Core Insights - Karyopharm Therapeutics (KPTI) shares fell 18.3% following mixed results from a late-stage study of selinexor combined with Incyte's Jakafi for treating myelofibrosis [1][7] Study Results - The phase III SENTRY study involved 353 patients randomized to receive either selinexor plus Jakafi or placebo plus Jakafi [2] - The study met its first co-primary endpoint, showing a statistically significant 35% or more reduction in spleen volume (SVR35) in 50% of patients receiving the combination therapy, compared to 28% for Jakafi alone [3][5] - However, the second co-primary endpoint, absolute total symptom score (Abs-TSS), was not met, with similar symptom improvements observed in both treatment arms [3][6] Drug Background - Selinexor, marketed as Xpovio, is FDA-approved for multiple myeloma and relapsed or refractory diffuse large B-cell lymphoma [4] - The drug is also available in the EU and UK under the name Nexpovio for multiple myeloma indications [4] Safety and Efficacy - The combination therapy demonstrated a manageable safety profile consistent with known effects of selinexor and Jakafi, with no new safety signals identified [11] - A promising overall survival trend was noted, with a hazard ratio of 0.43 suggesting potential survival advantages [9] Future Directions - Karyopharm plans to engage with the FDA to review the full SENTRY study dataset and discuss regulatory filing plans [15] - The company aims to present additional data from the SENTRY study at an upcoming medical conference [15] - Selinexor is also being evaluated in other oncology indications, and Karyopharm has another candidate, eltanexor, in mid-stage development for myelodysplastic neoplasms [16] Market Context - Karyopharm's stock has declined 20.8% over the past six months, compared to a 10.3% decline in the industry [6]

Core Viewpoint - Karyopharm Therapeutics Inc. reported mixed results from its Phase 3 SENTRY trial for myelofibrosis, leading to a decline in its stock price [1] Group 1: Trial Results - The SENTRY trial met its first co-primary endpoint, showing a significant improvement in spleen volume reduction of 35% or more for patients treated with selinexor plus ruxolitinib [2] - The trial indicated a promising overall survival signal, with a greater than 50% reduction in the risk of death compared to ruxolitinib alone [3] - 50% of patients on the combination achieved SVR35 at week 24, compared to 28% for those on ruxolitinib alone [4] Group 2: Symptom Scores and Secondary Endpoints - Patients on the combination treatment reported a 9.89-point improvement in symptoms, while those on ruxolitinib alone reported a 10.86-point improvement [5] - The trial did not meet its second co-primary endpoint of absolute total symptom score, and no meaningful differences were observed in secondary endpoints such as progression-free survival and hemoglobin stabilization [6] Group 3: Future Plans and Financials - Karyopharm plans to further evaluate trial endpoints and share additional data at an upcoming medical meeting, with a manuscript submission expected to a peer-reviewed journal [7] - The company announced a private placement of approximately $30 million, with potential additional gross proceeds of about $44 million if accompanying warrants are exercised [8] Group 4: Analyst Outlook - Analysts maintain a bullish outlook on Karyopharm, with the stock carrying a Buy Rating and an average price target of $42.17 [9] - Karyopharm shares were down 17.43% at $6.04 at the time of publication [9]

Brendan Strong, SVP, Investor Relations Opening Remarks Richard Paulson, President and Chief Executive Officer Phase 3 SENTRY Topline Results March 24, 2026 On Today's Call Welcome Phase 3 SENTRY Topline Results Dr. Reshma Rangwala, Chief Medical Officer and Head of Research Myelofibrosis Treatment Landscape Dr. John Mascarenhas, Principal Investigator of Phase 3 SENTRY Trial; Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and ...

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]

Financial Performance & Guidance - Karyopharm's Q2 2025 U S net product revenue was $29 7 million, a 6% increase from $28 0 million in Q2 2024[69] - The company anticipates full year 2025 U S XPOVIO net product revenue to be between $110 million and $120 million[69] - Karyopharm projects total revenue between $140 million and $155 million for 2025, with R&D and SG&A expenses ranging from $240 million to $250 million[88] Myelofibrosis (MF) Program - Selinexor has a peak U S revenue opportunity of up to ~$1 billion in myelofibrosis, pending positive data and regulatory approval[9, 19, 70] - In a Phase 1 trial, 79% of patients achieved SVR35 (spleen volume reduction of 35% or more) at week 24 with selinexor plus ruxolitinib[28] - Preliminary extrapolated data from the Phase 3 SENTRY trial suggests a potentially more favorable safety profile for selinexor plus ruxolitinib compared to ruxolitinib alone, with Grade 3+ anemia rates potentially lower at ~26% compared to 37%[35, 37] - Top-line data from the Phase 3 SENTRY trial of selinexor in myelofibrosis is expected in March 2026[9, 33] Endometrial Cancer (EC) Program - The company is focusing the Phase 3 XPORT-EC-042 trial on patients with TP53wt EC who are pMMR or dMMR and medically ineligible for checkpoint inhibitors[46] - Top-line data from the Phase 3 XPORT-EC-042 trial in endometrial cancer is anticipated in mid-2026[91] Multiple Myeloma (MM) Program - Enrollment is complete in the Phase 3 XPORT-MM-031 trial evaluating SPd in patients with previously treated multiple myeloma (n~120)[60] - Top-line data from the Phase 3 XPORT-MM-031 trial in multiple myeloma is expected in the first half of 2026[93]

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]