Karyopharm Therapeutics Inc. Q3 FY2020 Earnings Call

Good afternoon. My name is Kate, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics Third Quarter 2020 Financial Results Conference Call. Please be advised that the call is being recorded at the company's request.

Thank you, Kate, and thank you all for joining us on today's conference call to discuss Karyopharm's Third Quarter 2020 Financial Results and Business Update. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, Chief Executive Officer; Dr. Sharon Shacham, President and Chief Scientific Officer; Mr. Mike Mason, Chief Financial Officer; Mr. John Demaree, Chief Commercial Officer; Mr. Christopher Primiano, Chief Business Officer and General Counsel; and Dr. Jatin Shah, Chief Medical Officer. On the call today, Michael and John 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 third quarter 2020 financial results. We will conclude with the Q&A portion of our call. Earlier this afternoon, we issued a press release detailing Karyopharm's results for the third quarter of 2020. This release, along with the slide presentation that we plan to 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 provision under the Private Securities Litigation Reform Act of 1995. These include statements about future expectations, clinical developments and regulatory matters and timelines, 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 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 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 any references we make to clinical trial data during today's discussion refer to interim unaudited site data unless otherwise specified.

Thank you, Ian, and good afternoon, everyone. I'm pleased to report that Karyopharm has continued to make tremendous progress so far in 2020 with the achievement of numerous commercial pipeline and operational accomplishments, positioning us well for what we believe to be continued and sustained future growth. As we get closer to the end of 2020 and hopefully closer to an end of the COVID-19 pandemic, we are already preparing for numerous significant opportunities for our company and the patients we serve in 2021 and beyond. Before I begin, I'd like to take a moment to briefly put into some perspective a foundational and unique approach that we are taking towards innovating cancer drug therapies. On Slide 4, we've highlighted 5 core pillars of cancer drug therapy, which are all foundational and used across tumor types often in combination to give each patient the best chance at clinical improvement. XPOVIO is the first approved anti-cancer drug whose primary activity is the activation of tumor suppressor proteins. There are about 20 of these proteins, including p53, BRCA1 and 2, Rb in the inhibitor of NF-kB, which are critical parts of each cell's natural defense mechanism to prevent the generation of cancer cells and to direct the cell which has become cancerous to commit suicide. This broad anticancer mechanism is potentially relevant to any malignancy. Our goal is to continue to demonstrate the impact that XPOVIO can have in combination with drugs from all of the other pillars in order to maximize the impact that XPOVIO could have on improving outcomes for a large variety of cancers. Moving to Slide 5, I'll focus on our near-term and medium-term goals. First and foremost, we remain committed to increasing the positive impact we are having in the lives of patients battling cancer, and this is a core principle that guides everything we do at Karyopharm. And as you may have seen in the press release we issued this afternoon, we have just achieved another very important milestone with our announcement that the top line results from the Phase III SEAL study met its primary endpoint with a significant increase in progression-free survival in patients with unresectable dedifferentiated liposarcoma. Additionally, over the next 1 to 2 years, there are a number of key goals that will be critical for us, including, first, securing the U.S. approval for XPOVIO in second-line multiple myeloma, which we believe will help significantly drive total XPOVIO sales higher; second, receiving the initial approval for XPOVIO in Europe for patients with relapsed/refractory multiple myeloma; third, launching our first solid tumor indication in the U.S. based on the data just announced; and fourth, continuing to generate supportive clinical data for our growing clinical portfolio, which includes XPOVIO, eltanexor, and KPT-9274. Looking a bit further out to the next 3 to 5 years, we anticipate that XPOVIO could be approved in multiple oncology