Karyopharm outlines trial miss and FDA sNDA plan

Karyopharm Therapeutics reported topline Phase 3 results from its XPORT-EC-042 trial of selinexor maintenance in TP53 wild-type advanced or recurrent endometrial cancer; the study did not meet its primary endpoint of progression free survival.

Rhea-AI Filing Summary

Karyopharm Therapeutics reported topline Phase 3 results from its XPORT-EC-042 trial of selinexor maintenance in TP53 wild-type advanced or recurrent endometrial cancer; the study did not meet its primary endpoint of progression free survival.

In the modified intent-to-treat population (n=236), median PFS was 12.75 months with selinexor versus 7.43 months with placebo (hazard ratio 0.76; one-sided p=0.0791), and safety was consistent with the established profile, with no new signals. Ongoing selinexor studies in other indications are unchanged.

Karyopharm plans an August 2026 supplemental New Drug Application seeking FDA accelerated approval of selinexor plus ruxolitinib in myelofibrosis, based on Phase 3 SENTRY data showing statistically significant SVR35 spleen responses at week 24, supportive survival and biomarker findings, and overall safety. The company is also exploring financing transactions and strategic alternatives with advisors, including Centerview Partners.

Positive

• Phase 3 SENTRY data support planned myelofibrosis sNDA: a randomized, double-blind trial of selinexor plus ruxolitinib versus placebo plus ruxolitinib showed a statistically significant improvement in SVR35 at week 24, rapid and sustained spleen responses, a promising overall survival signal, biomarker reductions and a supportive safety package for an accelerated approval filing.

Negative

• XPORT-EC-042 did not meet its primary PFS endpoint: the Phase 3 trial of selinexor as maintenance-only therapy in TP53 wild-type advanced or recurrent endometrial cancer failed to achieve its prespecified progression free survival objective in sequential testing compared with placebo.
• Going-concern uncertainty remains a key risk: risk disclosures state that substantial doubt exists regarding the company’s ability to continue as a going concern, emphasizing reliance on successful financing or strategic transactions.

Filing Explained

The planned myelofibrosis application remains unfiled, while Karyopharm discloses substantial doubt about continuing as a going concern.

The filing says Karyopharm plans to submit a supplemental application for selinexor plus ruxolitinib in myelofibrosis in August 2026, but the FDA requires further discussion and additional data before submission. The regulatory step therefore remains planned rather than filed, and the filing also states that substantial doubt exists about the company’s ability to continue as a going concern.

The company says it will address the FDA’s requests before submission and seek Priority Review, which would depend on FDA granting that request. Its financing and strategic-alternative efforts remain exploratory; no transaction or terms are disclosed.

A going-concern qualification is a defined disclosure of substantial doubt about a company’s ability to fund operations for the next 12 months; here, the term appears in the filing’s risk disclosures.

The specific milestones to monitor are the additional FDA data discussions and the planned August 2026 submission, neither of which is reported as completed in this filing.

8-K Event Classification

Item 8.01 — Other Events

1 item

Item 8.01 Other Events Other

Voluntary disclosure of events the company deems important to shareholders but not covered by other items.

Key Figures

Median PFS selinexor arm: 12.75 months Median PFS placebo arm: 7.43 months Hazard ratio for PFS: 0.76 +5 more

8 metrics

Median PFS selinexor arm 12.75 months Modified intent-to-treat population in XPORT-EC-042

Median PFS placebo arm 7.43 months Modified intent-to-treat population in XPORT-EC-042

Hazard ratio for PFS 0.76 Selinexor vs placebo in mITT; 95% CI 0.51–1.12; one-sided p=0.0791

One-sided p-value 0.0791 PFS comparison in the modified intent-to-treat population

mITT population size 236 patients Patients included in the modified intent-to-treat analysis in XPORT-EC-042

Planned sNDA timing August 2026 Target submission date for selinexor plus ruxolitinib in myelofibrosis

Priority Review target period approximately six months PDUFA target action date after FDA receipt if Priority Review is granted

SVR35 assessment timepoint week 24 Timepoint for spleen volume reduction ≥35% endpoint in SENTRY trial

Key Terms

progression free survival, modified intent to treat population, supplemental New Drug Application, accelerated approval, +2 more

6 terms

progression free survival medical

"the trial did not meet its primary endpoint of <b>progression free survival</b>"

Progression free survival is the length of time during and after a treatment when a disease, such as cancer, does not get worse or spread. It is an important measure because longer periods of stability can indicate that a treatment is effectively controlling the condition. For investors, it provides insight into the potential durability and success of a therapy or medication.

modified intent to treat population medical

"a <b>modified intent to treat population</b> that included patients with TP53 wild-type tumors"

supplemental New Drug Application regulatory

"plans to submit a <b>supplemental New Drug Application</b> to the U.S. Food and Drug Administration"

A supplemental new drug application is a request submitted to regulatory authorities to make changes to an existing approved medication, such as adding new uses, strengths, or formulations. For investors, it signals that a pharmaceutical company is seeking approval for new product developments or expanded applications, which can impact the company's future sales, market potential, and stock value.

accelerated approval regulatory

"used to support an sNDA under the <b>accelerated approval</b> pathway"

Accelerated approval is a process that allows new medical treatments to be approved more quickly than usual if they address serious or life-threatening conditions and show promising early results. For investors, it signals that a treatment may reach the market sooner, potentially boosting a company's prospects, but it also involves some uncertainty since full evidence of effectiveness is still being gathered.

