• Total Revenue (Q4 2024): $30.5 million, down from $33.7 million in Q4 2023.
• Total Revenue (Full Year 2024): $145.2 million, compared to $146 million in 2023.
• US XPOVIO Net Product Revenue (Q4 2024): $29.3 million, up from $25.1 million in Q4 2023.
• US XPOVIO Net Product Revenue (Full Year 2024): $112.8 million, compared to $112 million in 2023.
• Gross to Net Discount for XPOVIO (Q4 2024): 33.3%, compared to 23.5% in Q4 2023.
• Gross to Net Discount for XPOVIO (Full Year 2024): 30.9%, compared to 22.3% in 2023.
• R&D Expenses (Q4 2024): $33.3 million, compared to $39.4 million in Q4 2023.
• R&D Expenses (Full Year 2024): $143.2 million, compared to $138.8 million in 2023.
• SG&A Expenses (Q4 2024): $27.2 million, compared to $30.7 million in Q4 2023.
• SG&A Expenses (Full Year 2024): $115.4 million, compared to $131.9 million in 2023.
• Cash Equivalents, Restricted Cash, and Investments (End of 2024): $109.1 million, compared to $192.4 million at the end of 2023.
• 2025 Revenue Guidance: $140 million to $155 million.
• 2025 US XPOVIO Net Product Revenue Guidance: $115 million to $130 million.
• 2025 R&D and SG&A Expenses Guidance: $240 million to $255 million.

• Warning! GuruFocus has detected 6 Warning Signs with KPTI.

Release Date: February 19, 2025

For the complete transcript of the earnings call, please refer to the full earnings call transcript.

Positive Points

• Karyopharm Therapeutics Inc (NASDAQ:KPTI) delivered solid financial results in 2024, meeting their guidance range with a profitable US commercial organization.
• The company is on track to complete enrollment in their phase 3 trial for myelofibrosis in the first half of 2025, with top-line data expected in the second half.
• Karyopharm received both fast track designation and orphan drug designation from the FDA for their myelofibrosis treatment, increasing the probability of success.
• The company has made significant progress in reducing SG&A expenses, contributing to overall cost savings.
• Karyopharm's XPOVIO net product revenue increased by 16% in Q4 2024 compared to the same period in 2023, demonstrating strong demand despite increased competition.

Negative Points

• Total revenue for Q4 2024 decreased to $30.5 million from $33.7 million in Q4 2023, primarily due to lower milestone-related revenue.
• The gross-to-net discount for XPOVIO increased significantly in 2024, driven by 340B utilization and Medicare rebates, impacting net revenue.
• Karyopharm's cash equivalents and investments decreased from $192.4 million at the end of 2023 to $109.1 million at the end of 2024, indicating a need for careful financial management.
• The company anticipates needing to explore various financing and business development activities to extend their cash runway into 2026.
• Enrollment in the phase 3 endometrial cancer study has been adjusted, with top-line data now expected in mid-2026, potentially delaying regulatory approval timelines.

Q & A Highlights

Q: For the myelofibrosis phase 3 trial, what reduction in Total Symptom Score (TSS) would be statistically significant, and how does this compare to previous trials? A: Reshma Rangwala, Chief Medical Officer & Head of Research, explained that they expect a meaningful improvement in absolute TSS, with a potential delta of 3-4+ points compared to ruxolitinib alone. Previous phase 3 trials have shown statistical significance with a narrower margin, suggesting a 2-point difference could be significant. This guides their powering assumptions for the ongoing phase 3 century trial.

Q: Can you provide more details on the discussions with the FDA regarding the endometrial cancer study and the focus on the pMMR population? A: Reshma Rangwala noted that discussions with the FDA were prompted by the evolving treatment landscape, including new therapies like checkpoint inhibitors. The FDA recommended focusing on the pMMR population, which represents 80% of endometrial cancer patients, as they benefit less from checkpoint inhibitors. The FDA is aware of the promising data from the [Sciendo] subgroup, which supports this focus.

Q: How are patient baseline profiles tracking in the Century study, and what are the expectations for discontinuation rates and dose reductions? A: Reshma Rangwala stated that patient profiles are consistent with previous trials, including phase 1 and other contemporary phase 3 trials. The study is blinded, so specific data on discontinuations and dose modifications are not available, but they are tracking as expected.

Q: Regarding the absolute TSS endpoint for the Century study, why is fatigue excluded, and how will the FDA assess this? A: Reshma Rangwala explained that fatigue is excluded from the primary analysis of absolute TSS, consistent with previous trials like the original comfort trials for Ruxolitinib. The FDA is aligned with this approach, and fatigue can be included in future analyses if needed.

Q: What are the characteristics of the dMMR population not eligible for checkpoint inhibitors, and how did they perform in the [Sciendo] study? A: Reshma Rangwala clarified that the dMMR population's ineligibility is due to comorbidities, not tumor characteristics. The [Sciendo] study suggested that p53 status is the key factor for efficacy with Selinexor, with robust improvements observed regardless of MMR status.

For the complete transcript of the earnings call, please refer to the full earnings call transcript.