Good morning, everyone. Thank you all for joining us today for Karyopharm's analyst event at ASH. Following our webcast today, the slides being presented here will be made available on the investor section of our website. I'm joined today by my colleague, Richard Paulson, President and CEO, and Dr. Reshma Rangwala, Chief Medical Officer. I'm also very pleased to be joined today by two recognized global thought leaders in the area of MPNs, Dr. Verstovsek and Dr. Ali. On this slide is an outline of what we will cover today. Before we begin, I'd like to remind you that various remarks we'll make today constitutes forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined here. It is now my pleasure to introduce Richard Paulson, President and CEO of Karyopharm. Richard? Thank you, Elhan. Good morning to everyone. We are delighted that you're able to join us today for Karyopharm's analyst event during the 64th annual meeting and exposition of the American Society of Hematology. On behalf of all our presenters, I would like to thank you for taking the time to join us today. Karyopharm was founded in 2008 as an innovation and patient-focused company, developing first-in-class oral selective inhibitors of nuclear export, which target XPO1. Fast-forwarding to Karyopharm today, where we are successfully leveraging this fundamental mechanism of action to build upon our existing multiple myeloma franchise, anchored around our commercial drug, XPOVIO. XPOVIO is now approved in 40 countries, and combined with increasing use in earlier lines in multiple myeloma, we are expecting revenue of between $155 million-$165 million in 2022. We are working to expand indications through advancing our focused clinical pipeline. This pipeline is comprised of mid- and late-stage clinical development programs that is being purposefully built and strategically focused to help patients who suffer from cancers with high unmet need to demonstrate efficacy at lower doses with improved tolerability, and where we believe we have the highest probability of success. Based on compelling data signals, we are pursuing opportunities in endometrial cancer, myelofibrosis, and myelodysplastic neoplasms. Collectively, we believe we have the potential to achieve multiple product approvals over the next two to four years. We've also evolved our leadership with highly accomplished executives from across the biopharmaceutical industry, specifically with commercialization and mid to late-stage clinical development experience to lead us in delivering our targeted mid and late-stage pipeline. With a strengthened leadership team in place, we believe we can achieve both scientific and commercial excellence while executing on our key corporate objectives. I will now turn to Reshma to discuss the science that informs everything we do. Reshma? Thank you, Richard. The nuclear pore is a complex gate between the nucleus and the cytoplasm, closely regulating the import and export of most large molecules, including many proteins. In humans, there are seven known exportins or nuclear export proteins. The most well-characterized is called exportin 1 or XPO1. Karyopharm's lead investigational drug candidates are first-in-class oral selective inhibitors of XPO1. XPO1 inhibitors block the nuclear export of tumor suppressor, growth and regulatory, as well as anti-inflammatory proteins, leading to an accumulation of these proteins in the nucleus and enhancing their anticancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. This novel mechanism is broadly applicable and foundational to cancer biology. We have prioritized and targeted core programs focused on improved patient outcomes in areas of high unmet need using the science I just described for you. Today, we will be focusing on myelofibrosis, where our drug selinexor has the potential to improve patient outcomes in both front line, as well as the relapse refractory myelofibrosis patient population. We are very pleased to have with us today two guest speakers who are distinguished global opinion leaders in the field of MPNs. First, we will hear from Dr. Verstovsek, MD, PhD, Director of Clinical Research for Myeloproliferative Neoplasms at the MD Anderson Cancer Center. Dr. Verstovsek? Good morning, everybody, and it's a great pleasure to be here this morning with the friends and family here. We say, "Go Croatia, go," for the World Cup, right. I see in public many people that I know well, and we follow each other. It's really nice to be here to talk about exciting new product that may help our patients with myelofibrosis. I have been at MD Anderson Cancer Center since 1998. And it's true that I lead the clinical research center for myeloproliferative neoplasms, which is the largest single institution