Karyopharm Therapeutics Inc. (KPTI) Earnings Call Transcript & Summary

Good afternoon, and welcome back to the 40th Annual JPMorgan Healthcare Conference. I'm Eric Joseph, senior biotech analyst at the firm. Our next presenting company is Karyopharm Therapeutics, and it's my pleasure to welcome CEO, Richard Paulson, to talk to us a little bit about the company. There's a Q&A session after the presentation. [Operator Instructions] So with that, Richard, thanks again for sharing some of your time with us this afternoon.

Thank you, Eric, and it's great to see you again. Thanks also to JPMorgan for hosting the event virtually today. Good afternoon, everyone, and thank you for listening. To help keep us synchronized through the presentation, I'll call out the slide numbers as I go. So before we begin, please turn to Slide 2, and I'd like to remind you that for various remarks we'll make they constitute forward-looking statements, and the actual results may differ materially from those indicated by these statements. So please consult in our SEC filings, including the Risk Factors section of our most recent 10-Q. So with that, please turn to Slide 3. At Karyopharm, we're leveraging the inhibition of nuclear export, it's a new mechanism to treat cancer, and we're passionately driven in our mission to positively impact patient lives and defeat cancer. I'm very pleased as we're coming off a very strong 2021. As I came on board in Q2 of '21, we've strengthened the organization. We've increasingly delivered through '21 and are starting '22 from a position of strength, to deliver for patients and shareholders this year and beyond. And to that end, there are 5 key pillars that will be driving our underlying value and providing opportunity for what we believe will be substantial future growth for Karyopharm. So let's look at those now. First, looking at multi myeloma and as we announced in our press release yesterday, our lead oncology asset, XPOVIO continued its net product revenue growth trajectory during the fourth quarter of '21, generating approximately $29.7 million in net product revenue for the quarter. And a key person driving the significant growth in net sales during the second half of the year was Sohanya Cheng, who we just announced yesterday was promoted to Chief Commercial Officer and will join us for our Q&A. In fact, in leveraging our strength in commercial capabilities and team, we delivered second half '21 growth of approximately 35% versus the first half of the year. And we expect to continue to grow sales in '22 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 quest post anti-CD38 and establish XPOVIO as a novel effective modality in the multiple myeloma treatment landscape. And globally, I'm also very pleased we have brought on board a new partner for Europe, Latin America and other key territories with our Menarini partnership that we finalized in December. With Menarini and our other global partners, we will increasingly bring XPOVIO to patients worldwide. And in near term, we are expecting the European CHMP to complete its review of the selinexor MAA in second line plus an issue an opinion during the first half of '22. Second, I'm excited and thankful for our teams, investigators and patients as we completed on schedule our recruitment for the SIENDO trial in Q4 of '21. We are focused and working tirelessly to bring selinexor patients with endometrial cancer as there are no approved treatments in the maintenance setting followed chemotherapy in any line of treatment. And in the very near term, we'll be reporting top line results from the Phase III SIENDO study, assuming the data are positive, endometrial cancer, which is the most common form of gynecological cancer has the potential to be Karyopharm's first marketed solid tumor indications. And third, we are advancing a clinical pipeline that has been consciously and strategically focused on targeted cancers with high unmet need, where our science enables us to make the biggest difference in the lives of patients and in areas with higher probability of success. And 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 3 to 4 years. And fourth, we have the right people in place and a strong leadership team with an exceptional ability to achieve both scientific and commercial excellence to execute on our key corporate objectives. And finally, to support our strategic and focused growth plan, we are well capitalized to fund our operations with a cash runway through to early 2024. So turning now to Slide 4. Driven by our vision, along with the breadth and depth of data, we are focused on 4 core programs: multiple myeloma, endometrial cancer, myelodysplastic syndromes and myelofibrosis. And for our focused and progressing pipeline, shown on Slide 5, let us now look at a more detailed view of the 4 core areas we are pursuing in clinical development. In addition to SIENDO and endometrial cancer, we continue to conduct studies aimed at expanding our presence in multi myeloma and also advancing 4 additional clinical studies in myelofibrosis and in myelodysplastic syndromes. So I'll now discuss our multiple myeloma program, which begins on Slide 6 and where XPOVIO is already marketed and it's been improving outcomes for patients. So if we move to Slide 7. So a brief overview of the multiple myeloma landscape and the opportunity. Multiple myeloma is the second most common blood cancer and as of today, remains incurable, and the prevalence continues to increase. The many advancements made over the past decade are improving survival for patients, underscoring the need for new active combinations and classes that can continue to improve patient outcomes. And one of the key principles in