Karyopharm (KPTI) Q1 2026 Earnings Transcript

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DATE

Thursday, May 14, 2026 at 8 a.m. ET

CALL PARTICIPANTS

• President and Chief Executive Officer — Richard Paulson
• Chief Medical Officer — Reshma Rangwala
• Chief Commercial Officer — Sohanya Cheng
• Chief Financial Officer — Laurie Macomber
• Vice President, Corporate Communications and Investor Relations — Brendan Strong

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TAKEAWAYS

• Total Revenue -- $35.1 million, up from $30 million in the prior-year period.
• U.S. XPOVIO Net Product Revenue -- $29.2 million versus $21.1 million last year, attributed to a decrease in gross-to-net to 21.8% from 45% in Q1 2025, largely due to lower realized discounts and returns.
• Gross-to-Net Adjustment -- 21.8% for the quarter, with underlying gross-to-net approximated at 26% after product return adjustment.
• R&D Expenses -- $33.8 million, remaining relatively stable year over year.
• SG&A Expenses -- $26.7 million, also relatively consistent year over year.
• Net Loss -- $22.4 million, improved from $23.5 million last year, with operational loss reduced by 20% due to increased revenue and expense control.
• Liquidity -- $91.2 million in cash, cash equivalents, and restricted cash at quarter-end, including $50 million raised in March financing.
• Operational Runway Guidance -- Current liquidity expected to fund operations into late Q3 2026 under present operating plans.
• 2026 Full-Year Revenue Guidance -- Reaffirmed total revenue outlook of $130 million to $150 million, comprising U.S. XPOVIO net product revenue of $115 million to $130 million and all remaining revenue as royalties.
• 2026 Operating Expense Guidance -- Combined R&D and SG&A expenses projected in the $230 million to $245 million range for the full year.
• SENTRY Trial SVR35 Endpoint -- 50% of patients on selinexor plus ruxolitinib achieved SVR35 at week 24, compared to 28% on ruxolitinib alone (p < 0.0001), with benefit sustained through week 36.
• SENTRY Overall Survival (OS) Signal -- Combination group hazard ratio was 0.43 (nominal p = 0.0222) at top-line compared to standard of care, marking the first potential OS signal improvement in myelofibrosis.
• Variant Allele Frequency Reduction -- 32% of combination-arm patients experienced at least a 20% variant allele frequency reduction by week 24, potentially indicating disease modification.
• SENTRY Safety Profile -- "Lastly, the combination demonstrated a generally manageable tolerability profile that was consistent with what we understand about each agent individually. We did not observe any new safety signals. Importantly, with the use of the lower dose of selinexor in dual antiemetics, we've seen an improved tolerability compared to the Phase I study.
• Export EC042 Enrollment -- Enrollment is complete at 257 patients for the Phase III study in endometrial cancer, with approximately 220 in the modified intent-to-treat (MITT) population for primary analysis.
• Export EC042 Timeline -- Top-line data expected in mid-2026, with statistical plan prioritizing MITT PFS significance before full intent-to-treat analysis.
• Commercial Opportunity in Myelofibrosis -- The selinexor and ruxolitinib combination is aimed at ~20,000 U.S. patients, with ~4,000 addressable first-line annually; U.S. peak annual revenue potential cited as up to ~$1 billion.
• Commercial Opportunity in Endometrial Cancer -- U.S. annual incidence is about 17,000 newly diagnosed advanced/recurrent patients, with the potential for rapid adoption among the approximately 50% with p53 wild-type and PMMR tumors.
• Commercial Preparedness -- Existing sales, marketing, and market access infrastructure positions the company to support launches in both myelofibrosis and endometrial cancer with "minimal incremental investment preapproval and only modest additional spend post launch."
• Upcoming Catalysts -- Key readouts include SENTRY at ASCO (oral late-breaker and expected mid-2026 publication) and export EC042 in mid-2026, both flagged as "major potential value-creating catalyst."

SUMMARY

The SENTRY Phase III trial delivered a statistically significant spleen volume response and the first potential overall survival benefit seen in myelofibrosis using selinexor plus ruxolitinib, with a favorable risk profile and no new safety findings. In endometrial cancer, the export EC042 study completed enrollment, and management reiterated both the sizable biomarker-driven patient segment and the mid-2026 top-line data timeline. Financially, the company reported rising revenues, sustained operating cost control, and reaffirmed its full-year revenue, spending, and operational runway guidance into late Q3 2026.

• Management affirmed the EC042 MITT population remains adequately powered for regulatory endpoints, despite slightly fewer total enrolled patients than originally planned.
• The company confirmed an improved tolerability profile for selinexor in EC042 through 60 mg dosing and mandated dual antiemetics in initial cycles, compared to the SIENDO trial protocol.
• Commercial teams are positioned to address both myelofibrosis and endometrial cancer launches quickly, leveraging concentrated account coverage and established provider relationships.
• "a late-breaking oral presentation at ASCO," was highlighted for SENTRY data, with expectations to spur both regulatory engagement and potential inclusion in NCCN and other compendia according to management discussion.
• Guidance was provided that, if successful, guideline listing alone (versus formal labeling) could drive up to approximately 50% of peak revenue potential for the myelofibrosis opportunity.