center. About 250 new patients every year in consultation, mostly with myelofibrosis. I am engaged in a number of different activities related to new drug development and after all, led the development of ruxolitinib as the first drug approved for myelofibrosis. It's an exciting time to talk about new findings with early findings with the selinexor. Before we go into the details about the findings, let me tell you a little bit more about myelofibrosis in a short introduction. This is what it is. It is myelofibrosis. Myeloid stands for the bone marrow cells, and fibrous in the bone marrow. You can see the fibers by the black color. These are the fibers, actually. The bone also is changed. The bone itself, that's called osteosclerosis. The two factors together, fibrosis and osteosclerosis, prevent bone marrow from functioning, leading to enlargement in the spleen in about 80%-90% of the patients, which is a blood organ, so it's a reactive enlargement. Then would also result in anemia. That's the blood film. Unfortunately, some patients, about 25% of the patients would have a progression to acute myeloid leukemia, and this would be blast in the blood as an indication of a progression. If you wanna summarize the clinical features of myelofibrosis, we typically talk about a 60-65-year-old person. That's the typical age of diagnosis. Myelofibrosis can be de novo, out of the blue. Basically, patients present with these findings or may have a history of polycythemia vera or essential thrombocythemia, more benign myeloproliferative neoplasms. With the annual incidence of about one new case per 100,000, which makes it about 20,000 people living in the United States with myelofibrosis. Clinically, because of fibrosis, you have splenomegaly with its own associated problems. A big spleen causes pain, inability to eat, loss of weight, and cachexia. The cytopenias, anemia, thrombocytopenia, bleedings, and transfusions, affect on multiple organs. Constitutional symptoms of different sorts, night sweating, bone aches and pains, itching. You can imagine how this actually looks like in a 65-year-old with a big spleen and loss of weight and all the symptoms. It's not very nice picture at all. The outcome is poor. The average survival, 5-7 years, mostly because of the progression of myelofibrosis. Only about a quarter of patients progress to acute myeloid leukemia. What does this mean then? Bigger and bigger spleen, bigger and bigger liver, organ failure, pulmonary hypertension, right-heart failure, ascites, leg swelling, cachexia, slow death in the hospice or at home, not in an acute setting. It's really not good at all. Okay. Now, we know now, since 2005, a lot about biology, and we keep learning. It is fair to say that in every single patient, there is a hyperactivity of the JAK-STAT pathway for different reasons, and the JAK-STAT pathway is involved in blood-making inflammation and immune function. In the bone marrow, due to different mutations, it will make cells grow without control with the reactive fibrosis, leading actually to too few cells being produced. The driver mutations, this is how we call the mutations that activate the JAK-STAT pathway, are of different sorts, typically mutually exclusive of each other, the most common being the JAK2 mutations, but there are others. The bone marrow fibrosis, it's, as we say, usually a reactive process to presence of malignancy, where cytokines in the bone marrow or stroma, the cells that support the growth of bone marrow cells, react in a way of autocrine and paracrine influence on what happens in the bone marrow through elevation in production of different inflammatory cytokines. The blood is not made, then anemia, thrombocytopenia over time slowly progress and contributes to the morbidity of the disease. This extramedullary hematopoiesis is one of the hallmarks of the disease, with big spleen and big liver. About 40% to 50% of patients have a big liver as well. It is really unusual, very transformative physically for the patients and in terms of quality of life as well, very terrible condition. What do we do? Well, we don't have a cure. The only cure is the bone marrow transplant. Just to clear that up, because you'll say, "Why don't we just send everybody to transplant?" Less than 10% of the patients actually go to transplant. Realistically, that's not possible, right? We have to manage patients and their condition. As you see a circled part here, why do we treat the patients? We treat the patients for constitutional symptoms. We try to use a questionnaire to objectify the quality of life and say, "Hey, your quality of life is bad. Let's treat you for that quality of life. Progressive organomegaly, spleen and liver needs to be reduced to improve quality of life and