Core Insights - Karyopharm Therapeutics Inc. announced that its abstract on selinexor monotherapy for myelofibrosis has been selected for presentation at the 2025 European Hematology Association Annual Meeting [1][2] - The data from the Phase 2 XPORT-MF-035 trial indicates that selinexor shows clinical activity in heavily pretreated myelofibrosis patients, demonstrating spleen volume reduction, hemoglobin stabilization, and symptom improvement [2][4] Summary by Sections Company Overview - Karyopharm Therapeutics is a commercial-stage pharmaceutical company focused on developing novel cancer therapies, particularly through its lead compound, XPOVIO (selinexor), which is a first-in-class oral exportin 1 (XPO1) inhibitor [4][11] - The company has received regulatory approvals for XPOVIO in multiple oncology indications in the U.S. and various international markets, including Europe and China [5][11] Clinical Trial Insights - The XPORT-MF-035 trial involved 24 patients, randomized 1:1 to receive either selinexor monotherapy or physician's choice treatment, with selinexor administered at 80 mg weekly for the first two cycles, then reduced to 60 mg [4] - Key findings from the trial include: - 67% of selinexor-treated patients achieved a spleen volume reduction of 25% or more compared to 38% in the physician's choice group [4] - 33% of selinexor patients achieved a spleen volume reduction of 35% or more versus 13% in the physician's choice group [4] - Patients on selinexor had higher mean hemoglobin levels and lower rates of red blood cell transfusions compared to those on physician's choice [4] Safety and Adverse Events - The most common treatment-emergent adverse events (TEAEs) in the selinexor arm included decreased weight (50%), asthenia (42%), and nausea (33%) [4] - Serious adverse reactions were reported in 52% of patients in the BOSTON trial, with a treatment discontinuation rate of 19% due to adverse reactions [9]

Core Insights - Karyopharm Therapeutics reported positive developments in its Phase 3 SENTRY trial for selinexor in JAKi-naïve myelofibrosis, which has passed a planned futility analysis and is approximately 80% enrolled [2][4] - The company experienced a 5% increase in demand for XPOVIO® (selinexor) in Q1 2025 compared to Q1 2024, with total revenue of $30.0 million [5][15] - Karyopharm reaffirmed its full-year 2025 revenue guidance of $140 million to $155 million, including U.S. net product revenue guidance of $115 million to $130 million [21] Financial Performance - Total revenue for Q1 2025 was $30.0 million, down from $33.1 million in Q1 2024 [15] - U.S. net product revenue was $21.1 million in Q1 2025, compared to $26.0 million in Q1 2024, impacted by a $5.0 million increase in product return reserves [16] - License and other revenue increased to $9.0 million in Q1 2025 from $7.1 million in Q1 2024, attributed to timing of revenue recognition from Menarini [17] Research and Development Highlights - The Phase 3 SENTRY trial is evaluating the combination of selinexor and ruxolitinib, targeting 350 patients for enrollment [4] - The Phase 2 XPORT-MF-035 trial showed promising results for selinexor monotherapy in hard-to-treat myelofibrosis patients, with 67% achieving spleen volume reduction of 25% or more [10] - Enrollment continues in the Phase 3 XPORT-EC-042 trial for selinexor as maintenance therapy in advanced endometrial cancer [6] Operational Objectives - Karyopharm aims to complete target enrollment for the Phase 3 SENTRY trial by June/July 2025 and report top-line results in late 2025/early 2026 [11] - The company is exploring alternatives to extend its cash runway, with cash and investments totaling $70.3 million as of March 31, 2025 [25][14] - R&D expenses for Q1 2025 were $34.6 million, slightly down from $35.4 million in Q1 2024, reflecting reduced personnel costs [19]