the management of multiple myeloma that's well established is the concept of switching classes of drugs between the lines of therapy or class switching. I'll elaborate on that and how we've moved into earlier lines on Slide 8. And here, we provide clarity on where there's clear unmet need. There's an increasing use, at least 80% and growing in the first 2 lines of an anti-38 based treatment. And at this time, there's really limited data in 1 to 4 lines of therapy from trials on how you manage patients whose disease progresses after an anti-CD38 based treatment. So the data gap is significant and it's seen clinics every day where there's a clear opportunity for selinexor. We've generated the data with XPOVIO-based combinations, including in combination with pomalidomide, carfilzomib and bortezomib in this specific setting with a specific goal of filling that data gap. And the beauty of this is it builds upon the well-established principle of class switching. Now on Slide 9, we show how XPOVIO dosing has rapidly evolved in 3 important ways over the past couple of years. On the left, from a high dose administered at 160 per week to lower doses of 60 to 100 per week; in the center from twice weekly to once weekly dosing; and on the right, evolving from a doublet in later lines to triplets in earlier lines. And this evolution, which is an important part of the drug's life cycle, it's common and it's occurred with many other multi myeloma treatments. And now on Slide 10 is our estimated fourth quarter '21 sales performance. Over the last few quarters, we accelerated growth and continued to make steady progress across key indicators. Preliminary unaudited net product revenue for XPOVIO for the fourth quarter of '21 is $29.7 million, representing 48% growth year-over-year. And we continue to see a positive shift from the penta-refractory setting toward earlier lines with the most rapid growth this year in the third line as we continue to focus our messaging on the white space of second to fourth line in the myeloma treatment journey. And the results of that can be seen in our second half versus first half growth of approximately 35%. Now on Slide 11, we can see a snapshot of the opportunity in multiple myeloma, where about 40,000 patients are treated in the second-line plus setting in the U.S. every year. And we believe we have a tremendous opportunity to continue expanding XPOVIO's breadth and depth of use through continued execution in our approved indications. And through the advancement of key late-stage trials, including the all-oral triplet combination, where we're studying selinexor with pomalidomide and dexamethasone in patients as early as the first relapse. And we believe that the ability to combine with other approved agents and being a new class of therapy will allow us to drive sustainable and long-term growth in the multiple myeloma marketplace. If you turn to Slide 12, there are 4 key differentiators with XPd that we believe position it well in the second line plus. First, with the majority of multiple myeloma patients being exposed to an anti-CD38 monoclonal antibody, there's an unmet need for a new class of therapy early. Second, XPd will be an all-oral combo, which is highly desirable with this patient population, potentially being only the second FDA-approved all-oral triplet. And third, our STOP data showed robust efficacy and good tolerability post anti-CD38 therapy. And fourth, we choose to combine with a very well-established backbone pomalidomide to widely used in earlier lines with about 20% of patients on a pom-based combo in second line. And here, you can see the design of Phase III XPd study, which will compare this triplet regimen to elotuzumab, pomalidomide and dexamethasone, or EPD. This will be a global study. It's expected to recruit up to about 280 patients, who've received 1 to 4 prior lines of therapy and we expect to dose the first patient during the first quarter of '22, and top line data is anticipated in 2024. So turning now to the XPOVIO regulatory expansion beyond the U.S. On Slide 13, 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 is being validated and is currently under review by the CHMP, and we expect this review to be completed during the first half of '22. Our partner Antengene recently received conditional approval for XPOVIO for heavily pretreated multiple myeloma in China, and there are also new drug submissions or applications for SPd submitted are on file in Canada and multiple Asia Pacific markets through our strategic partners and look forward to keeping you updated as these approvals happen. So if you turn now to Slide 14, the key takeaways from the multi-myeloma program are: first, we continue to see strong net product revenue growth. Second, we continue to drive adoption of XPOVIO-based combinations for second line plus for an effective new class of therapies as needed. And third, there is a critical need for efficacious novel combinations post anti-CD38 with the ability to combine with PIs and IMiDs. And finally, we're pursuing approvals in additional settings, including with the all-oral combo XPd. So if we move now from multiple myeloma to our second core program in endometrial cancer, which begins on Slide 15. I'm excited about the opportunity for patients because currently in this advanced setting, there are no approved treatments and patients have a watch-and-wait approach after completing chemotherapy. The potential for selinexor to extend remission in patients with advanced or metastatic disease is significant. In endometrial cancer, as shown on Slide 16, is the most common gynecological cancer and it arises from the lining of the uterus. And for patients with advanced or