possibly improve the longevity, as I'm gonna mention later. Anemia. Three areas of concern, anemia, splenomegaly, and bad quality of life. What do we do today? This is a copy of the NCCN guidelines. It's continuously updated, but there is not much of update to provide for patients with myelofibrosis, unfortunately, with the real new medications. Everything that we have so far is about the JAK inhibitors to control the signs and symptoms as much as you can, but they're lookalikes. They have a similar modes of actions. You see here that we would first divide the patients in the those that are symptomatic or not, and then platelets would matter. Pacritinib is approved, as we all know, for patients with lower platelets. For others, we use ruxolitinib and fedratinib. In second-line setting, if one doesn't work, we can use the other. More of the JAK inhibition. What do actually JAK inhibitors do? This is from the ruxolitinib, a very old slide, the COMFORT-II study comparing ruxolitinib to best available therapy, waterfall of a spleen response. Fair to say everybody have a degree of a spleen response. Primary refractory patients to ruxolitinib are very rare, maybe 2% or 3%. That's the orange color here. My goal as a physician is to get this waterfall to be equally low to 80%-100% elimination of the spleen in everybody. It's a waterfall. We want to have it a wall where everybody has a massive improvement in the spleen. There is much work to do, right? The standard practice, by the way, which is in blue, which is hydroxyurea, doesn't really work well. That's why the JAK inhibitors became the standard practice. As you can see here, much room for improvement. Plus, the standard frontline therapy with ruxolitinib causes anemia and thrombocytopenia, and those adjustments and management of patients with ruxolitinib is affected quite a bit and leads to underperformance of these drugs because of the anemia and thrombocytopenia. However, we can prolong the life of these patients with ruxolitinib when it's on its label. How can we do that? One marker of the success is the degree of a spleen reduction. Basically, the smaller the spleen becomes, the longer the life of the patient. That was done by measuring the spleen by volume and by MRI to the left in the studies and by palpation. Simply to the right, you see the palpation results, 50% spleen gone or not in Europe. Those that have a smaller spleen live much longer. This is a marker of disease, not that there is some magic about the spleen. This is just a marker. I usually say, "Look, if you shrink this, the tumor as small as possible, it just take much longer to come back, and people live with the controlled disease much longer." We wanna optimize the care. Unfortunately, the durability of ruxolitinib in clinical studies is not that good. It is on average. The lines here are from different studies and how the dropout went. On average, you would see that most of the lines would say that about 3 years is average duration of ruxolitinib. The black one that is extraordinary bad is for patients with low counts. These are platelets below 100. Why is this not longer, right? Underdosing because of anemia, thrombocytopenia, and inability really to provide this effectively for much more longer. We know now, if you follow the field very well, you would know that from community standpoint, the average duration of therapy with ruxolitinib in the United States is about 1 year, 1 and a half-years, not 3 years. Studies are always better than community practice, right? There is much room to improve here. Once you stop ruxolitinib, the story goes down. I mean, it's really, sorry to say, it's really devastating for the patients. This is our own experience, it's recapitulated by many other publications. The average survival once you stop Ruxolitinib is 14 months. You have obviously here a case to improve what Ruxolitinib does, build on it, or develop, and/or develop another agent that would be very effective after Ruxolitinib. You see the reasons for a and main reasons for a loss of response, it's not only about the dosing but the biology of the disease. With the clonal evolution, new other mutations developing in the patients while they're on Ruxolitinib leading to loss of response. Mechanisms of action with new mechanism action is important topic. We need something different than another JAK inhibitor after JAK inhibitor. Obvious need for new therapy. This is just a cartoon from a serious review on the topic identifying possibilities of attacking the malignant cells in myelofibrosis, where there are so many different abnormalities. Not to go through details here, but each white box gives you a name of the drug and the target. It's very active field to find something different