Karyopharm Therapeutics Inc.KPTINASDAQ
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Operator: Good morning. My name is Ludy, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics Third Quarter 2025 Financial 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 Brendan Strong, Senior Vice President, Investor Relations and Corporate Communications. Please go ahead.
Brendan Strong: Good morning, and thank you all for joining us on today's conference call to discuss Karyopharm's third quarter 2025 financial results and recent company progress. We issued a press release this morning detailing our financial results for the third quarter of 2025. This release, along with a slide presentation that we will reference during our call today, is available on our website. For today's call, as seen on Slide 2, I'm joined by Richard, Reshma, Sohanya, and Lori, who will provide an update on our results for the third quarter of 2025 and discuss recent clinical developments. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on Slide 3. 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 Form 10-Q or 10-K 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 later date. I'll now turn the call over to Richard. Please turn to Slide 4.
Richard Paulson: Thank you, Brendan, and thank you all for joining us today for Karyopharm's Q3 2025 Earnings Call. As we turn to Slide 5, I'm pleased to share that this has been a very productive quarter for Karyopharm, one defined by meaningful clinical progress and strengthened financial flexibility that together set the stage for our next chapter of growth. In Q3, we completed enrollment in our Phase III SENTRY trial in frontline myelofibrosis, marking a pivotal moment for Karyopharm. SENTRY represents a significant opportunity to redefine the standard of care for patients with myelofibrosis through the combination of selinexor plus ruxolitinib as a potential all-oral treatment option. With top-line results expected in March, we believe this trial could establish a new paradigm for how myelofibrosis is treated and further validate the relevance of XPO1 inhibition in hematological malignancies. The power of XPO1 inhibition is multidimensional. It simultaneously targets multiple pathways that enable malignant cell growth and proliferation. Targeting these relevant pathways concurrently overcomes the limitations of targeted therapies, such as ruxolitinib, a JAK inhibitor that mostly delivers symptomatic benefits that many consider palliative. This unique and potentially foundational mechanism could establish XPO1 inhibition as a key mechanism in myelofibrosis with further potential across the broader MPN landscape. In October, we made significant progress in strengthening our financial foundation. Through comprehensive refinancing and capital restructuring, we secured approximately $100 million of financial flexibility and additional capital, extending our cash runway into the second quarter of 2026. Turning to our financial performance. Our profitable multi myeloma commercial organization provides a solid foundation on which to build. In the third quarter, we delivered total revenue of $44 million, an increase of 13% year-over-year, and U.S. net product revenue grew 8.5%, reaching $32 million. This growth reflects the continued strength of XPOVIO in multiple myeloma and the disciplined execution of our commercial and operational teams. Importantly, we delivered this level of growth while continuing to reduce expenses. As we look ahead, our recent financing enables us to continue with focus and conviction around 3 core priorities. First, advancing our late-stage clinical programs, SENTRY and EC-042, which we believe have the potential to be truly transformative for patients and the company. Second, driving continued growth across our XPOVIO franchise; and third, maintaining financial discipline as we execute on our strategy and position Karyopharm for sustained success. Taken together, these underscore the momentum and transformation underway at Karyopharm. We are executing with clarity and purpose as we advance our mission to pioneer innovative cancer therapies that can meaningfully improve the lives of patients and deliver long-term value for all our stakeholders. As our next major milestone is the top-line myelofibrosis data from SENTRY, we will focus much of today's discussion on the science supporting this program and the significant commercial opportunity ahead. Now I'd like to turn the call over to Reshma to review our science.