indications across the globe with substantial revenue contributions from ex U.S. royalties and sales milestones. This next chapter is also anticipated to bring continued expansion of our pipeline across multiple assets and, finally, the broad establishment of XPO1 inhibition as a core therapeutic approach in cancer treatment. Please now turn to Slide 6, where I'll highlight the exciting news we announced earlier this afternoon regarding our randomized Phase III SEAL study. As a reminder, SEAL evaluated the efficacy and safety of single-agent XPOVIO in patients with advanced, unresectable dedifferentiated liposarcoma following 2 or more prior therapies. Unfortunately, there is no standard of care for patients with advanced disease, and we are thrilled to announce that the study met its primary endpoint with a significant increase in progression-free survival and a hazard ratio of 0.7 with a p-value of 0.023. We believe that these results not only represent a significant advance in the treatment of patients with dedifferentiated liposarcoma, but we believe these data further support XPOVIO's substantial potential across multiple solid tumors, representing a major advance for the development and commercial potential of XPOVIO in oncology more generally. This is also consistent with other earlier-stage positive results from ongoing XPOVIO studies in diseases such as endometrial cancer, GBM, melanoma, lung cancer, and others. Liposarcoma also represents an important entry point for XPOVIO into the solid tumor treatment landscape where 9 of the top 10 most common and fatal forms of cancer are solid tumors. We look forward to presenting the detailed results of SEAL at the upcoming Connective Tissue Oncology Society, or CTOS, annual meeting. We plan to submit a new drug application, NDA, in the first quarter of 2021, requesting the FDA approval of XPOVIO to treat the patient population studied in the SEAL Phase III trial. Please now turn to Slide 7. Our clinical strategy for XPOVIO continues to be innovating with a purpose. Specifically, our approach has been to demonstrate meaningful activity in difficult-to-treat patient populations and then to expand dramatically into earlier lines of treatment and additional tumor types, particularly in combination with other anticancer drugs. This strategy has been evident in our approach in both myeloma and DLBCL where we began with our successful STORM and SADAL studies and has led to subsequent development in earlier lines in combination settings. Similarly, now that we have seen positive Phase III SEAL data, we plan to follow the same path and continue with the expansion of our clinical development approach in a number of important and much larger solid tumor indications, including endometrial cancer with the SIENDO study, lung cancer, GBM, melanoma, and others, which have been selected based on encouraging earlier clinical data and commercial potential. Turning to Slide 8, I'll focus on other recent highlights. During the third quarter, we achieved record quarterly XPOVIO net sales of $21.3 million, the strongest quarter since our July 2019 launch in penta-refractory multiple myeloma. These results reflect a 15% increase compared to the second quarter of this year. These strong results were driven by demand for XPOVIO in both new multiple myeloma patient starts and initial prescriptions in patients with relapsed or refractory diffuse large B-cell lymphoma. For our pipeline progress, I'll remind you that the FDA recently accepted our supplemental new drug application seeking approval for XPOVIO for the treatment of myeloma after at least one prior line of therapy and has signed a PDUFA action date of March 19, 2021. In addition to a decision by the FDA, we are awaiting a decision in Europe from the EMA on our MAA, seeking approval of XPOVIO for the STORM population. In addition to the SEAL study, we also made important progress with our development programs in other solid tumors. This includes several presentations of data at ESMO in September, which showed promising results for XPOVIO in combination with Keytruda for the treatment of melanoma and XPOVIO in combination with carboplatin and paclitaxel for the treatment of advanced or metastatic solid tumors. Finally, on the financial front, we ended the quarter with a strong cash position of approximately $304 million that we expect will be sufficient to fund our plant operations into the second half of 2022. I'll now ask John Demaree, our Chief Commercial Officer, to provide some additional details on XPOVIO sales performance during the third quarter. John?

