Morning. My name is Vaishnavi, and I will be your conference operator for today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics 4th Quarter and Full Year 20 20 Financial Results Conference Call. Fees request. I would now like to turn the call over to Mr.
Ian Karp, Karyopharm's 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 4th quarter and full year 2020 financial results and business update. This is Ian Karp, and I'm joined today by Doctor. Michael Kauffman, our Chief Executive Officer Mr. Mike Mason, Chief Financial Officer Mr. John Demery, Chief Commercial Officer Doctor.
Jatin Shah, Chief Medical Officer and Mr. Steven Michener, Chief Business Officer. On the call today, Mike will provide an overview of key recent corporate developments and an update on our commercial 4th quarter and full year 2020 financial results. We will conclude with the Q and A portion of the call. Earlier this morning, we issued a press release detailing Karyopharm's results for the Q4 and full year of 2020.
This release, along with a slide presentation that we will reference, 3rd quarter are available on our website at karyopharm.com. Before we begin our formal comments, I'll remind you that various remarks we'll 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 3. These include statements about our future expectations, clinical developments and regulatory matters and time lines, the potential success of our products and product candidates, including our expectations related to the commercialization of Expovio, financial projections and our plans and prospects. Full year. 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 Factors section of our most recent quarterly report on Form 10 Q, which is on file with the SEC and in other filings that we may make with the SEC in the future.
Any forward looking statements represent our views as of today only. While we may elect to update these forward looking statements at some point, we specifically disclaim any obligation to do so, even if our views change. 4th quarter. 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 positive impact on the lives of patients battling cancer. Most notably, our year was marked by 2 U. S. FDA approvals for XPOVIO.
1st in June for the treatment of patients with relapsed or refractory diffuse large B cell lymphoma 4th quarter or DLBCL. And then in late December, once weekly XPOVIO received additional approval in combination with vortezomib and 4th quarter and 4th quarter. We expect to carry the momentum of these important achievements into 2021 and I've already started the year with several recent accomplishments as outlined on Slide 4. Expovio net product revenues for the Q4 and full year of 2020 were $20,200,000 76,200,000 respectively. More than 170,700 new physicians and accounts prescribed XPOVIA for the first time in Q4 and in 2020 overall, respectively.
These achievements are particularly encouraging keeping in mind that EXPOVIO was only first approved 4th quarter for use by the FDA in July of 2019 and of course for most of 2020, we've all been impacted in some shape or form by the ongoing COVID-nineteen 7. The expansion and launch of XPOVIO into the second and third line treatment settings significantly increases the addressable patient population for XBOVIO and represents a meaningful growth opportunity for Karyopharm in both the near and long term. Separately in December, The addition of 3 exovio 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 EXPOVIO'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 2017 in recommending the conditional approval for Nexpovo, the brand name for selinexor in Europe, in combination with dexamethasone for the treatment of myeloma in adult patients 4th quarter and 4th quarter. We have a very strong quarter with a strong quarter with a strong quarter with a strong quarter with
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with a strong quarter with a strong quarter with a strong quarter with a strong 19 accelerated approval issued by the FDA in the United States. I will talk a bit more about our expecting steps for Europe 4th quarter in just a few minutes. Additionally, we were excited to secure our first regulatory approval outside the United States 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 3 CENDO study evaluating exovio endometrial cancer past its planned interim futility and upsizing analysis, and we look forward to the top line results expected in the second half of this year.
In addition, the first patient in the Phase twothree export DLBCL-thirty 30 study evaluating XPOVIO in patients with DLBCL has now been treated and this study will serve as a confirmatory study for Xphobio's accelerated approval in DLBCL granted last year. Finally, on the financial front, we ended the quarter with a strong cash position 3rd quarter patients into late 2022. Let me now turn to Slide 5 to provide additional details on Expovio's sales performance through 2020. In the 1st three quarters of 2020, we generated steady increased sales for XPOVIO due to both 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 Q4 specifically were largely driven by prescription demand from both academic and C based oncologists for patients with 10 to refractory multiple myeloma.