INDUSTRY GLOSSARY

• XPO1: Exportin 1, a nuclear export protein targeted by selinexor for anticancer activity.
• SINE compounds: Selective Inhibitor of Nuclear Export compounds designed to block XPO1-mediated export of tumor suppressor proteins.
• SVR35: Spleen Volume Reduction of ≥35%, a standard clinical endpoint in myelofibrosis trials.
• TSS: Total Symptom Score, measuring symptom improvement in myelofibrosis studies.
• PFS: Progression-Free Survival, a key endpoint in oncology trials indicating time to disease progression or death.
• MITT: Modified Intent-to-Treat population, the pre-specified efficacy analysis group in the EC042 study.
• p53 wild type: Tumor cells with an unmutated TP53 gene, significant for biomarker-driven therapy stratification.
• MMR proficient (PMMR): Tumors demonstrating proficient DNA mismatch repair machinery, impacting treatment response.
• VAF: Variant Allele Frequency, refers to the proportion of mutated to wild-type alleles, used here as a biomarker of disease modification.

Full Conference Call Transcript

Brendan Strong: Good morning, and thank you all for joining us on today's conference call to discuss Karyopharm's first quarter 2026 financial results and recent company progress. We issued a press release this morning detailing our financial results for the first quarter of 2026. This release, along with the slide presentation that we will reference during our call today are 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 the results for the first quarter, highlight the importance of the results from our Phase III SENTRY trial in myelofibrosis and provide an update on our endometrial cancer program and related commercial opportunity.

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 we may make in the future with the SEC. 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 5.

Richard Paulson: Good morning, and thank you for joining us today. Karyopharm continues to execute through an important period for the company with the recent and upcoming milestones that we believe can unlock meaningful growth opportunities and shape our next phase. Over the past several quarters, we have focused our organization around 3 priorities: advancing our stage clinical programs, maintaining our commercial foundation of multi-myeloma and managing the business with discipline as we approach significant value-creating milestones.

Since our fourth quarter call, we have made meaningful progress across our key 2026 priorities, including reporting top line results from our Phase III SENTRY trial in myelofibrosis, concluding enrollment in export EC042 in endometrial cancer and strengthening our balance sheet through the financing completed in Q1. With these milestones and data in hand, we are now focused on the next phase of execution, advancing our regulatory and scientific engagement for SENTRY , preparing for the EC 042 top line data readout and continuing to manage the business with financial discipline.

SENTRY showed a compelling and differentiated profile for selinexor in combination with ruxolitinib, including rapid, deep and sustained spleen volume responses accompanied by a promising overall survival signal and evidence of potential disease modification, including greater reductions in variance frequency as early as week 24. These findings reinforce the potential of selinexor plus ruxolitinib to address an important gap in frontline myofibrosis treatment, where treatment options remain limited, and the need for therapies that improve long-term outcomes remain high. We are very encouraged by the level of interest and enthusiasm we are hearing from the myofibrosis KOL and patient group communities following the SENTRY readout.

Our next major catalyst is export EC042 in endometrial cancer, where enrollment is now complete and we continue to expect top line data in mid-2026. This is a biomarker-driven program focused on patients with TP53 wild-type endometrial cancer, particularly those with TMMR tumors where there remains a significant unmet need and no approved personalized biomarker-driven maintenance therapy. Commercially, we believe we have a strong foundation to build from. Our deep relationships across community and academic accounts and capabilities in sales, marketing, market access, patient support and medical affairs can be leveraged across future potential launches. In both endometrial cancer and myelofibrosis, we see concentrated treatment landscapes and clear unmet need. Financially, we remain disciplined.

We ended the quarter with increased liquidity following our financing in March, and we continue to manage spending with a clear focus on the clinical and regulatory milestones that matter most. Our current operating plan provides us with sufficient flexibility through our major near-term clinical and regulatory catalysts, including SENTRY next steps and the EC042 top line readout funding us into late Q3 2026. With that context, today's call will first cover the SENTRY highlights and next steps, followed by a deeper discussion of the upcoming export ECU for 2 readout, our commercial readiness and our financial performance with guidance. I'll now turn the call over to Reshma. Reshma?

Reshma Rangwala: Thank you, Richard. Before we dive into myelofibrosis in endometrial cancer, I want to take a step back and ground everyone in the biology of XPO1 inhibition and why we believe this novel mechanism has the potential to meaningfully improve outcomes for patients across both diseases as outlined on Slide 7. What's particularly compelling about XPO1 inhibition is that it allows the drug to simultaneously impact multiple highly relevant oncogenic pathways. Selinexor selectively binds to XPO1, a key nuclear export protein and blocks the transport of critical regulatory proteins out of the nucleus.

By doing so, selinexor drives the retention and activation of tumor suppressor proteins such as p53, FoxO, T21 and ICAP data within the nucleus where they can exert their anticancer effects. This effect is particularly notable for myelofibrosis and endometrial cancer, given that greater than 95% and 50% of these tumors, respectively, our p53 wild type. At the same time, it reduces the activity of oncogenic signaling pathways, including NS Capa beta, which is of relevance to myelofibrosis. Induction of cell cycle arrest independent of the p53 pathway is also critical pathway important to both endometrial cancer and myelofibrosis.

The net effect is a coordinated biological response, including decreased tumor cell proliferation, increased apoptosis and ultimately, the potential for durable disease control. We believe this multi-pathway mechanism is a key differentiator for selinexor and underpins the breadth of activity we've observed across multiple cancers, including both MS and EC. With that backdrop, let's turn to myelofibrosis and why we believe the SENTRY data are so compelling as outlined on Slide 9. There remains a clear opportunity to improve upon the current standard of care.

