Good morning. My name is Vaishnavi, and I'll be your Conference Operator for today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics fourth quarter and full year 2020 financial results conference call. There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Mr. Ian Karp, Karyopharm Senior Vice President, Investor and Public Relations. Please go ahead. Thanks so much, and thank you all for joining us on today's conference call to discuss Karyopharm's fourth quarter and full year 2020 financial results and business update. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, our Chief Executive Officer, Mr. Mike Mason, Chief Financial Officer, Mr. John Demaree, Chief Commercial Officer, Dr. Jatin Shah, Chief Medical Officer, and Mr. Stephen Mitchener, Chief Business Officer. On the call today, Michael will provide an overview of key recent corporate developments and an update on our commercial progress, and then Mike Mason will provide an overview of the fourth quarter and full year 2020 financial results. We will conclude with the Q&A portion of the call. Earlier this morning, we issued a press release detailing Karyopharm's results for the fourth quarter and full year of 2020. This release, along with the slide presentation that we will reference, are available on our website at karyopharm.com. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on slide three. These include statements about our future expectations, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, including our expectations related to the commercialization of XPOVIO, financial projections, and our plans and prospects. Actual results may materially differ from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factor 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, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. With that, I'll now turn the call over to Michael Kauffman, Chief Executive Officer. Thank you, Ian, and good morning, everyone. 2020 was a pivotal year for Karyopharm, and I'm extremely proud of the significant progress our team has made towards our commercial, clinical development, and operational objectives with the ultimate goal of having a positive impact on the lives of patients battling cancer. Most notably, our year was marked by two U.S. FDA approvals for XPOVIO, first in June for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma, or DLBCL, and then in late December, once-weekly XPOVIO received additional approval in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. We expect to carry the momentum of these important achievements into 2021 and have already started the year with several recent accomplishments, as outlined on slide four. XPOVIO net product revenue for the fourth quarter and full year of 2020 were $20.2 million and $76.2 million, respectively. More than 170 and 700 new physicians and accounts prescribed XPOVIO for the first time in Q4 and in 2020 overall, respectively. These achievements are particularly encouraging, keeping in mind that XPOVIO was only first approved for use by the FDA in July of 2019. For most of 2020, we've all been impacted in some shape or form by the ongoing COVID-19 pandemic. The expansion and launch of XPOVIO into the second-line and third-line treatment settings significantly increases the addressable patient population for XPOVIO and represents a meaningful growth opportunity for Karyopharm in both the near and long term. Separately, in December, the addition of three XPOVIO treatment regimens for multiple myeloma to the National Comprehensive Cancer Network's clinical practice guidelines in oncology represented another key achievement that we believe will help further expand XPOVIO's utilization. For our pipeline progress, we recently announced that the European Medicines Agency's Committee for Medicinal Products for Human Use, or CHMP, adopted a positive opinion recommending the conditional approval for NEXPOVIO, the brand name for selinexor in Europe, in combination with dexamethasone for the treatment of myeloma in adult patients with heavily pretreated disease, an indication nearly identical to the approved indication that XPOVIO received in the 2019 accelerated approval issued by the FDA in the U.S. I will talk a bit more about our expected steps for Europe in just a few minutes. We were excited to secure our first regulatory approval outside the U.S. in Israel for both myeloma and DLBCL, which we announced last week. Turning now to other program updates from our ongoing hematological and solid tumor clinical studies. Our phase III SIENDO study evaluating XPOVIO endometrial cancer passed its planned interim futility and upsizing analysis, and we look forward to the top-line results expected in the second half of this year. The first patient in the Phase II/III XPORT-DLBCL-030 study evaluating XPOVIO in patients with DLBCL has now been treated, and this study will serve as a confirmatory study for XPOVIO's accelerated approval in DLBCL granted last year. Finally, on the financial front, we ended the quarter with a strong cash position of approximately $276.7 million that, along with expected future revenues, we anticipate will be sufficient to fund our planned operations into late 2022. Let me now turn to slide five to provide additional details on XPOVIO's sales performance