that would be active and effective and simple to help our patients with myelofibrosis to build on the JAK inhibitors or to help after JAK inhibitors fail its control of the disease. As we know, there are several drugs in the red box to the left that are already in phase 3 studies for possible approval with a different mode of action. From BCL-xL inhibitor down all the way to telomerase inhibitor for different populations of patients. Not every patient is the same. This spans from the combinations in the first line to adding medications to people who have a suboptimal response, which is very large group of people, or the second line. Of course, each of these combination partners needs to fulfill some basic prerequisites, which would be safety and simplicity in delivery. Otherwise, you compromise further the delivery of the standard practice JAK inhibitor. That's why we are excited about today's presentation, and we'll learn in detail about what's happening with selinexor in combination with ruxolitinib in patients that have a treatment-naive myelofibrosis. Thank you very much for letting me introduce the next speaker to Dr. Ali, who will tell us all about the updates on the data. Thank you. Thank you. Good morning, everyone. I'll be talking about the results of the phase one study of basically using selinexor with ruxolitinib as upfront treatment for patients with myelofibrosis. Myelofibrosis is driven by three mutations, JAK2, CALR and MPL mutation, which are most common mutations we see in the myelofibrosis patient. Usually the JAK-STAT pathway is activated, that actually leads to activation of the downstream pathways, including AKT and ERK pathway. Most of these pathways actually lead to activation of the nuclear transfer protein that are involved in the progression of the myelofibrosis. With this, actually, we did the phase one study of using selinexor along with ruxolitinib in the previously untreated patient. Here's the key inclusion criteria, patient with the myelofibrosis DIPSS-1 or higher, intermediate 1 risk or higher, with a spleen volume of 450 or above. performance status ECOG 0 to 2, platelet count more than 100. In dose escalation, we tested two doses, 40 milligrams weekly versus 60 milligrams weekly, and the ruxolitinib was given at doses of 15 to 20 milligrams BID, depending on the platelet count. In the dose expansion, we had 18 patients with either 40 milligrams or 60 milligrams. The objective of the study was to explore the combination of selinexor and ruxolitinib and built on the single- agent activity of both compounds. We have presented this data in the ASCO earlier. Here we presented the update safety and preliminary efficacy data at week 24. The primary endpoint was the empty maximum tolerated dose and a recommended phase two dose and looking at the AEs. The secondary endpoint was very common that typically you'll see in other myelofibrosis study, SVR35, which is 35% volume reduction at 24 weeks. TSS50, 50% improvement in the total symptom score. Overall survival, anemia response, and also we look at the PK analysis. As of October 21st, we currently have 24 enrolled patient, and 10 patient in 40 milligrams arm and 13 patients in the 60 milligrams arm. There was 1 patient who received those 20 milligrams weekly and in the 60 milligrams was included in the 40 milligrams arm. Here are the baseline characteristic, which is quite typical what we would see in a myelofibrosis patient. Median age 64, in 40 milligrams, 58 versus 65. More male patients that it's typically expected of the disease. There was majority of the patient were transfusion-independent. There was 1 transfusion-dependent patient. There was a good breakdown between primary and secondary myelofibrosis. There was a good mixture of various risk categories, intermediate one, intermediate two, and high risk. A most common mutation, as typically we've seen in myelofibrosis, JAK2, followed by CALR and MPL mutation. Looking at the analysis, we have safety population of the patient who receive at least 1 dose. In the efficacy, I mean, we had patient who had at least 1 spleen volume measurable during the assessment and for symptoms, who had at least 1 symptom score collected. For the primary analysis included patients who have been treated until the relevant time points or discontinued prior to the relevant important time points. All patient who were hemoglobin stabilization population, all patient who had transfusion independent at baseline or followed up at 8 weeks. The data cut- off was October 21st, 2022. Here's the swimmer's plot. You can see that median duration of therapy was 25 weeks. It was much longer in the 60 milligrams arm, at 29 weeks. In the 40 milligrams cohort was 17 weeks. The reason for discontinuations