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]

Financing and Capital Structure - Karyopharm Therapeutics Inc. announced comprehensive financing and capital structure transactions expected to provide $100 million of financial flexibility, extending the cash runway into Q2 2026 [1] - The company is exploring potential financing and strategic alternatives to enhance liquidity and maximize value, with Centerview Partners acting as the financial advisor [2] - A private placement of approximately $8.75 million will involve the sale of 1.49 million shares and warrants to purchase 1.32 million shares at an exercise price of $6.64 per share [2] Revenue Expectations - The company expects total revenue, including license and royalty revenue from partners, to be between $42 million and $44 million, with U.S. XPOVIO net product revenue anticipated to be approximately $32 million for Q3 2025 [3] Clinical Trials - Enrollment continues in the Phase 3 XPORT-EC-042 trial evaluating selinexor as a maintenance-only therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer, with topline data expected in mid-2026 [4] - The company completed enrollment in the Phase 3 SENTRY trial, which evaluates selinexor in combination with ruxolitinib in JAKi-naïve myelofibrosis patients, with topline data anticipated in March 2026 [4][5] Stock Performance - Karyopharm stock is down 12.74% at $5.03 at the time of publication [5]

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]

Financial Performance - Karyopharm Therapeutics reported quarterly losses of $2.77 per share, which was better than the analyst consensus estimate of losses of $4.16 per share [1] - The company reported quarterly sales of $30.02 million, missing the analyst consensus estimate of $35.24 million [1] Clinical Trial Update - The Phase 3 SENTRY trial in patients with JAKi-naïve myelofibrosis has passed its pre-specified futility analysis and continues as planned without modifications [2] - New data in hard-to-treat myelofibrosis patients showed spleen volume reduction, symptom improvement, hemoglobin stabilization, and evidence of disease modification with selinexor monotherapy [2] Sales Guidance and Market Reaction - Karyopharm affirmed FY2025 sales guidance of $140.00 million to $155.00 million, compared to market estimates of $149.32 million [3] - Following the earnings announcement, Karyopharm shares fell 15.6% to trade at $5.17 [3] Analyst Ratings and Price Targets - Baird analyst Michael Ulz maintained an Outperform rating and lowered the price target from $54 to $42 [8] - Barclays analyst Peter Lawson maintained an Overweight rating and raised the price target from $5 to $10 [8] - RBC Capital analyst Brian Abrahams maintained an Outperform rating and lowered the price target from $34 to $33 [8]

Financial Data and Key Metrics Changes - Total revenue for Q1 2025 was $30 million, down from $33.1 million in Q1 2024 [46] - U.S. XPOVIO net product revenue decreased to $21.1 million from $26 million year-over-year, attributed to a $5 million increase in product return reserves [47] - Gross to net provisions for XPOVIO were 45% in Q1 2025 compared to 29.3% in the same period in 2024 [47] - Cash, cash equivalents, and investments at the end of Q1 2025 were $70.3 million, down from $109.1 million at the end of 2024 [48] Business Line Data and Key Metrics Changes - Demand growth for Q1 was 5% year-over-year, with net product revenue impacted by atypical returns of expired products [40] - Royalty revenue increased by 57% to $1.7 million in Q1 2025 compared to Q1 2024, reflecting growing global demand for XPOVIO [42] Market Data and Key Metrics Changes - The multiple myeloma market remains highly competitive, with expectations of additional new entrants this year [41] - The company anticipates a peak revenue potential of approximately $1 billion in the U.S. for selinexor in myelofibrosis if approved [10] Company Strategy and Development Direction - The company is focused on completing enrollment in the Phase III SENTRY trial for myelofibrosis and advancing the Phase III trial in endometrial cancer [7][38] - The strategy includes leveraging a profitable commercial organization in multiple myeloma to drive rapid commercialization in new disease areas [7] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of selinexor to redefine the standard of care in myelofibrosis, with encouraging clinical data supporting its efficacy [8][10] - The company is exploring various opportunities to extend its cash runway while focusing on advancing clinical trials and commercial performance [51][53] Other Important Information - The Phase III SENTRY trial successfully passed its pre-specified futility analysis, allowing the study to continue as planned [35] - The company expects to complete enrollment in the SENTRY trial by June-July 2025 [35][67] Q&A Session Summary Question: Can you talk about the futility analysis and its basis? - The futility analysis was based on efficacy and safety data from the first 61 patients, with thresholds for no worsening compared to ruxolitinib alone [55][56] Question: What are the assumptions for achieving full enrollment in June and July? - The company is currently 80% enrolled and expects to complete enrollment in the June-July timeframe, with a press release to follow [67] Question: What is driving utilization in multiple myeloma? - The company reported 5% growth in demand, with utilization driven by its flexible combination therapy positioning in both community and academic settings [82] Question: What is the normal run rate of return product? - The atypical returns of $5 million were related to high-dose products, and the company does not expect this to continue into future quarters [89] Question: How confident is the company in reaching its revenue guidance? - The company believes it can deliver at the lower end of its revenue guidance due to strong demand growth and global partner revenue [97]

Financial Data and Key Metrics Changes - Total revenue for Q1 2025 was $30 million, down from $33.1 million in Q1 2024 [44] - U.S. XPOVIO net product revenue decreased to $21.1 million from $26 million year-over-year, attributed to a $5 million increase in product return reserves [45] - Gross to net provisions for XPOVIO increased to 45% from 29.3% in the same period in 2024 [45] - Cash, cash equivalents, and investments at the end of Q1 2025 were $70.3 million, down from $109.1 million at the end of 2024 [46] Business Line Data and Key Metrics Changes - Demand growth for Q1 was 5% year-over-year, with net product revenue impacted by atypical returns of expired products [38] - Royalty revenue increased by 57% to $1.7 million in Q1 2025 compared to Q1 2024, reflecting growing global demand for XPOVIO [40] Market Data and Key Metrics Changes - The multiple myeloma market remains highly competitive, with expectations of additional new entrants this year [39] - The company anticipates a peak revenue potential of approximately $1 billion in the U.S. for selinexor in myelofibrosis if approved [8] Company Strategy and Development Direction - The company is focused on completing enrollment in the Phase III SENTRY trial for myelofibrosis and advancing the Phase III trial in endometrial cancer [5][36] - The strategy includes leveraging a profitable commercial organization in multiple myeloma to drive rapid commercialization in new disease areas [5] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of selinexor to redefine the standard of care in myelofibrosis, with encouraging clinical data supporting its efficacy [6][34] - The company is exploring various opportunities to extend its cash runway while focusing on advancing clinical trials and commercial performance [49] Other Important Information - The Phase III SENTRY trial passed its pre-specified futility analysis, allowing the study to continue as planned [33] - The company expects to complete enrollment in the SENTRY trial by June-July 2025 [67] Q&A Session Summary Question: Can you talk about the futility analysis and what it was based on? - The futility analysis was based on efficacy and safety data from the first 61 patients, focusing on SVR35 and absolute TSS [53][54] Question: What are the assumptions for reaching full enrollment in June and July? - The company is currently 80% enrolled and expects to complete enrollment in the June-July timeframe, with a press release to follow [67][68] Question: What is driving utilization in multiple myeloma? - The company reported 5% growth in demand, with strong performance in both community and academic settings, leveraging its differentiated mechanism of action [82] Question: What is the normal run rate of return product? - The atypical returns of $5 million were related to high-dose products and are not expected to continue into future quarters [88][89] Question: How confident is the company in reaching its revenue guidance? - The company believes it can deliver at the lower end of its revenue guidance due to strong demand growth and global partner performance [96]