through 2020. In the first three quarters of 2020, we generated steady increases in sales for XPOVIO due to both the unique attributes of XPOVIO as well as the hard work of our dedicated commercial team. Net sales for both the full year of 2020, as well as for the fourth quarter specifically, were largely driven by prescription demand from both academic and community-based oncologists for patients with penta-refractory multiple myeloma. The 5% decrease in product sales in the fourth quarter as compared to the third quarter was a result of the impact from both the recent surge in U.S. COVID-19 cases, as well as some increased competition for patients. More specifically, as we turn to slide six, we believe the surge in COVID-19 cases impacted both patient visits to their healthcare provider, as well as in-person access for Karyopharm's commercial team to its physician customers. Additionally, increased competition from recently launched drugs in penta-refractory myeloma and in refractory DLBCL settings also contributed to some additional sales pressure in the quarter. However, we are seeing a meaningful rebound in demand and new patient starts since the expanded approval, further reinforcing our confidence in the future growth potential for XPOVIO. As mentioned previously, the addition of multiple XPOVIO combination regimens to the NCCN guidelines and the expanded FDA approval of XPOVIO provided strong tailwinds for sales growth in December, following declines in October and November. We're still in the very early stages of the launch of XPOVIO into the second and third-line settings, but we expect to see significant increase in annual sales, largely driven by both earlier use and longer duration of treatment in patients with myeloma. Moving now to slide seven. The graph here shows the prescription refill rate for XPOVIO over 2020 for both the first and second refills for those patients eligible for those refills. These numbers have remained encouraging throughout 2020 and are significantly higher as compared to our initial launch period in 2019. These refill rates, coupled with an average of nearly three treatment cycles per patient as of the end of 2020, further reinforce the positive feedback we have received from physicians and patients regarding their experience and usage of XPOVIO. Importantly, the patient discontinuation rate due to side effects remained relatively low at 13%, which we believe is a testament to more and more physicians gaining comfort in helping their patients prevent and manage the side effects of XPOVIO with proper prophylactic and supportive therapies, as well as dose modification. In addition to the expanded label for XPOVIO in the U.S., we believe the future international expansion of XPOVIO in Europe will be another key strategic area of growth for Karyopharm, which I'll now highlight on slide eight. The CHMP positive opinion for neXPOVIO, which was issued at the end of January, could lead to our first regulatory approval in Europe and recognizes the positive clinical benefit risk profile of oral neXPOVIO. We look forward to the European Commission's final decision on our neXPOVIO submission, which is expected in April 2021. We intend to submit a second regulatory filing based on the data from the phase III BOSTON study with the goal of further expanding the global reach of neXPOVIO to additional patients in need of new treatment options. Encouragingly, even before a possible European regulatory approval, the European Hematology Association and European Society for Medical Oncology recently updated their treatment guidelines for myeloma in November of 2020 and added selinexor, VELCADE, dexamethasone regimen to their second-line recommendations and selinexor with dexamethasone to the third-line plus treatment guidelines. In parallel to the regulatory efforts, we're also continuing to evaluate potential collaborations with partners in Europe and Japan. We're committed to making neXPOVIO available in Europe if approved in April, with the greatest opportunity to come potentially before the end of 2021, when we would hope to receive an expanded approval in Europe based on the data from our phase III BOSTON study. I'd be remiss if I did not mention updates on a number of additional exciting pipeline opportunities that we are pursuing for XPOVIO, which can be seen on slides nine and 10. We have a robust clinical development plan for XPOVIO in both hematological malignancies and solid tumors. This includes our phase III SIENDO study in patients with endometrial cancer, where we expect to have a top-line data readout before the end of this year. I'll note that there are two additional new important clinical trials we plan to initiate in 2021, which we believe will help further define the broad clinical utility of XPOVIO as a potential partner of choice with other active anticancer agents. First, we expect to initiate a new randomized phase III study evaluating XPOVIO in combination with Pomalyst and dexamethasone in patients with previously treated myeloma. If the results of this trial are positive, this regimen would represent a potent all-oral drug option to patients with refractory disease. Next, we plan to initiate a new phase II study evaluating XPOVIO in combination with KEYTRUDA in patients with newly diagnosed or recurrent metastatic melanoma. We're particularly excited about this study based on some encouraging data from the MD Anderson investigator-sponsored trial evaluating this combination regimen, which was presented at the annual ESMO conference in 2020. With that, I'll now turn the call over to Mike Mason to review the quarterly financials. Mike? Thank you, Michael. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which begin on slide 12. Net product revenue for the fourth quarter of 2020 was $20.2 million compared to $17.7 million for the fourth quarter of 2019. Net product revenue for the year ended December 30, 2020, was $76.2 million compared to $30.5 million for the year ended 2019. The estimated gross net discount for XPOVIO in 2020 fell within our estimated range of 15%-20%. License and other revenue for the fourth quarter of 2020 was $14.9 million, compared to $0.4 million for the fourth quarter of 2019. This increase was driven by a $9.8 million payment from Antengene for milestone payments associated with regulatory filings in Asia. As well as a $5 million upfront payment from FORUS Therapeutics upon the execution of a commercial distribution agreement for Canada. License and other revenue in 2020 were $31.9 million compared to $10.4 million in 2019. R&D expenses for the fourth quarter of 2020 were $37.2 million, compared to $31.6 million for the fourth quarter of 2019. R&D expenses for the year ended 2020 were $150.8 million compared to $122.3 million for the year ended 2019. The increase in R&D expenses in 2020 compared to 2019 was primarily attributable to costs incurred related to our COVID-19 trial activity, which will not reoccur in 2021, and continued activity in our other ongoing clinical trials and regulatory activities. Selling, general, and administrative expense for the fourth quarter of 2020 was $33.9 million, compared to $28.4 million for the fourth quarter of 2019. The increase in SG&A expenses compared to the prior year was due primarily to activities to support the U.S. commercialization of XPOVIO. On slide 13, you can see that cash equivalents, restricted cash and investments as of December 30, 2020 totaled $276.7 million, compared to $265.8 million as of December 31, 2019. Finally, based on our current operating plans, Karyopharm expects non-GAAP R&D and SG&A expenses, which excludes stock-based compensation expense for the full year of 2021 to be in the range of $280 million-$300 million. The company expects that its existing cash equivalents, and investments and the revenue it expects to generate from XPOVIO product sales and other licensed revenues will be sufficient to fund its planned operations into late 2022. We are not providing revenue guidance for 2021 today, as we have just begun the initial launch of XPOVIO and its expanded indication. We do expect to see meaningful growth in 2021 relative to 2020, with the ramp of sales increasing in the second half of the year, as we expect to see the benefit of a longer duration of treatment for multiple myeloma patients being prescribed XPOVIO earlier in their treatment course and/or in combination with VELCADE. I'll now turn the call back over to Michael for some concluding remarks. Michael? Thank you, Mike. Before moving to the Q&A, let me highlight some of the key commercial, clinical, and regulatory milestones that we expect for 2021, shown on slide 14. First, we are actively in the process of launching XPOVIO into the second and third line settings in myeloma in the U.S., and we expect a significant increase in annual sales in 2021 as compared with 2020. Next, we anticipate a decision on the conditional approval of XPOVIO in Europe based on the STORM data in April, and plan to submit the BOSTON data via Type II variation shortly thereafter, which could result in an expanded approval in Europe later this year. Finally, in the second half of this year, we expect top-line data from the phase III SIENDO study in endometrial cancer, as well as multiple clinical trial initiations and the presentation of additional combination data with XPOVIO and other cancer therapies at various medical meetings. Before we open the call to questions, I do want to recognize our full Karyopharm team for a truly remarkable 2020. We've already started the new year off strongly, and I'm confident that we are well-positioned to execute on the commercial, clinical development, and operational goals and growth opportunities outlined today. We appreciate your ongoing support and look forward to keeping you updated on our future progress. I'll now turn the call over to the operator for questions. Operator? The first question comes from Maury Raycroft with Jefferies. Please go ahead. Hi, good morning, everyone, and congrats on the progress. Thanks for taking my question. For sales, we likely won't see a major rise in the number of refills in at least the next quarter. That's if the numbers are presented in aggregate. Would you consider breaking out that number or other sales numbers by line of treatment in 2021? I guess you plan on providing more granularity going forward? Let me turn it to Ian to start. Thanks, Maury. I think for now, the reality is, in terms of the clarity of data we get, from our distributors and specialty pharmacies, we don't get a level of data that tells us what