While JAK inhibitors have been an important advancement and remain the only approved class, we continue to see relatively rates of spleen volume reduction, limited impact on long-term survival and minimal evidence of true disease modification. As such, there is an unmet medical need for therapies that go beyond symptom control and deliver deeper, more durable benefit, and improve long-term outcomes like overall survival. Moving to Slide 10. As I presented a few weeks ago, we're very encouraged by the top line results from our Phase III SENTRy trial. The combination of selinexor plus ruxolitinib delivered rapid and clinically meaningful spleen volume reduction as early as week 12. Importantly, that benefit was sustained through week 36.

The co-primary endpoint of SVR35 at week 24 was 50% for the combination compared to 28% for ruxolitinib alone, corresponding to a statistically significant p-value of less than 0.0001. Our second co-primary endpoint was symptom improvement at week 24. While the difference in absolute TSS was not statistically significant, patients in both arms experienced important and similar improvement from baseline. What we find particularly exciting is the intriguing signal of overall survival, arguably the most important outcome for patients with myelofibrosis. The combination of selinexor and ruxolitinib is the first potential treatment in myelofibrosis to suggest an overall survival improvement relative to standard of care.

At the time of the top line data, the overall survival hazard ratio was 0.43 with a nominal p-value of 0.0222. In addition, post hoc analyses demonstrate that SVR35 predicts OS Consistent with published analyses in other myelofibrosis trials that have also shown the same. These findings underscore the importance of achieving rapid, deep and sustained SVR35. The greater proportion of patients on the combination arm at 32%, who experienced a variant allele frequency reduction of at least 20% may be indicative of an underlying effect on the disease biology, raising the potential for true disease modification.

The rapidity at which we see these VAT reductions reflect the anticlonal attributes of selinexor and mirrors both the substantial improvement in SVR35 as early as week 12. And the early improvements in overall survival. Lastly, the combination demonstrated a generally manageable tolerability profile that was consistent with what we understand about each agent individually. We did not observe any new safety signals. Importantly, with the use of the lower dose of selinexor in dual antiemetics, we've seen an improved tolerability compared to the Phase I study. We believe the combination of the XPO1 inhibitor selinexor and ruxolitinib delivers a very compelling and differentiated product profile with the potential to improve outcomes for patients with myelofibrosis. Turning to Slide 11.

We're excited that these data have been selected for a late-breaking oral presentation at ASCO, and we expect to have a manuscript published in a peer-reviewed journal in the middle of 2026. Overall, we remain very encouraged by the SENTRY results and look forward to productive discussions with the FDA. Let's now turn to endometrial cancer and why we're so excited about selinexor's potential to address a clear and meaningful treatment gap, particularly for patients with p53 wild-type MMR proficient tumors. As highlighted on Slide 13, this is a large and well-defined patient population. Approximately half of the patients are p53 wild type and about 80% has MMR proficient tumors. Importantly, this is not a niche segment.

It represents a substantial proportion of the overall endometrial cancer patients whose unmet need remains high. Equally important, molecular classification is already embedded in the standard of care today. That means clinicians are routinely identifying these patients in practice, which we believe positions selinexor very well for real-world adoption if our Phase III data are positive and pending regulatory approval. On Slide 14, we believe we have an opportunity to define a personalized biomarker-driven maintenance treatment option for patients with p53 wild-type endometrial cancer. Today, patients with advanced or recurrent EC have no personalized biomarker-driven maintenance-only therapy.

And although checkpoint inhibitors are approved in combination with chemotherapy followed by checkpoint inhibitor alone, patients whose tumors are both p53 wild type and MMR proficient gained the least benefit. The RUBY trial, which evaluated dostarlimab in combination with chemotherapy in advanced or recurrent EC patients showed a marginal PFS improvement of only 0.77 and in patients whose tumors were NSMP or p53 wild-type MMR proficient. This highlights the profound unmet need for the subgroup that comprises approximately 50% of all endometrial cancer patients and underscores the urgency to identify p53 wild-type directed therapies.

It also highlights the substantial benefit that potentially could be observed with selinexor in patients with p53 wild-type tumors and especially those whose tumors are both p53 wild type and MMR proficient. As seen on Slide 15, the top line data in the p53 wild-type subgroup of the SIENDO study showed a very strong PFS signal with the median PFS in the selinexor arm of 13.7 months versus 3.7 months for placebo, translating to a hazard ratio of 0.41. As you can see on Slide 16, with long-term follow-up, the median PFS benefit for the selinexor arm extends to 28.4 months corresponding to a hazard ratio of 0.44.

And when we focus on the patients whose tumors are p53 wild-type MMR proficient, the data become even more compelling. As shown on Slide 17, the median PFS approaches 40 months at long-term follow-up with a PFS hazard ratio of 0.36. These results compare very favorably to the Ruby data in which the MMR proficient p53 wild-type subgroup showed a PSS hazard ratio of 0.77 Taken together, what we see is not only a strong initial signal but a benefit that deepens and becomes more meaningful over time.

That's the dynamic we're aiming to replicate in export ECO42 to demonstrate a clear PFS advantage at top line, we also anticipate that the PFS benefit may continue to strengthen as the data mature. The safety profile on Slide 18 is from the long-term follow-up from Siendo. Given that the dose of selinexor was 80 milligrams in the Senda trial and prophylactic dual antiemetics for the first 2 cycles were not mandated we have an opportunity to observe a better safety and tolerability profile in the ongoing 042 trial. Similar to the SENTRY trial, we've been very deliberate in optimizing both the dose and supportive care.