are listed here. Clinical progression to AML, treatment-related adverse events, patient proceeding to stem cell transplant or withdrawal of consent. I mean, you can see in some of the patients, especially in the 40 milligrams arm, actually have not completed the 24 weeks, so data is continued to be collected as of the cutoff date. Here are the primary analysis. Looking at the volume responses at 24 weeks. SVR35. We see 11 out of 12 evaluable patient, about 92% of the patient had a spleen volume response. Looking at TSS50 in patients who actually submitted, we were able to collect the symptoms as about 67% TSS response by 50% or more. Here is the waterfall plot for spleen volume response. I mean, at both those levels you see a very good spleen volume response at week 24. I mean, here to note actually all patients actually responded. As the doctor showed that there was a few patients in the ruxolitinib arm that did not respond, here we see the response in pretty much all the patients. Again, here's the curve showing the responses by 12 weeks and 24 weeks. You do see a rapid reduction in the very beginning of the treatment with a 45% spleen volume response median. That continues to proceed at 24 weeks. I mean, here some of the patients were at low dose as low as 5 milligrams, but still they continued to have response despite being on the low dose of 5 milligrams of ruxolitinib. Here you see what happens to the hemoglobin in the patient. Typically with ruxolitinib, you'll see a dip in the hemoglobin in the first 2, 3 months, and subsequently actually it recovers. This typically, this is what we saw in the study as well. There was a drop in the hemoglobin, eventually actually it recovers. In some of the studies, they show that when the hemoglobin recovers, it may not go back to the baseline, but at least in the study what we saw it's actually going up to the baseline. If you look at number of patients who had hemoglobin below 10 and they had stabilized hemoglobin that actually did not drop from baseline by 2 gram per dL to about 81% of the patient and the 100% in the 40 milligrams and 60% in the 71% in the 60 milligrams arm. Here's a breakdown of adverse events. The most common adverse event was nausea, anemia and fatigue as well. The majority of the adverse events was actually grade 1. There was only 1 grade 3 nausea that was observed. 2 cases have grade 4 neutropenia that occurred at 60 milligrams dose. It was not clinically relevant, and there was no bleeding at the events that was seen in these patients. There was no treatment-related death. In conclusion, I mean, combination of selinexor with ruxolitinib demonstrated meaningful efficacy across relevant efficacy time points, including SVR35, 92%, at TSS 67%, and hemoglobin stabilization about 57% of the patient. AEs were generally manageable. Grade 3 to 4, they were not clinically relevant, and there was no bleeding, serious infection or clinical sequelae. The both 40 milligrams and 60 milligrams doses were well tolerated. Most common AE was nausea, fatigue, anemia and thrombocytopenia. Combination led to a rapid reduction in spleen volume in these treatment-naive patients. The data demonstrated that the combination of selinexor and ruxolitinib has the potential to be novel first-line agent for treatment-naive patients. Thank you. Thank you, Dr. Ali and Dr. Verstovsek for this wonderful presentation. Let's recap these important findings from the phase 1 portion of the XPORT-MF-034 study. Selinexor in combination with ruxolitinib demonstrates meaningful efficacy across three relevant efficacy endpoints in treatment-naive myelofibrosis patients. Specifically, key highlights include a rapid sustained spleen response observed in 92% of efficacy-evaluable patients, who achieved an SVR35 at week 24. 67% of efficacy-evaluable patients also experienced a greater equal to 50% reduction in their total symptom score at week 24. Lastly, 57% of transfusion-independent patients either maintained or improved their baseline hemoglobin levels. The study also showed a generally manageable side effect profile at both the 40 and the 60 milligrams doses, with the most common AEs being nausea, fatigue, anemia and thrombocytopenia. These data build on the single-agent activity of selinexor observed from the ESSENTIAL study in the JAK inhibitor-exposed myelofibrosis patient population and suggest selinexor could be utilized in both the treatment-naive and JAK inhibitor-exposed patient populations. A 30% SVR35 was observed at week 24, and a 40% SVR35 was observed at week 24 and beyond. In addition, we observed a 2-year probability of overall survival of 92%. Although the ESSENTIAL study is small and the data are still preliminary, the results build on compelling