line of therapy the XPOVIO prescription was given in. Right now, we don't have that clarity. We do get some of that information from market research, which we'll do later in the year, but that won't be available till later in the year. I think we'll see. Let the launch play out, and as we get more information, I think we'll be more specific in terms of where the growth is coming from. Got it. Okay, one follow-up just on potential BD opportunities in Europe. Just wondering if you could say anything additional on that and if that could take place prior to the BOSTON acceptance and approval there. Let me turn that over to Stephen Mitchener, our Chief Business Officer. Stephen? Yes. Hi, good morning, Maury. It's a great question, and certainly since we've gotten the positive opinion in Europe, there's been a lot of great momentum. We're currently under a number of discussions. For both Europe and Japan, and we're looking to make some decisions hopefully in the next few months where we can bring that effectively to our European patients. I think the other thing I would add, too, is that on a positive note, we've had a lot of interest beyond just the multiple myeloma indications, and something that we're looking to expose and help out beyond just the first part of our hematology portfolio. Great. Okay, thank you for taking my questions. The next question comes from Brian Abrahams with RBC Capital Markets. Please go ahead. Hey, good morning. Thanks for taking my questions. Congrats on all the progress. I'm curious what some of the key metrics that you guys are going to be looking for in order to assess earlier line uptake, I guess beyond new patient starts. Is this primarily duration? Is there anything that you might be able to tell from dose levels, just given the spread on that already? I understand you're not looking for, or not expecting a major inflection until closer to the back half of the year, but how quickly might you expect some of these potential leading indicating signals to manifest themselves? Are you starting to see any initial trends here since December, now that we're close to mid-February? Yeah, let me start with Ian and then move it over to John, our Chief Commercial Officer. Ian? Yeah, great question. Clearly, one of the most obvious indicators will be new patient starts. For some of the data that we received, we did mention on the call that we have seen an uptick in, or certainly growth in new patient starts. That's certainly encouraging. We'll continue to follow that. We've also seen a reduction in the percent of XPOVIO prescriptions at the 80 milligram twice a week dose, an increase in the doses that would indicate that XPOVIO is being used in combination, so doses lower than the 80 milligrams twice a week. We think that's also another positive indicator that more physicians are likely choosing to use XPOVIO as a combination regimen. Now, we don't have visibility as to what percent of that is with VELCADE, what percent of that is with another anti-myeloma agent. Certainly, we're encouraged that the percentage of prescriptions written for the 80 milligram dose is coming down quite significantly. Those are the kinds of things that we're looking at, and I think you mentioned as we get into probably the second half of the year, we'll really be looking at duration of treatment, and that is a metric that we can follow with at least half of our business that goes through the specialty pharmacies. We can see what the numbers of prescriptions that each individual patient is getting. Again, that's a number that we wouldn't expect to materially increase until we get to the back half of the year, as we get a benefit from the duration of treatment. I don't know, John, if there's anything that you'd add to that. Yeah. Thanks, Ian. In addition to duration of therapy and the SKU mix to look at what combinations we're getting, we also are doing monthly ATU readouts to look at intent to prescribe by line of therapy and by combination. That'll be a leading indicator of uptake. We also have pulse research going on a regular basis to measure physician opinions and prescribing intent, as well as the number of ad boards to track perception and perception changes over time. All of those of which will be leading indicators to the launch success and our uptake in the BOSTON space. Great. What are you seeing on some of those, I guess, just initially, with the label expansion and NCCN guideline inclusion? John? Yep. Yeah. Well, of course, we're still less than two months into launch. We're very encouraged by what we're seeing there. The feedback we're receiving from physicians in the one-on-one meetings, in the market research, in the ad boards, has been quite positive. We're already seeing an increase in prescription demand relative to what we saw, as mentioned, for October and November. We were able to launch immediately at approval across all functions in the company, which was imperative. We're seeing the impact of that in the context of the rapid promotional efforts. We're already seeing the shifts that Ian mentioned in terms of dosage and more patients now starting on XVd than starting on XD. Early signs from the market research and from the ad boards are positive. Again, it's early. The early leading indicators are headed the right direction. That's