Financial Performance Comparison - Karyopharm Therapeutics Inc. has a Return on Invested Capital (ROIC) of -1634.05% and a Weighted Average Cost of Capital (WACC) of 16.41%, indicating extremely poor capital utilization [1][5] - MacroGenics, Inc. has a ROIC of -37.98% and a WACC of 9.15%, resulting in a ROIC to WACC ratio of -4.15, which is less inefficient compared to Karyopharm [2][5] - TG Therapeutics, Inc. shows a positive ROIC of 15.75% against a WACC of 12.34%, yielding a ROIC to WACC ratio of 1.28, indicating effective capital management [2][5] Industry Context - Heron Therapeutics, Inc. has a ROIC of 0.82% and a WACC of 6.57%, resulting in a ROIC to WACC ratio of 0.12, which is still better than Karyopharm's performance [3] - Intra-Cellular Therapies, Inc. has a ROIC of -10.08% and a WACC of 5.90%, leading to a ROIC to WACC ratio of -1.71, indicating inefficiencies but still better than Karyopharm [3] - Agios Pharmaceuticals, Inc. reports a ROIC of -30.47% and a WACC of 7.57%, resulting in a ROIC to WACC ratio of -4.02, showing inefficiencies but not as severe as Karyopharm's [4]

Core Insights - Karyopharm Therapeutics has completed enrollment in the Phase 3 SENTRY trial, which is evaluating the combination of selinexor and ruxolitinib in patients with myelofibrosis [1][2] - The trial aims to provide top-line data in March 2026, with the potential for selinexor plus ruxolitinib to become the first approved combination therapy for myelofibrosis [2] - Myelofibrosis is a rare blood cancer affecting approximately 20,000 patients in the U.S. and 17,000 in the EU, with current treatment options limited to JAK inhibitors [3] 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 an oral exportin 1 (XPO1) inhibitor [5][12] - XPOVIO is approved in the U.S. for multiple oncology indications and has received regulatory approvals in various countries, including the EU and China [6][12] - The company is advancing its pipeline to address high unmet needs in cancers such as multiple myeloma, endometrial cancer, and diffuse large B-cell lymphoma [12] Clinical Trial Details - The SENTRY trial enrolled 353 patients and evaluates a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib [2] - Co-primary endpoints include spleen volume response rate of 35% at week 24 and average change in absolute total symptom score over 24 weeks [2] - The trial targets JAKi-naïve myelofibrosis patients with platelet counts greater than 100 x 10/L, with a randomization ratio of 2-to-1 favoring the selinexor arm [2] Industry Context - Myelofibrosis is characterized by bone marrow fibrosis, leading to anemia and other debilitating symptoms, with current treatments often resulting in transfusion dependence [3] - The myelofibrosis community is in need of new therapies, as existing JAK inhibitors have limitations, including a high discontinuation rate due to anemia [3] - The development of new combination therapies like selinexor plus ruxolitinib could significantly impact treatment paradigms for myelofibrosis patients [2][3]

Company Performance - Karyopharm Therapeutics reported a quarterly loss of $4.32 per share, which was worse than the Zacks Consensus Estimate of a loss of $3.8, and compared to a loss of $3 per share a year ago, indicating a significant decline in performance [1] - The company posted revenues of $37.93 million for the quarter ended June 2025, missing the Zacks Consensus Estimate by 5.37%, and down from $42.79 million in the same quarter last year [2] - Over the last four quarters, Karyopharm has surpassed consensus EPS estimates three times and topped consensus revenue estimates two times [2] Stock Movement and Outlook - Karyopharm shares have lost approximately 61.1% since the beginning of the year, contrasting with the S&P 500's gain of 8.6%, indicating significant underperformance in the market [3] - The current consensus EPS estimate for the upcoming quarter is -$3.58 on revenues of $39.87 million, and for the current fiscal year, it is -$12.57 on revenues of $149.93 million [7] Industry Context - The Medical - Drugs industry, to which Karyopharm belongs, is currently ranked in the top 35% of over 250 Zacks industries, suggesting a relatively strong position within the sector [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which could impact Karyopharm's stock performance [5]

