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

Good morning. My name is Gigi, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics Phase III Boston Study Top Line Results Conference Call. [Operator Instructions] 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's Vice President, Investor and Public relations.

Thank you, Gigi, and thank you all for joining us on today's conference call to discuss the positive top line results from the Phase III BOSTON study. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, Chief Executive Officer; Mr. Chris Primiano, Chief Business Officer and General Counsel, Mr. Mike Mason, Chief Financial Officer; and Mr. Perry Monaco, Senior Vice President of Sales. On the call today, Dr. Kauffman will provide a brief overview of the current treatment paradigm for patients with multiple myeloma and highlight the rationale and design for the randomized Phase III BOSTON study. We will then discuss the positive top line results from the study and the potential implications these may have on the future of myeloma treatment landscape. We will conclude with a Q&A portion of the call. Earlier this morning, we issued a press release detailing the positive top line results from the BOSTON study. This release as well as an accompanying slide presentation are available on our website at karyopharm.com. Before we begin our formal comments and for those following along on the slide presentation, please turn to Slide 3, and 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. 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 relating to the commercialization of XPOVIO, financial projections and our plans and prospects. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. In addition, please note that any references we make to clinical trial data during today's discussion refer to interim unaudited site data, unless otherwise specified. I'll now turn the call over to Dr. Michael Kauffman, Chief Executive Officer.

