Karyopharm Therapeutics Inc. Q1 FY2025 earnings call

• Phase 3 SENTRY trial in myelofibrosis passed prespecified futility analysis and continues as planned, with ~80% of 350-patient target enrolled and expected to complete in June-July.
• New clinical data on selinexor in JAKi-naïve myelofibrosis shows potential impact on key disease hallmarks, including spleen volume reduction, symptom improvement, hemoglobin stabilization, and disease modification.
• Progress in Phase 3 trial for endometrial cancer with enrollment progressing steadily, expecting top-line data in mid-2026. Phase 3 EMN29 SPd trial for multiple myeloma aims to offer an all-oral triplet option, expecting top-line data in first half of 2026.
• Cost optimization initiatives led to reduced R&D and SG&A expenses in Q1 2025, with R&D at $34.6M (down from $35.4M in Q1 2024) and SG&A at $27.4M (down from $29.5M in Q1 2024).

In Q1 2025, U.S. XPOVIO net product revenue was $21.1 million, down from $26 million in Q1 2024 due to a $5 million increase in the product return reserve from atypical returns of expired high-dose XPOVIO units. Royalty revenue from partners like Menarini and Antengene increased 57% to $1.7 million in Q1 2025. The multiple myeloma commercial organization is profitable and can support rapid commercialization if new approvals are gained.

• Total revenue guidance for 2025 is $140M-$155M, with U.S. XPOVIO net product revenue guidance $115M-$130M, but adjusted downward due to Q1 atypical product returns.
• R&D and SG&A expenses guided to $240M-$255M.
• Existing cash, cash equivalents, and investments, plus expected revenue from XPOVIO sales and license revenue, are expected to fund operations into early Q1 2026, but considering convertible note repayment and liquidity covenant, may fund into early Q4 2025.

• Atypical product returns in Q1 2025 due to expired high-dose XPOVIO units impacted revenue.
• Highly competitive multiple myeloma market with potential new entrants.
• Potential delays in clinical trial enrollments, as seen with the myelofibrosis Phase 3 trial being slightly behind schedule.

Q: Can you talk about what the futility analysis for the myelofibrosis Phase 3 trial was based on and the options?

A: The futility analysis was based on efficacy and safety observed in the first 61 patients followed for 24 weeks. For efficacy, it had prespecified thresholds related to SVR35 and absolute TSS. For safety, it was a qualitative assessment of the totality of the data. The DSMB recommended the study continue as planned.

Q: How are you expecting to hit the TSS delta in the myelofibrosis Phase 3 trial?

A: Assumptions include a 4-point delta and standard deviation of 12 for each arm, with overall power for absolute TSS greater than 80%. Clinically meaningful outcome is improvement above what ruxolitinib alone demonstrates.

Q: What's the normal run rate of product returns and risks of revenue shortfall in future quarters?

A: Atypical returns in Q1 were $5M from high-dose XPOVIO units related to the 2020 approval. Normal run rate is lower, and we don't expect this to carry into future quarters as returns are now more for 40mg and 60mg doses, which are more typical.