Karyopharm Therapeutics Inc. 2026 Q2 Earnings Call

Good morning, and thank you all for joining us on today's conference call to discuss Karyopharm's second quarter 2026 financial results and recent company progress. We issued a press release this morning detailing our financial results for the second 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 shown on slide 2, I am joined by Richard, Reshma, Sohana, and Lori, who will review our second quarter financial results, provide an update on the significant progress we have made advancing our myelofibrosis program, discuss the clinical and regulatory momentum supporting our planned sNDA submission, and review our financial position and capital allocation priorities.

Before we begin our formal comments, I will 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 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 will now turn the call over to Richard. Please turn to slide 5.

Thank you, Brendan, and good morning, everyone, and thank you for joining us today. The second quarter marked the beginning of an important new chapter for Karyopharm as we advanced selinexor from a compelling and differentiating phase III dataset toward our planned Supplemental New Drug Application under the FDA's Accelerated Approval pathway for patients with myelofibrosis. Over the past several months, we've remained focused, moved with urgency, and executed against an ambitious plan. From generating and presenting the SENTRY data to publishing the results in the Journal of Clinical Oncology to working collaboratively with the FDA to establish a regulatory pathway as we prepare our planned submission. The SENTRY study demonstrated statistically significant, rapid, deep, and sustained spleen responses together with preliminary overall survival findings and evidence of potential disease modification.

These findings have now been presented at leading international scientific meetings, published in a peer-reviewed journal, and continue to generate strong interest globally among the hematology community. Taken together, we believe these data reinforce the potential for selinexor to fundamentally change the treatment of patients with myelofibrosis. That same focus, urgency, and commitment to execution continues to guide every step as we advance into the next phase of our myelofibrosis program. Turning to slide 6. As we announced in July, we remain on track to submit our sNDA in August as we complete the final elements of our submission in collaboration with the FDA. Our interactions with the agency continue to be constructive, and we remain focused on delivering a high-quality submission. Our confidence in this opportunity continues to be grounded in both the consistency of the SENTRY data and our constructive regulatory engagement.

If approved, selinexor in combination with ruxolitinib would be the first approved combination therapy for patients with myelofibrosis, introducing a novel therapeutic mechanism for the treatment of this disease. Turning to slide 7. While our focus today is on the important progress we've made in myelofibrosis, I'd also like to briefly address the top-line results from our phase III XPORT-EC-042 study and the actions we've taken following those results. While we were disappointed that the study had not achieved statistical significance for its primary endpoint in the MITT population, I want to thank the patients, investigators, and study teams whose commitment made this important trial possible. Although we observed a numerical improvement in median progression-free survival favoring selinexor, the study did not meet the statistical threshold required to support our development plans in endometrial cancer.

Following these results, we made the deliberate decision to sharpen our focus on hematology with our opportunities in myelofibrosis and multiple myeloma, where we believe selinexor has the greatest potential to improve patients' lives and create long-term shareholder value. While we continue to follow patients in the near term, we are meaningfully reducing planned investment in endometrial cancer. Moving forward, our priorities are clear. Advancing our myelofibrosis program through the regulatory process, continuing to grow our multiple myeloma business, and leveraging the commercial, medical, and market access capabilities we have built over many years to support a rapid and efficient launch in myelofibrosis, if approved. As we execute against these priorities, we are equally focused on disciplined capital allocation.

As we'll discuss, we are actively evaluating a range of financing opportunities and strategic alternatives with the objective of maximizing long-term shareholder value while preserving strategic flexibility as we advance our myelofibrosis program through these important milestones. We are approaching this with the same focus, urgency, and discipline that have characterized our execution over the past several months. Looking ahead, we believe the company is entering one of the most important periods in its history. Turning to slide 8, over the coming quarters, we expect several important milestones, beginning with the potential inclusion in the treatment guidelines in compendia, our planned sNDA submission in myelofibrosis this month, followed by potential FDA filing acceptance of the sNDA and its potential to be accepted for Priority Review, and ultimately, a potential approval and launch as early as the first quarter of 2027.

Additionally, we remain on track to report top-line data from the 60-milligram cohort of the phase II SENTRY-2 study in the second half of this year, which we expect will further establish the role of selinexor in myelofibrosis. We are entering this next phase with a clear strategy, a focused organization, and an established hematology platform that positions us well for what lies ahead. With that, I'll turn the call over to Reshma, who will discuss the clinical and regulatory foundation supporting our planned submission for the first-ever combination and why we believe selinexor as a novel therapeutic mechanism has the potential to fundamentally change the treatment of patients with myelofibrosis.

Reshma? Thank you, Richard. As Richard discussed, we believe selinexor has the potential to fundamentally change the treatment of patients with myelofibrosis.

I'd like to spend the next few minutes discussing why we believe the scientific evidence supporting that opportunity has continued to strengthen, why it supports our planned sNDA submission, and how we continue to build the clinical foundation for selinexor in myelofibrosis. Turning to slide 10, the biological rationale for combining XPO1 and JAK inhibition is compelling. JAK-STAT activation is a key driver of malignant clone proliferation, splenomegaly, and disease-related symptoms, while XPO1 activity is important for malignant cell survival. By targeting these complementary pathways simultaneously, we believe selinexor has the potential to complement JAK inhibition and improve outcomes beyond symptom control alone. Turning to slide 11, myelofibrosis remains a disease with a high unmet need, given clinical activity with the currently approved therapies is modest.

As a result, spleen volume reduction of at least 35% is observed in less than a third of patients. Overall survival improvements are limited, and meaningful modification of the underlying disease is not observed. Turning to slide 12, a distinctive profile has been observed from the SENTRY trial, given the compelling SVR35 results that are rapid, deep, and sustained. A promising OS signal, a first-of-a-kind prediction between SVR35 and OS, and a safe and manageable adverse event profile. These data appear to support SVR35 as a reasonably likely surrogate endpoint, enabling an sNDA under the Accelerated Approval pathway. Turning to slide 13, at week 24, a nearly double spleen response rate was observed with the combination of selinexor plus ruxolitinib versus ruxolitinib alone. What is particularly important is the quality and kinetics of that response.

As shown on slide 14, the responses were rapid, emerging as early as week 12, and deep, with greater average spleen volume reductions relative to baseline observed with the combination. Both response rates and depth of response were sustained through week 36. Importantly, as seen on slide 15, the benefit was consistent across pre-specified patient subgroups, reinforcing the robustness of the treatment effect in the vast majority of frontline myelofibrosis patients. Especially important is the subgroup analysis by ruxolitinib dosing, as seen on slide 16. Even with average suboptimal doses of ruxolitinib less than 15 milligrams per day, SVR35 rates with the combination were as high as 50% compared to 0 observed with ruxolitinib alone, indicating that with the combination, SVR35 is driven by selinexor and supported by modest doses of ruxolitinib.