Thank you, Ian, and good morning, everyone. I am thrilled to be here today with you to discuss our highly significant top line results from the randomized Phase III BOSTON study. This is now the first randomized Phase III study to demonstrate clinically significant activity of once-weekly XPOVIO in combination with the current standard of care anti-myeloma treatment in patients who had previously received 1 to 3 prior therapies. We are tremendously excited about these top line results and believe they could lead to a significant investment in the treatment of patients with relapsed or refractory multiple myeloma with increased convenience. While XPOVIO in combination with dexamethasone received accelerated approval from the FDA in July last year for patients with heavily pretreated myeloma, the top line data from the BOSTON study demonstrates the benefit XPOVIO may offer to patients earlier in their disease progression and in combination with one of the most commonly used anti-myeloma drugs available, Velcade. This, of course, will be subject to obtaining future regulatory approvals based on these and other clinical data. Most importantly, these positive data represent the next critical step in Karyopharm's unwavering mission to help improve the lives of patients with cancer and other serious diseases. For those following along in the slide presentation, please now turn to Slide 4. Unfortunately, despite all of the progress that's been made over the past 5 to 10 years, multiple myeloma remains an incurable disease where patients and physicians are in need of new therapeutic options. Myeloma is the second most common form of blood cancer with approximately 32,000 new patients diagnosed each year and nearly 130,000 U.S. patients living with and battling the disease. And despite a number of highly active drugs available to patients, approximately 13,000 people will die from this disease each year in the U.S.A. alone. Moving to Slide 5. I will briefly highlight the current treatment paradigm, which can be quite complex as physicians seek to tailor their treatment decisions to best meet the needs of individual patients. There are currently 4 main classes of drugs commonly used to treat patients with multiple myeloma, which include proteasome inhibitors, immunomodulatory agents, monoclonal antibodies and now a nuclear export inhibitor, where, of course, XPOVIO is the only drug in the class currently available. Patients typically receive 1 or 2 of these highly active agents in combination with a steroid such as dexamethasone in each line of therapy and they are usually treated until their disease progresses. Physicians will then typically prescribe another combination including steroids in each of the subsequent lines of therapy. Our experience is that physicians generally prefer drugs that have proven single agent clinical activity with or without steroids even when used in combination. In addition, those patients who are eligible may decide to receive a highly active combination regimen so-called induction therapy, followed by a high dose of melphalan and rescue of their hematopoietic system with stem cell transplantation. Although the various drug combinations in this autologous stem cell transplantation are quite active, none of these approaches are curative and nearly all patients will require multiple subsequent lines of therapy during their treatment course. One of the most commonly used drugs in both the first and subsequent lines of therapy is Velcade, sometimes referred to by its generic name bortezomib. This is a proteasome inhibitor administered subcutaneously in the doctor's office and often combined with either an immunomodulatory drug or a monoclonal antibody in addition to low-dose dexamethasone. Standard Velcade therapy is dosed twice weekly and as I said, must be given in the physician's office. Unfortunately, prolonged usage is often limited due to its main side effect, peripheral neuropathy, and most patients will eventually develop either intolerable side effects or their disease will become resistant or refractory to Velcade. In order to reduce the development of refractory disease, Velcade is often combined with other agents such as Revlimid or Pomalyst. And in order to reduce the risk of peripheral neuropathy, Velcade may be administered only once per week, but this lower dose has reduced anti-myeloma activity. Revlimid is the most commonly prescribed anti-myeloma drug and patients typically receive it in combination with dexamethasone and at least one other agent as a first-line therapy. Increasingly, patients with newly diagnosed myeloma are receiving Revlimid in combination with Darzalex, which has robust activity and low rates of peripheral neuropathy. However, despite available treatments, essentially all patients develop refractory disease and require additional combination therapies with mechanisms of action not utilized on their current therapy. In particular, agents with a novel mechanism of action are badly needed as the number of patients with myeloma is markedly increased. Please now move to Slide 6. The BOSTON study was designed in 2016 to '17 in order to address the growing need for combinations of novel agents following front-line regimens with or without autologous stem cell transplantation. As Revlimid is ubiquitously used in the front line and increasingly in combination with Darzalex, second-line regimens based on Velcade or other proteasome inhibitors are becoming more important. BOSTON is the first study to evaluating novel myeloma drug in combination with Velcade for at least -- for patients with at least one prior therapy. Karyopharm began enrollment in the BOSTON study in 2017 -- in June 2017 to evaluate treatment with weekly selinexor, now known as XPOVIO, Velcade and dexamethasone compared to standard twice weekly Velcade and dexamethasone or Vd in patients with multiple myeloma after 1 to 3 prior therapies. Our confidence and rationale for initiating this large randomized study was primarily driven by the following factors: first, we had established strong preclinical evidence of synergies when combining XPOVIO and a proteasome inhibitor. Next, based on our Phase I/II STOMP study, we have seen encouraging efficacy data from 42 patients who were treated with the SVd regimen. And finally, we