Thank you, Michael, and good afternoon, everyone. As Michael noted earlier, I am proud of the commercial momentum seen during the quarter, a direct result of the dedicated Karyopharm commercial organization that continues to drive our educational initiatives forward, both virtually and in person, where appropriate, in support of our greater multiple myeloma and diffuse large B-cell lymphoma communities of patients, families, and caregivers. On Slide 9, we outlined results for market research that highlight the key features of XPOVIO treatment that are resonating most with healthcare providers in helping to drive the increased usage of XPOVIO that we've now seen over the past few quarters. Specifically cited are XPOVIO's rapid response data with some responses reported as early as 1 week as well as the positive STORM data that showed a strong objective response rate in very difficult-to-treat patient populations, which included 100% of patients being refractory to daratumumab and 57% having high-risk cytogenetics. Next, physicians noted that XPOVIO is the first and only FDA-approved oral XPO1 inhibitor that selectively binds to and blocks XPO1 whose over-expression in cancer cells is increasingly being recognized as a core driver of tumor growth. And finally, there is increasing recognition and experience that XPOVIO's side effect profile can typically be manageable and reversible with dose modifications in prophylactic treatments. Slide 10 shows the positive and increasing quarterly sales and prescription trends for XPOVIO so far in 2020. The third quarter saw a 15% increase in both net sales and patient demand compared to the second quarter. Importantly, we saw a robust increase in new myeloma patient starts in the third quarter compared to the second quarter. The majority of prescriptions for the quarter continue to come from multiple myeloma patients, but we did see important initial contributions from DLBCL patients as we continue to introduce XPOVIO to this segment of the market and build momentum in this new indication. Slide 11 highlights the increase in new account growth for the third quarter, which jumped to 202 new accounts prescribing XPOVIO, bringing the total to 543 new accounts for the year. New accounts secured this quarter reflect multiple myeloma and DLBCL treating physicians. These results are particularly promising as physician education in many geographies continues to be conducted via virtual and web-based tools due to ongoing restrictions related to the COVID-19 pandemic. The graph on Slide 12 shows the prescription refill rate for XPOVIO over time for both the first and second refill for those patients eligible for these refills. These numbers remain stable for the third quarter but are significantly higher as compared to our initial launch period. For instance, in September of 2019, which marked the end of the first quarter that XPOVIO became commercially available, roughly 42% of patients were going on to get a second prescription. One year later, that number stands at 60%, a substantial increase. These promising and increasing refill rates, coupled with an average of 2.9 treatment cycles per patient as of the end of September, further reinforced the positive feedback we've received from patients and physicians regarding their experience and usage of XPOVIO. Importantly, the patient discontinuation rate due to side effects remains relatively low at 13%, which we believe is a testament to more and more physicians gaining comfort in helping their patients manage the side effect profile of XPOVIO with proper prophylactic therapies and dose modifications. The third quarter of 2020 represented the first full quarter of our launch in relapsed/refractory DLBCL following approval in late June. On Slide 13, we're pleased to share preliminary launch metrics for this period, which showed 2/3 of prescriptions have come from community-based physicians. Early retail trends have been strong as well at 60%, which matches what we've seen in the multiple myeloma space, and we were able to secure Category 2A NCCN compendia listing within 2 weeks of approval. These efforts have translated into positive initial feedback from treating physicians and their patients. Based on our market research, target physicians are most attracted to XPOVIO's response rate as a single agent, oral option, and the ability to treat DLBCL patients in a completely new way. Additionally, we've seen positive payer dynamics with no on-label patient denials seen to date. And finally, the feedback we are hearing regarding XPOVIO's side effect profile has also been positive with most physicians reporting the 60-milligram twice-weekly dose, the approved dose, being manageable for patients. We will continue to fully leverage the newly approved indication in DLBCL to access our key stakeholders, educate on this new indication and also generate increasing excitement in multiple myeloma to help more patients impacted by these diseases.