Reshma Rangwala: Thank you, Richard. There is a substantial need to develop new treatment options for patients with myelofibrosis. As shown on Slide 7, this disease is heterogeneous and is defined by 4 hallmarks or defining features. These hallmarks include an enlarged spleen, abnormal blood cell production, bone marrow fibrosis, and constitutional symptoms. Furthermore, the median overall survival for intermediate to high-risk myelofibrosis patients is only 4 to 5 years. Lastly, JAK inhibitors are the only approved therapy for myelofibrosis. And while they may decrease symptom burden and lead to very modest spleen reduction, relevant JAK inhibitors, including ruxolitinib, the standard of care in frontline myelofibrosis, do not target all of the relevant pathways implicated in myelofibrosis, including NF-kappa beta, p53, and fibrosis-inducing pathways. As a result, treatment of frontline myelofibrosis patients with monotherapy JAK inhibitors do not adequately address the relevant drivers of pathogenesis in myelofibrosis. On Slide 8, our confidence in selinexor's potential in myelofibrosis is based upon a growing body of preclinical, nonclinical, translational and clinical efficacy and safety data sets. These data suggest XPO1 inhibition is a key mechanism that may facilitate potential synergy with ruxolitinib and other drugs relevant in myelofibrosis. This multi-targeted approach enables treatment of the underlying mechanisms that lead to myelofibrosis, and we believe may lead to meaningful efficacy across the key treatment drivers as well as a generally safe and manageable side effect profile. This is supported by our blinded safety data, which I will take you through in a few slides as well as our substantial safety database with selinexor, where approximately 30,000 patients have been treated in clinical trials and in the post-market setting. This underscores our confidence in the ongoing Phase III SENTRY trial. As seen on Slide 9, while JAK inhibitors directly inhibit the JAK-STAT pathways, multiple other pathways downstream of JAK-STAT support malignant clone proliferation and survival, bone marrow fibrosis, cytokine storms and proliferation of abnormal megakaryocytes. These pathways include NF-kappa beta, PI3-kinase, AKT/mTOR, and TGF-β, a multifaceted approach with dual XPO1 and JAK inhibition simultaneously target upstream and downstream effectors of the JAK-STAT pathway, ultimately enabling apoptosis or cell death of the malignant clones. Let's now focus on the key treatment drivers in myelofibrosis as seen on Slide 10, spleen reduction, symptom improvement and lower rates of Grade 3+ anemia. First, spleen volume reduction. As a reminder, note that only approximately 1/3 of patients achieved a spleen volume reduction of greater than 35% with ruxolitinib alone. In contrast, our Phase I data suggests that the combination could more than double the SVR35 rate at 79%. A substantial proportion of patients achieving an SVR35 is coupled with very encouraging durability, specifically a 100% duration of response as of the data cutoff. Second is symptom improvement. Data from this trial also showed an average 18.5-point improvement in absolute TSS at week 24, which suggests this combination could provide a meaningful improvement over the 11 to 14 points achieved by patients on ruxolitinib as observed in the Phase III MANIFEST-2 and TRANSFOR-1 trials. Third is lower rates of Grade 3+ anemia. The data that we presented in June at EHA from our Phase II 035 monotherapy trial showed lower rates of all grade and Grade 3+ anemia in myelofibrosis patients previously treated with JAK inhibitor therapies. Blinded safety data from the ongoing Phase III SENTRY study suggests a similar trend. Meaningful improvement of these treatment drivers requires disease modification or the elimination of the underlying mechanisms leading to development of an enlarged spleen constitutional symptoms and worsening cytopenias. Data observed from selinexor monotherapy studies in a pretreated myelofibrosis population as well as our Phase I combination data in JAK inhibitor-naive myelofibrosis suggest meaningful reductions in key cytokines that are critical to myelofibrosis pathogenesis, symptom development and anemia as well as improvements in bone marrow fibrosis, increases in erythroid progenitors and mutational burden. Turning to Slide 11. We are super excited that our Phase III SENTRY trial has completed enrollment with top line data expected in March 2026. The co-primary endpoints in SENTRY are SVR35 and absolute TSS, which are tested sequentially. As we have discussed before, it is important to reemphasize based upon learnings from other myelofibrosis trials that we believe we have optimized SENTRY for success. In alignment with the FDA, we changed the co-primary endpoint of TSS50 to absolute TSS and exclude the fatigue domain in the primary analysis of absolute TSS due to the ambiguity of patients' assessment of their fatigue. We are certainly not the first to exclude fatigue. In fact, both the pivotal trials that