Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced positive top-line results from the Phase 3 portion of the randomized, double blind, placebo controlled, cross-over, SEAL study evaluating single agent, oral XPOVIO® (selinexor) versus matching placebo in patients with advanced unresectable dedifferentiated liposarcoma. The SEAL study met its primary endpoint of a statistically significant increase in progression-free survival (PFS); hazard ratio=0.70; p=0.023. These data indicate that treatment with XPOVIO reduced the risk of disease progression or death by approximately 30%, compared to placebo. The trial allowed patients on placebo with objective progression to cross over to the XPOVIO treatment arm. Among those patients who received XPOVIO, there was a trend towards an improvement in the median overall survival compared to those patients who began on the placebo arm of the study and never crossed over to the XPOVIO treatment arm. The safety profile for XPOVIO was consistent with previous clinical studies with fewer hematologic and infectious adverse events as compared to XPOVIO studies in patients with multiple myeloma and diffuse large B-cell lymphoma (DLBCL).

The detailed results from the SEAL study will be presented virtually in an oral presentation at the Connective Tissue Oncology Society (CTOS) Annual Meeting on Friday, November 20, 2020 at 10:30 AM ET.

"We are delighted to share these significant top-line results from the Phase 3 portion of the SEAL study, the first, late-stage clinical data for XPOVIO in a solid tumor indication," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "The top-line results from the SEAL study are particularly encouraging as advanced dedifferentiated liposarcoma represents a very difficult to treat cancer with no established standard of care and limited treatment options available to patients. XPOVIO may be particularly promising as it represents the first oral therapy to show activity in patients with previously treated liposarcoma. We look forward to presenting the detailed results at the upcoming CTOS Annual Meeting and plan to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2021 requesting the approval of XPOVIO to treat the patient population studied in SEAL. If approved, XPOVIO would represent the first oral, non-chemotherapy agent available for patients with dedifferentiated liposarcoma. The encouraging data from the SEAL study also provide additional rationale for advancing the clinical development of XPOVIO in other solid tumor indications, including in endometrial, glioblastoma, lung and other cancers where Karyopharm is currently conducting clinical studies."

XPOVIO is currently approved by the FDA as a treatment for patients with relapsed or refractory multiple myeloma and relapsed or refractory DLBCL. XPOVIO is currently the only XPO1 inhibitor approved by the FDA and has been extensively tested in clinical trials across numerous cancer indications worldwide since 2012. Karyopharm has also submitted a supplemental New Drug Application (sNDA) for XPOVIO that is currently under review by the FDA for the expansion of XPOVIO's label to include XPOVIO as a treatment for patients with multiple myeloma after at least one prior line of therapy. The sNDA has been assigned an action date by the FDA of March 19, 2021 under the Prescription Drug User Fee Act (PDUFA).The full Prescribing Information for XPOVIO is available at www.XPOVIO.com.