Financial Data and Key Metrics Changes - Total revenue for Q4 2025 was $34.1 million, an increase of 11.8% compared to Q4 2024 [51] - For the full year 2025, total revenue was $146.1 million, a slight increase from 2024 [51] - U.S. XPOVIO net product revenue for Q4 2025 was $32.1 million, an increase of 9.6% compared to Q4 2024 [52] - For the full year, U.S. XPOVIO net product revenue was $114.9 million, an increase of 1.9% from 2024 [52] - The company reported a net loss of $102.2 million, or $5.71 per share on a GAAP basis in Q4 2025 [60] - The full year net loss was $196 million, or $17.93 per diluted share for 2025 [60] Business Line Data and Key Metrics Changes - Xpovio net product revenue grew to $32.1 million in Q4 2025 and $114.9 million for the full year 2025 [36] - The company expects to guide towards $115 to $130 million of Xpovio net product revenue in 2026 [36] - License and other revenue was $2 million in Q4 and $31.2 million for the full year 2025 [53] Market Data and Key Metrics Changes - Demand for Xpovio was consistent year-over-year in 2025, with the community setting driving approximately 60% of total U.S. sales [37] - The company is targeting approximately 4,000 newly diagnosed patients with intermediate to high-risk myelofibrosis [45] Company Strategy and Development Direction - Karyopharm is focused on expanding its oncology franchise, particularly in myelofibrosis and endometrial cancer [7][8] - The company is preparing for pivotal data readouts from its late-stage clinical programs, with significant opportunities in myelofibrosis and endometrial cancer [63] - The strategy includes evaluating a range of financing and strategic options to maintain flexibility and align capital decisions with value creation [12] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming data readout from the phase three SENTRY trial in March, which is expected to address an unmet need in myelofibrosis [9][26] - The company is managing its business with discipline, focusing on near-term value-creating milestones while maintaining flexibility [64] - Management emphasized the importance of executing well and generating high-quality data to define the next phase of the company [64] Other Important Information - The company ended the year with $64.1 million in cash, cash equivalents, restricted cash, and investments, compared to $109.1 million as of December 31, 2024 [61] - The full year 2025 included $15 million of R&D reimbursement from Menarini, which will not be received in future years [53] Q&A Session Summary Question: Can you discuss the differences in exposure and activity between the 40 mg and 60 mg doses? - Management indicated that the 60 mg dose showed a clear benefit-risk profile compared to the 40 mg dose, with maximized efficacy in the 60 mg group [70] Question: What are your thoughts on Novartis' recent plans in myelofibrosis? - Management noted that the continued investment in the myelofibrosis space highlights the unmet need and significant market value [74] Question: Can you elaborate on the strategy for eltanexor and other MPNs? - Management stated that eltanexor is a second-generation XPO1 inhibitor with potential applications beyond myelofibrosis, including other MPNs [78] Question: What updates can you provide on the blinded safety data? - Management confirmed that no updates have been made beyond previously disclosed data, and they are looking forward to the upcoming data readout [85] Question: How do you view the potential for symptomatic improvement in your trials? - Management emphasized the goal of achieving statistical significance for both spleen volume reduction and symptomatic improvement [104]

Financial Data and Key Metrics Changes - Total revenue for Q4 2025 was $34.1 million, an increase of 11.8% compared to Q4 2024. For the full year, total revenue was $146.1 million, a slight increase from 2024 [50]. - U.S. XPOVIO net product revenue for Q4 2025 was $32.1 million, an increase of 9.6% compared to Q4 2024. For the full year, it was $114.9 million, an increase of 1.9% from 2024 [51]. - The company reported a net loss of $102.2 million, or $5.71 per share for Q4 2025, and a net loss of $196 million, or $17.93 per diluted share for the full year 2025 [59]. Business Line Data and Key Metrics Changes - Xpovio net product revenue grew to $32.1 million in Q4 2025 and $114.9 million for the full year 2025, with expectations to reach $115 million-$130 million in 2026 [35]. - License and other revenue was $2 million in Q4 and $31.2 million for the full year 2025, including $15 million of R&D reimbursement from Menarini, which will not continue in 2026 [52]. Market Data and Key Metrics Changes - Demand for Xpovio remained consistent year-over-year in 2025, with the community setting driving approximately 60% of total U.S. sales [36]. - The U.S. market for myelofibrosis includes approximately 20,000 patients, representing a multibillion-dollar marketplace, with about 6,000 newly diagnosed patients each year [43]. Company Strategy and Development Direction - The company aims to expand its oncology franchise, focusing on myelofibrosis and endometrial cancer as key growth areas [6][7]. - Karyopharm is preparing for pivotal data readouts from late-stage clinical programs, with the SENTRI trial for myelofibrosis data expected in March 2026 and the EXPORT EC042 trial for endometrial cancer data expected in mid-2026 [8][9]. Management's Comments on Operating Environment and Future Outlook - Management emphasized the importance of optimizing