Now I'd like to turn the call back over to Michael to discuss our regulatory updates and clinical development priorities. Michael? Thank you, John. On Slide 14, I'll provide a brief update on our key upcoming regulatory activities. The positive results from the BOSTON study served as the basis for our sNDA submitted to the FDA for the treatment of patients with multiple myeloma after at least one prior line of therapy. Our sNDA was accepted for filing in July with the decision expected by March 19, 2021. In Europe, we've submitted the final additional remonitoring data from the STORM study requested by the EMA in September of 2019. And in October 2020, Karyopharm received a further updated list of outstanding issues from the CHMP, summarizing the remaining topics for Karyopharm to address and indicating the CHMP intends to consult its scientific advisory group for additional advice. We continue to expect the decision from CHMP by the end of this year. In addition, continuing upon and following receipt of CHMP's opinion, we expect to submit an MAA based on the data from the BOSTON study before the end of 2020. For DLBCL, we're still in the process of evaluating the optimal approach and timing of future regulatory submissions, and we look forward to providing you with an update in the future. Please now turn to Slide 15. The potential expansion of our XPOVIO label based on the promising BOSTON data results represent an important turning point in the multiple myeloma treatment paradigm. XPOVIO's current penta-refractory multi-myeloma indication is largely applicable to the approximately 6,000 patients in the United States who are treated in the fourth and later lines of therapy annually. If approved, an expanded label based on the population studied in the BOSTON trial would expand XPOVIO's potential impact to over 30,000 patients annually in the U.S. treated in the second and third-line settings. This slide highlights some of the key differences between the STORM and BOSTON population study and data generated from these trials. As you can see, the patient studies in the BOSTON trial have been previously treated with far fewer therapies than the patients in STORM and had disease that was far less refractory to treatment, i.e., a median of 8 prior therapies in STORM as compared to 2 in the BOSTON study. Subsequently, the response rate in median PFS in the BOSTON study was substantially higher than in the STORM study. This was also driven by the mechanistic approach of combining 2 drugs with different and additive or synergistic mechanisms of action in the BOSTON study as XPOVIO, an XPO1 inhibitor was given in combination with once-weekly Velcade, a proteasome inhibitor, along with standard low-dose dexamethasone. Importantly, the mean duration of treatment was 10 months in the BOSTON study as compared to 3 months in the STORM study. This comparison of studies is key to why we believe XPOVIO has just begun to make an impact on the treatment paradigm in multiple myeloma. We believe the greatest utility for XPOVIO in the future will be as combination therapy with other potent anti-myeloma drugs, such as Velcade and taken only once per week instead of the currently approved dose of twice per week. And finally, I'd be remiss if I didn't mention some updates for a number of other exciting pipeline opportunities we're pursuing for selinexor, which can be seen on Slide 16. In the hematologic malignancy space, we expect to dose our first patient by the end of the year in our confirmatory Phase III DLBCL trial, which will study selinexor in combination with rituximab and a chemotherapy regimen of gemcitabine, dexamethasone, and platinum-based therapy. We have also recently initiated 2 new trials in myelofibrosis where we have been encouraged by some smaller investigator-initiated studies, and we expect to begin enrollment in these new studies in 2021. And as I mentioned earlier, we have a number of important ongoing studies in the solid tumor setting, both as a single agent and in combination, which followed nicely from the positive SEAL results we announced today. With that, I'll 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 18. Net product revenue for the third quarter of 2020 was $21.3 million. Third quarter sales were driven by patient demand from academic and community-based physicians with channel inventory sales growing in line with actual prescription growth. The estimated gross-to-net discount for XPOVIO in the third quarter was approximately 16%. We continue to expect the gross-to-net discount to fall between 15% and 20% through the remainder of the year. Research and development expense for the third quarter of 2020 was $37 million compared to $26.3 million for the third quarter of 2019. The increase in R&D expenses compared to the third quarter of 2019 was mainly attributable to COVID-19 trial activity and continued activity in our other ongoing clinical trials. SG&A expense for the third quarter of 2020 was $30.9 million compared to $25.3 million for the third quarter of 2019. The increase in SG&A expenses compared to the prior year was primarily due to activities to support the U.S. commercialization of XPOVIO, including expenses related to the launch of XPOVIO as a treatment for patients with relapsed or refractory DLBCL. As noted on Slide 19, cash, cash equivalents, and restricted cash investments as of September totaled $304.2 million compared to $265.8 million as of December 31, 2019. We currently project XPOVIO sales to grow modestly through the remainder of 2020 based on expected catalysts with more significant growth expected following the potential expanded approval of XPOVIO based on the results from the BOSTON study. Based on our current operating plans, we expect our non-GAAP R&D and SG&A expenses for the full year 2020 to be in the previously projected range of $240 million to $260 million. In addition, we currently expect that our existing cash, cash equivalents, and investments and the revenue we expect to generate from XPOVIO product sales will be sufficient to fund our planned operations in the second half of 2022. 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 clinical and regulatory milestones that we expect for the remainder of 2020, as shown on Slide 20. As you can see, we have achieved many key milestones throughout the year but still have important goals to accomplish by the end of this year. First, we expect a decision from the EMA on the STORM MAA. Next, we plan to submit the full BOSTON data to the EMA before the end of the year, continuing upon and following receipt of CHMP's decision on the STORM MAA. And finally, we anticipate initiating our confirmatory Phase III study of XPOVIO and DLBCL in support of our recent accelerated approval. And of course, we'll continue to support the FDA through the review of our sNDA based on the BOSTON study where we expect a decision from the FDA on or before the PDUFA date of March 19, 2021. We appreciate your ongoing support, and look forward to keeping you updated on our future progress.