metastatic disease, the current standard of care is combination chemotherapy for 4 to 6 cycles. Now unfortunately, this is not curative and remission is typically short lived for 4 to 6 months, patients responding to the first-line chemotherapy treatment. So clearly, there's a need for new approaches that can prolong time and remission, which is the goal of our SIENDO study with selinexor, having the potential to be the first and only treatment following chemotherapy in the frontline maintenance setting. And as we've discussed over the past year, our excitement regarding a potential positive outcome from SIENDO is supported by the results from the prior Phase II SIGN study in patients with more advanced disease. And the patients in the SIGN study were treated in the third-line setting, had chemotherapy refractory disease. And in this very difficult setting, selinexor demonstrated a median duration of disease control for 6.3 months for 1/3 of patients. Again, importantly, the SIENDO study is in the first-line setting and chemotherapy-sensitive disease as you can see on Slide 17. The SIENDO study enrolled approximately 248 patients, randomized 2:1 to receive either 80 milligrams of selinexor once weekly or placebo. Eligible patients include those who have Stage IV or recurrent disease who've completed a course of taxane-platinum combination chemo and achieved either a partial or complete response. The primary endpoint of the trial was improvement in progression-free survival as defined from time of randomization to death or disease progression. We completed SIENDO recruitment on schedule in December of 2021, and we expect to report top line data, which is the event driven during the first quarter of this year. We're excited about the market opportunity for this indication, and as shown on Slide 18, we are targeting the approximately 14,000 U.S. patients receiving chemotherapy for their advanced endometrial cancer. And if SIENDO data are positive, selinexor once again could be the first and only approved drug in the maintenance setting, as there are currently no other approved drug therapies. Now ultimately, our goal is to establish once weekly oral selinexor as the standard of care in maintenance treatment in advanced or metastatic endometrial cancer versus the current watch-and-wait approach. So if we turn now to Slide 19, the key takeaways from endometrial cancer program are: first, we believe we're addressing a significant unmet need for a potential new maintenance therapy with a growing number of patients. Second, we believe we are well positioned to be the first and only treatment post chemotherapy in the maintenance setting that has potential to extend time and response and remission. And finally, we look forward to reporting top line Phase III SIENDO data this quarter, followed by a rapid submission of an sNDA in this indication. Now if we turn to Slide 20 for our third program, targeting myelodysplastic syndromes where we believe eltanexor, our second novel compound has the potential to improve survival in patients with hypomethylating agent refractory MDS. The first, a little background. So if you look on Slide 21, you can see that approximately 15,000 patients are diagnosed each year in the U.S. with intermediate to high-risk MDS who need therapy. And currently, the only class of drugs that are approved or hypomethylating agents, also known as HMAs. And once the disease progresses in HMAs, there are no approved therapies and survival is very short, along the lines of about 4 to 6 months. So there's a clear high unmet need and an opportunity to improve survival and outcomes for patients with MDS that is refractory to HMAs. And on Slide 22, you will see in our Phase I study, single-agent eltanexor showed clear activity in patients with primary refractory MDS to HMAs. And in that study, eltanexor demonstrated a 53% overall response rate and a median overall survival of 9.9 months, doubling historical controls of 4 to 6 months. At the recommended Phase II dose of 10 milligrams, eltanexor monotherapy was well tolerated with a low incidence in grade of gastrointestinal events. Exacerbations of cytopenia is incurred in 20% to 40% of patients. But based on the promising signal observed in Phase I study, we rapidly initiated dosing in the ongoing Phase II expansion, the design of what you can see on Slide 23. So the MDS program takeaways on Slide 24. Our first, we believe we're addressing a significant unmet need for patients with HMA-refractory MDS. And second, single-agent eltanexor is showing robust responses in survival in HMA refractory MDS with the potential to be the first approved new class of therapy. Third, a Phase II study is ongoing in patients with HMA-refractory MDS with top line data expected in the first half of '23. And finally, we have also initiated an eltanexor study in combination with HMAs in Phase I in frontline MDS. So if we turn now to Slide 25 for our fourth and final priority program, myelofibrosis, where we believe selinexor has the potential to improve outcomes for patients with JAK inhibitor refractory disease. And if you turn to Slide 26, there are approximately 5,000 patients per year in the U.S. diagnosed with myelofibrosis, which is a specific type of blood cancer that affects the bone marrow that leads to extensive scarring or fibrosis in the bone marrow and is associated with significant anemia, weakness, fatigue and spleen enlargement. The only class of drugs approved in myelofibrosis are JAK inhibitors. And unfortunately, these are not curative and 60% of patients do not respond. And among the 40% of patients who do respond initially, the responses lasts at most about 4 years. There is no other class of drugs approved and survival is short, typically less than 14 months for these patients once JAK inhibitors stop working. So it's in this setting, we have promising data with once-weekly, low-dose selinexor. So turning to Slide 27, new data that were reported at ASH 21 show that for patients on study for at least 24 weeks, 40% of patients achieved an SVR35 and 60% of patients achieved SVR25. These are very compelling results in this patient population. And as you can see on Slide 28, the median treatment of duration was 11 months with a range of 2.8 to 28.8 months. So based on these data, and as shown on Slide 29, we've rapidly moved into a global randomized Phase II trial that's recruiting patients who had at least 6 months of prior JAK inhibition and randomizes them to once weekly low-dose selinexor or a physician's choice. 