XPOVIO-based triplets. Now, the triplets are broken down into a variety of regimens, which include primarily XVD, our approved indication, and then a couple of other regimens as well, the combination with pomalidomide as well as the combination with Kyprolis, as you mentioned, on the NCCN guidelines. As I mentioned, it's about half of our use is triplets, of which there is a split with a majority of those three regimens up there in the triplets. In terms of eltanexor, we're currently evaluating eltanexor in patients with myelodysplastic syndrome (MDS). We have two cohorts. One is a relapsed refractory patient population, another is a first line in which we are combining eltanexor with HMA inhibitors, which, as you know, are standard of care in this patient population. We're very excited to be presenting data in the second half of 2022 from the relapsed refractory phase II patient population, and this is from a pre-planned interim analysis that is fully enrolled at this point. Great. Thank you. Thanks, Ed. We'll just take one more question, operator, toward the top of the hour. Thank you. Next question is from the line of Jonathan Chang with SVB Securities. Please go ahead. Hey, guys. Thanks for squeezing us in. It's Jonathan. Just wanted to ask, what could the registrational strategy in myelofibrosis look like, and how are you thinking about pursuing the frontline versus the relapse opportunity? Like, is this an either/or could you pursue both? Thanks for the question. I mean, overall, I think, and I'll touch on it overall, but then we wanna turn to Reshma to talk to it. You know, overall, approaching both is really important for us 'cause I think there's opportunities to really build a nice franchise in the myelofibrosis area in terms of those relapsed patients or, you know, in combination up in the frontline. Reshma, maybe you can talk and expand on that. Yeah, absolutely. I mean, we've got a robust clinical development program in myelofibrosis covering both the first line as well as the relapsed refractory patient population. In the first line setting, we are evaluating selinexor in combination with Jakafi, and we anticipate that combination versus Rux alone, again, in that first line patient population. In the relapsed setting, there really is no standard of care. In that relapsed setting, we are likely going to evaluate selinexor versus physician's choice chemotherapy. Both trials are currently enrolling, and likely anticipate that the second, the relapsed refractory patient population would read out first. But again, both trials are on track. Thank you. Thanks for the question. Thank you. This concludes our question and answer session. I would like to turn the conference back over to Mr. Richard Paulson for any closing comments. Thank you, operator, and thank you to everyone for joining us on the call today. We're excited to continue moving forward and focusing on our key priorities and continuing to focus on delivering for patients over the rest of this year. That concludes our call.