non-clinical and pre-clinical data by demonstrating monotherapy activity and highlights the potential of this novel class of therapy to improve outcomes, including durable spleen volume reduction. We continue to enroll on our most advanced MF study at the ongoing phase 2 XPORT-MF-035 study. Here is a preliminary schema for the randomized portion of the selinexor and ruxolitinib combination in treatment-naive MF patients. Specifically, we will compare the SVR35 and TSS50 at week 24 for the combination compared to ruxolitinib alone. We look forward to discussing this trial design with the FDA in early 2023 and expect to start the randomized portion of the study in the first half of next year. We continue to strive each day for patients with unmet needs as we advance our pipeline with a number of key near-term catalysts and corporate milestones. With that, I will open up to the Q&A, which Elhan will facilitate. For the people attending the webcast, you can submit your questions in the box, below the slide. We will first start taking questions from the audience here. Should work, I guess. Yeah. Jonathan. Jonathan Chang from SVB Securities. Congrats on the data, thanks for taking my questions. First question, how do you see the selinexor plus ruxolitinib combination comparing to other ruxolitinib combinations in development, in the competitive landscape? Secondly, could you just comment on how you're thinking about dose selection, and the tolerability profile of each agent, and to what degree dose modifications or discontinuations were reported? If I may start with the first question, multiple questions. Excellent. Thank you, Jonathan. The comparison at the level of everybody having a different follow-up or different level of development of their own assets is somewhat limited. When you see the results of this quality with such high percentages of control of the spleen and symptoms, you are very much intrigued. The efficacy is tied to the safety and the simplicity. This is a drug that is given once a week, you already have a check on the simplicity. The tolerability is something that can be controlled or can be improved on, but it's really good already without major new discoveries. I would say that if you combine the three things together, higher efficacy than any other, very simple, unlike any other, and tolerability, which is acceptable, this, in my view, is very compelling for further development. Others will talk about the dose selection. Yeah, I mean, the dose selection, we really want to wait for the 24- weeks data to have a pretty complete set of data to finalize the dose selection. I mean, we have not decided what dose we're gonna move forward with. Reshma, you can... Yeah. Yeah, I appreciate that. I think this is, you know, sort of the next steps that we're gonna be looking at is identify the recommended phase 2 dose, as Dr. Ali just mentioned. It really is gonna be incorporating the efficacy, the safety, as well as incorporating that pharmacokinetic data. We'll use those 3 data sets to again, identify the dose that we wanna take into the phase 3. Of course, discuss that with the FDA, and then all of that's gonna drive to initiation of the study next year. Are you able to comment on the degree of dose modifications or discontinuations in the experience to date? I think, we have that on the slide, and for the reason of discontinuation. I mean, you know, about the modification you did. We have. Yeah, I can certainly take that one. We haven't provided the dose modification, dose reduction rates at this point. We are still waiting for the data to mature. Of course, we will provide that data in future updates. You know, with that said, we're very encouraged by the dose intensity that we're seeing. 82%, 83% respectively for Seli and Rux in terms of the dose intensity. Those data suggest to me at least that, you know, the planned doses that the investigator had indicated for the patients by and large are getting, you know, administered to the patients. We don't see a lot in terms of dose modification reductions that will alter again that treatment plan. To Dr. Verstovsek's, you know, earlier comment, you know, this is a relatively simple, easy combination that ultimately can be provided to the patients. We will provide additional data on that question going forward. Thanks. It's Leo Wan here for Brian from RBC. I just wanna dive also a little deeper into the safety profile. I guess, what are the kinetics of when patients are seeing these adverse events? Is it when they're taking that dose for the first time in a week that they're getting this vomiting? I guess, is it something that they can keep doing through? Does it, you know, fade over time? Maybe for Dr. Verstovsek, d o you see the need to maybe, you