112 patients are expected to be enrolled, and the first patient was already dosed in late '21. Top line data from this trial is expected during the second half of 2023. So the key myelofibrosis program takeaways, as you see on Slide 30, our first, we believe we are addressing a significant unmet need for patients with JAK inhibitor refractory myelofibrosis . Second, single agent selinexor is showing robust responses in JAK refractory myelofibrosis, with the potential to be the first approved new class of therapy. And third, a Phase II study is ongoing in patients with previously treated myelofibrosis with top line data expected in the second half of '23. And finally, we've also initiated a Phase I selinexor study in combination with JAK inhibition in frontline myelofibrosis. So if you move to Slide 31 now, I'll discuss our partnerships, financial highlights and key milestones for '22 and '23. Turning to Slide 32. As Karyopharm continues to focus on global R&D and U.S. commercialization, our business development activities continue to focus on leveraging strategic partners to support commercialization outside the U.S. And as I mentioned earlier, in December of '21, we signed an exclusive license agreement with the Menarini Group, whereby Menarini will develop and commercialize NEXPOVIO in the European Union, the U.K. and Latin America, among other territories. And in exchange, Karyopharm received an upfront payment of $75 million and is eligible to receive up to 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 EU-based partner with over $4 billion in annual revenue. They operate in over 140 countries and have a deep commitment to developing treatments addressing oncological and hematological disease. This deal adds to our growing global footprint, bringing NEXPOVIO to patients worldwide with our partners FORUS in Canada, Neopharm in Israel and Antengene in Asia Pacific. And if you look on Slide 33, it shows a large patient pool in second line plus multiple myeloma and endometrial cancer outside the U.S. that could benefit from NEXPOVIO, with approximately 60,000 patients in myeloma and approximately 40,000 patients eligible for maintenance therapy in endometrial cancer in our ex-U.S. markets as shown on this slide. So if we turn now to Slide 34, we believe we are well funded to advance our focused pipeline in multiple myeloma, endometrial cancer, MDS and myelofibrosis. Cash, cash equivalents and restricted cash and investments as of September 30, '21, totaled $209.3 million, which in combination with the revenue we expect to generate from XPOVIO product sales, and other license revenues is expected to be sufficient to fund our planned operations into early 2024. And we plan for the first time to give annual and net product revenue guidance when we announce our full year results in February. And as we have previously guided that we expect to reduce overall R&D expenses in 2022 by approximately 15% compared to 2021. So as we look ahead to '22 and beyond, the following are the corporate milestones we will be working toward as shown on Slide 35. For the multiple myeloma program, we expect to leverage our strong commercial capabilities striving to become the standard of care in second line plus post anti-CD38 and increased U.S. XPOVIO sales throughout the year. Dosed 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 and in patients with multi myeloma following at least one prior therapy in the first half of '22. For the endometrial cancer programs, we expect to report top line data from the Phase III study in endometrial cancer in the first quarter. And assuming a positive outcome from SIENDO submit a new sNDA requesting approval for selinexor as a maintenance therapy in endometrial cancer. We're going to continue the prelaunch activities for selinexor which began in '21, and we're going to continue through '22 to ensure launch readiness by approval, and we look forward to a potential approval and launch as a maintenance therapy during the first half of '23. For the MDS program, we expect to report preliminary Phase I eltanexor data in combination with an HMA in frontline MDS in '22, and to report top line Phase II data in HMA refractory MDS in the first half of '23. And 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 '22 and to report top line Phase II data in previously treated myelofibrosis patients during the second half of '23. So in closing, I would like to thank our teams for a very strong '21. I'm confident that our 5 key pillars can drive our underlying value and provide opportunity for what we believe will be substantial future growth for Karyopharm as we increasingly deliver for patients and shareholders this year and beyond. And with that, Eric, let me turn it back over to you and have Sohanya and Mike, Stephen and Jatin, join us for Q&A. I think you might be muted, Eric. I think you might still be muted.

