Core Viewpoint - Karyopharm Therapeutics (KPTI) shows significant upside potential with a mean price target of $33.07, indicating a 521.6% increase from its current price of $5.32 [1] Price Targets and Analyst Consensus - The average price target consists of seven estimates ranging from $8 to $67.47, with a standard deviation of $23.37, suggesting a high variability in analyst predictions [2] - The lowest estimate indicates a potential increase of 50.4%, while the highest suggests an upside of 1168.2% [2] - A low standard deviation among price targets indicates strong agreement among analysts regarding the stock's price movement direction [9] Earnings Estimates and Analyst Optimism - Analysts exhibit strong agreement in revising KPTI's earnings estimates higher, which correlates with potential stock price increases [4][11] - Over the past 30 days, one estimate has increased, leading to a 4.9% rise in the Zacks Consensus Estimate for the current year [12] - KPTI holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate factors [13] Caution on Price Targets - While price targets are commonly referenced, they can mislead investors, as empirical research shows they rarely indicate actual stock price movements [7][10] - Analysts may set overly optimistic price targets due to business incentives, which can inflate expectations [8]

Core Insights - Karyopharm Therapeutics Inc. announced that its abstract on selinexor monotherapy for myelofibrosis has been selected for presentation at the 2025 European Hematology Association Annual Meeting [1][2] - The data from the Phase 2 XPORT-MF-035 trial indicates that selinexor shows clinical activity in heavily pretreated myelofibrosis patients, demonstrating spleen volume reduction, hemoglobin stabilization, and symptom improvement [2][4] Summary by Sections Company Overview - Karyopharm Therapeutics is a commercial-stage pharmaceutical company focused on developing novel cancer therapies, particularly through its lead compound, XPOVIO (selinexor), which is a first-in-class oral exportin 1 (XPO1) inhibitor [4][11] - The company has received regulatory approvals for XPOVIO in multiple oncology indications in the U.S. and various international markets, including Europe and China [5][11] Clinical Trial Insights - The XPORT-MF-035 trial involved 24 patients, randomized 1:1 to receive either selinexor monotherapy or physician's choice treatment, with selinexor administered at 80 mg weekly for the first two cycles, then reduced to 60 mg [4] - Key findings from the trial include: - 67% of selinexor-treated patients achieved a spleen volume reduction of 25% or more compared to 38% in the physician's choice group [4] - 33% of selinexor patients achieved a spleen volume reduction of 35% or more versus 13% in the physician's choice group [4] - Patients on selinexor had higher mean hemoglobin levels and lower rates of red blood cell transfusions compared to those on physician's choice [4] Safety and Adverse Events - The most common treatment-emergent adverse events (TEAEs) in the selinexor arm included decreased weight (50%), asthenia (42%), and nausea (33%) [4] - Serious adverse reactions were reported in 52% of patients in the BOSTON trial, with a treatment discontinuation rate of 19% due to adverse reactions [9]

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]

Core Viewpoint - Karyopharm Therapeutics reported a quarterly loss of $2.77 per share, significantly better than the Zacks Consensus Estimate of a loss of $4.21, marking an earnings surprise of 34.20% [1] Financial Performance - The company posted revenues of $30.02 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 16.18%, compared to $33.13 million in the same quarter last year [2] - Over the last four quarters, Karyopharm has surpassed consensus EPS estimates four times and topped consensus revenue estimates three times [2] Stock Performance - Karyopharm shares have declined approximately 40.7% since the beginning of the year, while the S&P 500 has decreased by 3.8% [3] - The current consensus EPS estimate for the upcoming quarter is -$3.90 on revenues of $39.29 million, and for the current fiscal year, it is -$14.05 on revenues of $150.29 million [7] Industry Outlook - The Medical - Drugs industry, to which Karyopharm belongs, is currently ranked in the top 27% of over 250 Zacks industries, indicating a favorable outlook compared to lower-ranked industries [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]