led to ruxolitinib and fedratinib approvals also excluded fatigue in their TSS50 analyses. Encouragingly, amongst approximately 350 patients enrolled in SENTRY, the mean baseline TSS, excluding fatigue is approximately 22.5. Note that the 21.9 that you will see in our ASH abstract today was preliminary data and before enrollment was completed. Our mean baseline of approximately 22.5 compares favorably to other comparable trials. Importantly, as you compare our number to other trials, please remember other Phase III trials may include fatigue in their baseline scores. How does the fatigue domain affect the score? Given that in the Phase III MANIFEST-2 trial, the average fatigue score at baseline was approximately 5 points. Our baseline score, if we included fatigue, would be approximately 5 points higher, which gives us confidence in the patient population that we have enrolled. Shifting back to our trial design, absolute TSS in the Phase III SENTRY trial will be analyzed using the mixed models repeated measure approach, or MMRM, which is viewed as a more sensitive and potentially more robust method by which to analyze absolute TSS. Now let's review the encouraging preliminary blinded aggregate safety data from this trial. As these are preliminary and blinded data, please keep in mind that this data may not be reflective of the trial's actual top line results. The data on Slide 12 are from the first 61 patients that enrolled in the Phase III portion of SENTRY that have now been followed for a median of over 12 months. These patients were included in the successfully passed futility analysis conducted in the beginning of the year. We have continued to track the safety events over time and took a snapshot of the blinded safety data from these 61 patients on July 1, 2025, which continue to look favorable. The most common TEAEs are provided for the first 61 patients randomized to the trial and include patients randomized to both the combination of selinexor plus ruxolitinib or ruxolitinib arms in a 2:1 ratio. Because these are blinded data, we do not know the rates by each arm. In an effort to improve comparability, we then took our analysis one step further. Knowing that the 61 patients were randomized 2:1, we used the historical data on ruxolitinib to extrapolate the preliminary safety data for the approximately 40 patients that received the combination, which is shown in the orange boxes in the middle of the slide. The number that I am most optimistic by is the extrapolated rate of Grade 3/4 anemia. At approximately 26%, the extrapolated rate of Grade 3/4 anemia for the combination is meaningfully lower than the 37% historically reported for ruxolitinib. Grade 3/4 thrombocytopenia rates are relatively similar, with 9% suggested for the combination treated patients compared with the approximately 6% reported for ruxolitinib alone. Finally, the extrapolated rate of treatment-emergent adverse events leading to discontinuation is only approximately 5% to 7% for the combination, lower than the 6% to 11% range that has been historically reported from ruxolitinib, which we view as an encouraging observation. We are very encouraged about these data and what it could mean for patients if we see something similar in the top-line results in the Phase III SENTRY trial. Specifically, it could suggest a combination therapy that has a safety profile similar, if not potentially better than standard of care ruxolitinib, given that both Grade 3 plus anemia and thrombocytopenia are similar, if not better, than ruxolitinib alone, could suggest decreased blood draws for the patient and reduced monitoring burdens for physicians and health care staff. As we await our Phase III data, it is informative to review a case study on Slide 13 that shows meaningful efficacy, overall tolerability, and the potential for disease modification. This patient is enrolled in the Phase I combination study of selinexor and ruxolitinib and has been on the study treatment for over 3.5 years. This 81-year-old female was diagnosed with myelofibrosis secondary to polycythemia vera. She initiated treatment with selinexor 60 milligrams in combination with ruxolitinib in March 2022. Her baseline spleen volume was 2,058 cubic centimeters for TSS without fatigue at baseline was 7, and variant allele frequency burden or VAF was 83%, meaning that 83% of her cells had a cancer-driving mutation. She achieved an SVR35 and TSS50 at week 24 and complete resolution of her symptoms by approximately week 52. Furthermore, her VAF levels decreased to 0, signifying eradication of the cancer-driving mutation. To this day, she still continues on therapy with minimal side effects, with more than 3.5 years on therapy. This patient exemplifies the potential a multi-pathway approach can deliver in a disease as complex as myelofibrosis. XPO1 inhibitors' unique ability to simultaneously target multiple relevant pathways suggest their foundational potential in all patients with MS as well as other myeloproliferative neoplasms. I will now turn the call to Sohanya.