In the ECO 4Q trial, selinexor is dosed at 60 milligrams once weekly, and we've mandated dual antiemetics during the first 2 cycles, which is when patients are most likely to experience nausea and vomiting. There is the potential that with an improved safety profile, patients stay on treatment longer translating to improved efficacy. Overall, we feel very good about how the program has evolved in delivering a more optimized and patient-friendly treatment approach. Finally, turning to Slide 19.

As Richard mentioned, I'm very pleased that we have successfully completed enrollment in our Phase III export EC 042 trial, We enrolled 257 patients in the intent-to-treat population, with approximately 220 patients in the modified intent-to-treat population, which is the primary analysis population for the study. As a reminder, our statistical plan is designed to be both rigorous and efficient. We will first assess progression-free survival in the MITT population. -- if that analysis is statistically significant, the alpha will then pass down sequentially to the full ITT population. As we approach the prespecified number of PFS events that will trigger the primary analysis, we remain on track to report top line results in the near term.

Stepping back, I'm incredibly excited about the opportunity in front of us, not only in endometrial cancer, but also in myelofibrosis. In both areas, we have the potential to establish new standards of care and deliver meaningful benefits for patients where significant unmet need remains. I will now turn the call to Sohanya.

Sohanya Cheng: Thank you, Reshma. As shown on Slide 21, we delivered strong net product revenue growth this quarter, driven primarily by favorable gross-to-net dynamics, which Laurie will cover in more detail. Underlying demand for XPOVIO was lower compared to the first quarter of 2025, reflecting the impact of new competitive entrants. This is not new territory for us. We've successfully navigated competitive dynamics and returned to drive demand growth. Turning to Slide 22. There are 2 ways that XPOVIO is positioned that we believe sets us up for future growth amidst an evolving and competitive landscape.

First, our focus remains on the community setting, which represents approximately 60% of total U.S. sales where many community-based physicians and patients value XPOVIO as a flexible and convenient oral option in the second to fourth line. . Second, our distinct positioning for XPOVIO as a differentiated mechanism of action in the peri T cell engaging therapy setting allows selinexor to be used in patients prior to a CAR T, which is an important position given anticipated future expansion of CAR Ts and also in patients progressing on a T cell engaging therapy. Therefore, despite an evolving competitive landscape, we remain confident in our ability to drive growth in XPOVIO net product revenue.

Now as we turn to Slide 23, if we look at our future potential launches in myelofibrosis and endometrial cancer, these are areas where there is strong overlap with community-based accounts with fewer treatment alternatives and higher unmet need than the multiple myeloma market. As we prepare for these potential launches, I would like to underscore the strength and value of our highly experienced teams. We have established capabilities across sales, marketing, market access and medical affairs, all of which can be utilized to educate on the relevant disease states. This allows us to prepare for launch with minimal incremental investment preapproval and only modest additional spend post launch.

Let's now discuss the potential commercial opportunity in both myelofibrosis and endometrial cancer, starting with myelofibrosi on Slide 25. In myelofibrosis, the only treatment options that patients currently have are JAK inhibitors and with ruxolitinib monotherapy being the standard of care for the past 15 years and only about 1/3 of patients that receive ruxolitinib achieve a spleen volume reduction of 35% or more with 2/3 of patients not adequately responding. Slide 26 provides an outline of the potential market opportunity. selinexor plus ruxolitinib targets a sizable U.S. myelofibrosis market with roughly 20,000 patients living with the disease and limited approval approved options beyond JAK inhibitors.

With around 7,000 newly diagnosed first-line patients annually, about 4,000 of whom are addressable we see a clear path to meaningful adoption. We believe the combination of selinexor and ruxolitinib has the potential to deliver up to approximately $1 billion in U.S. peak annual revenue. Our sales organization is well positioned for a potential launch in male fibrosis. We have deep relationships with the key accounts where the majority of patients are treated. As outlined on Slide 27, 70% of myelofibrosis patients are treated in the community setting and 30% are treated in academic centers.

Across both settings the majority of patients are treated in a concentrated group of accounts, which enables us to move quickly and execute a focused high-impact launch, if approved. Turning now to Slide 28. We're energized by the opportunity to reshape frontline myelofibrosis treatment by pairing selinexor with the current standard of care and pending approval to drive rapid uptake and potentially transform patient outcomes. Turning to Slide 30. I'd like to share how we are thinking about the commercial opportunity in endometrial cancer. -- which is the most common gynecologic malignancy in the United States with 17,000 newly diagnosed advanced or recurrent patients each year and incidents and mortality rates on the rise.

As Reshma mentioned, we believe we have a clear opportunity to establish selinexor as the standard of care in patients whose tumors are p53 wild site and PMMR. These patients comprise approximately 50% of all endometrial cancer patients. As we look at other therapies that have driven meaningful benefit in the treatment landscape, for example, the uptake of checkpoint inhibitors in dMMR endometrial cancer and PARP inhibitors in the maintenance setting in ovarian cancer. They achieved peak share within 18 to 24 months of launch. Similarly, given the high unmet need for a maintenance therapy in p53 wild site patients as well as our established commercial capabilities, we would expect adoption to be rapid.

On duration, our assumptions are influenced by the fact that this would be a maintenance option. While we don't equate PS directly with duration, the strength of our PFS data from SIENDO gives us confidence that patients can remain on therapy for an extended period. Putting this together, this represents a significant opportunity within a multibillion-dollar marketplace. Turning to Slide 31. In summary. From a commercial perspective, if approved, Selinexor is positioned to rapidly transform treatment in p53 wild-type endometrial cancer. We're very encouraged by the opportunity ahead and confident in our commercial readiness to support successful launches. With that, I'll turn the call over to Laurie starting on Slide 33.