know, medicate the patients for the constipation, the vomiting, and the nausea adding to the complexity of the treatment and, you know, could this impact real-world use compliance, and duration of treatment? Thank you. Who starts with this one? Yeah, Dr. Ali. I mean, in terms of the symptoms of the nausea, not always vomiting, but where nausea typically would happen, on the day the patient would receive treatment. Patient would get a pre-medication, Zofran to help with the nausea and continue the post- dose. Usually, the symptoms are predominantly in the first two cycles, but then after that actually is very tolerable. The patients don't even feel it that much. There's actually an improvement in the symptoms after the first couple of cycles. I can provide a little bit of color to, you know, the kinetics. We've got a much larger data set, especially from our multiple myeloma experience. It's exactly what Dr. Ali was describing is what we see in multiple myeloma too. From the BOSTON study, we know that, you know, patients experience that nausea very early on with a substantial improvement at the end of cycle 1. By the end of cycle 2, almost 92% of patients resolve their nausea. It is limited to the first 2 cycles and, you know, going forward, really not a problem for that patient population. Antiemetics too are also further controlling. In this study, we only required one antiemetic. You know, going forward, we'll require the two antiemetics and further, you know, hopefully have an opportunity to further improve that nausea. Last thing I will mention is that, you know, none of the patients discontinued due to nausea. You know, patients by and large, while they were experiencing that grade 1, were able to maintain their therapy, stay on, which ultimately drove that efficacy. Learning along as we go in management of GI toxicity is certainly very important. Providing a prophylactic or preventative anti-nausea medications would be the key to start well and not allow the patients to have a toxicity that would then question the doctor's decision to prescribe this medication. We see successful management of this problem by others. We have, for example, Pacritinib that causes about 60% of patients having diarrhea. That comes together with the anti-diarrhea when you prescribe the pacritinib, and you don't hear anything about diarrhea causing any problem with the Pacritinib for people with low platelets below 50. I would predict that this would be something that would be common practice here with selinexor, comes together with anti-nausea medication, and patients just take it, and that resolves the issue of nausea. Hi, this is Kevin Strang on for Mori from Jefferies. Congrats on the update this weekend. I just had a question on the TSS50 more. Is there sort of a specific bar that you're looking for for TSS50? You know, when could you have enough data to sort of make a decision there? Just given the, you know, the better-looking AE profile so far for the lower dose, do you think that that would potentially influence the TSS50 score for those patients and potentially, you know, have those patients have a higher score there? How do you sort of think about if the SVR35 is maybe numerically lower for those patients, but the TSS50 is higher? I guess what goes into that, recommended phase two dose decision? I can take. You want to take it? I can certainly answer that. This is very good one. Very good question so far. The control of quality of life and the spleen are equally important. You can't have a drug that does one thing and doesn't do the other. We have problems with other drugs in development like that. That's why the question, first question was, how do you compare? Well, this one, as you can see in both, in both of the benefits, is much more than what you would expect with the ruxolitinib alone. You don't wanna have a discrepancy of a large discrepancy between the two. For example, it's good to have those about the same, right? At the same level. Fine-tuning dosing perhaps, or how the management of early introduction is with the lower and then higher dose or, perhaps, finding a middle dose of... There is work to be done on that part not to lose the sight of the both factors together. Your concept, what you're asking about is crucial for overall success 'cause you wanna have a smaller spleen and a better quality of life together. Thank you. It will certainly be taken in. It, you know, we are not identifying the recommended phase 2 dose, as you know. You know, based upon this data set, we are looking for more maturity, especially in that 40 milligrams. To your point, I mean, that is exactly one of the factors that we'll be taking into consideration. In terms of the... I just wanna also comment in terms