The 5% decrease in product sales in the 4th quarter 4th quarter as compared to the Q3 was a result of the impact from both the recent surge in U. S. COVID-nineteen cases as well as some increased competition for patients. More specifically, as we turn to Slide 6, we believe the surge in COVID-nineteen cases impacted both patient visits to their healthcare provider from recently launched drugs in pentorefractory myeloma and in refractory DLBCL studies 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 XBOVIO, as mentioned previously, the addition of multiple XBOVIO combination regimens to the NCCN guidelines and the expanded FDA approval of EXPOVIO provided strong tailwinds for sales growth in December, following declines in October November.
We're still in the very early stages of the launch of EXPOVIO 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 7. The graph here shows the prescription refill rate for EXPOVIO over 2020 for both the first and second refills to those patients eligible for these refills. These numbers have remained encouraging throughout 2020 are significantly higher as compared to our initial launch period in 2019. These refill rates coupled with an average of nearly 3 treatment cycles per patient as of the end of 20 further reinforce the positive feedback we have received from physicians and patients regarding their experience and uses of EXPOVIO.
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 EXPOVIA with proper prophylactic and supportive therapies as well as dose modification. In addition to the expanded label for EXPOVIO 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 8. The CHMP positive opinion for NextFovio, which was issued at the end of January, could lead to our 1st regulatory approval in Europe and recognizes the positive clinical benefit risk profile of oral NexboVio. We look forward to the European Commission's final decision on an NexboVio submission, which is expected in April 2021.
We intend to submit a second regulatory filing based on the data from the Phase 3 BOSTON 4th quarter. We're also pleased with the goal of further expanding the global reach of MYXBOVIA to additional patients in need of new treatment options. And 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 3rd line plus treatment guidelines. In parallel to the regulatory experts, We're also continuing to evaluate potential collaborations with partners in Europe and Japan. We're committed to making Xpovio available in Europe, if approved in April with the greatest opportunity come potentially before the end of 2021, when we would hope to receive an expanded approval in Europe 4th quarter based on the data from our Phase 3 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 910. We have a robust clinical development plan for XPOVIO in both hematological 3rd malignancies and solid tumors. This includes our Phase 3 CENDO 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 2 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 3 evaluating XPOVIO in combination with pomelist and dexamethasone in patients with previously treated myeloma.
If 4th quarter. If the results of this trial are positive, this regimen would represent a potent oral drug option to patients with refractory disease. Next we plan to initiate a new Phase 2 study evaluating EXPOVIO 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, 4th quarter, which begin on Slide 12. Net product revenue for the Q4 of 2020 was $20,200,000 compared to $17,700,000 for the Q4 of 2019. Net product revenue for the year ended December 30, 2020 was $76,200,000 compared to $30,500,000 for the year ended 2019.
The estimated gross to net discount for exfolio in 2020 fell within our estimated range of 15% to 20%. License and other revenue for the Q4 of 2020 was $14,900,000 compared to $400,000 for the Q4 of 2019. This increase was driven by a $9,800,000 payment from Antigene for milestone payments associated with regulatory filings in Asia as well as a $5,000,000 upfront from Forest Therapeutics upon the execution of a commercial distribution agreement for Canada. License and other revenue in 2020 were $31,900,000 compared $10,400,000 in 2019. R and D expenses for the Q4 of 2020 were $38,800,000 for the Q4 of 2019.
R and D expenses for the year ended 2020 were $150,800,000 compared to 100 $2,300,000 for
the year
ended 2019. The increase in R and D expenses in 2020 compared to 2019 was primarily attributable to costs associated with incurred related to our COVID-nineteen trial activity, which will not reoccur in 2021, and continued activity in our other ongoing clinical trials and regulatory activities. Selling, general Q4 was due primarily to activities to support U. S. Commercialization of Spovial.