Priority Review regulatory

"the Company intends to request <b>Priority Review</b> at the time of submission"

Priority review is a regulatory fast-track that shortens the time an agency spends evaluating a drug, vaccine or medical device application so a decision comes sooner than normal. For investors, it matters because a faster review is like an express lane to market: it can speed revenue potential and reduce regulatory uncertainty, but it does not guarantee approval and still requires the product to meet safety and effectiveness standards.

variant allele frequency medical

"a promising overall survival signal, reductions in <b>variant allele frequency</b> and the overall safety data package"

Variant allele frequency is the proportion of DNA molecules in a sample that carry a specific genetic change, usually measured by sequencing and expressed as a percentage. Think of it as the share of colored marbles in a jar: a higher share means the mutation is more common in the measured tissue or virus. For investors, VAF matters because it helps assess how strongly a mutation drives disease, how likely a targeted therapy will work, and whether resistance or diagnostic tests will be commercially relevant.

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Karyopharm (KPTI) report from the XPORT-EC-042 endometrial cancer trial?

Karyopharm reported that Phase 3 XPORT-EC-042 did not meet its primary endpoint of progression free survival in TP53 wild-type advanced or recurrent endometrial cancer. Selinexor was tested as once-weekly oral maintenance therapy versus placebo after prior treatment.

How did selinexor perform on progression free survival in KPTI’s mITT population?

In the modified intent-to-treat population (n=236), selinexor achieved a median PFS of 12.75 months versus 7.43 months for placebo, with a hazard ratio of 0.76 (95% CI: 0.51–1.12) and a one-sided p-value of 0.0791, showing a numerical trend favoring selinexor.

What is Karyopharm (KPTI) planning for selinexor in myelofibrosis?

Karyopharm plans to file a supplemental New Drug Application in August 2026 seeking FDA accelerated approval of selinexor plus ruxolitinib for myelofibrosis, supported by Phase 3 SENTRY data on spleen volume reduction, overall survival signals, variant allele frequency reductions and safety.

What feedback did the FDA give Karyopharm (KPTI) on the myelofibrosis sNDA?

FDA feedback indicated that SVR35 can serve as a reasonably likely surrogate endpoint for accelerated approval in myelofibrosis, with long-term overall survival from SENTRY planned to confirm benefit. Additional FDA correspondence requested further discussion and data on how the sNDA will support conversion to traditional approval.

What strategic and financing actions is Karyopharm (KPTI) exploring?

Karyopharm, assisted by advisors including Centerview Partners, is exploring financing transactions to extend its cash runway and broader strategic alternatives. The company cautions there is no assurance any transaction will occur or what its terms might be, and does not plan updates until a specific deal is approved or disclosure is warranted.

Do the XPORT-EC-042 results affect other selinexor trials for KPTI?

Karyopharm stated that the XPORT-EC-042 outcome does not affect ongoing selinexor trials in other potential indications. Programs such as the Phase 3 SENTRY myelofibrosis study continue as planned, with data being used to support an accelerated approval strategy.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Available on EDGAR 07/31/2026 - 08:30 AM Accepted by SEC EDGAR 07/31/2026 - 08:30 AM Learn about SEC filing dates

false 0001503802 0001503802 2026-07-30 2026-07-30

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of

the Securities Exchange Act of 1934

Date of report (Date of earliest event reported): July 30, 2026

Karyopharm Therapeutics Inc.

(Exact Name of Registrant as Specified in Charter)

Delaware		001-36167		26-3931704
(State or Other Jurisdiction of Incorporation)		(Commission File Number)		(IRS Employer Identification No.)

85 Wells Avenue, 2nd Floor Newton, Massachusetts		02459
(Address of Principal Executive Offices)		(Zip Code)

Registrant’s telephone number, including area code: (617) 658-0600

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock, $0.0001 par value		KPTI		Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 8.01 Other Events.

XPORT-EC-042 Trial Topline Data

On July 30, 2026, Karyopharm Therapeutics Inc. (the “Company”) announced topline results from its Phase 3 XPORT-EC-042 trial evaluating selinexor as a maintenance-only therapy compared to placebo in adult patients with TP53 wild-type advanced or recurrent endometrial cancer. The trial did not meet its primary endpoint of progression free survival (“PFS”). In the trial, patients were randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The trial included two patient populations, for which the primary endpoint of PFS was designed to be tested sequentially: (1) a modified intent to treat population (“mITT”) that included patients with either (a) TP53 wild-type tumors with proficient mismatch repair status (“pMMR”) or (b) TP53 wild-type tumors with deficient mismatch repair status (“dMMR”), who are medically ineligible to receive checkpoint inhibitors; and (2) the trial’s original intent to treat (“ITT”) population, which included all patients enrolled in the trial whose tumors are TP53 wild-type, regardless of MMR status.

