Karyopharm Therapeutics Q1 Earnings Call Highlights
Karyopharm Therapeutics (NASDAQ:KPTI) said it entered 2026 with several near-term clinical and regulatory catalysts, led by new Phase 3 data in myelofibrosis and an expected midyear readout in endometrial cancer, while reporting higher first-quarter revenue and reaffirming full-year guidance.
On the company’s first-quarter earnings call, President and CEO Richard Paulson said Karyopharm has focused its organization on advancing late-stage clinical programs, maintaining its commercial base in multiple myeloma and managing expenses as it approaches “significant value-creating milestones.”
Paulson said the company is now focused on regulatory and scientific engagement for its Phase 3 SENTRY trial in myelofibrosis, preparing for top-line results from XPORT-EC-042 in endometrial cancer and maintaining financial discipline. He said Karyopharm’s current operating plan is expected to fund operations into late in the third quarter of 2026.
SENTRY Data Show Spleen Volume Benefit, Survival Signal
Chief Medical Officer and Head of Research Reshma Rangwala said Karyopharm remains encouraged by top-line results from SENTRY, which evaluated selinexor in combination with ruxolitinib in myelofibrosis. The company said the combination produced rapid and sustained spleen volume reductions, with the co-primary endpoint of SVR35 at week 24 reached by 50% of patients on the combination versus 28% on ruxolitinib alone. Rangwala said that result was statistically significant, with a P value of less than 0.0001.
The trial’s second co-primary endpoint, symptom improvement at week 24, was not statistically significant by absolute total symptom score difference, though Rangwala said patients in both arms had “important and similar improvement from baseline.”
Karyopharm also highlighted what it described as an “intriguing” overall survival signal. Rangwala said the overall survival hazard ratio was 0.43 at the time of the top-line data, with a nominal P value of 0.0222. She said post hoc analyses showed SVR35 predicts overall survival, consistent with previously published analyses in other myelofibrosis trials.
The company also pointed to variant allele frequency reductions as potential evidence of disease modification. Rangwala said 32% of patients receiving selinexor plus ruxolitinib had at least a 20% reduction in variant allele frequency, which she said may indicate an effect on disease biology.
Rangwala said the combination had a generally manageable tolerability profile, consistent with the known profiles of the individual agents, and that no new safety signals were observed. She said use of a lower selinexor dose and dual antiemetics improved tolerability compared with an earlier Phase 1 study.
Karyopharm said SENTRY data have been selected for a late-breaking oral presentation at ASCO, and the company expects a manuscript in a peer-reviewed journal in mid-2026. Rangwala said Karyopharm looks forward to discussions with the FDA, though she did not provide a specific timeline for regulatory feedback.
Endometrial Cancer Readout Expected in Mid-2026
The company’s next major catalyst is XPORT-EC-042, a Phase 3 trial in endometrial cancer. Paulson said enrollment is complete and top-line data remain expected in mid-2026.
Rangwala said the study is focused on patients with TP53 wild-type endometrial cancer, especially those with mismatch repair-proficient tumors, where Karyopharm sees a significant unmet need and no approved personalized biomarker-driven maintenance-only therapy. She said approximately half of endometrial cancer patients are TP53 wild-type and about 80% have MMR-proficient tumors.
Rangwala reviewed prior SIENDO trial results, saying the TP53 wild-type subgroup had median progression-free survival of 13.7 months for selinexor versus 3.7 months for placebo at top line, corresponding to a hazard ratio of 0.41. With longer-term follow-up, she said median PFS in the selinexor arm extended to 28.4 months, with a hazard ratio of 0.44. In TP53 wild-type, MMR-proficient patients, she said median PFS approached 40 months at long-term follow-up, with a hazard ratio of 0.36.
In the ongoing XPORT-EC-042 trial, selinexor is being dosed at 60 milligrams once weekly, compared with 80 milligrams in SIENDO. Rangwala said the study also mandates dual antiemetics during the first two cycles, when nausea and vomiting are most likely to occur. She said the adjusted dose and supportive care approach could improve tolerability and help patients remain on treatment longer.
The trial enrolled 257 patients in the intent-to-treat population, including approximately 220 patients in the modified intent-to-treat population, which is the primary analysis population. Rangwala said the study will first assess progression-free survival in the mITT population, with alpha passing sequentially to the full ITT population if the first analysis is statistically significant.
XPOVIO Revenue Rises, But Demand Faces Competition
Chief Commercial Officer and Head of Business Development Sohanya Cheng said first-quarter net product revenue growth was driven primarily by favorable gross-to-net dynamics. However, she said underlying demand for XPOVIO was lower than in the first quarter of 2025, reflecting new competitive entrants.
Cheng said Karyopharm continues to position XPOVIO as a flexible oral option in the second- to fourth-line community setting for multiple myeloma, and as a differentiated mechanism in the peri T-cell engaging therapy setting, including use before CAR T therapy or after progression on a T-cell engaging therapy.
Looking ahead, Cheng said Karyopharm believes its sales, marketing, market access and medical affairs capabilities could be leveraged for potential launches in myelofibrosis and endometrial cancer with limited incremental investment before approval and modest additional spending after launch.
In myelofibrosis, Cheng said the U.S. market includes roughly 20,000 patients living with the disease and about 7,000 newly diagnosed frontline patients annually, around 4,000 of whom Karyopharm considers addressable. She said the company believes selinexor plus ruxolitinib has potential to generate up to approximately $1 billion in U.S. peak annual revenue, if approved.
First-Quarter Revenue Increases; Guidance Reaffirmed
Chief Financial Officer Lori Macomber said total first-quarter revenue was $35.1 million, up from $30 million in the prior-year period. U.S. XPOVIO net product revenue was $29.2 million, compared with $21.1 million a year earlier.
Macomber said the increase was driven by a lower gross-to-net rate of 21.8%, compared with 45% in the first quarter of 2025, which had been affected by an atypical product return adjustment. Excluding those adjustments, she said underlying gross-to-net was approximately 26% in the latest quarter.
Research and development expenses were $33.8 million, while selling, general and administrative expenses were $26.7 million, both relatively consistent year over year. Net loss was $22.4 million, compared with $23.5 million in the prior-year period. Macomber said loss from operations fell 20%, reflecting higher revenue and expense discipline.
Karyopharm ended the quarter with $91.2 million in cash, cash equivalents and restricted cash, including approximately $50 million raised during the quarter. The company reaffirmed 2026 guidance for total revenue of $130 million to $150 million, U.S. XPOVIO net product revenue of $115 million to $130 million and combined R and SG expenses of $230 million to $245 million.
Paulson closed the call by saying Karyopharm is focused on SENTRY next steps, including FDA engagement, ASCO presentation, publication planning and potential compendia inclusion, while preparing for the endometrial cancer readout in mid-2026.
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.
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