knew that the current standard indicated dose of twice-weekly Velcade and dexamethasone was frequently reduced to once per week in real-world clinical practice due to the high incidence of peripheral neuropathy and added once-weekly office visit convenience, even though all Phase III trials with Velcade in relapsed myeloma have been conducted with utilizing the standard twice-weekly dosing schedule, both in the experimental arm and in the control arm. And unfortunately, there is not a lot of published clinical data demonstrating what efficacy physicians can expect for their patients when using once-weekly Velcade in combination after at least one regimen. For all of these reasons, we decided to conduct the BOSTON study as a confirmatory Phase III trial to support the accelerated approval of XPOVIO. And based on this morning's announcement for top line data, we're thrilled with the outcome. Please now turn to Slide 7 where I'll review the design of the BOSTON study. This study is a randomized Phase III active comparator controlled, open-label, multicenter study designed to compare the efficacy, safety and certain health-related quality of life parameters of SVd versus Vd in adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy. As mentioned previously, patients on the SVd arm received Velcade once per week, while those in the Vd arm received Velcade at the standard twice-weekly schedule. Importantly, these differences -- these dosing differences result in patients in the SVd arm receiving approximately 40% less Velcade and 25% less dexamethasone than those in the Vd arm and having about 30% fewer clinic visits over the first 24 weeks of treatment. The BOSTON study enrolled approximately 402 patients and the primary end point of the study is progression-free survival. Key secondary end points include overall response rate, overall survival and rates of peripheral neuropathy, amongst others. Additionally, the BOSTON study allows for patients on the Vd control arm to cross over to the SVd arm following objective progression of their disease. The BOSTON study was conducted at over 150 clinical sites internationally. Please now turn to Slide 8. I am pleased to report that based on the top line data, the BOSTON study met its primary end point of a statistically significant increase in progression-free survival or PFS. More specifically, there was a 47% increase in median PFS on the SVd arm as compared to the Vd arm, representing a 4.47-month improvement in median PFS. The median PFS in the SVd arm was 13.93 months compared to 9.46 months in the Vd arm. The overall hazard ratio was 0.70 and the p-value for this was 0.0066. These data are highly positive, especially when considering the patients in the SVd arm received Velcade only once per week and less dexamethasone in addition to once-weekly oral XPOVIO. Furthermore, we believe these top line data represent a very meaningful improvement in PFS in the treatment of patients with relapsed or refractory disease. Importantly, there were no new safety signals seen in the SVd arm relative to those previously reported adverse events from other selinexor multiple myeloma trials. Additionally, there was no imbalance of patient deaths across both treatment arms. And in fact, there were fewer deaths numerically in the SVd arm. As expected, with the use of a triple combination, the incidence of adverse events was higher amongst patients receiving SVd than those receiving Vd overall. We plan to further analyze the clinical data from this study and then submit them for formal presentation of future medical meetings. Finally, while there are, of course, many limitations when trying to compare clinical data from across different studies, it's important to understand what additional data are available from other trials that have used Vd as the comparator arm. One most recent relevant study may be the OPTIMISMM trial, which was a Phase III study that evaluated Velcade plus dexamethasone with or without Pomalyst. In this trial, the Vd arm demonstrated a 7.1-month median PFS, while the Vd plus Pomalyst arm had a PFS of 11.2 months and a hazard ratio of 0.61. So while we can't directly compare these data to BOSTON, I think it does help to provide some context as to what we've seen in the other recent trial using Vd as the comparator arm. As we mentioned previously, peripheral neuropathy is amongst the most common causes of treatment limitation and discontinuation of Vd in combination and combination Vd regimens. I'm pleased to report that in the BOSTON study, the rate of peripheral neuropathy on the SVd arm was significantly lower than the rate in the Vd control arm, and we will report the full details on this data point at an upcoming medical meeting. Importantly, we have seen particularly high rates of peripheral neuropathy in other Phase III trials that have studied Vd as the control arm. Often, and in most cases, triple Vd regimens have an even higher rate of peripheral neuropathy than the Vd control arm, as seen in both the CASTOR and the OPTIMISMM Phase III studies. We believe the rate of peripheral neuropathy demonstrated in the BOSTON study will be a very important feature of the SVd regimen pending future regulatory approvals. To help put into perspective the potential size of the opportunity XPOVIO may have in the future, I'll highlight the number of myeloma patients currently being treated in the United States by line of therapy. There are approximately 20,000 patients treated in the second line and 12,000 in the third line, which is dramatically larger than the 6,000 patients in the fourth line and later, where XPOVIO is currently being used based on its current FDA-approved indication. Turning to Slide 11. You can see that the worldwide annual sales of the 5 most frequently prescribed myeloma drugs. All of these drugs, which have demonstrated stand-alone anti-myeloma activity with or without steroids and are approved as first or second-line treatment have achieved annual sales of $1 billion or greater. While Revlimid leads the group with $11 billion in sales in 2019 based on its broad utilization in the first-line and maintenance settings as well as in lymphoma, each of the other 4 drugs are selling between $1 billion and $3 billion annually. Please now turn to Slide 12. The graph on this slide shows some additional detail about the most commonly prescribed anti-myeloma drugs. Specifically, it shows the percentage of patients treated by line of therapy based on market research Karyopharm conducted with 120 U.S.