clinical programs and maintaining a disciplined approach to capital allocation [63]. - The company is focused on executing well, generating high-quality data, and allowing these results to define the next phase of the company [63]. Other Important Information - The company ended the year with $64.1 million in cash and equivalents, down from $109.1 million at the end of 2024 [60]. - Research and development expenses for Q4 2025 were $27.7 million, a decrease of 17% from Q4 2024, reflecting cost reduction initiatives [53]. Q&A Session Summary Question: Can you discuss the differences in exposure and activity between the 40 mg and 60 mg doses? - Management noted that the 60 mg dose showed a clear benefit-risk profile favoring efficacy and safety compared to the 40 mg dose [68]. Question: What are your thoughts on Novartis' recent plans in myelofibrosis? - Management highlighted the importance of targeting the right patient population and expressed confidence in establishing their product as the standard of care pending positive data [72][75]. Question: Can you elaborate on the strategy for eltanexor and other MPNs if myelofibrosis data is positive? - Management indicated that eltanexor, a second-generation XPO1 inhibitor, has potential in other MPNs and is looking to expand beyond myelofibrosis [78]. Question: What updates can you provide on the blinded safety data and discontinuation rates? - Management confirmed that no updates have been made beyond previously disclosed data, but they are optimistic about the upcoming data readout [84]. Question: What is the expected threshold for symptomatic improvement in the upcoming trials? - Management aims for statistical significance in both spleen volume reduction and symptomatic improvement, emphasizing the importance of both metrics in their analysis plan [103].

Financial Data and Key Metrics Changes - Total revenue for Q4 2025 was $34.1 million, an increase of 11.8% compared to Q4 2024. For the full year, total revenue was $146.1 million, a slight increase from 2024 [26]. - U.S. XPOVIO net product revenue for Q4 2025 was $32.1 million, an increase of 9.6% compared to Q4 2024. For the full year, U.S. XPOVIO net product revenue was $114.9 million, an increase of 1.9% from 2024 [26]. - Gross to net provisions for XPOVIO were 26.9% in Q4 and 31.2% for the full year 2025 [26]. - The company reported a net loss of $102.2 million, or $5.71 per share in Q4 2025, and a net loss of $196 million, or $17.93 per diluted share for the full year 2025 [32]. Business Line Data and Key Metrics Changes - Xpovio net product revenue grew to $32.1 million in Q4 2025 and $114.9 million for the full year 2025, with expectations to deliver revenue growth in 2026, guiding towards $115 million-$130 million [18]. - The community setting continues to drive approximately 60% of total U.S. sales for Xpovio [18]. Market Data and Key Metrics Changes - In the myelofibrosis market, the only treatment options currently available are JAK inhibitors, with ruxolitinib being the standard of care for the past 15 years [21]. - There are approximately 20,000 patients living with myelofibrosis in the U.S., representing a multibillion-dollar marketplace, with about 6,000 newly diagnosed patients each year [22]. Company Strategy and Development Direction - Karyopharm is focusing on expanding its oncology franchise, particularly in myelofibrosis and endometrial cancer, with pivotal data expected in March and mid-2026, respectively [4][5]. - The company aims to establish a new standard of care in frontline myelofibrosis by combining selinexor with ruxolitinib, addressing the unmet need in the market [21][24]. - The strategy includes evaluating a range of financing and strategic options to maintain flexibility and align capital decisions with value creation [5]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming data readouts from pivotal trials, which could significantly expand the role of the oncology franchise [35]. - The company is managing its business with a clear focus on near-term value-creating milestones while maintaining flexibility in capital allocation [35]. Other Important Information - Research and development expenses for Q4 2025 were $27.7 million, a decrease of 17% from Q4 2024, driven by lower personnel costs and focused clinical trial expenses [29]. - Selling, general, and administrative expenses were $22.8 million for the quarter, a decrease of 16% compared to Q4 2024 [29]. Q&A Session Summary Question: Can you discuss the differences in exposure and activity between the 40 mg and 60 mg doses? - Management indicated that the 60 mg dose showed a clear benefit-risk profile compared to the 40 mg dose, with maximized efficacy in the 60 mg group [38][39]. Question: What are the implications of Novartis' new plans in myelofibrosis? - Management noted that Novartis' investment in myelofibrosis highlights the unmet need in the market, and Karyopharm aims to establish itself as the standard of care pending positive data [41][44]. Question: What is the strategy for eltanexor and other myeloproliferative neoplasms (MPNs)? - Eltanexor is a second-generation XPO1 inhibitor with potential applications in other MPNs, and the company is excited about expanding beyond myelofibrosis [46][47][48]. Question: Can you provide updates on the blinded safety data and any changes in discontinuation rates? - Management confirmed that no updates have been made beyond previously disclosed data, and they are looking forward to the upcoming data readout [52][55].