Okay, great. Excellent. Excellent. Okay, good. So thanks for that presentation, Richard, really helpful. Just maybe -- just to start out by way of questions, we can pick up on XPOVIO performance in the fourth quarter and also kind of looking forward a little bit, right? You're preannouncing the quarter and highlighting sort of the sequential growth. But I think looking out to 2022, of course, we'll be providing guidance, and we look forward to that. That being said, as you -- I'm curious to know what kind of visibility you have in terms of where uptake of the product is occurring by line of treatment. And what levers there are to sort of -- well, actually, what metrics, I guess, investors should track as evidence of increasing share within earlier line and sort of what levers you have at Karyopharm to promote uptake within the current label indications with XPOVIO.

Yes. Sure, Eric. Thanks. Maybe I'll turn to Sohanya to lead the response on that question.

Absolutely. We feel very good about our Q4 performance 48% for the quarter year-over-year. And there's really 3 metrics that I'll draw your attention to as we think about what drove our growth in Q4 as well as a continued growth in 2022. So the first is the most rapid growth that we saw continues to be in the third line. And in fact, in 2021, XPOVIO was the fastest-growing multiple myeloma agent in the third line. So we are seeing that shift from the late lines where originally it was a doublet use to now increasing use of the trip XPOVIO-based triplet regimens, and that includes our -- the regimen that we promote and is approved in combination with bortezomib, but also other triplet regimens, including the combination with pomalidomide, carfilzomib as well as daratumumab, all of which are now on the NCCN guidelines. So that's a growth driver number 1. Number 2 is we continue to expand on the breadth and depth of utilization of the product. So when I mean breadth, we continue to add new accounts every quarter, and we'll continue to do that through 2022. In addition, with depth, we are increasing our penetration at the top myeloma account. So about top 25% of accounts contribute to about 80% of the business. And within that top segment, we're seeing progressively increased penetration at those accounts. And then finally, it's the qualitative data that we get through our intent to prescribe data plus the conversations that we have daily with our physician customers. And what we see is a growing confidence in managing these patients and using XPOVIO in earlier lines. So we feel really good about going into 2022 with strong execution, the strong positioning that we have in that white space post anti-CD38 between second line and fourth line. And we've also strengthened our commercial capabilities, our data partnerships, and we feel very confident about going into 2022.