-based physicians in October of 2019. What you can clearly see is that beyond the first-line setting, there is no dominant or standard regimen used in the second, third or fourth line or later sets. The most prominent myeloma drugs are used in a range from about 5% to 45% of patients in each line of treatment, often in a variety of combinations, depending on our label indications, individual patient needs and based on which drugs patients have already received in prior lines of treatment. It's our belief that this dynamic will continue well into the future even with the addition of new anti-myeloma therapies. Based on the BOSTON clinical data and XPOVIO's once-weekly oral delivery, we believe XPOVIO, pending potential future regulatory approvals, will be a welcomed option for patients in the second and third line settings. Importantly, you can also see on this chart the impact XPOVIO is already having in the fourth line and later settings where XPOVIO's patient share is estimated at 18%. We believe this is a testament to the receptivity by physicians for new treatment options with meaningful efficacy data and a novel mechanism of action. Please turn now to Slide 13. One dynamic that we believe could help create additional opportunity for XPOVIO pertains to the growing use of Darzalex in the first-line setting. While Darzalex, an anti-CD38 monoclonal antibody, was first approved by the FDA in 2015 for patients who had received at least 3 prior lines of therapy, it was subsequently approved in the 1 to 3 prior regimen setting and has recently been approved for use in combination with other myeloma drugs in the first-line setting for both transplant ineligible and transplant eligible patients. In fact, our own market research, which I just shared a few moments ago, indicated that Darzalex patient share is already up to 10% in the first-line setting and is most commonly prescribed with -- in combination with Revlimid. We expect the earlier usage of Darzalex in combination with Revlimid will continue to increase in the future, especially in patients ineligible for transplant, which represents a majority of patients across the United States. If this trend continues, we believe this would create an even stronger rationale to treat patients with Velcade plus XPOVIO and dexamethasone in the second-line setting, if approved, as these are different mechanisms of action drugs. Even for those patients who are receiving a stem cell transplant, shown on the right side of this slide, we believe there could also be a strong rationale to use XPOVIO in the second line, if approved as well. While many of these patients are receiving Velcade plus Revlimid in the first-line as part of their induction regimen with or without Darzalex, prior to high-dose chemotherapy, they are typically only receiving Velcade for 4 to 6 cycles. Following the autologous transplant, most patients will go on to receive maintenance therapy with Revlimid for 1 to 2 years before relapse. Thus, given the use of these drugs in the first line, we think there could be a strong rationale to treat these patients with XPOVIO plus Velcade or another proteasome inhibitor in the second line, if approved, once their disease progresses. Turning now to Slide 14. Finally, as I mentioned earlier, the BOSTON study was, in part, conducted based on the encouraging earlier data we saw from the STOMP Phase Ib/II trial evaluating XPOVIO and low-dose dexamethasone in combination with one of several approved myeloma therapies in patients with relapsed or refractory myeloma. We continue to be strongly encouraged by the data from the additional arms of STOMP study, which indicated additive or synergistic activity with XPOVIO, especially when you view the data in the context of historical benchmarks. For example, in the XPOVIO plus Kyprolis plus dexamethasone or SKd arm of the trial, we have seen an overall response rate of 71%, which compares to an ORR of 23% in the benchmark study of Kyprolis and dexamethasone alone. Additionally, in the XPOVIO plus Pomalyst plus dexamethasone or SPd arm, we have seen a 56% ORR and a 12.2-month median PFS, which compares quite favorably to an ORR of 29% and a PFS of 3.6 months in a benchmark Pomalyst plus dexamethasone alone Phase III trial. While, of course, there are many limitations when trying to compare data across different clinical trials, the STOMP data shown here clearly provides strong rationale for further clinical investigation of selinexor in combination with standard approved therapies beyond just Velcade. Please turn to Slide 15, our final slide, where I will highlight our key next steps following today's exciting announcement. In the very near term, we will submit the full data from the BOSTON trial for presentation of future medical meetings so that we can share the complete details with the myeloma community. However, our top priority remains patient-focused and we plan to submit the BOSTON data as part of a supplemental New Drug Application requesting approval for XPOVIO in combination with Velcade and dexamethasone as second-line treatment for adult patients with multiple myeloma. We are hoping to have this sNDA submitted during the second quarter of 2020. Finally, depending on the FDA review time and outcome of our expected sNDA, we could potentially commercially launch XPOVIO in the second-line treatment setting in the U.S. before the end of this year. This would be a truly remarkable achievement for Karyopharm and more importantly, an important new option for the multiple myeloma patient community. With that said, let me take this opportunity before the Q&A to offer my very sincere appreciation to all of the patients, their families, their physicians, caregivers, efficacy organizations and Karyopharm employees and investors in our company who have helped us get to this monumental day. There is no way we could have gotten here without all of your dedication and persistence. And for that, we are immensely thankful. I'd like to turn the call back over to the operator so that we can answer some of your questions. Operator?

