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].

Karyopharm Therapeutics Conference Summary Company Overview - Karyopharm Therapeutics is a U.S.-based, innovation-focused, commercial-stage oncology company specializing in areas of high unmet need, particularly in multiple myeloma and myelofibrosis [5][6] - The lead compound, Selinexor (XPOVIO), is already commercialized for multiple myeloma and approved in over 50 countries [5] Key Developments - Karyopharm is excited about two upcoming Phase III trials: one for myelofibrosis and another for endometrial cancer, with results for the myelofibrosis trial (SENTRY) expected in March 2026 [5][6] - The SENTRY trial aims to establish a new standard of care using Selinexor in combination with Ruxolitinib [6] Scientific Rationale - Selinexor is an XPO1 inhibitor that modulates various pathways relevant to myelofibrosis, including the NF-kappa B pathway and tumor suppressors like P53 [9][10] - The Phase I study showed that 79% of patients achieved a spleen volume reduction of 35% (SVR35) at week 24 when treated with Selinexor and Ruxolitinib, compared to 30%-35% with Ruxolitinib alone [12] Safety Profile - The safety profile of Selinexor in combination with Ruxolitinib appears manageable, with lower rates of nausea and vomiting compared to previous studies [18][20] - Only 7% of patients discontinued treatment due to adverse events in the Phase III study, indicating a favorable safety profile [18] Clinical Insights - Dr. Claire Harrison, a leading expert in myelofibrosis, emphasized the need for treatments that provide deeper and more durable responses than current JAK inhibitors [26] - The combination of Selinexor and Ruxolitinib is expected to be well-tolerated, with manageable side effects, particularly nausea [32][66] Trial Design and Endpoints - The SENTRY trial involves a two-to-one randomization of 353 patients to receive either Selinexor plus Ruxolitinib or Ruxolitinib plus placebo [40] - Primary endpoints include SVR35 and absolute total symptom score (TSS), with a focus on achieving a statistically significant improvement over Ruxolitinib alone [41][46] Baseline Characteristics - The baseline TSS in the SENTRY trial is higher than in previous trials, which may enhance the likelihood of demonstrating a meaningful treatment effect [52][54] - Dr. Harrison noted that a higher baseline TSS could lead to more accurate assessments of treatment efficacy [54] Future Expectations - A successful outcome in the SENTRY trial would likely lead to the combination being used as a first-line treatment for myelofibrosis patients [63] - The community of physicians is eager for new treatment options, and there is a strong interest in the results of the SENTRY trial [69] Additional Considerations - The trial's design excludes fatigue from the primary endpoints, which has been a challenge in previous studies [44] - The combination therapy is expected to improve hemoglobin levels, which is a critical prognostic factor in myelofibrosis [60] This summary encapsulates the key points discussed during the Karyopharm Therapeutics conference, highlighting the company's focus on innovative treatments for myelofibrosis and the anticipated impact of the SENTRY trial results.