Financial Data and Key Metrics Changes - Total revenue for 2025 was $37.9 million, down from $42.8 million in 2024, primarily due to $6 million of non-recurring license-related revenue recognized in 2024 [38] - U.S. XPOVIO net product revenue for 2025 was $29.7 million, compared to $28 million in 2024, reflecting a 6% increase [32][39] - The gross to net provisions for XPOVIO in Q2 2025 were 26.8%, down from 45% in Q1 2025 and 29.3% in 2024 [39] - The company reported a net loss of $37.3 million or $4.32 per share on a GAAP basis, which includes $11.2 million in interest expense [42] Business Line Data and Key Metrics Changes - XPOVIO net product revenue was consistent, with the community setting driving approximately 60% of total U.S. sales [32] - The company expects net product revenue for the full year 2025 to be in the range of $110 million to $120 million [39] Market Data and Key Metrics Changes - The peak revenue potential for selinexor in myelofibrosis is estimated to be up to $1 billion annually in the U.S. alone [10][35] - Royalty revenue increased by 28% to $1.6 million in 2025 compared to 2024, reflecting increased global demand for XPOVIO and NexpoVIO [34] Company Strategy and Development Direction - The company is focused on enhancing liquidity and maximizing value while preparing for potential launches in myelofibrosis and endometrial cancer [6][45] - The company aims to redefine the standard of care for myelofibrosis with the combination of selinexor and ruxolitinib, pending positive data from ongoing trials [9][45] Management's Comments on Operating Environment and Future Outlook - Management acknowledged financial constraints with a near-term debt maturity in October and is actively engaged with lenders to enhance liquidity [6] - The company remains optimistic about the potential for selinexor plus ruxolitinib to improve treatment outcomes for myelofibrosis patients [9][45] Other Important Information - The company announced a 20% reduction in workforce to optimize costs, expecting to lower annual spend by approximately $13 million in 2026 [43] - The company exited 2025 with cash and equivalents of $52 million, down from $109.1 million at the end of 2024 [43] Q&A Session Summary Question: Concerns about myelofibrosis readout and preparation for multiple data readouts - Management expressed excitement about the upcoming readouts and confidence in leveraging existing commercial capabilities to prepare for potential launches in myelofibrosis and endometrial cancer [50][51] Question: Impact of higher baseline TSS on trial results - Management indicated that higher baseline TSS could lead to more meaningful outcomes in the trial, with ongoing monitoring of patient characteristics [60][61] Question: Reasons for lower rates of grade three anemia with combination therapy - Management attributed lower rates of grade three anemia to potential disease modification effects of selinexor, including reductions in key cytokines [62][63] Question: Confidence in blinded safety data holding once unblinded - Management expressed optimism about the safety profile observed in blinded data, noting consistency with historical ruxolitinib safety data [71][72]

August 11, 2025 Second Quarter 2025 Financial Results & Business Update On Today's Call • Welcome Brendan Strong, SVP, Investor Relations and Corporate Communications • Overview Richard Paulson, President and Chief Executive Officer • Pipeline Update Dr. Reshma Rangwala, Chief Medical Officer and Head of Research • Commercial Highlights Sohanya Cheng, Chief Commercial Officer and Head of Business Development ©2025 KARYOPHARM THERAPEUTICS INC. 2 • Financial Results and Guidance Lori Macomber, Chief Financial ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-36167 Karyopharm Therapeutics Inc. (Exact name of registrant as specified in its charter) (State or other juri ...