[Operator Instructions] Our first question comes from the line of Eric Joseph from JPM.

And congrats on the successful Phase III. I think that's really great. Just a couple of questions from me. On the tolerability side here in BOSTON, I'm wondering whether you can have any qualitative comments around the rate of discontinuation or dose reductions compared to what was observed in STORM or the -- on the commercial experience today. And on the point of peripheral neuropathy, where you're describing significantly lower rates compared to the twice-weekly regimen with Velcade, anything that you can comment on the weight of -- in the way of high-grade neuropathy that was observed? And as you've previously talked about the potential of incorporating peripheral neuropathy benefit in the label, how are you currently thinking about likelihood of that benefit being integrated? And what sort of -- what shape might it take?

Yes, Eric. Thanks so much for your question. This is Ian Karp. I think as a general backdrop, unfortunately, because we just announced the top line data today, and we'll be hopefully presenting this data at future medical meetings, there's not a lot of additional color or detail that we can provide in terms of the data itself beyond what we've publicly announced this morning. I don't know, Michael, is there anything that -- color that you potentially could give? Or really, do we need to wait for the data?

I think we should -- we need to wait. I think it's worth just noting historically with selinexor presentations, the discontinuation rate and the side effects are generally dose and schedule dependent. So just consider that the approved dose is 80 milligrams twice a week, which is much higher than the currently used dose in BOSTON of 100 milligrams once a week. And also, the patient population is much healthier in the BOSTON study, just given that they have 1 to 3 prior therapies versus 7 prior therapies on STORM. This -- the other point on peripheral neuropathy is that I'll just state -- and you'll see this on clinicaltrials.gov, that peripheral neuropathy was a prespecified secondary end point, which was concluded in the statistical analysis plan. So we do believe this is an important end point, and we will work to ensure that the results of this analysis are included in as many places as we can.

Our next question comes from the line of Maury Raycroft from Jefferies.

Congrats on the update today. I was also wondering on some specifics, but I'm not sure how much you can comment on it. So for the overall response rate, if you can disclose what that is. Or maybe if you can comment on the complete response in VGPR rate in the SVd arm and how that could have contributed to the PFS curve separation in hazard ratio, and then if you're seeing anything on OS trend at this point.

Yes, Maury. Again, all great questions. And I think in due time, all of that will be made clear. Again, at this point, as we're -- as we need to preserve obviously data beyond what's in the press release for future medical meetings, we just can't provide any more details beyond what was in the press release today. I don't know, Michael, if there's anything else you have?

Good.

But all great questions.

Okay. And then maybe one more follow-up. I guess based on the market research that you did, did you test a profile similar to what you're observing with the Phase III results? And do you have a sense of what proportion of patients you could end up treating with XPOVIO in the second line and third line?

I don't know. Is Perry -- I don't know if Perry's on the line. Maybe I'll start. I mean -- so yes, we certainly do market research to test various efficacy parameters. And certainly, in our market research, the profile that we see from the BOSTON study certainly, we believe, would be well received by physicians and patients. Beyond that, I don't know, Perry, if there's anything else that -- any insights that you gleaned from the line of research that you could share?

Not necessarily. I think this puts XPOVIO in the game, and that's what the important thing is. And I think the other important thing is it expands the patient population significantly. And when we do have approval, you're going to have patients that are in various points along their journey. And this puts XPOVIO in the game at any point within the relapsed/refractory multiple myeloma setting.