Financial Data and Key Metrics Changes - Total revenue for Q3 2025 was $44 million, an increase of 13.4% compared to $38.8 million in Q3 2024 [26] - U.S. net product revenue for XPOVIO grew 8.5% year over year to $32 million [26] - License and other revenue was $12 million in Q3 2025, up nearly 30% from Q3 2024 [27] - Gross to net provisions for XPOVIO were 27% in Q3 2025, consistent with Q2 2025 and down from 31% in Q3 2024 [26] - The net loss was $33.1 million, or $3.82 per share on a GAAP basis, with more than half of this loss driven by non-operational items [29] Business Line Data and Key Metrics Changes - XPOVIO net product revenue in Q3 2025 was $32 million, reflecting continued strength in the multi-biomodal market [20] - The company is focused on advancing late-stage clinical programs, particularly SENTRY and ECO42, which are expected to be transformative [6] Market Data and Key Metrics Changes - The company sees a significant opportunity in the myofibrosis market, with approximately 20,000 patients living with the condition in the U.S. [23] - There are about 4,000 newly diagnosed patients each year in the U.S. with intermediate to high-risk myofibrosis who could benefit from the combination therapy [23] Company Strategy and Development Direction - The company aims to redefine the standard of care for myofibrosis through the combination of selinexor and ruxolitinib [4] - The strategy includes maintaining financial discipline while driving growth across the XPOVIO franchise and advancing clinical programs [6] - The company is preparing for a potentially transformative commercial launch in myofibrosis, driven by high unmet needs and lack of innovation in the market [21] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming top-line data from the SENTRY trial, expected in March 2026, which could reshape treatment paradigms [4] - The company has secured approximately $100 million in financial flexibility, extending its cash runway into Q2 2026 [5] - Management emphasized the importance of executing with clarity and purpose to deliver innovative cancer therapies [7] Other Important Information - The company has completed enrollment in the phase three SENTRY trial, marking a pivotal moment for its myofibrosis program [4] - The company has a strong commercial foundation and existing capabilities that will support a rapid launch if the trial data is positive [25] Q&A Session Summary Question: Can you walk through what we should see for MF data in March 2026? - Management anticipates providing top-line details, including primary endpoints of SVR35 and absolute TSS, with potential secondary endpoints [34][35] Question: What is the size of the sales force for myofibrosis? - Minimal additions to the commercial structure are expected due to strong overlap with existing capabilities [36] Question: Are there any milestones associated with recent financial restructuring? - No specific triggers related to positive data were mentioned, but positive data could significantly enhance value [37] Question: Can you discuss the commercial potential launch in myofibrosis? - The company is leveraging learnings from multiple myeloma to optimize trial design and patient outcomes [48][49]

Karyopharm Therapeutics (KPTI) Conference Summary Company Overview - Karyopharm Therapeutics is an innovation-driven commercial stage oncology company focusing on myelofibrosis and endometrial cancer treatments [3][4] Key Points on Myelofibrosis - The company is conducting two transformative Phase 3 studies: one for myelofibrosis and another for endometrial cancer, with top-line data expected by the end of 2025 or early 2026 [2][4] - The potential peak opportunity for myelofibrosis treatment is projected to exceed $1 billion [5] - The ongoing Phase 3 program targets JAK naive patients, with a focus on the efficacy of selinexor in combination with ruxolitinib [5][6] - Selinexor has shown promising results in heavily pretreated patients, demonstrating significant spleen volume reduction and symptom improvement [6][16] - The combination therapy has achieved a 79% SVR 35 rate compared to the 30-35% rate seen with ruxolitinib alone [16][28] - The durability of response is notable, with a 100% probability of maintaining spleen volume reduction among patients achieving SVR 35 [18] - The company emphasizes the importance of modifying the underlying disease and improving patient outcomes through innovative treatment approaches [34] Key Points on Endometrial Cancer - Karyopharm is leveraging the p53 wild type biomarker in endometrial cancer, which is present in approximately 50% of patients [38][39] - Selinexor has demonstrated a median progression-free survival (PFS) of 28.4 months in p53 wild type patients, significantly outperforming placebo [40] - The ongoing Phase 3 trial for endometrial cancer will evaluate selinexor as a monotherapy in a maintenance setting, with a planned enrollment of 276 patients [41] Additional Insights - The company has established commercialization capabilities to rapidly launch treatments upon receiving positive data [9][10] - The focus on innovative therapies aims to transform treatment standards in both myelofibrosis and endometrial cancer, enhancing patient outcomes [44] - The management team expresses confidence in the potential of selinexor to address unmet needs in oncology, particularly in challenging patient populations [11][12] Conclusion - Karyopharm Therapeutics is positioned for significant advancements in oncology with its innovative treatments for myelofibrosis and endometrial cancer, backed by promising clinical data and a strong commercialization strategy [44]