A trend favoring the selinexor arm was observed in the mITT population (n=236), with a median PFS of 12.75 months in the selinexor arm compared to 7.43 months in the placebo arm (hazard ratio=0.76 [95% CI: 0.51, 1.12]; one-sided p-value=0.0791).

The safety and tolerability profile of selinexor was consistent with its established safety profile, with no new safety signals observed. The Company intends to complete a full evaluation of the data from the XPORT-EC-042 trial and plans to present the data at a future medical meeting. The results of the XPORT-EC-042 trial do not affect ongoing trials of selinexor in other potential indications.

Myelofibrosis Update

On July 30, 2026, the Company announced that it plans to submit a supplemental New Drug Application (“sNDA”) to the U.S. Food and Drug Administration (“FDA”) in August 2026 seeking accelerated approval of selinexor in combination with ruxolitinib for the treatment of patients with myelofibrosis.

The planned submission follows productive engagements with the FDA, including written feedback that spleen volume reduction ≥ 35% (“SVR35”) appears to qualify as a reasonably likely surrogate endpoint to predict overall survival and can be used to support an sNDA under the accelerated approval pathway. The Company plans to use overall survival data from long-term follow-up of the ongoing Phase 3 SENTRY trial to verify clinical benefit. Overall survival is a pre-specified secondary endpoint of SENTRY. The trial does not permit patient crossover; patients, investigators and the Karyopharm study team remain blinded to treatment assignment during ongoing follow-up.

The planned sNDA will be based on results from the randomized, double-blind, Phase 3 SENTRY trial that compared selinexor in combination with ruxolitinib against placebo in combination with ruxolitinib, including the statistically significant improvement in SVR35 at week 24, the rapid, deep and sustained nature of the spleen responses, a promising overall survival signal, reductions in variant allele frequency and the overall safety data package.

The Company intends to request Priority Review at the time of submission of the sNDA, which, if granted, would result in a Prescription Drug User Fee Act target action date approximately six months following the FDA’s receipt of the application.

The Company is actively engaged with the FDA on the final details of the sNDA submission. Contemporaneously with the Company’s announcement, the Company received additional correspondence from the FDA indicating that the FDA requires further discussion on the data to be used to support the sNDA and convert potential accelerated approval to traditional approval. The Company intends to address the FDA’s requests and provide the FDA with additional data and information prior to the submission of the sNDA in August 2026.

2

Corporate Update

The Company, with the assistance of its advisors, including its financial advisor Centerview Partners, is exploring potential financing transactions to extend its cash runway along with strategic alternatives in order to maximize both near and long-term value for all stakeholders. The Company’s ability to successfully consummate a financing transaction or execute on a strategic alternative is dependent on a number of factors. There is no assurance that these efforts will result in any type of transaction or, if they do, what the ultimate terms of any such transaction would be. The Company does not intend to discuss or disclose further developments unless and until its Board of Directors has approved a specific transaction or the Company otherwise determines that further disclosure is appropriate.

Forward-Looking Statements

This Current Report on Form 8-K contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor and eltanexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, and other diseases; expectations with respect to the clinical development plans; expectations with respect to the timing and submission of a potential sNDA for selinexor in combination with ruxolitinib in myelofibrosis; the Company’s ongoing engagement with the FDA; the potential availability of the accelerated approval pathway for selinexor in myelofibrosis; whether the FDA will agree to the use of long-term overall survival data from the SENTRY trial to confirm the SVR35 benefit observed at week 24; the potential availability of priority review; and the Company’s exploration of financing transactions and strategic alternatives. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond the Company’s control, that may cause actual events or results to differ materially from the Company’s current expectations. For example, there can be no guarantee that the Company will successfully complete any financing or other strategic transaction on terms acceptable to the Company or at all. Additionally, there can be no guarantee that the Company will successfully commercialize XPOVIO or that any of the Company’s drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of the Company’s drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of the Company’s drug candidate portfolio will result in stock price appreciation. Management’s expectations and, therefore, any forward-looking statements in this Current Report on Form 8-K could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of the Company’s drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of the Company’s drug candidates that receive regulatory approval; the Company’s results of clinical trials and preclinical trials, including subsequent analysis of existing data and new data received from ongoing and future trials; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical trials; the ability of the Company or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; the Company’s ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; substantial doubt exists regarding the Company’s ability to continue as a going concern; development or regulatory approval of drug candidates by the Company’s competitors for products or product candidates in which the Company is currently commercializing or developing; and the Company’s ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, which was filed with the Securities and Exchange Commission (SEC)

3

on May 14, 2026, and in other filings that the Company may make with the SEC in the future. Any forward-looking statements contained in this Current Report on Form 8-K speak only as of the date hereof, and, except as required by law, the Company expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

4

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

				KARYOPHARM THERAPEUTICS INC.
Date: July 31, 2026				By:		/s/ Michael Mano
						Michael Mano
						Executive Vice President, Chief Legal Officer and Secretary

5

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