Material Event (Form 8-K)

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.

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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.