Lori Macomber: Thank you, Sohanya, and good morning, everyone. I will focus on the key highlights from our first quarter financial performance and how those results position us relative to our full year expectations. Starting with revenue. Total revenue for the first quarter was $35.1 million compared to $30 million in the prior year period. U.S. XPOVIO net product revenue was $29.2 million compared to $21.1 million last year. This increase was driven by a decrease in gross to net, which was 21.8% this quarter versus 45% in the first quarter of 2025 and that was impacted by an atypical product return adjustment. Our gross to net reflected lower realized discounts and returns this quarter.

Excluding these adjustments, our underlying gross to net was approximately 26% this quarter. Turning to expenses. We remain focused on disciplined execution. R&D expenses were $33.8 million, and SG&A expenses were $26.7 million, both relatively consistent year-over-year. This reflects our continued focus on prioritizing investment in our highest value clinical programs while maintaining overall cost controls. Net loss was $22.4 million for the quarter. compared to $23.5 million in the prior year. As a reminder, net loss includes noncash mark-to-market adjustments related to our financing structure. From an underlying operating perspective, performance improved meaningfully with a 20% reduction in loss from operations, driven by the increase in total revenue and continued expense discipline. Turning to the balance sheet.

We are managing the business with a clear focus on our clinical catalysts and ended the quarter with $91.2 million in cash, cash equivalents and restricted cash which includes the approximately $50 million rate this quarter. Based on our current operating plan, we expect our existing liquidity to fund operations into late in the third quarter of 2026. We remain focused on prudent capital management, as we advance our pipeline and prepare for our upcoming Phase III readout in endometrial cancer. Turning to guidance. We are reaffirming our full year 2026 outlook.

We continue to expect total revenue in the range of $130 million to $150 million, with license and other revenue, consisting entirely of royalties over the next 3 quarters and U.S. XPOVIO net product revenue of $115 million to $130 million. Finally, we also continue to expect combined R&D and SG&A expenses in the range of $230 million to $245 million in 2026. Overall, we believe our first quarter performance and operating discipline position us well to deliver against our full year expectations in 2026. With that, I'll turn the call back over to Richard.

Richard Paulson: Thank you, Reshma, Sohanya and Lori. As we have discussed today, Karyopharm has made meaningful progress against the priorities we laid out entering 2026. across both myelofibrosis and endometrial cancer, we believe the story is consistent. Selinexor has a differentiated mechanism of action, the clinical programs have been refined based on experience, and the commercial opportunities are meaningful. We have also worked hard to optimize how selinexor is used, including dose selection and proactive supportive care with the goal of delivering the right balance of efficacy tolerability and real-world usability. Looking ahead, our focus is clear. We are advancing the next steps for SENTRY, including FDA engagement, presentation of the data at ASCO, publication planning and potential compendia inclusion.

In endometrial cancer, we are preparing for the export EC 042 top line readout in mid-2026, which we believe represents a major potential value-creating catalyst for Karyopharm. Across the business, we will maintain operational and financial discipline as we execute while continuing to evaluate opportunities to strengthen our financial position and extend our runway. We have an important few months ahead and we are focused on executing with urgency, discipline and a clear commitment to bring meaningful new treatment options to patients in 2 areas of high unmet need. We'll now open the call for questions. Operator?

Operator: [Operator Instructions]Your first question comes from Brian Abrahams from RBC Capital Markets.

Brian Abrahams: Congrats on all the progress. So maybe just on the MF study. I guess, I'm wondering -- have you done any additional work since the top line presentation to look into some of the deaths that occurred for patients on the placebo rux arm relative to the Selleys rux arm, anything standing out that wasn't apparent at all? And initially? And then anything -- like, I guess, what should we be expecting beyond these initial top line data you reported at ASCO .

Richard Paulson: Yes. Thanks, Brian. I think overall, again, we'll have a totality of our results, as we shared at ASCO, but I'll turn to Reshma to expand on that.

Reshma Rangwala: Yes. Thanks, Brian, for the question. So absolutely, we're looking at the debt that occurred specifically the 23 deaths that were reported at the time of the top line, we haven't provided a greater granularity in terms of the types of deaths or the deaths across the 2 arms. I mean with that said, when I look at them, they're very consistent with what you would expect, right, not only in MF, but other oncology trials, right? So we're going to see a lot of deaths due to progression of disease, adverse events, et cetera.

So nothing inconsistent with what you would expect and more to come, right, as we continue to evaluate these data we'll certainly look at opportunities in which we can present it at upcoming medical congresses. .

Operator: And your next question comes from Ted Tenthoff from Piper Sandler.

Edward Tenthoff: Great. Thank you very much, and thanks for all the updates really an exciting time for Karyopharm and you guys just keep on fighting. So I appreciate that. I'm looking forward to the endometrial cancer data coming up. My question is on myelofibrosis and looking forward to the presentation at ASCO, can you give us a little bit more information about the potential timing or sort of preparation that you're doing for the meeting with the FDA, and when could we found out sort of where their head is on a potential sNDA, I think?

Richard Paulson: Yes. Again, I think overall, Ted, as we've shared, we're very pleased with the results and feel the SENTRY data is very compelling and meaningful for MF patients. And I'll turn to Reshma again to kind of expand on our planned engagement with the agency.