really helpful. Then maybe just a quick follow-up, if I could. With respect to the competitive landscape, I'm curious what your market research and on-the-ground physician discussions are telling you are some of the key considerations for docs in their choice of a new myeloma treatment to add on in later stage refractory patients. I'll hop back in the queue. Thanks. Let me start here, and then we'll turn it over to some of the others on the call. I think the main point here is that while there are a number of different therapies people can take in the second and third-line settings, the XVD regimen is really unique in many ways. First of all, it is the therapy that appears to have the fewest number of overall doses and the least amount of clinic time that a patient's required to spend. That's a super important point at any time, especially when you consider that three-quarters of the patients are over 70 years old, and really don't have ease of transportation and so on. In fact, no patient really wants to spend a lot of time at the hospital, and that's even more important during COVID. The second point is that the data we get from this study are potentially very relevant to the real world due to the fact that we used once-weekly VELCADE in the experimental arm. This is the only study that's resulted in a VELCADE-based approval that's used actually what doctors are treating with. It's a very unique regimen. The last point to make is, and I think John's research has really honed this carefully for us, is that we represent the fourth independent mechanism for use in the early levels of disease.Obviously, the proteasome inhibitors, IMiDs, and CD38 monoclonal antibodies are very important in these areas. When a patient goes through them, and sometimes now in front line, patients are getting all three of these regimens plus steroids, it begs the question of what to do in the second and third lines. We represent the fourth independent mechanism that's now approved in combination for the use there, and not only approved for VELCADE, but has NCCN guidance beyond that for Pomalyst and Darzalex with data, of course, with KYPROLIS. Jatin, do you want to add anything, and then John? No, I think you're exactly right, Michael. The key consideration is really novel mechanism of action. They have their PIs and IMiDs that they're giving, including CD38s in the first line. New mechanisms are a key consideration. Convenience at the end of the day, because a lot of these patients will live for many years. Having something that's well-tolerated, without residual long-term side effects is key for these, when they're thinking about sequencing and what they're looking at in earlier lines of therapy. Those are the two key considerations. I think they uniquely position this combination well. Thanks so much. That's a really helpful color. Appreciate it. The next question comes from Peter Lawson with Barclays. Please go ahead. Hi. Thanks for taking my questions. I guess the first one's just around what the current duration of treatment is, if you can give us any kind of sense around that and where that could potentially increase to over time. Sure. Ian? Yeah. What we've said, and certainly we said it on the call, it's about three months right now through 2020. That's been consistent for probably the last couple of quarters. Also consistent with the data that we saw coming out of the original STORM study that showed about a three-month average duration of treatment. Now remember, there'll be patients that are on for a month, and there'll be patients that are on for over a year, but the average is about three. What we did see in the BOSTON study was that the average was about 10 months on therapy. I think that gives you sort of the range from the clinical studies. Our hope is that, obviously, we're able to grow the average duration of therapy from a point of three today to something closer to 10. Obviously, time will tell how effective we are at moving as many patients as we can to our early lines of treatment. That's where the numbers stand today, and I think that gives you some sense of how high they could possibly go. Is there any kind of sense that they are ticking up, or do you think that's more of a kind of back half of the year event? Yeah. It's way too early to know that. Yeah. The 10 months I was talking about was from the BOSTON study, just to be clear. Yeah. Again, it's way too soon to know if there's been any changes to the average duration of treatment. Okay. Thank you. Is there any way of kind of quantifying the COVID impact on whether it's the number of scripts or the number of new docs and kind of what gives you the confidence that this is a kind of a temporary event versus a kind of hidden penetration? John, do you want to talk about that? Yeah. We do think the COVID impact is having multiple impacts. We know in-person visits by our sales force, nurse liaisons, payer teams to key stakeholders continues to be impacted in most parts of the country. Research estimates that we've seen are that 15%-20% of HCPs can be seen in person. We continue to believe that it's challenging to educate physicians in this environment and are putting in place multiple tactics, both digitally and with additional training on virtual engagements to try and enhance that. We