Jefferies Global Healthcare Conference June 5, 2025 Forward-looking Statements and Other Important Information This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's beliefs about the market opportunity and annual peak revenue opportunities for selinexor; expectations with respect to commercialization efforts; the ability of selinexor to treat patients with multiple ...

Summary of Karyopharm Therapeutics (KPTI) Conference Call Company Overview - **Company**: Karyopharm Therapeutics (KPTI) - **Key Products**: Selinexor (XPOVIO) - **Focus Areas**: Oncology, specifically multiple myeloma and myelofibrosis Key Points Commercial Performance and Product Dynamics - **Q1 Demand Growth**: KPTI reported a 5% year-over-year demand growth for XPOVIO in Q1, despite a one-time impact of $5 million from atypical returns related to high-dose selinexor [3][4] - **Real-World Utilization**: The company is focusing on increasing the utilization of selinexor in both community and academic settings, with a particular emphasis on lower doses [4][5] - **Community Treatment**: Selinexor is primarily used in the community setting for multiple myeloma patients, positioned in the second to fourth line of treatment [5][6] Growth Drivers and Future Outlook - **T Cell Engaging Therapies**: KPTI is generating data to support the use of selinexor in conjunction with T cell engaging therapies, which are becoming more prevalent in earlier treatment lines [9][10] - **Myelofibrosis Opportunity**: The ongoing SENTRI trial is evaluating selinexor in combination with ruxolitinib, with promising early data showing a 79% SVR 35 rate at week 24 compared to 30-35% for ruxolitinib alone [12][13][15] - **Durability of Response**: The company reported a 100% durability of response for patients achieving SVR 35 or TSS 50, indicating sustained benefits from treatment [17] Clinical Trials and Data - **Phase III Trials**: KPTI is focused on executing its Phase III trials for both myelofibrosis and endometrial cancer, with the latter leveraging a biomarker (p53 wild type) for patient selection [45][46] - **Endpoint Changes**: The transition from TSS 50 to absolute TSS is seen as a more sensitive measure for symptom improvement, gaining positive feedback from investigators and regulators [28][29] Safety and Tolerability - **Antiemetic Use**: KPTI has incorporated dual antiemetics in its Phase III trials to mitigate nausea and vomiting, achieving over 85% compliance and lower rates of these side effects [36][38] - **Safety Profile**: The safety profile of selinexor is evolving positively, with improvements noted in gastrointestinal side effects [17][38] Commercial Strategy - **Market Positioning**: KPTI aims to target all frontline myelofibrosis patients, leveraging existing commercial infrastructure to facilitate rapid uptake among physicians [41][42] - **Unmet Need**: Research indicates a significant unmet need in the myelofibrosis market, with 75% of physicians willing to adopt therapies that address key disease hallmarks [42] Financial Discipline - **Operational Focus**: KPTI is maintaining a disciplined approach to operational expenditures, concentrating resources on Phase III readouts and shutting down non-essential programs [48][49] Additional Insights - **Endometrial Cancer Landscape**: The company anticipates that selinexor will address a sizable unmet need in patients with p53 wild type tumors, with enrollment for the Phase III trial progressing well [46][47] - **Future Readouts**: KPTI is positioned for significant upcoming data readouts that could transform treatment paradigms in both myelofibrosis and endometrial cancer [49]