Sohanya Cheng: Thank you, Reshma. As shown on Slide 15, our commercial organization executed well this quarter within the highly competitive multiple myeloma market. XPOVIO net product revenue in Q3 grew 8.5% year-over-year to $32 million. Demand for XPOVIO was consistent year-over-year, with the community setting continuing to drive approximately 60% of total U.S. sales. XPOVIO is positioned in both the community and academic settings as a flexible therapy with a differentiated mechanism of action, oral convenient option, and increasingly used in the third line in patients before a T cell therapy or in patients who cannot access these complex therapies. Additionally, it is used in the fourth line plus setting once patients progress on a T cell therapy. Based on our results year-to-date, we are confident in our ability to deliver within our full year guidance range of $110 million to $120 million. Now turning to myelofibrosis outlined on Slide 17. We are excited to be working towards a potentially transformative commercial launch that we expect will redefine the way that frontline myelofibrosis patients are treated. Our conviction is driven by the high unmet need in myelofibrosis, combined with the fact that there has been no real innovation in the market beyond JAK inhibitors over the past 14 years. Ruxolitinib has been the standard of care for more than a decade and is being used in the vast majority of intermediate to high-risk patients, even though fewer than 35% of these patients achieve an SVR35. Physicians and patients want to see deep and durable reduction in spleen volume. And as Reshma discussed, the data from our Phase I trial highlights our potential in this area, with selinexor plus ruxolitinib helping more than twice as many patients achieving a spleen volume reduction of 35% or more. In addition, many patients experience constitutional symptoms and anemia, both of which negatively affect patient quality of life. And these are areas where we believe the selinexor plus ruxolitinib combination may make a meaningful difference. So, this presents us with a significant opportunity to improve upon the standard of care in combination with the market leader. Slide 18 provides an overview of our potential commercial opportunity. We have the opportunity to redefine the standard of care, expand the market, and lead with a new frontline combination therapy that may offer very differentiated results for patients. This isn't an incremental change in the treatment landscape. It is a potentially transformational change for patients. Here are some figures that help inform our view that selinexor's peak revenue opportunity could be up to approximately $1 billion annually in the U.S. If you look at the overall prevalent market, there are 20,000 patients living with myelofibrosis in the U.S., which represents a multibillion-dollar marketplace. As we look at the opportunity for patients that can benefit from selinexor plus ruxolitinib, there are approximately 4,000 newly diagnosed patients each year in the U.S. with intermediate to high-risk myelofibrosis that have a platelet count above 100,000. This is our target market. Most of these patients receive ruxolitinib today. 75% of U.S. physicians showed an intent to treat with combination therapy based on third-party market research. There is a clear appetite among physicians to evolve from a monotherapy to a combination treatment approach. Finally, the real-world duration of therapy for ruxolitinib is approximately 13 months. Our assumption is that the combination of selinexor plus ruxolitinib would be used for at least 13 months. Looking at all of this together, you will see that our peak revenue opportunity may approach $1 billion annually in the U.S. alone. As we prepare for potential commercialization, we have spent the past year speaking with leading KOLs at academic medical centers as well as community-based physicians and have received overwhelming support for the need to improve upon the current standard of care. Our position in the market, if approved, will be very clear and focused. If you're going to prescribe ruxolitinib to a patient with newly diagnosed myelofibrosis, prescribe selinexor plus ruxolitinib instead. Finally, our existing commercial capabilities are highly synergistic in myelofibrosis and prepare us for a rapid and successful launch, as shown on Slide 19. We have market access, a patient support hub, scientific and medical affairs, marketing, and a sales team with deep relationships with potential prescribers. In the academic setting, we already call on all the key institutions. In the community setting where a majority of newly diagnosed myelofibrosis patients are treated, there's approximately 80% overlap with our existing customer base. Pending positive data and subsequent regulatory approval, our commercial team will be ready to drive rapid and strong uptake as we bring this transformative therapy to patients. Now I'll turn the call over to Lori.