On Slide 13, You can see that cash, cash equivalents, restricted cash and investments as of December 30, 2020, totaled 2 $176,700,000 compared to $265,800,000 as of December 31, 2019. Finally, based on our current operating plans, Karyopharm expects non GAAP R and D and SG and A expenses, which excludes stock based compensation expense, for the full year of 2021 to be in the range of $280,000,000 to $300,000,000 The company expects that its existing cash, cash equivalents and investments and the revenue it expects to generate from exovio product sales and other license revenues will be sufficient to fund its planned operations into late 2020 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 4th quarter as we expect to see the benefit of a longer duration of treatment for multiple myeloma patients being for Stratus exfolio earlier in their treatment course and or in combination 4th quarter with Bellcade. I'll now turn the call back over to Michael for some concluding remarks.
Michael?
Thank you, Mike. Before moving to the Q and A, let me highlight some of the key commercial, clinical and regulatory milestones that we expect for 2021 shown on Slide 14. 1st, 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 of 2021 as compared with 2020. Next, we anticipate a decision on the conditional approval of MYX FOBIO in Europe based on the STORM data in April and plan to submit the BOSTON data via Type 2 variations shortly thereafter, which could result in expanded approval in Europe later this year.
Finally, in the second half of this year, we expect top line data from the Phase III CENDO study in endometrial cancer as well as multiple clinical trial initiations presentation of additional combination data with XPOVIO and other cancer therapies at various medical meetings. Before we open the call to questions, I do 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
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. So for sales, we likely won't see a major rise in the number of refills And at least the next quarter. And so if the numbers are presented in and that's if the numbers are presented in aggregate. So 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.
Yes. Thanks, Maury. I think for now, the reality is in terms of the clarity of data we get, We don't see from our distributors and specialty pharmacies, we don't get a level of data that tells us What line of therapy the ex phobia prescription was given in. So we 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 will be available for later in the year.
So I think we'll see kind of let's let the launch play out. And 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. And then, 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 Steven Michener, our Chief Business Officer. Steven? 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. So we're currently under a number of discussions for both Europe and Japan, and 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 it's something that we're looking to expose and help out beyond just the first part of our hematology portfolio.
5th. So 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 4th quarter. And 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 potentially 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?
Yes. Let me start With Ian and then move it over to John, our Chief Commercial Officer. Ian?
Yes, great question. I mean clearly one of the most obvious indicators will be new patient starts. And for some of the data that we receive And we did mention on the call that we have seen an uptick in or certainly growth in new patient starts. So that's certainly encouraging and And we'll continue to follow that. We've also seen a reduction in the percent of EXPOLIO prescriptions at the 80 milligram twice a week dose and an increase in the doses that would indicate that EXPOMIO is being used in combination, so doses lower than the 80 milligrams twice a week.
So we think that's also another positive indicator that more physicians are likely choosing to use exfolio 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. But certainly We're encouraged that the percentage of prescriptions written for the 80 milligram dose is coming down quite significantly. So 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 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. But again, that's a number that we wouldn't expect to materially increase until we get to the back half of the year As the duration, we get a benefit from the duration of treatment. I don't know, John, if there's anything that you'd add to that.
Yes. Thanks, Ian. In addition to duration of therapy and the SKU mix So 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. So that will be a leading indicator uptake.
We also have pulse research going on, 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. And what are you seeing on some of those, I guess, just initially, as with the label expansion and NCCN guideline inclusion?
John?
Yes. Well, of course, we're still less than 2 months into launch. We're very encouraged by what we're seeing there. The feedback we're receiving from physicians in the 1 on 1 meetings in the market research in the ad boards has been quite positive and we're already seeing an increase and prescription demand relative to what we saw as mentioned for October November. We were able to launch immediately at approval across all functions in the company, which was imperative, and we're seeing the impact of that in the context of the rapid promotional efforts.
We're already seeing The shift that Ian mentioned in terms of dosage in more patients now starting on XPD than starting on XD. So early signs from the market research from the ad boards are positive. Again, it's early, but the early leading indicators are headed the right direction.
And And 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 and their choice of a new myeloma treatment to add on in later stage refractory patients?
