Karyopharm Therapeutics (KPTI) investor relations material

Key presentations and scientific insights

• Selinexor, an XPO1 inhibitor, is being developed in combination with ruxolitinib for frontline myelofibrosis, aiming to set a new standard of care.

• Phase I data showed 79% of patients achieved SVR35 at week 24, more than doubling historical rates for ruxolitinib alone.

• The combination demonstrated rapid, deep, and durable spleen reductions with meaningful symptom improvements.

• Safety profile at lower selinexor doses is manageable, with transient nausea and low discontinuation rates.

• Blinded phase III safety data suggest similar or better tolerability compared to ruxolitinib alone, with lower grade 3-4 anemia rates.

Industry analysis and clinical context

• Myelofibrosis patients often receive ruxolitinib as first-line therapy, but responses are not always durable, and anemia is a key challenge.

• There is a significant unmet need for therapies that provide deeper, more durable responses and better tolerability.

• Recent trials with other agents (navitoclax, pelabresib) faced challenges with thrombocytopenia and symptom endpoints.

• The SENTRY phase III trial is robustly designed, with a two-to-one randomization and co-primary endpoints of SVR35 and absolute TSS, excluding fatigue for clarity.

• Baseline TSS in SENTRY is higher than in prior studies, potentially increasing the likelihood of demonstrating meaningful benefit.

Forward-looking statements and commercial outlook

• Phase III SENTRY trial results are expected in March, with high power to detect differences in both SVR35 and TSS.

• If positive, the selinexor plus ruxolitinib combination could be rapidly adopted as frontline therapy, with a $1 billion peak revenue opportunity projected in the U.S.

• The combination fits seamlessly into current clinical workflows, requiring no additional testing or logistical changes.

• Recent refinancing extends cash runway into Q2 2026, supporting potential launch and commercialization.

• The company is positioned for rapid execution and growth, with international partnerships in place.