Lori Macomber: Good morning, everyone, and thank you, Sohanya. Turning to our financials. Since we issued a press release earlier today with the full financial results, I will focus on the highlights and reviewing our guidance for 2025 on Slide 21. Total revenue for the third quarter of 2025 was $44 million, an increase of 13.4% compared to $38.8 million in the third quarter of 2024. U.S. XPOVIO net product revenue for the third quarter of 2025 was $32 million, an increase of 8.5% compared to $29.5 million in the third quarter of 2024. Gross to net provisions for XPOVIO were 27% in the third quarter, consistent with the second quarter of 2025 and down from 31% in the third quarter of 2024. We expect gross to net provisions to remain relatively consistent with the third quarter levels in the fourth quarter of 2025. License and other revenue was $12 million in the third quarter, up nearly 30% from third quarter of 2024, primarily driven by higher milestone revenue from our partner, Menarini. This included the final amount of revenue that we will record from Menarini related to the $15 million of annual R&D reimbursement. In the fourth quarter, our license and other revenue will primarily be royalty revenue since we do not expect to achieve any significant additional milestones in Q4 2025. Turning to expenses. We continue to be very disciplined in managing our operating expenses and prioritizing our pipeline investments, including additional cost reduction initiatives that we implemented in the third quarter. Research and development expenses for the third quarter of 2025 were $30.5 million, down 16% compared to $36.1 million in the third quarter of 2024. The decrease was primarily driven by lower clinical trial and related costs for selinexor in multiple myeloma, reflecting the reduced scope of our Phase III trial, as well as lower personnel and stock-based compensation expenses resulting from previously implemented cost reduction initiatives. Selling, general, and administrative expenses were $26.6 million for the quarter, down 4% compared to $27.6 million in the third quarter of 2024. The decrease was primarily attributable to the continued realization of our cost reduction initiatives. Taken together, our loss from operations improved by approximately 42% in the third quarter of 2025 compared to the third quarter of 2024. Interest expense was $11 million in the third quarter of 2025 compared to $11.4 million in the third quarter of 2024. Other expense was $7.4 million in the third quarter of 2025 compared to $3.8 million of other income in the third quarter 2024. This nonoperational item is primarily driven by reoccurring noncash fair value remeasurements of embedded derivatives and liability classified common stock warrants related to the refinancing transactions completed in the second quarter of 2024. We reported a net loss of $33.1 million or $3.82 per share on a GAAP basis. More than half of this loss is driven by below-the-line items, including interest expense, which is almost entirely noncash at this point and the $7.4 million of noncash mark-to-market adjustments that I just mentioned. Excluding these items, our underlying operating performance continues to show meaningful improvement. Finally, prior to the receipt of approximately $36 million of gross proceeds from the financing transactions that we announced in October, we ended the third quarter with $46.2 million in cash, cash equivalents, restricted cash and investments compared to $109.1 million as of December 31, 2024. On a pro forma basis, after deducting transaction-related expenses, we would have had approximately $78 million in cash. Importantly, from a cash perspective, our interest payments do not start again until June 2026, and our royalty payments do not begin again until the third quarter of 2026. Based on our current operating plans, our guidance for the full year 2025 is as follows: total revenue of $140 million to $155 million, consisting of U.S. XPOVIO net product revenue and license, royalty and milestone revenue expected to be earned from our partners, primarily Menarini and Antengene; U.S. XPOVIO net product revenue to be in the range of $110 million to $120 million. We are lowering our range of R&D and SG&A expenses to $235 million to $245 million, down from $240 million to $250 million. With the financing that we announced last month, we expect our existing liquidity, including the revenue we expect to generate from XPOVIO net product sales as well as revenue generated from our license agreements will be sufficient to fund our planned operations into the second quarter of 2026. I will now turn the call back to Richard for some final thoughts.
Richard Paulson: Thank you, Lori. Before we close on Slide 23, I want to emphasize how far Karyopharm has come and where we're heading. This quarter reflects clear execution against our priorities and the progress we've made has positioned us to enter 2026 with confidence. With SENTRY enrollment complete, a strong commercial foundation and a reinforced balance sheet, we are focused squarely on what matters most, delivering 2 potentially transformative Phase III readouts that could reshape the future for patients with myelofibrosis and endometrial cancer. Our team's dedication, scientific rigor and focus on patients continue to drive everything we do. We believe the opportunities ahead are significant, and we are executing with purpose and discipline to realize them. Thank you for your continued support and confidence in Karyopharm. We look forward to updating you as we advance towards these important milestones. I would now like to ask the operator to open the call up to the Q&A portion of today's call. Operator?