Reshma Rangwala: Yes, absolutely. And thank you, Ted, for the question. I just want to reiterate what Richard said. I think we're very compelled by the profile that we saw at the time of the top line results. It's not just about the spleen, right? We know that other Phase III trials have shown these spleen reductions. I think what is so compelling is that it's occurring in conjunction with this very promising overall survival signal, again, as early as the data cutoff, and then it's reflected by this rapid VAF reduction, which again is a potential signal of disease modification.

And we believe this is happening because of the unique aspects of XPO1 that are specifically targeting the clone causing this anticlonal activity and again, reflected in the clinical endpoints of SBR OS and then, of course, this disease modification as well. We look forward to engaging with the FDA. They've been strong partners with us from the very beginning of the SENTRY trial. And we hope to elaborate on our next steps over the course of the next couple of quarters?

Edward Tenthoff: Great. Excellent. Thank you so much. Looking forward to the presentation at ASCO.

Operator: And your next question comes from Colleen Kazi from Baird. .

Unknown Analyst: Congrats on the progress. Just for myelofibrosis, could you discuss the gating factors for potential [indiscernible] inclusion for selinexor? And Iseli is included on guidelines in the future. Could you discuss how you view this opportunity versus an approval? And I just had a quick follow-up after that as well.

Reshma Rangwala: Sure. I'll take the first part of the question, and thank you, Nick, for this important question around Compendia. So we know that NCCN and other compendia, they are independent bodies. With that said, from our understanding, they're constantly looking at the literature, whether it's published literature, presented data whether new treatments should be incorporated as part of their guidelines. We do expect that they will be well aware of the data that we present at ASCO in the next couple of weeks. . And then any publication that we do anticipate should be published in the middle of the year.

So we anticipate because, again, of the importance of these data that they will be convening either ad hoc or 1 of their scheduled meetings. And then hopefully, fingers cross, they agree the data are compelling and will be incorporated into the guidelines. I'll let Richard take the second part of your question.

Richard Paulson: Yes. Nick, and on the second part, and I think as you know, in myofibrosis is there only is 1 class of therapies. And again, ruxolitinib being approved over 15 years ago and really a high unmet need for these patients. as Reshma has touched on, it's very typical in these areas with new data to work to get that guideline listing pretty rapidly. And if you look at analogs over the years, rituximab mevacizumab, gemcitabine, et cetera, generated meaningful revenue based on physicians deciding to prescribe based on NCCN guidelines. So given the strong unmet need, .

I think you typically see if you only achieve NCCN listing without a label, products can achieve approximately about 50% of what peak may be if they had a way. So obviously, this isn't an area that we would actively promote to, but it's an area where physicians can choose to use a medicine to make sure they're fulfilling the best interest of the patients. Great. And then just on the follow-up for the endometrial for with 257 patients enrolling to ITT, that was just a bit under the 276 number originally, you said. Does that still provide sufficient powering to [indiscernible] the broader ITT population? .

Reshma Rangwala: Yes, yes. No, I really appreciate the question, Nick. So when we originally incorporated this new MITT population, again, that MITT population, by and large, consists of these patients who are going to be p53 wild type and MMR. Yes, you can anticipate a small subgroup of patients -- these tumors are going to be MMR and they're also medically eligible to receive a checkpoint inhibitor. But by and large, just assume this is going to be your p53 wild type. MMR proficient subgroup. When we originally incorporated that MITT, we assumed just based upon our proportion that, that 220 that we were targeting for that important MITT would likely equate to approximately 276 patients in that ITT.

What we found though is that the proportion was a little bit different. We are still very much targeting the 220 for the MITT, that's the key population for the FDA. And based upon the distribution, we landed up with 257 patients for the because the benefit of selinexor is driven by the P53 status and not the MMR status, Yes, we are very well powered to show both meaningful benefit in the MITT as well as ITT populations.

Operator: Our next question comes from Jenny from [indiscernible]

Richard Paulson: I don't think Yani is from Karyopharm, but Yani thank you for the question. .

Unknown Analyst: 1 It's aspirational. No -- operational execution here. I guess just 2 quick ones. Now that, that enrollment has completed here for the trial. Just looking back at the SIENDO results for endometrial. Obviously, the outcomes really improved with additional follow-up. And so curious if you can at least kind of directionally guide us in terms of thoughts on where median follow-up would fall here for this trial? Is it going to be kind of closer to what we saw for SIENDO top line or maybe close to the 30-plus month follow-up for the longer-term data cut.

Reshma Rangwala: Yes. I appreciate the question, JANI. So we anticipate that it's probably going to be in between the 2. So we had a top line results, which showed a median PFS specifically in that p53 wild-type subgroup of about 13.7 months, on the placebo arm was 3.1 months. We then performed subsequent cuts that demonstrated the median PFS had increased to approximately 22 months. And then, of course, the most recent data, that long-term follow-up increased again to the median PFS of about 28 months. So over those 3 cuts, we anticipate EC042 to likely land in between the top line and the second cut.

Now we'll see ultimately, when we cut the data, it's going to be driven by when the events occur, right? But that is my anticipation going into the top line results of ECO42.

Unknown Analyst: Got it. Okay. Very helpful. And then a quick follow-up on myelofibrosis. I guess with SENTRY 2, I think, slated to also put out data later this year. How does that kind of integrate with the effort here to get a publication out and potentially be included in Compendia listing?