Exhibit 99.1 Karyopharm Reports Second Quarter 2025 Financial Results and Highlights Recent Company Progress – New Patient Screening for Phase 3 SENTRY Trial in Myelofibrosis Expected to Close This Week; Top-Line Results Anticipated in March 2026 – – Total Revenue was $37.9 Million; U.S. XPOVIO® (selinexor) Net Product Revenue was $29.7 Million, up 6% compared to Second Quarter of 2024 – – Reaffirms Full-Year 2025 Total Revenue Guidance of $140 Million to $155 Million; Updates U.S. XPOVIO Net Product Revenu ...

Core Insights - Karyopharm Therapeutics is nearing the completion of patient enrollment for its Phase 3 SENTRY trial in myelofibrosis, with top-line results expected in March 2026 [2][9] - The company reported total revenue of $37.9 million for the second quarter of 2025, with U.S. XPOVIO (selinexor) net product revenue at $29.7 million, reflecting a 6% increase compared to the same quarter in 2024 [1][15] - Karyopharm has reaffirmed its full-year 2025 total revenue guidance of $140 million to $155 million and updated its U.S. XPOVIO net product revenue guidance to $110 million to $120 million [1][13] Financial Performance - Total revenue for Q2 2025 was $37.9 million, down from $42.8 million in Q2 2024 [15] - U.S. net product revenue for Q2 2025 was $29.7 million, compared to $28.0 million in Q2 2024 [5][15] - License and other revenue decreased to $8.2 million in Q2 2025 from $14.8 million in Q2 2024, primarily due to non-recurring license-related revenue recognized in the previous year [16] - R&D expenses for Q2 2025 were $32.8 million, down from $38.4 million in Q2 2024, attributed to reduced personnel and clinical trial costs [18] - SG&A expenses decreased to $28.5 million in Q2 2025 from $31.1 million in Q2 2024, reflecting cost reduction initiatives [19] - The company reported a net loss of $37.3 million for Q2 2025, compared to a net income of $23.8 million in Q2 2024 [22] Clinical Development - The Phase 3 SENTRY trial is targeting 350 patients and is evaluating the efficacy of 60 mg once-weekly selinexor in combination with ruxolitinib [5][9] - Preliminary safety data from the first 61 patients in the SENTRY trial suggest potential improvements in treatment-emergent adverse events compared to previous studies [5] - Karyopharm is also enrolling patients in the Phase 3 XPORT-EC-042 trial for endometrial cancer and has completed enrollment in the Phase 3 XPORT-MM-031 trial for multiple myeloma [7][8][11] Strategic Initiatives - The company is exploring financing transactions and strategic alternatives to extend its cash runway and enhance liquidity [1][14] - Karyopharm's cash position as of June 30, 2025, was $52.0 million, down from $109.1 million at the end of 2024 [23]

Core Points - Karyopharm Therapeutics Inc. will report its second quarter 2025 financial results on August 11, 2025, at 8:00 a.m. ET [1] - A conference call and audio webcast will be hosted by the management team to discuss the financial results and company updates [1] Company Overview - Karyopharm Therapeutics Inc. is a commercial-stage pharmaceutical company focused on pioneering novel cancer therapies, particularly oral compounds that address nuclear export dysregulation [3] - The company's lead compound, XPOVIO® (selinexor), is an oral exportin 1 (XPO1) inhibitor approved in the U.S. for three oncology indications and has received regulatory approvals in various international markets, including Europe and China [3] - Karyopharm has a focused pipeline targeting high unmet need cancers, including multiple myeloma, endometrial cancer, myelofibrosis, and diffuse large B-cell lymphoma (DLBCL) [3]

The market expects Karyopharm Therapeutics (KPTI) to deliver a year-over-year decline in earnings on lower revenues when it reports results for the quarter ended June 2025. This widely-known consensus outlook is important in assessing the company's earnings picture, but a powerful factor that might influence its near-term stock price is how the actual results compare to these estimates. The earnings report might help the stock move higher if these key numbers are better than expectations. On the other hand, ...