Operator: [Operator Instructions] Our first question comes from the line of Peter Lawson with Barclays.
Peter Lawson: I guess first is just around the MF data that we're seeing March '26. If you could just kind of walk through what we should see if it's like SVR PFS and OS trends if that's going to be staged across other medical meetings in 2026. And then a follow-up question would just be around the size of the sales force. I know you've kind of talked about 80% overlap, but interested to see how many you would add or dedicate to MF and also the kind of the ex-U.S. strategy.
Richard Paulson: Thanks, Peter. So maybe the first part, Peter, are you asking about when we plan to share the data post March? It wasn't quite clear the question in the first part.
Peter Lawson: Just the level of detail we'd see in -- for MF, whether it's SVR, TSS, OS trends and then -- or if it's kind of spread across the year kind of thing.
Richard Paulson: Sure. Yes, I'll turn to Reshma for that first part, and then I'll turn to Sohanya for the second part with regards to our commercial capabilities.
Reshma Rangwala: Yes. Thanks, Peter. This is Reshma. So, the top line results, you're correct, expected more to 2026. I anticipate at this point, really just providing again sort of those top line details. So, you're correct, the primary endpoints of SVR35 at week 24, absolute TSS, potentially, right, some other secondary endpoints, including hemoglobin and/or disease modification. And then, of course, we'll touch upon safety. But we'll get granular as we get closer to that milestone.
Sohanya Cheng: Peter, as far as the sales force, as you mentioned, very strong overlap, particularly in the community setting, of course, with our current organization. And in the academic setting, we already call on those accounts. So, we expect really minimal additions to our commercial structure. Our capabilities are already highly synergistic. As far as ex-U.S., we'll continue to work with our ex-U.S. partners to drive launches in each of the countries and additional royalty and milestone revenues globally.
Operator: And your next question comes from the line of Ted Tenthoff with Piper Sandler.
Edward Tenthoff: Congrats on all the progress both on the clinical side and financial side. Can you remind us, are there any milestones associated with data or warrants or things like that for the recent financial restructuring that could extend that capital beyond the second quarter? And are there any geographies where you don't currently have distributors in place for myelofibrosis?
Richard Paulson: Thanks, Ted. Maybe on the first part, are you just asking about milestones from a financing perspective with regards to positive data? Or maybe just clarify that part of the question.
Edward Tenthoff: Yes. So, milestones were there any warrants or anything like that, that could trigger to extend the June or the 2Q deadline. I was trying to remember back.
Richard Paulson: From a pure warrant or financing perspective, no specific triggers with regards to positive MF data. Obviously, pending positive data, we think that will be a very, very strong inflection and value point for us. And on the second part with regards to our partnerships globally, no, we have well-established partners for selinexor globally. And as Sohanya mentioned, I think they're very excited and engaged and looking forward to positive data and moving forward with a registration strategy and commercialization strategy globally, which we would be able to do. With the exception, one market we still don't have partnered is Japan. That would be the only additional market we would look to partner with in the future moving forward.
Operator: And your next question comes from the line of Colleen Kusy with Baird.
Colleen Hanley: Congrats on all the progress. Hopeful for the baseline TSS number, 22.5%, I think you said, Reshma, quite a lot higher than what you had enrolled in the Phase I, I believe. And based on the data that you had at AACR in 2023, it actually looks like fairly similar response for TSS above and below 20, which could just be due to the small end, but just curious how you would expect that might impact the read-through from Phase I to the pivotal Phase III? And then I'll have a follow-up after.
Reshma Rangwala: Yes. It's a great question, Colleen. I think we're very encouraged by how the baseline TSS is evolving. As you mentioned, 22.5%, approximately 22.5 in almost the full ITT. I think you're right. Sort of the Phase I, it's small. So, we're very encouraged by those numbers. Clearly, it suggests that absolute TSS as well as TSS50 can be achieved with the combination relative to historical ruxolitinib data. I think what we were trying to accomplish in the Phase III was to drive that baseline TSS without fatigue as high as possible. And so again, very encouraged with that 22.5%, especially as I compare it to other contemporary trials in which that 22.5 likely is higher than even those. So, it really suggests that we could see a potentially meaningful improvement for absolute TSS with our combination versus ruxolitinib alone.