Yes, 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 XPD 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 And the least amount of clinic time that a patient is required to spend. And 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. And And most 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, because 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 people, what doctors are treating with. So it's a very unique regimen. And the last point to make is, And I think John's research has really honed this carefully for us is that we represent the 4th 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.
But when a patient goes through them and sometimes now in frontline patients are getting all three of these regimens, plus steroids. It begs the question of what to do in the second and third lines. And we represent the 4th 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 PAM and Dara with data of course with Kyprolis. Jaeme, 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 PI image that they're giving, including CD38s in the first line. New mechanisms are a key consideration and And then convenience at the end of the day because a lot of these patients will live for many years. And so having something that's well tolerated without residual long term side effects is key, Lisa, sequencing and what they're looking at in earlier lines of therapy.
So those are the 2 key considerations, and I think it uniquely positions this combination well.
Thanks so much. That's really helpful color. Appreciate it.
The next question comes from Peter Larson with please go
ahead. Hi. Thanks for taking my questions. I guess the first one is 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?
Yes, I mean, well, and what we've said and certainly we said it on the call, it's about 3 months right now or through 2020. And that's been consistent for probably the last couple of quarters, and also consistent with the data that we saw coming out of the original STORM study It showed about a 3 month average duration of treatment. And remember, there will be patients that are on for a month and there will be patients that are on for Over a year, but the average is about 3. What we did see in the BOSTON study was that the average was about 10 months of therapy. So I think that gives you sort of the range from the clinical studies.
And our hope is that obviously, we're able to grow the average duration of therapy from 0.3 today to something closer to 10. But obviously time will tell how effective we are at moving as many patients as we can to early launch treatment. So 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?
Yes, it's way too early to know that. Yes, the 10 months I was talking about was from the BOSTON study, just to be clear. Yes, there's again, there's it's way too soon to know if there's been any changes to the average duration of treatment.
Okay. Thank you. And then is there any way to kind of quantify 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 Hitting penetration.
John, do you want to talk about that?
Yes. We do think the COVID impact It's having multiple impacts. We know in person visits by our sales force, nurse liaisons, payer 4th quarter teams to key stakeholders continues to be impacted in most parts of the country. Research estimates that we've seen are that 15% to 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 Q4. So a dual impact we saw from COVID in the context of the Q4.
But it sounds like this is definitely Kind of a temporary issue as opposed to you kind of capping out on multiple myeloma.
Yes, absolutely. We're seeing a lot more doctors get interested in this. And remember, this is a fundamentally different asset now in 2nd and third line setting, with patients now getting a new option, a very convenient option, a very real life Set up data to in which to base the clinical decision to administer XVD and then, as we said, additional support with the other. So we absolutely believe this is the fundamental is the beginning of a fundamentally new asset and ramp for EXPOVIO in myeloma.
The next question comes Jonathan Chang with SVB Leerink. Please go ahead.
Good morning and 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, but shouldn't it reflect the significantly increased number of patients available in the earlier line setting?
Yes, I'll turn that to Ian to start.
Yes, yes. We certainly we do expect that. I'm not sure. So I'm sorry if that wasn't clear. We actually do expect growth beginning in this Q1 of this year.
So absolutely we expect to see growth because to your point, we should have additional patients that we do have additional Patients that we're now eligible to treat, and that's a much larger patient pool. So we absolutely expect to see growth relative to Q4 of last year. I think the point that we're making is that, that growth should accelerate throughout the year and certainly as we get into the second 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. So that was the 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.
Yes. I mean most
4th? Nearly all drugs are used multiple times in a given patient during their journey on therapy. And so The real use of XPOVIO will not be really the storm administration, but it will be in earlier lines, we expect it will be mostly XPOVIO VELDEX with some XPOVIO Palmdex, if someone wants to use an NCCN guided all oral therapy. And then later on, it could be Xpovio Daradex or Xpovio Kyprolisdex in the later line. So we do expect that we will see multiple uses of Xpovio.
We don't So many data on it yet. Anecdotally, we've heard of a couple of patients who are getting their second course of EXPOVIO in their treatment journey. But right now, it's too small numbers.
Got it. Thank you.