also know the impact of COVID includes reduced patient visits that we saw from different data sources, particularly with the spike, as mentioned in the fourth quarter. A dual impact we saw from COVID in the context of the fourth quarter. It sounds like this is definitely kind of a temporary issue as opposed to you kind of capping out on multiple myeloma. Yeah, absolutely. We're seeing a lot more doctors get interested in this. Remember, this is a fundamentally different asset now in the second and third line setting, with patients now getting a new option, a very convenient option, a very real-life set of data in which to base a clinical decision to administer XVD, then, as we said, additional support with the other. We absolutely believe this is the beginning of a fundamentally new asset and ramp for XPOVIO in myeloma. Great. Thanks for taking my questions. The next question comes from Jonathan Chang with SVB Leerink. Please go ahead. Good morning, thanks for taking my questions. First question, why wouldn't we see an inflection in sales until the second half for BOSTON? As I understand, the first half numbers might not fully reflect a longer duration of treatment. Shouldn't it reflect the significantly increased number of patients available in the earlier line settings? I'll turn that to Ian to start. Yeah. We do expect that. I'm sorry if that wasn't clear. We absolutely do expect growth, beginning in this first quarter of this year. Absolutely, we expect to see growth, because to your point, we should have additional patients, and we do have additional patients that we're now eligible to treat, and that's a much larger patient pool. We absolutely expect to see growth relative to the fourth quarter of last year. I think the point that we're making is that growth should accelerate throughout the year, and certainly as we get into the second half of the year, because not only do you have the benefit of more patients, but you have the benefit of the longer duration of treatment for patients that are getting treated today. That's the dynamic that we expect to see. Understood. Just one follow-up to that. Could BOSTON and the earlier line sales cannibalize the STORM opportunity, and are you seeing any evidence of that? Thank you. Yeah. Nearly all drugs are used multiple times in a given patient during their journey on therapy. The real use of XPOVIO will not be really the STORM administration, but in earlier lines, we expect it'll be mostly XPOVIO-VELCADE-dex with some XPOVIO-pomalidomide-dexamethasone if someone wants to use an NCCN guided all-oral therapy. Later on it could be XPOVIO-daratumumab-dexamethasone or XPOVIO-KYPROLIS dex in the later lines. We do expect that we will see multiple uses of XPOVIO. We don't have any data on it yet. Anecdotally, we've heard of a couple patients who are getting their second course of XPOVIO in their treatment journey, but right now it's too small numbers. Got it. Thank you. The next question comes from Eric Joseph with JP Morgan. Please go ahead. Good morning. This is Hannah on for Eric. Thanks for taking our questions. Just a couple from us. First, what is the status of commercial preparations for XPOVIO in the EU? Are you scaling for the penta-refractory population or scaling more in anticipation of accessing the third and second line patient populations with the BOSTON submission? I have another one after that. Yeah. Stephen, you want to take that? Sure. As we mentioned before, we are very excited that we got the positive opinion on the STORM indication. We are having a number of discussions right now, both internally and with external partners on the best way to leverage that opportunity with the pending BOSTON indication that should come hopefully by the end of this year. It's something that we're just really working through in terms of how to best bring that asset to that market appropriately with all the different pricing implications and sequencing that we can work through. Hopefully that answered your question. Just to add, we absolutely have the drug. We'll make the drug available once it's got European Commission approval, assuming that goes well. The real market opportunity here is clearly in the BOSTON type population. The big push that we're going to have is going to be for the BOSTON approval by the end of the year. We will have the drug available for patients on time. Okay, great. Thank you. That's helpful. Then also in that vein, do you expect that physician prescribing patterns will differ between the EU and the U.S.? Just preliminary thoughts on that. Jatin, do you want to take that? In terms of prescribing patterns? I can just jump in and do it real quick and add that one of the problems in Europe is that one of the challenges is that there's a lot less reimbursement for off-label use. Physicians tend to be restricted to what's on label, at least in most of the countries. There are some countries that are more liberal, provided that the line of therapy is appropriate, physicians would be using the drug as they see fit. I think the main difference will be just on the restricted access or reimbursement. John, do you want to pick up on that? I would say while prescribing patterns may differ somewhat across the U.S. and Europe, early research that we've done does get a positive reaction