Colleen Hanley: That's super helpful. And then in that same AACR update, it looks like there was some variability in response for platelet count above and below 200,000, which again could just be driven by small end. But curious if you have the baseline platelet count and what your kind of thoughts are on the activity based on platelet count.
Reshma Rangwala: Yes. We're seeing more than half of the patients with baseline platelet counts above 200 which again is what I would expect. There's nothing biological or mechanistic that would suggest that platelet count is a key variable that would impact the overall SVR35 rate or even the absolute PSS. So again, it's a number we're watching. It's a baseline characteristic that I think is very consistent with other Phase III trials. In general, that variable as well as all of the other variables are in line with what we would expect and again, very encouraged with how this patient population is enrolled and who they represent across the frontline myelofibrosis population.
Operator: And your next question comes from the line of Maurice Raycroft with Jefferies.
Maurice Raycroft: Congrats on the progress. So, ASH abstracts are coming out pretty soon. Just confirming, it sounds like your Phase III baseline data is going to be at ASH. Can you talk more about what's in the abstract and then what is going to be at the conference?
Reshma Rangwala: Yes. Thanks for the question, Maurice. So, the ASH, so it's going to be an abstract only. We're not going to present an additional poster. So, any additional data in the full ITT is going to be presented with the top line results in March of 2026. So, when the data come out in about 20 minutes, really, what you're going to see is just the baseline characteristics amongst 320 patients. So, this is a subset. These were the available patients at the time of the data cutoff. And as I mentioned on my prepared remarks as well as with some of the questions today, just very encouraged with how that patient population has evolved and again, very consistent with what we would expect.
Maurice Raycroft: And maybe as a follow-up, for the slightly lower treatment-emergent adverse events leading to discontinuation for the 61 patients in the blinded safety review. Can you comment on whether that rate is mostly in line with what you're seeing for the full study? I guess, any additional perspective there that you could share?
Reshma Rangwala: Yes, great question. So, one of the things that I'm very encouraged by is that we've followed these 61 patients and taken a snapshot across their AE summary, including their treatment discontinuation rates as well as the specific AEs as well as a couple of Grade 3 plus AEs. And what I'm encouraged by, again, is that despite whether we look at a 7-month median follow-up or even a 12-month median follow-up, rates, including treatment-emergent discontinuation rates are remarkably stable, right? So, it really suggests that a majority of the events, including discontinuations potentially are occurring early, and we don't continue to see this accumulation as the patients are followed over time. Now what the top line results are going to show, we'll see at the top of the -- at the time that we report the top line results, but again, very encouraged by how the 61 patients are evolving.
Operator: Your next question comes from the line of Brian Abrahams with RBC Capital Markets.
Brian Abrahams: Congrats on all the progress. I wanted to drill down a little bit more on some of the market research findings, in particular, the high 75% intent to treat with the combo in frontline MF. I'm curious if you could talk a little bit more about sort of the types of patients that you're hearing physicians would try on a combo. Ruxolitinib initially, whether or not some of the payer feedback maybe you've been getting the early payer feedback has been aligned with what you're hearing from physicians in terms of the degree of frontline use. And then with the space expected to evolve and more targeted treatments like mccarls and more targeted JAKs, what impact do you think that might have on the way selinexor is ultimately positioned should it be successful in Phase III?
Richard Paulson: Yes. Thanks, Brian. Maybe I'll start kind of with the second part of your question, and I'll turn it over to Sohanya to talk to. I think broadly, in myelofibrosis, as you know and as Sohanya talked about, there's been really no new innovation in the front line, only JAK inhibition in myelofibrosis. So, there's significant opportunity across the whole space to improve outcomes for patients and to bring new innovation to patients, which is exactly what we're focused on. We're bringing a novel MOA such as selinexor and XPO1 inhibition, which we think can have a really meaningful benefit to patients. And when we look across the space again, I think the data we've shown, as we've talked about, we've been working on myelofibrosis for over 7-plus years. Reshma talked about the breadth of our data and showing impact as a monotherapy and obviously, as a combination. And I think what we're excited about, obviously, is to work to deliver that positive Phase III trial and then to continue expanding in MPNs as well as with selinexor, with eltanexor, our novel second-generation XPO1 inhibitor and a whole suite of XPO1 inhibitors that we have, which we think may be able to have an impact across a broad range of MPNs. With regards to the CALR, we need to wait. We haven't seen any data in myelofibrosis. So again, I think there's a lot of opportunity for innovation and improvement. And what we're excited about again is in the very near-term to read out a potentially positive trial in a combination with such an impact for patients. And I'll let Sohanya talk to that because that's really what our market research indicates when we talk about the 75% intent to prescribe that combination therapy upfront for treatment-naive patients.
