Karyopharm Therapeutics Inc. Q4 FY2025 earnings call

• 2026 is a defining phase with important late-stage clinical milestones, including Phase III SENTRY trial data in myelofibrosis in March and Phase III EXPORT EC042 trial data in endometrial cancer in mid-2026.
• In myelofibrosis, selinexor in combination with ruxolitinib shows potential due to multi-targeted approach addressing underlying mechanisms, with data suggesting synergy and manageable side effects.
• In endometrial cancer, the Phase III EXPORT EC042 trial is on track to report top-line data, with the trial updated to evaluate specific patient subgroups and long-term follow-up data from prior trials showing encouraging results.
• Commercially, XPOVIO net product revenue was $32.1 million in Q4 2025 and $114.9 million for full year 2025, with expectations for revenue growth in 2026, and the commercial opportunity in myelofibrosis is greater due to unmet need and different patient populations/dosing.

In 2025, U.S. XPOVIO net product revenue was $32.1 million in the fourth quarter and $114.9 million for the full year. License and other revenue was $2.0 million in the fourth quarter and $31.2 million for the full year 2025. XPOVIO net product revenue grew to $32.1 million in Q4 2025 and $114.9 million for full year 2025, with community setting driving approximately 60% of total U.S. sales.

• Total revenue for 2026 is expected to be $130 million to $150 million, consisting of U.S. XPOVIO net product revenue and license, royalty, and milestone revenue.
• U.S. XPOVIO net product revenue is guided to be in the range of $115 million to $130 million.
• R&D and SG&A expenses are expected to be in the range of $230 million to $245 million.
• Cash runway extends into the second quarter aligning with key near-term clinical milestones.

Forward-looking statements made may differ materially from actual results due to factors discussed in the Risk Factors section of recent Form 10-Q or 10-Ks with the SEC, including various important factors that could impact results.

Q: Colleen Margaret Kusy asked about the difference in exposure and activity between 40 mg and 60 mg in the myelofibrosis Phase I data.

A: Reshma Rangwala stated there's a clear benefit-risk in favor of the 60 mg cohort due to maximized efficacy, though safety differences aren't stark; Richard Paulson mentioned focus on data from 60 mg in Phase III trial.

Q: Yichun Qian inquired about blinded safety data and ruxolitinib dosing in the SENTRY trial.

A: Reshma Rangwala said no refresh of blinded safety data, but TSS evolution is encouraging; ruxolitinib dose modifications follow local label, and selinexor dose can be reduced with specified guidelines.

Q: Brian Corey Abrahams asked about baseline characteristics and DSMB in the SENTRY trial.

A: Reshma Rangwala noted patient population is milder but not impacting efficacy; DSMB evaluates data regularly, and no issues mentioned so far.

Q: Maury Raycroft asked about dose reductions in the first 61 patients of SENTRY and recruitment regions.

A: Reshma Rangwala said dose reduction details not meaningful yet, but selinexor dose intensity was >95%; patients were globally recruited, primarily from North America and EU.

Q: Wei Ji Chang asked about confidence in the TSS endpoint of the SENTRY study.

A: Reshma Rangwala cited multiple aspects like Phase I study results, absolute TSS improvement, cytokine level decreases, and FDA's support for absolute TSS as a measure; Richard Paulson added confidence in the patient population and set targets for meaningful TSS scores.