Financial Performance & Guidance - Q1 2025 XPOVIO净产品收入为2110万美元，受到非典型过期产品退货的影响，减少了约500万美元[86, 87] - 公司预计2025年总收入为140-155百万美元[112] - 公司预计2025年美国XPOVIO净产品收入为115-130百万美元[112] - 公司预计2025年研发和SG&A支出为240-255百万美元，其中包括约2000万美元的非现金股票补偿[112] Myelofibrosis Program - Myelofibrosis的美国峰值年收入机会高达约10亿美元[7, 19] - 在JAKi初治的骨髓纤维化患者中，Selinexor联合Ruxolitinib治疗的SVR35达到79%[28] - 75%的美国医生表示有意采用联合疗法治疗骨髓纤维化[21, 99] Clinical Trials & Pipeline - SENTRY试验的顶线数据预计在2025年末/2026年初公布[7, 59] - XPORT-MF-035试验中，Selinexor单药治疗使脾脏体积缩小率增加了一倍以上，SVR25为67%，SVR35为33%[35, 36] - 完成了评估SPd治疗既往接受过治疗的多发性骨髓瘤患者的3期全球研究（XPORT-MM-031/EMN291）的患者招募，预计在2026年上半年获得顶线数据[78, 79, 81] Commercial Strategy - Selinexor已在超过45个国家获得批准[7, 90] - 现有销售团队已覆盖约80%的社区骨髓纤维化客户[21]

Revenue Performance - For the three months ended March 31, 2025, product revenue decreased by $4.95 million (19%) to $21.05 million compared to $26.01 million in the same period of 2024, primarily due to an increase in the gross-to-net provision[105]. - License and other revenue increased by $1.84 million (26%) to $8.96 million for the three months ended March 31, 2025, driven by a $1.2 million revenue recognition for reimbursement of development-related expenses from Menarini[108]. - Total revenue for the three months ended March 31, 2025, was $30.02 million, a decrease of $3.11 million (9%) from $33.13 million in the same period of 2024[105]. Operating Expenses - Operating expenses decreased by $3.61 million (5%) to $63.27 million for the three months ended March 31, 2025, compared to $66.89 million in 2024[110]. - Selling, general and administrative expenses decreased by $2.2 million to $27.4 million in Q1 2025 compared to Q1 2024[115]. - Research and development expenses for Q1 2025 decreased by $0.8 million to $34.6 million compared to Q1 2024[113]. Net Loss and Financial Position - The net loss for the three months ended March 31, 2025, was $23.46 million, a reduction of $13.90 million (37%) from a net loss of $37.36 million in the same period of 2024[105]. - As of March 31, 2025, the company had an accumulated deficit of $1.6 billion and substantial doubt regarding its ability to continue as a going concern within one year[101]. - The company expects to incur significant operating losses in the foreseeable future, raising substantial doubt about its ability to continue as a going concern[120]. Cash and Investments - As of March 31, 2025, the company had $69.9 million in cash, cash equivalents, and investments, with a loss of $23.5 million for the quarter[119]. - Cash, cash equivalents, and investments amount to $69.9 million as of March 31, 2025[132]. - The company has a requirement to maintain at least $25.0 million in cash and equivalents at all times due to debt obligations[130]. Future Obligations - Headquarters lease costs amount to $10.9 million through September 30, 2030[131]. - Future obligations related to the 2025 Notes total $25.2 million through October 2025[131]. - Future obligations related to the 2029 Notes are $144.7 million through May 2029[131]. - Future obligations under the Credit Agreement are $141.9 million through May 2028, with a requirement to maintain at least $25.0 million in cash and equivalents[131]. - Future royalty obligations to HCRx under the Amended Revenue Interest Agreement total $117.8 million by October 1, 2031[131]. Clinical Development and Strategy - The company plans to continue clinical trials and seek additional approvals for selinexor as a single agent or in combination with other therapies to expand treatment options[100]. - The company expects net product revenue to increase in the second quarter of 2025 due to improved gross-to-net favorability with product returns aligning with historical averages[107]. - Clinical trial costs for Selinexor in myelofibrosis increased by $5.0 million to $11.4 million, while costs for multiple myeloma decreased by $2.1 million to $1.9 million[113]. - The company anticipates research and development expenses to remain consistent in Q2 2025 as it continues to invest in clinical trials[114]. Other Financial Information - Other income increased by $13.4 million to $9.8 million in Q1 2025, primarily due to a $20.0 million non-cash gain from remeasurement of derivatives[117]. - Net cash used in operating activities decreased by $4.7 million to $39.0 million in Q1 2025 compared to Q1 2024[121]. - The company entered into refinancing transactions in May 2024, borrowing $100 million and exchanging $148 million of existing notes for new secured convertible senior notes[102]. Risk Factors - Company is exposed to interest rate sensitivity, but a 100 basis point shift would not materially affect the investment portfolio's fair market value[132]. - Company does not hedge foreign currency exchange rate risk, exposing it to fluctuations in foreign currency rates[134]. - Contracts with organizations in Canada, the UK, and Europe are denominated in foreign currencies, impacting budget stability[134]. - Company cannot provide assurance against potential losses on deposits and investments due to financial institution instability[133].