Congrats on the positive SEAL readout. First question, can you talk about the dedifferentiated liposarcoma treatment landscape? How do you see this commercial opportunity? And what, if any, read-through this has on your broader thinking regarding the solid tumor opportunity for XPOVIO?

Sure. Let me provide a brief overview. Unfortunately, the treatment options for dedifferentiated liposarcoma mainly consist of parenteral chemotherapy cytotoxic agents. Nearly all patients receive anthracyclines like Adriamycin combined with gemcitabine or other cytotoxic agents, and most will also be treated with eribulin and/or trabectedin during their treatment. There are no other therapies with clear documented effectiveness that are commonly used. XPOVIO could potentially be the first oral therapy approved for this condition. Additionally, this is the largest study on liposarcoma ever conducted, and we believe it is the most focused study dedicated to liposarcoma. We think that our drug can become a significant option for patients after chemotherapy, offering a better tolerated oral alternative for those who have received extensive pre-treatment.

Got it. Just one follow-up question then on a different topic. Can you provide additional color on the outstanding questions from the CHMP that you received in October, I think, you said?

Yes, I'll turn that over to Dr. Shacham to comment.

I'm sorry, Michael, can you start and I will follow up?

Sure. I understand the question is about providing more details on the inquiries from the EMA that are still pending. As we have mentioned before, the EMA has asked for additional information concerning some of the laboratory analyses conducted on patients involved in the study, particularly those who are responding to treatment, and we have submitted that information to them. Furthermore, to address the EMA's request for a continued justification of the benefit-risk ratio, we have also provided the BOSTON data to support the STORM MAA application.

This is Mitchell on for Peter. Congratulations on the positive data. So the first question I have is for SEAL. The hazard rate came in like 0.7, or just wondering did the FDA say what would qualify as meaningful. And how much do you beat those expectations by?

The FDA does not explicitly state that. Both the FDA and EMA have offered guidance, particularly scientific advice from EMA and post-meeting insights from the FDA, indicating that this trial could possibly be used as the basis for an approval. Generally, this means meeting the statistical threshold of 0.05, which we achieved, and ensuring that the trial is well-conducted and internally consistent, which we also believe it is. We believe we have met the necessary benchmarks. I should also note that the hazard ratio in the Phase II part of this study was nearly the same as in Phase III. The FDA and EMA were aware of this, and they approached this Phase III trial anticipating a hazard ratio of about 0.7, which is what it was designed to achieve.

