Karyopharm Therapeutics (NASDAQ:KPTI) executives highlighted upcoming late-stage clinical catalysts, continued revenue growth for its multiple myeloma franchise, and a tighter cost structure during the company’s fourth-quarter and full-year 2025 earnings call.
Management repeatedly pointed investors to myelofibrosis as the most significant near-term value driver, with top-line results from the Phase 3 SENTRY trial expected in March. The company also said it remains on track to report top-line data in mid-2026 from the Phase 3 XPORT-EC-042 trial in biomarker-selected endometrial cancer.
Myelofibrosis: Phase 3 SENTRY top-line data expected in March
Rangwala reviewed the company’s rationale for combining XPO1 inhibition (selinexor) with ruxolitinib, explaining that dual inhibition could impact upstream and downstream pathways beyond JAK-STAT, including NF-κB and fibrosis-inducing pathways. She outlined three “key treatment drivers” the company is focused on in myelofibrosis:
- Spleen volume reduction (noting that only about one-third of patients achieve SVR35 with ruxolitinib alone, while the company’s Phase 1 combination data suggested higher rates)
- Symptom improvement (discussing Phase 1 observations in absolute total symptom score change at week 24 relative to baseline)
- Lower rates of grade 3+ anemia (citing prior monotherapy data and blinded safety observations in early SENTRY enrollment versus historical ruxolitinib data)
Rangwala said Karyopharm optimized SENTRY by recruiting a more symptomatic patient population and refining how symptoms are analyzed, including focusing on absolute TSS at week 24 relative to baseline and analyzing TSS without fatigue. She noted the mean baseline TSS without fatigue in approximately 350 patients was about 22.5, which management said could be among the highest baseline symptom burdens seen in a frontline Phase 3 myelofibrosis trial.
During Q&A, management said the Phase 1 experience supported selecting selinexor 60 mg over 40 mg for myelofibrosis, citing higher exposure and a benefit-risk profile that favored the higher dose due to stronger efficacy measures, while safety differences were described as less pronounced. Rangwala also said the independent data safety monitoring board reviews safety approximately every four to six months, and that prior futility review recommended continuing the study without modification.
Endometrial cancer: Phase 3 XPORT-EC-042 mid-2026 readout remains on track
Rangwala said the number of progression-free survival events accrued in XPORT-EC-042 remains consistent with projections, supporting management’s expectation for top-line data in mid-2026. She described the study as biomarker-driven, enrolling patients with p53 wild-type endometrial cancer, and noted the protocol was updated to reflect a treatment landscape where checkpoint inhibitors are used for dMMR tumors.
Management revisited long-term follow-up from the prior Phase 3 SIENDO trial, which showed encouraging signals in exploratory subgroups, including p53 wild-type populations. Rangwala also contrasted SIENDO’s dosing and antiemetic approach (80 mg once weekly, without mandated dual antiemetics early in therapy) with XPORT-EC-042, which uses 60 mg once weekly and mandates dual antiemetics during the first two cycles.
Commercial update: Xpovio revenue growth and 2026 outlook
Chief Commercial Officer Sohanya Cheng said the company executed “well” in 2025 in a highly competitive multiple myeloma market. She reported that Xpovio net product revenue was $32.1 million in the fourth quarter and $114.9 million for the full year 2025, with demand described as consistent year-over-year. Cheng said the community setting drove approximately 60% of total U.S. sales.
Cheng also discussed use of selinexor in multiple myeloma around emerging T-cell engaging therapies, citing a growing body of evidence about a potential role in preserving the T-cell environment.
Looking to potential expansion, Cheng characterized the myelofibrosis opportunity as “much greater” than multiple myeloma, citing differences in dose, patient population, and competitive dynamics. She said Karyopharm’s commercial focus would be on roughly 4,000 newly diagnosed intermediate- to high-risk U.S. patients with platelet counts above 100,000, within an estimated prevalent U.S. population of 20,000 myelofibrosis patients and about 6,000 newly diagnosed per year. Based on company market research, Cheng said 75% of physicians expressed intent to treat with a combination therapy, and she stated Karyopharm believes peak U.S. revenue potential in myelofibrosis “may approach $1 billion annually,” contingent on positive data and regulatory approval.
Financial results: lower operating expenses, cash runway into Q2 2026
Chief Financial Officer Lori Colgan reported total revenue of $34.1 million for Q4 2025, up 11.8% from Q4 2024, and total revenue of $146.1 million for full-year 2025, described as slightly higher than 2024.
Key financial line items discussed on the call included:
- U.S. Xpovio net product revenue: $32.1 million in Q4 2025 (up 9.6% year over year) and $114.9 million for full-year 2025 (up 1.9%)
- Gross-to-net provisions: 26.9% in Q4 2025 and 31.2% for full-year 2025
- License and other revenue: $2.0 million in Q4 2025 and $31.2 million for full-year 2025; Colgan noted the full year included $15 million of R&D reimbursement from Menarini, and 2025 was the last year for that reimbursement
Colgan said operating expenses declined year over year, citing cost reduction initiatives and prioritization of Phase 3 programs. R&D expenses were $27.7 million in Q4 (down 17%) and $125.6 million for the year (down 12%), while SG&A expenses were $22.8 million in Q4 (down 16%) and $105.2 million for the year (down 9%).
The company reported a GAAP net loss of $102.2 million, or $5.71 per share, for Q4 2025 and a GAAP net loss of $196.0 million, or $17.93 per diluted share, for full-year 2025. Colgan attributed much of the year’s net loss to “below-the-line” items, including interest expense, non-cash fair value remeasurements tied to refinancing-related instruments, and a loss on extinguishment of debt in 2025.
Karyopharm ended 2025 with $64.1 million in cash, cash equivalents, restricted cash, and investments, down from $109.1 million at the end of 2024. Colgan said existing liquidity is expected to fund current operating plans into Q2 2026.
For 2026, the company guided to total revenue of $130 million to $150 million and Xpovio net product revenue of $115 million to $130 million, with combined R&D and SG&A expenses expected to be $230 million to $245 million.
Paulson said the company is “actively evaluating a range of financing and strategic options” as it aligns capital decisions with upcoming clinical milestones, while prioritizing execution and data generation as it approaches key readouts.
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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