Exhibit 99.1 Karyopharm Reports First Quarter 2025 Financial Results and Announces New Data in Myelofibrosis that Further Suggests Selinexor May Lead to Meaningful Spleen Volume Reduction, Symptom Improvement, Hemoglobin Stabilization and Disease Modification – New Randomized Phase 2 Monotherapy Data from XPORT-MF-035 Trial in a Hard-to-Treat Patient Population Further Strengthens Conviction in Selinexor's Potential in Combination with Ruxolitinib in JAKi-Naïve Myelofibrosis in Ongoing Phase 3 SENTRY Trial ...

Core Insights - Karyopharm Therapeutics reported positive developments in its Phase 3 SENTRY trial for selinexor in JAKi-naïve myelofibrosis, which has passed a planned futility analysis and is approximately 80% enrolled [2][4] - The company experienced a 5% increase in demand for XPOVIO® (selinexor) in Q1 2025 compared to Q1 2024, with total revenue of $30.0 million [5][15] - Karyopharm reaffirmed its full-year 2025 revenue guidance of $140 million to $155 million, including U.S. net product revenue guidance of $115 million to $130 million [21] Financial Performance - Total revenue for Q1 2025 was $30.0 million, down from $33.1 million in Q1 2024 [15] - U.S. net product revenue was $21.1 million in Q1 2025, compared to $26.0 million in Q1 2024, impacted by a $5.0 million increase in product return reserves [16] - License and other revenue increased to $9.0 million in Q1 2025 from $7.1 million in Q1 2024, attributed to timing of revenue recognition from Menarini [17] Research and Development Highlights - The Phase 3 SENTRY trial is evaluating the combination of selinexor and ruxolitinib, targeting 350 patients for enrollment [4] - The Phase 2 XPORT-MF-035 trial showed promising results for selinexor monotherapy in hard-to-treat myelofibrosis patients, with 67% achieving spleen volume reduction of 25% or more [10] - Enrollment continues in the Phase 3 XPORT-EC-042 trial for selinexor as maintenance therapy in advanced endometrial cancer [6] Operational Objectives - Karyopharm aims to complete target enrollment for the Phase 3 SENTRY trial by June/July 2025 and report top-line results in late 2025/early 2026 [11] - The company is exploring alternatives to extend its cash runway, with cash and investments totaling $70.3 million as of March 31, 2025 [25][14] - R&D expenses for Q1 2025 were $34.6 million, slightly down from $35.4 million in Q1 2024, reflecting reduced personnel costs [19]