Great. And then if you could just comment on discontinuation rates for the SEAL study. Is that consistent with the 13% you've seen in the real world for myeloma? And then, what additional data should we expect at CTOS beyond PFS?

I can't provide the exact discontinuation rate, but I can mention that these patients are not as heavily pretreated as those with last-line myeloma. They also have significantly fewer systemic comorbidities compared to late-stage myeloma patients. Therefore, we would expect the dropout rate to be lower. Additionally, the dose used in this study was lower. The dose in the SEAL study is more comparable to the DLBCL SADAL study. A comprehensive presentation will be provided at the CTOS by our lead investigator, which should include a complete data set.

I'll offer my congrats on the liposarcoma data as well. I'll ask a question about myeloma. So for XPOVIO in 3Q and also DLBCL too, can you talk about the COVID impact? And for new myeloma patients, what line of treatment are you seeing with some of the new patients? And if you can break out combo preferences as well. And then you mentioned the average treatment cycles per patient at 2.9. Just wondering if you expect that to continue to increase in the current market opportunity in the last-line setting. Or do you see it leveling off around 2.9? And then when you get into the expansion with the earlier-line patients, that number could potentially go up.

Wow, Maury, that was quite detailed. So I'll ask John Demaree, our Chief Commercial Officer, to start addressing that, and we'll keep it brief. Go ahead, John.

If I miss any of those, keep me honest. But let me answer the one about BOSTON first. And are we seeing XPOVIO use with Velcade in earlier lines of therapy. Currently, the majority of use for XPOVIO is in fourth-line plus, as indicated. We obviously do expect that to move earlier once the BOSTON indication in combination with Velcade is approved. We do know from our market research that many of the academic and community-based physicians are prescribing XPOVIO in combination with other drugs. So it's not just XPOVIO plus dexamethasone, but they're using it primarily in that fourth-line-plus setting now currently where it's indicating. Again, we do expect significant acceleration in earlier lines of usage once we get the new indication for patients with approval, one prior line of therapy. In terms of second question around the impact of the pandemic. We do think the pandemic does still continue to have multiple effects. In-person visits by our sales force, nurse liaisons, and payer teams to our key stakeholders continue to be impacted. Our data and research suggests about 15% to 20% of HCPs can be seen via in-person visits. We do continue to believe it's harder to appropriately educate changed behavior in a virtual environment as compared to maintaining prescribing habits like the goal of more established brands. We have done and are doing a number of initiatives to offset the impact of being virtual, including increasing peer-to-peer education, increasing other nonpersonal promotion and digital content, training our field teams on how to be more effective in the virtual environment and, finally, targeting some large physician networks and their EMR systems to better identify patients in the penta-refractory setting. So it's 2 of the questions. What were the other questions?

One of the questions was about the average duration of treatment with a number of cycles. I can say that we are at 2.9 through the end of September, which we are excited about so soon after our launch. As we approach the launch in the BOSTON population, we hope that number will increase significantly. The average duration of treatment in BOSTON was 10 months, compared to 3 months in STORM. Therefore, it may increase further, but realistically, we are nearing BOSTON approval. Patients starting treatment earlier with XPOVIO should ideally stay on the medication longer.

Congrats on the SEAL data. I'm curious how frequently physicians are looking to use XPOVIO in earlier-line myeloma post the BOSTON presentation, but maybe can't do to access. And the degree to which inclusion in NCCN guidelines might open up earlier-line access even prior to label expansion. Any update on timing there or timing for the BOSTON publication?

We expect the Boston publication to be released soon, ideally before the year ends, although the exact timing is uncertain. It will be featured in a reputable peer-reviewed journal, which should help support an addition to the NCCN guidelines. However, we cannot predict how quickly that addition will happen. Our belief is that there are several locations where NCCN guidelines can be used to secure insurance coverage, which is currently a significant barrier to earlier-line adoption. We think that the combination of selinexor, XPOVIO, along with Velcade dex once a week is the most straightforward regimen for relapsed/refractory myeloma patients who have undergone one prior therapy, and thus, could be very advantageous for those patients. We are hopeful that we can improve access once the NCCN guidelines are published, and eventually through FDA approval.