Our next question comes from the line of Brian Abrahams from RBC Capital Markets.

My congratulations on the data as well. I recall when we had spoken years ago, when BOSTON was being started, I think you guys had pegged the potential response -- this potential PFS at 13 to 14 months for the seli arm and 9 to 10 months for the control arm, so kudos to the team on the trial design. A few quick questions for me. I guess, first off, on overall survival, it sounds like the mortality data directionally favored seli. I'm just wondering, should we be expecting a more significant separation over time as the data mature? And is there any sort of requirement there with respect to label expansion? Or should we assume that's going to be unlikely just given the crossover design? And then I had a couple of quick follow-ups.

Yes. Thanks, Brian. I think you hit the nail on the head. First of all, it's -- these are just numerical -- these are numerical results, we haven't presented any details. It would be highly unlikely for, in this day and age, with so many options in myeloma for any study, whether it had crossover or not to show a mortality benefit. Certainly not early on, but even an extended mortality benefit, given the new drugs that are coming would be tough to prove because of that. Now this is compounded, as you said correctly, by the crossover design where patients on the Vd arm, once they get confirmed objective progression, they are permitted to cross over. So that even compounds it further. There was agreement from all -- from the FDA and the EMA on the design of this trial that the overall survival would not be expected to be superior because of the crossover, but to make sure that it was not going to be negative or inferior. And we feel very comfortable at this point that there is no imbalance at all as mentioned.

That's really helpful context. And then I know just given the nature of the trial design, there was a process by which the progression events were reviewed by a data monitoring committee. And in IRC, the FDA was informed as well. Can you maybe remind us if there has been any opportunity for initial feedback from the agency during this process over the last several weeks and what that might look like?

Yes. The way the protocol is designed, which is specified there and then followed up by the statistical analysis plan, is that all potential progression events are submitted to an independent review committee, which consists of 4 myeloma experts who are not participating in the trial. So all of the events are adjudicated by those before they are considered confirmed events. Once the number of required events was hit for this analysis, we then submitted the data. Actually, we didn't. It went to a third-party statistical review firm to -- so that we were not aware of the results. And that was compiled by that third-party firm, and then it was sent on, again confidentially, to the Data Safety Monitoring Committee, which consists of 3 myeloma doctors and a statistician. All different from the Independent Review Committee, and they basically have the protocol defined as statistical analysis plan to find right to discuss the data and decide on the future of the study and that is their purview. FDA respects these. The FDA obviously weighed in on the protocol and SAP. And we just, as part of our post-marketing requirements for the accelerated approval, we did notify the FDA. First, confidentially through the third party. And then subsequently, when we were unblinded that this was our process, and they have accepted our process and they've allowed us to move forward. So they are not an active participant per se, but they had to be notified as part of the post-marketing requirement.

That's really helpful. One last quick one for me. Any views on the potential pricing of the agent and how that might evolve as it expands into earlier line settings?

Yes. I think at this point, it's a bit premature to think about pricing right now. Certainly, it's something that we're always taking into consideration. We obviously want our drugs to have as broad access to the patients that need them. So I think at this point, it's still a bit premature to comment on any potential changes or not, that there would be in pricing strategies.

Our question comes from the line of Jonathan Chang from SVB Leerink.

Congrats on the results. First question, from a company strategy perspective, now that BOSTON is positive, in terms of plans you had that were pending the BOSTON outcome, how are you thinking about next steps of the company and in terms of prioritizing additional XPOVIO development opportunities?

