Clinical Trial Updates - Phase 3 SENTRY试验的顶线数据预计在2026年3月公布[8, 25] - Phase 3 XPORT-EC-042子宫内膜癌试验的顶线数据预计在2026年中期公布[8, 67] - 评估SPd治疗复发性多发性骨髓瘤患者的3期全球研究(XPORT-MM-031/EMN29)的顶线数据预计在2026年上半年公布[70, 73] - SENTRY (XPORT-MF-034) 是一项针对JAKi初治骨髓纤维化患者，Selinexor联合Ruxolitinib的3期试验，已于2025年9月完成患者招募，共353名患者[23, 24] Commercial Performance - 2025年第三季度，美国XPOVIO净产品收入为3200万美元，比2024年第三季度的2950万美元增长8.5%[37] - 公司重申2025年全年净产品收入指导范围为1.1亿美元至1.2亿美元[37, 54] - 社区环境持续驱动约60%的美国整体净产品收入[37] Financial Highlights - 2025年第三季度总收入为4400万美元，高于2024年第三季度的3880万美元[51] - 预计现有流动资金，在计入2025年10月8日宣布的融资交易的影响后，足以支持公司计划运营至2026年第二季度[53] - 研发和SG&A费用预计为2.35亿美元至2.45亿美元[54] Myelofibrosis Market Opportunity - Selinexor联合Ruxolitinib疗法在美国市场可能达到每年约10亿美元的净销售额峰值[41, 43] - 约75%的患者有意愿接受联合治疗[42]

August 11, 2025 Second Quarter 2025 Financial Results & Business Update On Today's Call • Welcome Brendan Strong, SVP, Investor Relations and Corporate Communications • Overview Richard Paulson, President and Chief Executive Officer • Pipeline Update Dr. Reshma Rangwala, Chief Medical Officer and Head of Research • Commercial Highlights Sohanya Cheng, Chief Commercial Officer and Head of Business Development ©2025 KARYOPHARM THERAPEUTICS INC. 2 • Financial Results and Guidance Lori Macomber, Chief Financial ...

Myelofibrosis Opportunity - Karyopharm is focused on the transformative myelofibrosis opportunity in 2025, building on its foundation in multiple myeloma[4,10] - The peak annual revenue opportunity for selinexor in myelofibrosis is estimated to be up to approximately $1 billion[4,12] - In a Phase 1 trial, 78.6% of intent-to-treat patients achieved SVR35 (spleen volume reduction of 35% or more) at week 24 with selinexor 60 mg + ruxolitinib[24] - In the Phase 1 trial, the average improvement in Absolute TSS (Total Symptom Score) was 18.5, suggesting a positive outcome for the SENTRY Phase 3 trial[31,32] - Selinexor meaningfully decreased transfusion burden by approximately 50% compared to physician's choice in the XPORT-MF-035 trial[58] Endometrial Cancer Opportunity - Karyopharm is focusing the Phase 3 XPORT-EC-042 trial on patients with TP53wt EC (endometrial cancer) that are pMMR or dMMR and medically ineligible to receive a checkpoint inhibitor[74] - Data from the SIENDO trial showed an encouraging signal of long-term median PFS (progression-free survival) benefit of 28.4 months in the TP53 wild-type subgroup[78] - In the SIENDO Trial, the median PFS benefit was 39.5 months in the TP53 Wild-Type/pMMR Subgroup[81] Commercial and Pipeline Strategy - XPOVIO net product revenue in 2024 was approximately $113 million[11] - The company aims to maintain its profitable commercial foundation in the competitive multiple myeloma marketplace and drive increased XPOVIO revenue in 2025[91] - The company is actively enrolling patients in the Phase 3 SENTRY trial in myelofibrosis, with top-line data expected in late 2025/early 2026[4,39,40] - The company is actively enrolling patients in the Phase 3 XPORT-EC-042 trial in endometrial cancer, with top-line data anticipated in mid-2026[85,88]

Myelofibrosis Opportunity - Karyopharm is focused on the transformative myelofibrosis opportunity in 2025, with a peak annual revenue opportunity of up to approximately $1 billion[4, 12] - The company expects top-line data from the Phase 3 SENTRY trial of selinexor in myelofibrosis in late 2025/early 2026[4] - Data from a Phase 1 trial showed that 78.6% of intent-to-treat patients achieved SVR35 at week 24 with selinexor 60 mg + ruxolitinib[24] - In the Phase 1 trial, the average improvement in Absolute TSS (Abs-TSS) was 18.5, suggesting a positive outcome with Abs-TSS can be achieved in the SENTRY Phase 3 trial[33] Clinical Trial Data and Development - The Phase 2 XPORT-MF-035 trial showed that spleen volume reduction rates more than doubled with selinexor compared to physician's choice, with 33% achieving SVR35 compared to 13%[48, 49] - In the XPORT-MF-035 trial, patients who progressed on physician's choice (Rux) and received selinexor showed a meaningful spleen volume reduction[51] - Selinexor meaningfully decreased transfusion burden by approximately 50% in the XPORT-MF-035 trial[59] - The SENTRY (XPORT-MF-034) Phase 3 trial of selinexor in combination with ruxolitinib in JAKi naïve myelofibrosis has passed futility analysis and continues as planned, with top-line data expected in late 2025/early 2026[39, 41] Endometrial Cancer - Karyopharm is focusing the Phase 3 XPORT-EC-042 trial on patients with TP53wt EC that are pMMR or dMMR and medically ineligible to receive a checkpoint inhibitor[75] - Data from the SIENDO trial (ASCO 2024) showed an encouraging signal of long-term median PFS benefit of 39.5 months in the TP53 Wild-Type/pMMR subgroup[82]

Financial Performance & Guidance - Q1 2025 XPOVIO净产品收入为2110万美元，受到非典型过期产品退货的影响，减少了约500万美元[86, 87] - 公司预计2025年总收入为140-155百万美元[112] - 公司预计2025年美国XPOVIO净产品收入为115-130百万美元[112] - 公司预计2025年研发和SG&A支出为240-255百万美元，其中包括约2000万美元的非现金股票补偿[112] Myelofibrosis Program - Myelofibrosis的美国峰值年收入机会高达约10亿美元[7, 19] - 在JAKi初治的骨髓纤维化患者中，Selinexor联合Ruxolitinib治疗的SVR35达到79%[28] - 75%的美国医生表示有意采用联合疗法治疗骨髓纤维化[21, 99] Clinical Trials & Pipeline - SENTRY试验的顶线数据预计在2025年末/2026年初公布[7, 59] - XPORT-MF-035试验中，Selinexor单药治疗使脾脏体积缩小率增加了一倍以上，SVR25为67%，SVR35为33%[35, 36] - 完成了评估SPd治疗既往接受过治疗的多发性骨髓瘤患者的3期全球研究（XPORT-MM-031/EMN291）的患者招募，预计在2026年上半年获得顶线数据[78, 79, 81] Commercial Strategy - Selinexor已在超过45个国家获得批准[7, 90] - 现有销售团队已覆盖约80%的社区骨髓纤维化客户[21]