Reshma Rangwala: Yes. Really exciting trial. I love this trial, right, because it really demonstrates hopefully will demonstrate monotherapy activity of selinexor in a front-line population. I do want to reiterate, it's not exactly the same population of SENTRI 2, largely because we do allow patients with platelet counts as low as 50,000 to be enrolled. So slightly different. But again, it allows us to better understand monotherapy activity of selinexor because investigators have that opportunity to add a JAK inhibitor as early as week 12. We also get some really important combination data. My hope is with this trial is that we could significantly change the landscape in MS, right? JAK inhibitors have always been thought to be in the backbone.

My hope is that we changed and we now change the paradigm to XPO1 inhibitors as that backbone. Important data, I think it's going to be relevant for the patient community as well as the physician community. We look forward to presenting the data in the second half of 2026. And then absolutely, if the guideline committee choose to adopt and incorporate that as part of the NCCN, obviously, that's up to them. But potentially, and again, pending the data, it could be a meaningful opportunity for this patient population.

Richard Paulson: Thanks, Jani. Looking forward to get your resume.

Operator: And your next question comes from Murray Raycroft from Jefferies.

Maurice Raycroft: Congrats on progress. Just wondering, when you meet with FDA on SENTRI, do you plan to share a more mature OS cut or other specific analyses, and who are you going to bring with you to the meeting? And is there more an ex-U.S. interaction strategy that you can share? Do you plan to meet with FDA first? Or do you want to align interactions with FDA and EMA?

Reshma Rangwala: Yes. Thanks, Maurice, for the question. Give me a chance to present the data at ASCO first. I don't want to get ahead of ourselves. I think there's going to be a lot of really important data that Dr. Mascarenas is going to present on behalf of all the investigators of SENTRI, and keep in mind, right, just as we reported a few weeks ago, even the SVR data, right, sort of like not only shows the We24data, but you also got some initial glimpses at week 36 as well. So we do has a little bit longer follow-up as part of SVR as part of those top line results. We haven't commented on any future data cuts, right?

But I will say that the study was designed to follow for long-term outcomes, especially for overall survival. . So patients and physicians remain blinded to the arm to which they were randomized. They continue on treatment. They continue again on the arm to which they were assigned and will continue to follow up for overall survival. We haven't guided on 1 of those subsequent steps or presentations will occur, but that's an opportunity based upon the trial design. In terms of the FDA 2, right? So as I mentioned earlier, we look forward to providing updates over the course of the next quarters.

At this point, we're not providing any granular details around any of our conversations either with the FDA or the broader rest of world regulatory agencies.

Richard Paulson: And overall, our team overall, Maurice, is working well with our partners globally, and as Reshma touched to here in the U.S. in terms of preparing for an sNDA and preparing and working with regulatory agencies around the world to really advance this rapidly given the high area of unmet need for these patients.

Maurice Raycroft: Got it. That's helpful. And then maybe a quick follow-up. For EHA, we're seeing the SENTRY 2 placeholder abstract there but the time -- the guidance for data second half, I guess, will EHA, is that something that -- is the data going to be at EHA or can you clarify on that point?

Reshma Rangwala: Yes. So that is a trial in progress -- so what's you're going to be at EHA, so that abstract, yes. So that's just going to be a trial in progress. And yes, we anticipate data from that trial again in the second half of this year. .

Operator: Thanks. And your next question comes from Jonathan Chang from Leerink Partners.

Jonathan Chang: First, can you remind me what dose is used in the 042 study and how that compares to the SIENDO study, and what gives you confidence in the 042 study dose. And as a follow-up to that, can you remind me what the safety profile and SIENDO looked like and what gives you confidence that patients can stay on selinexor in the maintenance setting for an extended period of time?

Reshma Rangwala: Yes, I really appreciate the question, Jonathan. So in Sendo, we had a dose of 80 milligrams of selinexor. So these patients took 80 milligrams once weekly, dual antiemetic was not consistently used in that protocol. The reason I mentioned both of those is because both of those differentiate with EC 042. So in EC042, the ongoing Phase III trial, we optimized the dose the dose is going to be the same SENTRY in that it's now 60 milligrams of selinexor again, dosed weekly. And in the EC042, we also require the incorporation of dual anti-emetics prior to each dose for the first 2 cycles.

And we did that because we know nausea and vomiting are known side effects of selinexor because of the kinetics, i.e., the onset usually occurs in the first 2 cycles. We mandated again just for those first 8 weeks. And then, of course, it's optional thereafter. How did we pick the dose? We really looked at a comprehensive data set. So again, we know end that the median dose was 60 milligrams a majority of the dose reductions occurred very early largely because of the nausea, vomiting and hematologic toxicity. We also look at comprehensive clin pharm data.

And this is really where the AEC is when we look at 80 milligrams, AUC is achieved with 80 milligrams. at 60 milligrams, there's a lot of overlap in terms of the progression-free survival that was observed across those 2 data points. So yes, a lot of confidence that, that 60 milligrams should be able to improve the safety profile of selinexor. This improvement in the safety profile is going to enable patients to stay on longer and hopefully drive what could be even potentially better efficacy than what we observed as part of Sendo.

One other thing that I will mention is that -- we know that the 60 milligrams does improve the safety and tolerability profile, I say that because of our SENTRY data, right? The SENTRY again, incorporated 60 milligrams in combination with ruxolitinib from that data set, very pleased to see reductions both in the rates as well as grades, especially of these GI toxicities of nausea and vomiting that have been well observed with selinexor.