of the AEs. You know, what we know, and Dr. Ali mentioned this, is that the median duration on treatment is quite different for the 60 milligrams and the 40 milligrams. There too, that maturity in those 40 milligrams really will allow us to better compare the AE profile for the 60 and the 40. We may just see a numerically higher, you know, rate in the 60 milligrams again, just because they've had longer duration of treatment. Great. Thank you. Hi, I'm Eric Joseph with JP Morgan. The impact on anemia and the change in hemoglobin is pretty interesting. I guess I'd be interested from Dr. Verstovsek's perspective, just sort of how anemia correction or management thereof is. How does that ranks among endpoints like spleen volume and symptom score. As for the data themselves, is there any indication of a dose response or dose sensitivity to the change in hemoglobin or the return of hemoglobin count that you're observing? Thanks. Well, I am not aware, and we just talked about the dose modifications and how this works out very well in the patients. Overall outcome of the experience so far is pretty good. People don't have a reason to stop the therapy because of anemia. The degree of anemia that we saw on that graph is less pronounced than with ruxolitinib alone. Therefore, I'm happy to say that there is no contribution of mild suppression to management of patients with the ruxolitinib alone, because that's a common problem when you add another agent that is causing anemia or thrombocytopenia in particular, compromising the simplicity and safety of the combination. That does not appear to be a concern. Later on, we will have a more detailed analysis of the dose adjustments and modifications to answer to some precision. First look, looks really favorable. I want to add on that, typically patient when they present, I mean, with all the symptoms of fatigue and different things that are also being driven by the cytokines. Typically if you see a drop in the hemoglobin in the patients, but generally when the symptoms still continues to improve despite the drop in the hemoglobin, because generally patients are feeling better, their spleen is smaller, they're gaining weight, there's less night sweat. It can correlate with the symptoms, but most of the time in the beginning of the treatment, it actually doesn't. It gives you a time for the initial period for the hemoglobin to recover, so it does not become an issue. Any other questions from the audience? We have a few questions from the webcast, from Edward, from H.C. Wainwright. He has 2 questions. Why did the 1 patient get 20 milligrams for 3 cycles? The other question is, can you give us an update on the phase 2 MF 035 study? The last question is, path to approval for combination and monotherapy and expected timing. Maybe we can start with the first 1, 20 milligramss for 3 cycles. It was a very simple, you know, answer. The patient just took the 20 milligrams, so they were prescribed a higher dose, but they took the 20 milligrams. They took that 20 milligrams for the first 3 cycles and then, you know, we just increased them up to the 60 milligrams. You know, ultimately, when we took the average of the dose, you know, it came to 40 milligrams, which is why we included that patient in the 40 milligrams analysis. There was no greater explanation than an error. Thank you. In terms of the 035 studies, the 035 study again is in a JAK-exposed patient population. This randomized study is comparing selinexor monotherapy compared to physician's choice therapy. This trial is currently enrolling in multiple sites throughout the world. In the last question, was the registration path? Yeah, path to approval for combination and monotherapy and expected timing. Yeah. great question. You know, this is gonna be part of our discussion that we have with the FDA in the beginning of next year. We'll be talking about our entire myelofibrosis program, including the design and the details of the design that I just mentioned earlier in the presentation today. Of course, also monotherapy opportunities from for approval. Yeah, I don't see... I mean, there is another question from Michael from Morgan Stanley. We already answered that, and it was about the 40 milligram versus 60 milligrams. We're fine there. I'll turn to the audience in case there's a last question from anybody. I think we're all set here. I'll thank- Thank you, Elhan. Thank you to everyone for joining us today and great questions. Thank you to our guests, speakers, and all the employees who helped make this event possible today. We look forward to seeing many of you in person again. It's wonderful to be in person at the JP Morgan conference in January. Have a great day everyone, and enjoy the rest of your ASH conference.