Got it. And then just as a follow-up, you mentioned some of the continued multiple effects that the pandemic is having. Looking forward, I guess, in the near to medium term, I'm curious about your expectations for the second or even third wave of COVID that we're seeing may impact near-term use and uptake. I guess I'm wondering if you'd expect continued challenges to physician and patient engagement. Or conversely, if you might be able to take advantage of some of the benefits of oral administration and perhaps fewer facilities available for the administration of CAR-T and DLBCL.

So I think the answer to your question is, yes, there are opportunities and there are challenges in the current COVID situation. Obviously, for many patients, an oral therapy is preferred, particularly with fewer visits during the time of peak pandemic impact. I think it is also, as you mentioned, more difficult to engage physicians in person. We have tried to offset that and are continuing to do more and more to offset in terms of some of the digital nonpersonal promotion initiatives that I just mentioned earlier.

First, in relation to the SEAL and the liposarcoma opportunity, I'm curious to get a sense of whether you see an opportunity to advance selinexor earlier up in the treatment paradigm for liposarcoma, either as an alternative to chemo or as maintenance and whether that's strategically of interest. And then I have a follow-up on XPOVIO.

Liposarcoma, particularly the dedifferentiated type, affects about 2,000 patients annually. It's a significant disease that requires effective treatment options. There has been considerable interest from various groups regarding the SEAL data, and we plan to pursue more studies in earlier treatment lines, likely in collaboration with external organizations. This approach allows us to allocate our internal resources to larger tumor types where we are seeing positive results. Our ongoing SIENDO study is a Phase III randomized blinded trial comparing once-weekly selinexor to a matching placebo in endometrial cancer patients who have completed frontline chemotherapy and achieved at least a partial response, which is about 80% of these individuals. Currently, there are no maintenance therapies available for these patients, and all are expected to relapse. Therefore, we are conducting the SIENDO study to explore maintenance treatment post-first-line chemotherapy. This is a significant area of focus for us, and we anticipate having data before the end of next year. This population represents a considerable unmet medical need and will be a primary focus for us in solid tumors. Additionally, we have shared some early data at ESMO and other venues regarding the clear single-agent activity in GBM, which we plan to continue exploring.

Got it. That's helpful. I have a question about XPOVIO's commercial performance. It seems like you have good visibility on the demand between myeloma and DLBCL. Could you clarify how much demand is actually coming from DLBCL? I'm also trying to reconcile the conservative growth expectations for the rest of the year. How much growth opportunity do you see in third-line DLBCL? Are you experiencing competition from other agents in that community? What does the near-term growth opportunity look like for third-line DLBCL?

So to address the first question, for competitive reasons, we don't break out sales separately between multiple myeloma and DLBCL, but we can tell you is that the majority of prescriptions in the third quarter came from multiple myeloma. The DLBCL patients were an important contributor that we believe will continue to grow over time.

Yes. In terms of the competitive landscape and growth moving forward, we are pleased to report a 15% growth quarter-over-quarter this quarter. The myeloma metrics continue to look favorable, and we are beginning to see contributions from DLBCL, although we are still navigating the challenges posed by the ongoing COVID pandemic. Additionally, there are new competitive entrants, particularly in the DLBCL space. However, we anticipate several catalysts, including the publication of BOSTON data, updates to NCCN guidelines, and the DLBCL launch gaining momentum. All these factors present both opportunities and challenges. Our focus remains on the BOSTON submission and collaboration with the FDA and our efforts in Europe, as we recognize that the primary driver of growth in the near term will depend on BOSTON approval and our ability to sell into second-line multiple myeloma. These are the key elements we believe will drive growth in the coming months, and we look forward to staying updated on all developments.

