Karyopharm Therapeutics (NASDAQ:KPTI) said it remains on track to submit a supplemental New Drug Application in August for selinexor in combination with ruxolitinib for patients with myelofibrosis, while it evaluates financing options and strategic alternatives ahead of a September debt payment.
The company’s planned filing would seek accelerated approval based on results from the Phase III SENTRY study. Richard said the application could support the first approved combination therapy for myelofibrosis if cleared by the Food and Drug Administration. Karyopharm said a potential approval and launch could occur as early as the first quarter of 2027.
Myelofibrosis filing centers on SENTRY data
The filing itself will be based primarily on week-24 data, including the study’s spleen volume reduction endpoint. The company said selinexor plus ruxolitinib produced a nearly doubled spleen response rate at week 24 compared with ruxolitinib alone. It also reported that responses emerged as early as week 12, were deeper than with ruxolitinib alone, and remained sustained through week 36.
Karyopharm said the FDA provided written feedback indicating that a spleen volume reduction of at least 35%, known as SVR35, appears to qualify as a reasonably likely surrogate endpoint for predicting overall survival. Reshma said the company believes the combination of SENTRY data, the relationship observed between SVR35 and survival, and the unmet need in myelofibrosis supports its accelerated-approval approach.
At the top-line analysis, the company reported an overall-survival hazard ratio of 0.43, although patients remain under follow-up and the survival data are still maturing. It also cited a post-hoc landmark analysis suggesting that patients achieving SVR35 at week 24 had improved overall survival regardless of treatment assignment.
Karyopharm plans to submit additional longer-term data as available, including some data from patients followed through week 48. However, Reshma said the application’s primary emphasis will remain on week-24 results. The company expects top-line data from the 60-milligram cohort of its Phase II SENTRY-2 study in the second half of 2026.
Company narrows focus after endometrial cancer setback
Karyopharm also discussed the Phase III XPORT-EC-042 study in endometrial cancer, which did not achieve statistical significance on its primary endpoint in the MITT population. The company said it observed a numerical improvement in median progression-free survival favoring selinexor, but the result did not meet the statistical threshold needed to support further development plans in that indication.
Following the result, Karyopharm said it is meaningfully reducing planned investment in endometrial cancer and sharpening its focus on hematology, particularly myelofibrosis and multiple myeloma. The company will continue near-term patient follow-up and complete remaining trial-related clinical and operational activities.
Richard said the company intends to use its existing hematology infrastructure, built through commercialization of XPOVIO, to support a potential myelofibrosis launch. Sohana said the company already has medical, market-access, key-account and patient-support capabilities that could be used without building a commercial organization from the ground up.
Karyopharm estimates that approximately 20,000 people in the U.S. are living with myelofibrosis, with roughly 4,000 newly treated frontline patients annually. The company said selinexor plus ruxolitinib could potentially generate up to approximately $1 billion in peak annual U.S. revenue, if approved.
XPOVIO revenue rises, but total revenue declines
For the second quarter, Karyopharm reported total revenue of $33.4 million, down from $37.9 million in the prior-year period. The decline reflected the end of Menarini’s reimbursement of development-related expenses at the end of 2025, which reduced quarterly revenue by about $6.5 million year over year.
U.S. XPOVIO net product revenue rose to $30.8 million from $29.7 million a year earlier. The company said underlying demand was relatively consistent with the prior-year quarter despite a more competitive multiple-myeloma treatment environment.
- Research and development expense was $29 million, down 12% year over year.
- Selling, general and administrative expense was $25.9 million, down 9% year over year.
- Net loss was $67 million, compared with $37.3 million in the prior-year quarter, including non-cash mark-to-market adjustments tied to the company’s financing structure.
Karyopharm reaffirmed its 2026 outlook for total revenue of $130 million to $150 million, including expected U.S. XPOVIO net product revenue of $115 million to $130 million. It continues to project combined R&D and SG&A expense of $230 million to $245 million, excluding certain potential one-time costs related to the endometrial cancer program and financing or strategic-transaction evaluations.
Liquidity and debt payment remain immediate priorities
Karyopharm ended the quarter with $65.4 million in cash equivalents, restricted cash and investments. Based on its operating plan, the company said existing liquidity and anticipated cash flow from product, license and other revenue are expected to fund operations into September 2026.
The company has a $16.8 million principal payment due Sept. 10 under its senior secured term loan. Karyopharm said that if it makes the payment without additional financing or a lender waiver, its cash and investments would fall below a $10 million minimum-liquidity covenant, constituting an event of default under the term loan.
Richard said Karyopharm is in discussions with lenders and is evaluating financing opportunities and strategic alternatives intended to extend its cash runway, preserve flexibility and support upcoming regulatory milestones.
About Karyopharm Therapeutics (NASDAQ:KPTI)
Karyopharm Therapeutics (NASDAQ: KPTI) is a clinical-stage biopharmaceutical company focused on discovering and developing novel first-in-class drugs that target the nuclear export protein XPO1. The company’s lead product, selinexor (marketed as XPOVIO), is an oral selective inhibitor of nuclear export (SINE) compound approved for treatment of multiple myeloma and diffuse large B-cell lymphoma. In addition to selinexor, Karyopharm’s pipeline includes second-generation SINE compounds and combination studies in solid tumors and hematologic malignancies.
Founded in 2008 and headquartered in Newton, Massachusetts, Karyopharm has built a research platform around modulation of nuclear export pathways.