The next question comes from Eric Joseph with JPMorgan. Please go ahead.
Good morning. This is Hannah on for Eric. Thanks for taking our questions. Just a couple from us. So first, what is the status of commercial preparations for an exovio in the EU?
Are you scaling for the penta refractory population or scaling more in anticipation of second line patient populations with the Dostin submission? And then I have another one after that.
Yes. Steven, you want to take that?
Sure. So as we mentioned before, we are very excited that we got 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 So 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. So 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 here is clearly in the Boston type population. And so the big push that we're going to have is going to be for The Boston, hopefully the Boston approval by the end of the year, but we will have the drug available for patients on time.
Okay, great. Thank you. That's helpful. And then also in that vein, do you expect that physician prescribing patterns will differ between the EU and the U. S?
Just preliminary
pharma? Jaeson, do you want to take that?
In terms of prescribing patterns,
I can just jump in and
just real quick. One of the problems in Europe is One of the challenges is that there's a lot less reimbursement for off label use. And so physicians Tend to be restricted to what's on label, at least in certain in most of the countries. There are some countries that are more liberal and provided that the line of therapy is appropriate physicians would be using the drug as they see fit. But 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 the positive reaction for the XED or BOSTON profile. So we do expect to have good penetration in the European market as well once we launch in that indication.
The next question comes from Mike Ulz with Baird. Please go ahead.
Hi, guys. Thanks for taking Congratulations on all the progress as well. Maybe I could just ask a follow-up on some of the prior questions related to Covio trends.
So you guys sort
of mentioned an increase in demand starting in December and also in January. So just curious the month over month trend, were you seeing an acceleration there? And then I have a follow-up.
Yes. 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. So we'll leave that to our quarterly summation when we have these kinds of calls. I I think suffice it to say, we are pleased with the early indicators and the growth that we're seeing since approval. And And again, I think when we get to our full Q1 numbers, it will be much clearer in terms of how we've done overall for the full Q1.
Got it. That's fair. And 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 POMALIST and DARZALEX. And 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?
Sure, glad to address that.
So 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. And as you mentioned, NCCN recently added 3 different exovio regimens, the vortezumab regimen or XPD in combination with daratumumab or XPD and with pomalidomide or XPD. Importantly, the once weekly XPD Benjamin was approved with Category 1 recommendation, which represents Highest level assigned by the NCCN. As we track in secondary market research, as he has mentioned, we're doing going forward, we will look at a breakout and see How much use is in XPD versus XPD versus XKD, etcetera?
It's too early to have those data to date, but those are data we'll gather for market research as we go throughout the year.
The
next question comes Ed White with H. C. Wainwright.
Maybe
if 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.
Yes. Well, those are all these are all sort of equal priorities. We're Enrolling patients into our own studies and all the ones that you mentioned, lung, colorectal and GBM, you We have single agent activity in GBM, which we've talked about 10%. And we've seen activity as well in colorectal and And we've seen an investigator sponsored trial, I've mentioned, that's been ongoing now with some activity in lung. So 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.
And That's because this is a fundamental mechanism of we attack a fundamental mechanism of cancer, which is inactivation of tumor suppressor proteins, and we reactivate those tumor suppressor proteins. And then of course, don't forget, we have our CENDO Phase 3 study readout by the end of this year where we're using Expovio versus placebo in the maintenance setting after frontline therapy. So broadly active drug and we're being very 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 expeditious
Maybe just talking about resources, a question for Mike or Ian. Did you use the ATM In the Q4 or thus far in 2021. And Are you including any proceeds from the ATM in the cash runway guidance? Thanks.
Mike? Yes. So we certainly don't comment on ongoing fundraising. The ATM, we definitely did not use it during the Q4, and we don't include that in our guidance. It's more on current Improving indications plus current collaborations that we already have in place offset by spend, Which we guide, it would be somewhere between $280,000,000 $300,000,000 in 2021.
Okay. Thanks, Mike. And 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?
So We don't include any new when we make that 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. But, no, it does not include any significant payments for new alliances.
This concludes our Q and 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.