Okay. I should think that as you kind of expand within third line, we might see kind of lengthening mean duration on therapy and perhaps some of that is reflected in fourth quarter results. Is that something that you similarly have visibility on kind of going forward, looking at patients that are new to brand? Is that something that you kind of track? And where does kind of mean duration sort of sit today? And where do you think it lives at the end of 2022?

Yes. I mean, from a high level, I think as we've talked to and I'll turn to Sohanya, really reporting out our mean duration is difficult number because of all the different data sources because of all the different lines. So I think as we move forward, it's really sharing the evolution and talking about it broadly, and I'll turn to Sohanya to talk about how that evolves and what we're doing from a data perspective to better understand that.

Absolutely. So we need to triangulate multiple data sources to better understand duration because it's very complicated to get the duration data by line of therapy. However, preliminary data is showing the continued positive trend that in earlier line patients, we're seeing longer durations of therapy. And we continue -- we saw that trend in the second half of 2021, and we will continue to see that trend as we shift this patient population from the later lines into earlier lines. But again, to Richard's point, this data still needs to mature, and we're still in that dynamic phase of the launch where we're transitioning from late to early lines.

Okay. All right. As you look to expand the label within myeloma, you just kind of spoke length or just walked us through the trial at length of the SPd regimen. Here, your -- you have guided to when the readout from that study would take place. Nevertheless, I'm curious to know how you expect the patient -- the pace of patient -- how do you expect the pace of the study to the pace of the trials to accrue? And what geographies you'd be recruiting from? And then similarly, given the use of EPD as the elotuzumab as part of the comparator regimen there. I guess what is the physician feedback on the use of that regimen as a sort of a proxy for participation in the study.

Yes. I think Eric, when you look at the potential recruitment kind of where it's happening and the EPD comparator, I'll turn to Jatin to talk to that. Jatin?

Yes, absolutely. So number one, I think we expect rapid enrollment in that study for a couple of reasons. Number one, growing patient population because this is a target for patients who've seen a prior CD38 based therapy. So that population is increasing. So there's a huge need. Number two, we don't know how to manage patients post a CD38 based therapy. So this is going to be important to provide that. So there's a lot of interest in answering this question. And number three, the trial design is also important. We're looking at our triplet versus the triplet, which also has significant interest from an accrual perspective for both patients and physicians. And we specifically look at the feedback on the EPD really from a drug development perspective, there's 2 options. We can use the 2 potential comparative arms, a doublet of the PD and the only other pom-based triplet that's approved is pom-elo-dex and that's only other regimen approved. And so that's a strong comparator and a strong clinical trial design.

And then, Jatin, maybe just talk to where we're running those trials?

Yes, absolutely. This will be a global study both in the U.S. as well as with our EU partner, so we'll see a global study enrolling both here in U.S. and in EU.

Okay. Okay. Similar sort of composition and geographic composition is BOSTON, is that a fair assessment or?

Yes. I mean I think in BOSTON, we saw additional sites of enrollment, including in India as well. So India won't be part of the SPd study. So that's one big comparison. And also remember, in BOSTON, we're looking at our triplet versus doublet, a little bit harder to enroll to that type of study in the U.S. We're looking at our triplet versus the triplet. So I think there's increased the U.S. enthusiasm to participate.

Fair point. Okay. Yes. I appreciate that. Okay. it shifting a little bit -- gears a little bit to the solid tumor opportunities, particularly SIENDO I mean, with [ reiteration ] of our top line readout in the first quarter, I guess, is there any additional granularity you might provide? I guess, are you targeting a readout for any particular forum? Or should we expect kind of a company-led disclosure and perhaps a call? And I guess how much -- and then in terms of just how the study would -- what would in terms of what the readout would comprise in that top line readout. Maybe you can just sort of maybe kind of preview a little bit for us what investors can anticipate beyond just sort of a hazard ratio?

And then Eric, Yes. So I'll start with it and turn it to Jatin to talk about the potential readout. But we're -- the study recruited on time, and we talked about that the recruitment ended in December. So it's event-driven, 2:1 randomization in favor of selinexor. And when we get the events and of the team works through the data and obviously reviews it with the DSMB, we'll probably look to have a company event announce that. I don't know if it will perfectly line up with every event that may be happening externally. So as soon as we can, we want to be able to share that data. And Jatin, maybe you can talk to what we expect that to look like.