Sohanya Cheng: Thanks, Richard. Just to kind of add a little bit more to that. The target patient in the market research would be the newly diagnosed intermediate to high-risk patient with greater than 100,000 platelets. And the market research kind of just a little bit of background was comprised of both community and academic physicians. The proportions were in line with what we've seen in real world, the majority community physicians that are treating newly diagnosed myelofibrosis patients. So, the value proposition for selinexor is very simple, clear and focused. If a prescriber is already prescribing or planning to prescribe rux alone for a newly diagnosed myelofibrosis patient upon approval, they will then just do a seli plus rux combination. So, we are not competing with ruxolitinib, which is the standard of care go-to treatment for our target patient population. We're simply an addition with ruxolitinib, the current market leader. As we look at the sort of payer environment, we don't anticipate any kind of pushback with the payers. And generally, as Richard pointed out, there really has been little innovation beyond the JAK inhibitors. So, there's a tremendous appetite to move these physicians from a monotherapy to a combination treatment approach.
Operator: And our last question will come from Jonathan Chang with Leerink.
Jonathan Chang: Just regarding the commercial potential launch in myelofibrosis, can you discuss any relevant learnings from the multi myeloma experience?
Richard Paulson: Yes. I think broadly, Jonathan, the learnings from our multi myeloma experience really have been built in into the trial design, where in multi myeloma came to the marketplace, as you know, at a much higher dose at 80 milligrams twice weekly or 160 milligrams. And what we've learned over the past number of years is the importance and the ability to use selinexor at a lower dose. And we've obviously built that in with our trial now being at 60 milligrams once weekly. And we've also learned the importance of the dual antiemetics to use for the first couple of cycles as patients initiate therapy on XPO1 inhibition. We know that the nausea is transient and gets better over time. So, we've seen both those learnings over our multiple myeloma experience. We've built that in already to the design of the trial. And so, I think moving forward and what we've seen already and what Reshma has shared in the blinded safety data is really the benefit to patients, the benefit overall to the tolerability profile. And as we saw from the very low TAE discontinuations, the benefit for patients. And I think the case study Reshma talked to with the patient on the combination for over 3.5 years and so benefiting really talks to the outcomes for patients from those learnings we've built in. So, we feel very positive about the learnings we've built in and the potential to transform outcomes for myelofibrosis patients in the front line.
Reshma Rangwala: Yes. I would add that the kind of biggest differentiating point between the 2 landscapes is the degree of competition. Myeloma, highly competitive with overlapping competitors across classes, very different situation in myelofibrosis, really little to no innovation beyond the JAK inhibitors. Also, I would say the myelofibrosis space is primed to be what the myeloma space was over a decade ago. Over a decade ago in myeloma, they were using monotherapies and then evolving to doublets. That is the level of transformation, I think we're about to see in myelofibrosis. The second point is given that we have established a commercial organization that has worked very closely with community physicians who will be the majority of prescribers for the newly diagnosed patients, there's a high degree of synergy, and we expect to launch rapidly with myelofibrosis.
Operator: And that concludes today's question-and-answer session. I would like to turn it back to Richard Paulson for closing remarks.
Richard Paulson: Thank you, operator, and thank you to everyone again for joining us on today's call. As you can tell, we are very excited about our prospects to redefine the current standard of care for the majority of frontline myelofibrosis patients. We look forward to sharing top line data with you in March and pending future regulatory approvals, our organization is well prepared to rapidly deliver on the commercial opportunity. Once again, thanks for joining today.
Operator: Thank you. And ladies and gentlemen, this concludes today's conference call. Thank you all for joining. You may now disconnect.