for the XVD or BOSTON profile. We do expect to have good penetration in the European market as well once we launch in that indication. Okay, great. Very helpful. Thanks for taking the question. The next question comes from Mike Ulz with Baird. Please go ahead. Hi, guys. Thanks for taking the questions, and congratulations on all the progress as well. Maybe I could just ask a follow-up on some of the prior questions related to XPOVIO trends. You guys sort of mentioned an increase in demand starting in December and also in January. Just curious, the month-over-month trend, were you seeing an acceleration there? I have a follow-up. Yeah. I think we'll leave it at, again, we don't want to get too into the weeds in terms of weekly or monthly prescription trends. We'll leave that to our quarterly summation when we have these kinds of calls. I think suffice it to say, we are pleased with the early indicators and the growth that we're seeing since approval. Again, I think when we get to our full Q1 numbers, it'll be much clearer in terms of how we've done overall for the full first quarter. Got it. That's fair. Then maybe just a follow-up on NCCN guidelines. Obviously you've got recommendation in combination with VELCADE, which is on label, but you've also got recommendations off label with Pomalyst and Darzalex. I know it's early, but just since those guideline updates, have you noticed an uptick sort of in off-label use in those combinations? Thanks. John, you want to take that? Yeah. Sure. Glad to address that. Our sales team and marketing team will of course only promote XPOVIO on its approved FDA label, which is the XVD combination. We do know that many physicians and payers rely on the NCCN guidelines to help make treatment decisions. As you mentioned, NCCN recently added three different XPOVIO regimens, bortezomib regimen or XVD in combination with daratumumab or XVD and with pomalidomide or XPD. Importantly, the once-weekly XVD regimen was approved with category 1 recommendation, which represents the highest level assigned by the NCCN. As we track in secondary market research, as Ian mentioned we're doing going forward, we will look at a breakout and see how much use it is in XVD versus XPD versus XKD, et cetera. It's too early to have those data to date, but those are data we'll gather from market research as we go throughout the year. Got it. Thank you very much. The next question comes from Edward White with H.C. Wainwright. Please go ahead. Morning, everyone. Maybe if I can ask a question on the pipeline, if you can list your priorities in solid tumors. You had mentioned the endometrial and metastatic melanoma studies, but I just wanted to get an update for lung colorectal cancer and GBM. These are all sort of equal priorities. We're enrolling patients into our own studies in all the ones that you mentioned, lung colorectal and GBM. We have single agent activity in GBM, which we've talked about 10%, and we've seen activity as well in colorectal, and we've seen an investigator-sponsored trial I've mentioned that's been ongoing now with some activity in lung. This drug seems to be a very important add-on therapy or addition to some of the active drugs that are used across multiple different indications. That's because we attack a fundamental mechanism of cancer, which is inactivation of tumor suppressor proteins, and we reactivate those tumor suppressor proteins. Then, of course, don't forget, we have our SIENDO phase III study reading out by the end of this year, where we're using XPOVIO versus placebo in the maintenance setting after frontline therapy. Broadly active drug and we're being very careful about how we use our precious resources, but we see it across a number of different therapies, and we'll pick the best winners and move them forward as expeditiously as possible. Great. Thanks, Michael. Maybe just talking about resources, a question for Mike or Ian Karp. Did you use the ATM in the fourth quarter or thus far in 2021? Are you including any proceeds from the ATM in the cash runway guidance? Thanks. Mike? I can take that one. Yeah. We certainly don't comment on ongoing fundraising activities. The ATM, we definitely did not use it during the fourth quarter. We don't include that in our guidance. It's more on current approved indications plus current collaborations that we already have in place offset by spend, which we guide to would be somewhere between $280 million-$300 million in 2021. Okay. Thanks, Mike. Also just as far as that guidance goes on the runway, does that include any milestone payment or potential milestone payment from a European partnership? We don't include, when we look back at guidance, any new collaborations. Obviously, it's something that's a big part of Stephen's focus for 2021 as well as the entire company to make sure we're ready to commercialize in Europe. No, it does not include any significant payments for new alliances. Okay, great. Thanks for taking my questions. Sure. This concludes our Q&A session. I would like to turn the conference back over to Michael Kauffman, CEO, for any closing remarks. Thank you, everybody, for joining today's call, and we do look forward to updating you on our progress as soon as we can. Talk to you soon. Bye-bye. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.