Karyopharm Therapeutics Inc. Q3 FY2024 earnings call

• Announced a favorable regulatory update for the Phase 3 SENTRY trial in myelofibrosis, changing the co-primary endpoint to absolute TSS and remaining on track to report top-line data in the second-half of next year. - SELINEXOR has unique mechanism of action, compelling data, and ongoing cost management, positioning well to advance late-stage pipeline. - In myelofibrosis, if data from SENTRY is supportive, could transform treatment paradigm with first combination therapy in Jack-naive myelofibrosis, with estimated annual U.S. peak revenue opportunity of approximately $1 billion. - In endometrial cancer, data in TP53 wild-type endometrial cancer offers potential of meaningful and unique mechanism in maintenance therapy, with approximately $1 billion annual U.S. peak revenue opportunity. - Reshma highlighted clinical programs, including ongoing Phase 3 studies, unique potential of late-stage pipeline, updates on SENTRY trial co-primary endpoint change, safety profile of selinexor, and progress in endometrial cancer trial. - Sohanya discussed commercial highlights, with XPOVIO net product revenue up 5% q-o-q, on track to deliver in upper half of annual guidance, and global expansion with reimbursement and regulatory approvals. - Michael mentioned financial highlights, including total revenue, R&D and SG&A expenses, and revised guidance for full-year 2024.

XPOVIO net product revenue was $29.5 million in the third quarter of 2024, up 5% compared to the second quarter. Net U.S. XPOVIO revenue for the third quarter of 2024 was $29.5 million, compared to $30.2 million for the third quarter of 2023. Total revenue for the third quarter of 2024 was $38.8 million, compared to $36 million for the third quarter of 2023. XPOVIO's revenue in the U.S. has seen three consecutive quarters of net product revenue growth, and is on track to deliver revenue in the upper half of the guidance outlined at the start of the year. The gross-to-net discount for XPOVIO in the third quarter of 2024 was 31%, driven by increased 340B utilization and Medicare rebates.

• Total revenue expected to be in the range of $145 million to $155 million, narrowing from previous guidance of $145 million to $160 million. - U.S. XPOVIO net product revenue expected to be in the range of $110 million to $115 million, narrowing from previous guidance of $105 million to $120 million. - R&D and SG&A expenses expected to be in the range of $255 million to $265 million, including approximately $20 million of non-cash stock based compensation expense. - Cash runway expected to fund planned operations into Q1 2026, and into Q4 2025 when considering repayment of 2025 convertible notes and minimum liquidity covenant.

Not explicitly detailed in the provided transcript, but generally, risks include factors discussed in the Risk Factors section of the most recent Form 10-Q, such as uncertainties related to clinical trial results, regulatory approvals, market acceptance of new indications, and potential impact of competitive products.

Q: Brian Abrahams from RBC Capital Markets asked about the magnitude of the average total symptom score change influencing powering assumptions and if TSS50 is still a secondary endpoint.

A: Reshma Rangwala responded that the average TSS data is meaningful, showing substantial improvement, and TSS50 is not a co-primary endpoint anymore, with regulators aligning on absolute TSS.

Q: Ed White from H.C. Wainwright asked about the endometrial market and entering the maintenance therapy market.

A: Sohanya Cheng replied that they are excited about the opportunity in endometrial cancer as a biomarker-specific oral maintenance therapy, with strong market research support and overlap with treating physicians.

Q: Peter Lawson from Barclays asked about quarter-over-quarter growth trends, mix of price and volume, and academic vs community settings.

A: Sohanya Cheng said they've had three quarters of q-o-q growth, with strong growth in community and academic settings driven by T-cell fitness evidence.

Q: Peter Lawson also asked about the multiple myeloma SPd Phase 3 study.

A: Reshma Rangwala said they leveraged positively evolving data, sent an amendment to the FDA, and expect feedback in the next few weeks to update top-line results timeline.

Q: Maury Raycroft from Jefferies asked about the myelofibrosis study's long-term follow-up.

A: Reshma Rangwala said patients continue on therapy beyond 24 weeks, but key regulatory decisions focus on week 24 data.