Yes, absolutely. So consistent with what we presented before, for example, in the BOSTON study, will present similar data that we presented when we released the BOSTON top line data.

Okay. Okay. great. And some of the more recently announced expansion indications that you're pursuing particularly myelofibrosis. Maybe you can just spoke a little bit just the level of unmet need following JAK or not met by JAK inhibitors. Is it primarily SVR reduction where you see the incremental benefit from the addition of XPOVIO or might sort of the impact go beyond that looking at hematologic improvement?

Yes. I think, again, I'll lead that and then turn it over to Jatin, I think if it's a great question, Eric, and we just released that data at ASH from IST. So I think there's a number of areas that Jatin can talk to. Obviously, SVR35 is a key, but also a number of areas where we see a potential opportunity for patient benefits post the JAKs and also potentially even in the front line in combination with the JAK. So Jatin, maybe you can talk to that.

Yes, absolutely. I think the first question you asked, Eric, was the level of unmet need. And I think that's a significant level of unmet need, [ mere in ] myelofibrosis is only a single class of drugs that has approved JAK inhibitors and very little innovation in the last 10 years since ruxolitinib has been approved. So as those patients progress off of JAK inhibitor, clearly, there's no therapies for these patients, unfortunately. So significant, significant level of unmet need for these patients and a huge opportunity. And number two, when you look at the data, you're absolutely right, there's multiple ways to look at myelofibrosis and the way we impact the disease. SVR35 is just one of those metrics. And when we look at that metric alone, we see a 40% response rate mind you, that's a high response rate. And if you look at every other drug in development, the response rates are much, much lower in the single digits or low teens. Also keep in mind, there's a number of other metrics that we look at to see the efficacy of drugs in myelofibrosis. I think number two, you can look at overall survival. Overall survival in this patient population is 12 to 14 months, and we showed is a 92% overall survival at 2 years from our early experience. So that's important. Number 3, we also showed an improvement in transfusion dependence as well as improvements in hemoglobin. These patients have significant anemia, and so we saw about 50% of patients actually had an improvement in their hemoglobin, how substantial and quantifiable by 2 grams or became transfusion independent. That's significant, right? And I think when you're looking at patients who are getting weekly transfusions to become transfusion independent, not coming to the hospitals every week is significant. And the fourth metric I'll just point out is the disease modifying a capability, not only are we shrinking this [indiscernible], making patients live longer, improving their symptom burden, but also modifying the disease. And when we look at our patient who had week 72 weeks of therapy, that patient had an improvement in their bone marrow fibrosis from Grade III to Grade I. So that disease-modifying capability is actually really important as well. So every metric that we look at, we see this is a positive trend and a clear signal just in addition to the SVR35.

And then Jatin, maybe talk about how we work in the JAKs and potentially combining even in the front line with JAKs may make it a good opportunity.

Yes, absolutely. So that's part of our total comprehensive development program. Our first step is actually in the relapsed/refractory space. And that pivotal trial has started or the registration-enabling trial is started. In parallel, we're also looking at combination in frontline in combination with ruxolitinib. That Phase I trial has also been started in Q4 of 2021, enrollment is going well. Importantly, when we look at combinations with ruxolitinib, 2 important things. One, having high single agent activity is going to be important when you're combining 2 drugs. But importantly, when you combine those, one of the rate limiting steps we see is thrombocytopenia that we see both with JAK inhibitors as well as many of the other drugs in development. That's a big limitation, which leads to dose reductions and impacts your overall responses. What we see actually with once weekly low-dose selinexor is that ability, we don't have significant thrombocytopenia allow us to better combine with ruxolitinib or other JAK inhibitors. So we're excited about that. And some of these rate-limiting steps that we see with other combinations, we don't see with single-agent once-weekly selinexor.

Okay. Okay. All right. Well, thanks for time. We're going to have to leave it there, but I want to thank everybody from the Karyopharm team for joining us this afternoon, and thanks, everyone, for tuning into this session.

Thank you, Eric.

Thanks, Eric.

Okay.