Operator: [Operator Instructions] And your next question comes from Ted Tenthoff.

Edward Tenthoff: I didn't realize that there were openings at Karyopharm to submit my resume as well. Especially in the commercial group, since that's going to be expanding. And that was kind of my follow-up question for -- what additional prep are you guys doing both from a drug supply side as well as what kind of additions need to be made to the commercial organization if EC hits. And if we get on compendium, we'll ultimately get approval in myelofibrosis, how does that change to the organization?

Richard Paulson: Yes, I'll start at Ted. Great question, and I would love to talk, of course, if you're interested. But I'll turn to Sohanya for the later parts. But overall, the organization is really well established.

And obviously, he's been working over the last couple of years to make sure we leverage the strong capabilities we've built from a supply perspective, a very solid supply chain, very solid manufacturing here in the U.S. and well ready to drive and support uptake for endometrial cancer and myelofibrosis as we continue to work to achieve labels and be able to commercialize in both those areas, but I'll turn to Sohanya because meaningful work has been already in progress and meaningful opportunities as we move forward.

Sohanya Cheng: Thanks, Richard. Yes, I'm very proud of the established team that we've set up, and there is a significant amount of prelaunch activities underway right now. So I break it down into 2 components, the global medical and scientific affairs obviously, has been engaging strong with KOLs, strong presence at Congress is really understanding the treatment landscape and gathering those insights. From a commercial landscape, we've been extremely busy developing, messaging, both promotional branded messaging, payer messaging, key account mapping, segmentation and so on. So lots of work going on. Again, as Rich had mentioned, we have very strong capabilities.

And then from a customer-facing model standpoint, there is very strong overlap at the key accounts and coverage on the key accounts. Specifically in malofibrosis, it's a very concentrated group of accounts. . So we should be able to hit the ground running. In terms of endometrial cancer and the sales force coverage, again, strong coverage at key accounts, both in the academic and community medical oncology setting. In terms of the specialty gynocs, there'll obviously be an incremental increase in sales coverage -- This is the specialty Gaynon group really is also a very concentrated group of treating physicians. So we're very excited coming from a position of strength here and ready to have you join our team.

Operator: And your last question comes from Michael King from Rodman & Renshaw.

Michael King: A couple of quick ones, if I may. Just wondering, are the data that we'll see at ASCO, how closely is that going to map -- I mean I always know the FDA gets a lot more data than what we see in public. But just as far as the data analysis and the timing is concerned, how much more will -- when you take -- I guess the question, will you take another product of data before you present it to the FDA after investors and your peers see it at ASCO.

Reshma Rangwala: Yes. Thanks for the question. So we're not commenting on the data that we're presenting to the FDA, right? In general, as I mentioned earlier, we'll provide greater clarity on our interactions with the FDA and next steps over the course of the next couple of quarters. really excited about ASCO, right? I mean these are the first time the data are going to be presented by publicly. I mean, obviously really proud of the team. for all the work that they've put into it, really excited to see Dr. Mascarenas, one of the leading KOLs present these data on behalf of all the SENTRY investigators, .

And I think it's a great opportunity for people to really appreciate, right, sort of the benefit that selinexor in combination with ruxolitinib can provide to this population and the key differentiating aspects of this combination relative to other treatments that have been evaluated in myelofibrosis and certainly the current standards of care. So I hope you can be there live. I think it's going to be a great show.

Michael King: I wouldn't miss it for all the money.

Reshma Rangwala: That's awesome. That's great -- that's great. But yes, I think it's going to be a really great opportunity, especially for the patients.

Michael King: But to pick up on your comment about precedent, FDA is a precedent driven organization. And all the approved MF drugs have had some kind of a glitch in their data set. I mean, so you guys didn't hit SVR35, but you did hit VAF, you did hit survival. I just want -- if you can just help us put it in the context relative to approvals for things like acitinib momelotinib, et cetera.

Reshma Rangwala: Sure. So we know that pacritinib and momoletinib, those are 2 great examples because while their focus also was on SVR and TSS pacritinib clearly got an accelerated approval on SBR only really important precedents because I think it highlights the FDA's appreciation and the importance of as an important endpoint in myelofibrosis. In momoletinib, I think that example is also very relevant. -- although those trials were also focused on SBR, TSS, those trials didn't necessarily show benefit as per their statistical analysis plan. In this situation, the FDA definitely showed flexibility, I would say, creativity in identifying populations and other endpoints that clearly demonstrate that unmet need.

So I provide those examples because it shows that this FDA is really willing to look at the totality of the data, the data beyond just what's included as part of the primary end points. they're willing to look at other measures of clinical benefit and potentially provide a path forward for those meaningful treatments.

Operator: And there are no further questions at this time, Mr. Richard Paulson, President and Chief Executive Officer, you may continue.

Richard Paulson: Thank you, operator, and thank you again to everyone for joining us today and for your continued interest in Karyopharm. As you've heard, we are very encouraged by the progress we have made across our late-stage programs, and remain very focused and disciplined in our execution to the next stage of important milestones. Most importantly, we remain committed to advancing selinexor's potential to bring meaningful new options to patients with both endometrial cancer or in the areas of endometrial cancer and myelofibrosis. And as we've heard, we look forward to seeing many of at ASCO during our oral presentation of our SENTRY results. Thank you for joining us today.

Operator: Ladies and gentlemen, this does conclude your conference call for today. We thank you very much for your participation, and you may now disconnect. Have a great day, everyone.

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