Well, we'll invite you all to a long seminar on that. Great question. I think as you alluded to, Jonathan, there's a lot we can do with this drug, and there's a lot that we are doing with it. As you know, we have a pending sNDA in front of the FDA for relapsed/refractory diffuse large B-cell lymphoma. We have upcoming Phase III data in our randomized study in key differentiated liposarcoma, and we have an ongoing study in the first-line maintenance setting, this is a Phase III study, first-line maintenance in patients with uterine cancer who have received platinum taxol induction therapy and then are in a response, and then we have a maintenance regimen versus placebo, that SIENDO study is ongoing with data expected next year. So there's a lot going on already. At our JPMorgan conference recently, we outlined some of the key next studies that we'll be doing. Some of those are featured prominently, and those would be the randomized study in diffuse large B-cell lymphoma with XPOVIO in combination with chemotherapy versus the chemotherapy alone. In second-line DLBCL, we have additional studies now initiating in solid tumors. In lung cancer with docetaxel and in colon cancer with a PD-1 antagonist. And we have additional studies with eltanexor, our second-generation compound, moving on from myelodysplastic syndrome. And finally, I'll just remind that we have ongoing studies in glioblastoma multiforme where the drug has shown clear single-agent activity with about a 10% confirmed response rate. And we'll be looking at XPOVIO in combination with front-line therapies as well as in the relapsed setting in GBM. So that's just a small smattering of the kinds of things we'll be moving ahead aggressively with. As I mentioned, there's a lot going on here and we're trying to hit on all of these cylinders. So that's what you can expect going forward with more indications to come at the end of this year and later next.

Got it. And second and final question, are you willing to comment on how the BOSTON study population breaks out by line of therapy?

We can't give additional details right now, but I think it's -- given the 9.5-month PFS, I think it's fair to say it broke out like a lot of these kinds of studies that you see in this line. So we'll be able to give a lot more color on all of this and all the details at an upcoming medical meeting.

[Operator Instructions] Our next question comes from the line of Mike Ulz from Baird.

Congratulations on the data as well. Just had a question in terms of the strategy in Europe. So you mentioned filing in Europe here potentially adding in the BOSTON data. Just curious if there could be a slight change in time lines or if you have been in discussions with the EMA already here. And then secondly, just more broadly in terms of your strategy in Europe, now that you have positive BOSTON data, has that changed any at all?

Yes, thanks. I think on the first question, we shared the results with the EMA as we did with the FDA prior to this call, and we'll be engaging with them to figure out the most optimal path forward for XPOVIO. Can you just hit the second question again, please?

Yes. Just your strategy in Europe, you kind of mapped out previously a couple of different scenarios of doing it alone or partnering it, things like that. And I'm just wondering, is that still the case or things changing now that you have this data in hand?

Yes, thanks. This is Chris. So in general, I think the way that we're thinking about Europe is still relatively consistent with the way that we've talked about it before. We've talked about there sort of being 2 ends of the spectrum, right, a full out-licensed partnership and then the go it alone and then perhaps something in the middle where there's more of a hybrid where you leverage your existing infrastructure that you have in Europe. So those are all on the table, and we're actively exploring all of those options, and we will certainly report back at the right time.

Our next question comes from the line of Arlinda Lee from Canaccord.

Congratulations on the great data set. I am curious about the market research that you guys have done showing that you guys are moving into third line. Can you talk more about when you thought that, that might have happened? And what might be driving that? And as well, just trying to figure out if you think that you could move earlier, sooner than, I guess, an approval?

Yes, let me take that one. So to be clear, we do believe that, that is -- that utilization is consistent with our current label. As you recall, most patients in the myeloma treatment paradigm will get 2 to 3 drugs in each line of therapy. So there certainly is a small percentage of patients by the time that they get to the third line, whoever already received the 5 major drugs or those classes of drugs that are in our approved label. So we believe that, that -- I think it was 3% of share estimate in that market research in the third line. We still believe that those are, in fact, patients who have already received a 5 -- 2 proteasome inhibitors, 2 IMiDs and an anti-CD38 antibody. In terms of moving, I guess, more fundamentally into the second and third lines, clearly, that will be dependent on a hopeful approval based on this BOSTON data.

At this time, I am showing no further questions. I would like to turn the call back over to CEO, Michael Kauffman, for closing remarks.

Well, thanks again, everybody, and thanks for spending time with us on this very exciting day. We will talk to you soon, and have a great day. Bye-bye.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.