Karyopharm Therapeutics Inc. Q4 FY2024 earnings call

Key Points

• In 2024, the company delivered solid financial results with a profitable U.S. commercial organization and growing global demand in multiple myeloma. They reduced total expenses, particularly SG&A, while focusing on Phase 3 clinical trials.
• For 2025, the company expects to grow XPOVIO net product revenue, further reduce expenses, and advance Phase 3 trials in myelofibrosis and endometrial cancer. They remain on track to complete enrollment in the Phase 3 SENTRY Trial in myelofibrosis in the first half of 2025 and announce top-line data in the second half. Modifications to the Phase 3 endometrial cancer trial were made following FDA discussions, with top-line data now expected in mid-2026.
• In myelofibrosis, the company has a transformational opportunity with the Phase 3 SENTRY Trial, which showed strong signal benefit for Selinexor plus Ruxolitinib. The shift to absolute TSS as a co-primary endpoint is seen as favorable.
• Commercially, XPOVIO had $29.3 million in Q4 2024 net product revenue, with full-year 2024 revenue at $112.8 million. International reimbursement approvals triggered milestone payments, and there's potential for growth in myelofibrosis and endometrial cancer due to physician overlap and patient population size.

In the fourth quarter of 2024, U.S. XPOVIO net product revenue was $29.3 million. For the full year 2024, U.S. XPOVIO net product revenue was $112.8 million, up from $112 million in 2023. XPOVIO was the key product, with net product revenue contributing significantly to the company's financials.

Guidance

• Total revenue for 2025 is projected to be $140 million to $155 million, with U.S. XPOVIO net product revenue in the range of $115 million to $130 million.
• R&D and SG&A expenses for 2025 are expected to be $240 million to $255 million.
• Cash runway is expected to fund planned operations into Q1 2026, with consideration of repayment of 2025 convertible notes and minimum liquidity covenant, potentially extending to Q4 2025.

Risks

• Uncertainties related to clinical trial outcomes, including the success of Phase 3 trials in myelofibrosis and endometrial cancer.
• Regulatory approval challenges, as the company depends on favorable outcomes from FDA reviews and discussions.
• Competitive landscape, with new treatments entering the market that could impact XPOVIO's revenue and market share.
• Fluctuations in gross-to-net discounts due to factors like 340B utilization and Medicare rebates, which can affect revenue.

Q: For the myelofibrosis Phase 3, what reduction in TSS would make it statistically significant?

A: Reshma Rangwala stated that the data suggests a delta of three, four plus points could show a meaningful difference, and previous Phase 3 trials showed statistical significance with a narrow delta. The company is using this to guide powering assumptions in the Phase 3 SENTRY Trial.

Q: Can you give more color on the conversation with the FDA around the endometrial study?

A: Reshma Rangwala explained that the FDA recommended focusing on the pMMR patient population due to the evolving treatment landscape with checkpoint inhibitors. The FDA acknowledged lower efficacy in pMMR tumors and the need to align with the changing standard of care.

Q: For the SENTRY study, how are patient baseline profiles tracking?

A: Reshma Rangwala said patient baseline profiles are tracking with contemporary Phase 3 trials, including demographics like platelet counts, spleen size, and hemoglobin levels. Discontinuation rates and dose modifications are blinded in the study, and the company hasn't provided specific blinded data beyond demographics.

Q: How should we think about cash runway guidance relative to Phase 3 study timelines?

A: Lori Macomber mentioned the company has a profitable revenue-generating business in multiple myeloma. They are evaluating financing options like business development, collaborations, equity raises, or extending debt to ensure cash runway for Phase 3 study readouts, including evaluating options for myelofibrosis and endometrial cancer trials.