Given that prescription demand increased from 12% to 15% from second quarter to third quarter, sales growth ultimately stayed pretty similar between the 2 quarters, how is the cadence of those prescriptions relative to sales over the quarter? And what dynamics, I guess, are at play causing the conversions?

Yes. I think if we look at the timing on a monthly basis, we typically don’t disclose that information monthly. Regarding where the prescriptions are originating, in the case of DLBCL, they mainly come from community-based physicians, which differs from the initial uptake we observed in multiple myeloma, where prescriptions were sourced from both large academic centers and community-based locations. I believe that addresses your question. If I missed anything, John, feel free to add.

Well, I think you kind of look at that, I mean, at a high level. Ultimately, as we've talked about before, the last few quarters, the sales trends reflect a steady improvement in utilization as we continue to build our presence across multiple oncology indications. There is a lot of growth ahead of us, and we see that as we get BOSTON approved and as we see NCCN guidelines updated. So, overall, our focus is around making our message as consistent as possible during the pandemic and working with the physicians' office on how they stay that can be done. We believe that will lead to a greater proportion of patients actually receiving treatment. Once we see the publication, that publication is what leads to the NCCN guidance. That guidance is what will allow the insurance companies to give better access. And that really will be a driver of adoption. That's taking into account everything we believe is happening with the competitive landscape going forward, including our addition of expansion of access based on BOSTON with Velcade. We believe this combination is actually a really attractive, well-tolerated regimen that should ultimately translate into an elevated patient mean time on treatment. So to summarize, what we believe we're doing is steadily building the momentum in our name, especially in myeloma, and we believe we can push that into this new indication as we broaden out the use of XPOVIO.

Congratulations on the sarcoma data. Will you be able to submit that to the EU, or will a different trial be necessary? How should we consider the patients you can initially treat with that data as a label?

This trial received positive guidance from the EU scientific advice group. It was discussed and approved with them, and we believe it could support approval in the EU. The proposed indication would target patients with dedifferentiated liposarcoma who have already undergone at least two prior systemic therapies.

What number of patients are we considering since there are around 2,000 patients?

That's the way yes.

Okay. And then on the endometrial, is that the next data after sarcoma? Or what should we think about as the next solid tumor data?

In terms of randomized Phase III data, I can say with a bit of humor, it's challenging to conduct many of these large trials, especially for a company of our size. However, that is the next one, and we expect it to be available by the end of next year. Throughout the year, we will have updates regarding other combinations, including in both hematologic and solid tumors, as well as potentially new data in myelofibrosis and other areas within the next year.

Got you. And then just on multiple myeloma DLBCL. Do you get a sense of the duration of treatment in multiple myeloma or DLBCL?

Across our specialty pharmacy network, the average duration per patient is about 3 months. However, for DLBCL, since it just started, those patients may not reach that average yet. You'll have some patients remaining on treatment for 10 or 12 months, and others who may not respond after 1 or 2 months. Currently, the average is around 3 months, and it has been increasing. When asked how much higher it could go, we believe it will likely increase further, especially if we obtain the BOSTON indication, as patients in the second and third line tend to remain on the drug for longer durations.

Great. And just a final question, just around guideline changes. When do you think that happens?

I assume you mean for myeloma. The procedure requires a publication, which we believe will be released before the end of the year. This publication will appear in a peer-reviewed journal and will be submitted to the NCCN committee, which will decide when to include the regimen in their recommendations.

Could that be year-end? Or do you think that kind of is more of a 2020?

Naturally. It really depends on the publication timing and the timing of the NCCN committee. In addition to BOSTON publication, we will be submitting the other single-arm study results, particularly with daratumumab, Kyprolis, and Pomalyst, and those could potentially follow. But all of this is dependent upon, of course, publication and NCCN adjudication. Well, thank you, everybody. I appreciate your following with us, and we look forward to talking to you again in the near future as fast.

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