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]

Financial Performance & Guidance - Karyopharm's Q2 2025 U S net product revenue was $29 7 million, a 6% increase from $28 0 million in Q2 2024[69] - The company anticipates full year 2025 U S XPOVIO net product revenue to be between $110 million and $120 million[69] - Karyopharm projects total revenue between $140 million and $155 million for 2025, with R&D and SG&A expenses ranging from $240 million to $250 million[88] Myelofibrosis (MF) Program - Selinexor has a peak U S revenue opportunity of up to ~$1 billion in myelofibrosis, pending positive data and regulatory approval[9, 19, 70] - In a Phase 1 trial, 79% of patients achieved SVR35 (spleen volume reduction of 35% or more) at week 24 with selinexor plus ruxolitinib[28] - Preliminary extrapolated data from the Phase 3 SENTRY trial suggests a potentially more favorable safety profile for selinexor plus ruxolitinib compared to ruxolitinib alone, with Grade 3+ anemia rates potentially lower at ~26% compared to 37%[35, 37] - Top-line data from the Phase 3 SENTRY trial of selinexor in myelofibrosis is expected in March 2026[9, 33] Endometrial Cancer (EC) Program - The company is focusing the Phase 3 XPORT-EC-042 trial on patients with TP53wt EC who are pMMR or dMMR and medically ineligible for checkpoint inhibitors[46] - Top-line data from the Phase 3 XPORT-EC-042 trial in endometrial cancer is anticipated in mid-2026[91] Multiple Myeloma (MM) Program - Enrollment is complete in the Phase 3 XPORT-MM-031 trial evaluating SPd in patients with previously treated multiple myeloma (n~120)[60] - Top-line data from the Phase 3 XPORT-MM-031 trial in multiple myeloma is expected in the first half of 2026[93]

Financial Performance - For the three months ended June 30, 2025, product revenue increased by $1.6 million (6%) compared to the same period in 2024, reaching $29.7 million, primarily due to lower 340B discounts[109]. - For the six months ended June 30, 2025, total revenue decreased by $7.97 million (10%) to $67.94 million, with product revenue declining by $3.3 million (6%) compared to the same period in 2024[108]. - The company reported a net loss of $60.7 million for the six months ended June 30, 2025, compared to a net loss of $13.6 million for the same period in 2024[108]. - As of June 30, 2025, the company had an accumulated deficit of $1.6 billion[103]. - The company expects net product revenue to increase in the second half of 2025 due to lower product returns and increased demand[111]. Operating Expenses - Operating expenses for the three months ended June 30, 2025, decreased by 13% to $85.3 million compared to the same period in 2024[108]. - Total operating expenses for the three months ended June 30, 2025 decreased by $8.6 million (12%) compared to the same period in 2024, driven by reductions in research and development and selling, general, and administrative expenses[115]. - Research and development expenses for the three months ended June 30, 2025 decreased by $5.6 million (15%) compared to the same period in 2024, mainly due to a $1.7 million decrease in costs for selinexor in multiple myeloma[118]. - Selling, general and administrative expenses for the three months ended June 30, 2025 decreased by $2.6 million (8%) compared to the same period in 2024, attributed to a reduction in headcount and contractors[121]. - Selling, general and administrative expenses are anticipated to remain stable in the second half of 2025, influenced by ongoing cost reduction initiatives[123]. Cash Flow and Liquidity - Cash, cash equivalents, and investments as of June 30, 2025 totaled $51.7 million, with the company incurring a loss of $60.7 million for the six months ended June 30, 2025[127]. - Net cash used in operating activities for the six months ended June 30, 2025, was $57.7 million, a 30% improvement from $82.2 million in the same period of 2024[129]. - Net cash provided by investing activities decreased by $39.6 million to $33.6 million for the six months ended June 30, 2025, compared to $73.2 million in 2024[130]. - Net cash provided by financing activities dropped significantly by $40.6 million to $0.4 million for the six months ended June 30, 2025, compared to $41.4 million in 2024[131]. - The company expects cash runway to fund operations into January 2026, excluding repayment of the 2025 Notes and minimum liquidity covenant[141]. Future Obligations and Financing - Future obligations include $24.9 million related to the 2025 Notes due by October 15, 2025, and $142.9 million related to the 2029 Notes due by May 2029[144]. - The company entered into refinancing transactions in May 2024, borrowing $100 million to limit indebtedness and provide additional working capital[104]. - The company is exploring potential financing transactions and strategic alternatives, including a possible merger or sale[105]. - The company is exploring potential financing transactions and strategic alternatives, including a merger or sale, to maximize stockholder value[142]. Research and Development - The company is focusing on expanding the use of XPOVIO in its currently approved indications and developing new cancer therapies[102]. - The company plans to report top-line data from its Phase 3 myelofibrosis trial in March 2026[106]. - Research and development expenses are expected to remain relatively consistent in the second half of 2025 as the company continues to invest in ongoing clinical trials[120]. Market Risks - The company is exposed to market risk related to changes in foreign currency exchange rates due to contracts with organizations in Canada, the United Kingdom, and Europe[147]. - Contracts with clinical trial sites outside of the U.S. often involve budgets denominated in foreign currencies, increasing exposure to currency fluctuations[147]. - The company does not currently hedge its foreign currency exchange rate risk, leaving it vulnerable to market volatility[147]. Other Income and Losses - Other income (expense), net for the three months ended June 30, 2025 decreased by $64.8 million compared to the same period in 2024, primarily due to a prior year gain on extinguishment of debt[125]. - The company anticipates significant operating losses in the foreseeable future, raising substantial doubt about its ability to continue as a going concern within one year from the issuance of the financial statements[128]. - The company expects license and other revenue to decrease in the second half of 2025, primarily due to limited reimbursement of development-related expenses from Menarini[114]. - License and other revenue for the three months ended June 30, 2025 decreased by $6.5 million (44%) compared to the same period in 2024, primarily due to $6.0 million of non-recurring license-related revenue recognized in 2024[113].

[Executive Summary & Recent Highlights](index=1&type=section&id=Executive%20Summary%20%26%20Recent%20Highlights) Karyopharm's Q2 2025 financial and operational highlights, including revenue, guidance, and strategic efforts, are presented alongside CEO commentary [Q2 2025 Financial & Operational Overview](index=1&type=section&id=Q2%202025%20Financial%20%26%20Operational%20Overview) Karyopharm reported Q2 2025 total revenue of $37.9 million, with U.S. XPOVIO net product revenue up 6% to $29.7 million, reaffirming full-year guidance while exploring strategic alternatives | Metric | Q2 2025 | YoY Change | | :----------------------------- | :-------- | :--------- | | Total Revenue | $37.9 Million | N/A | | U.S. XPOVIO Net Product Revenue | $29.7 Million | +6% | - Reaffirms Full-Year 2025 Total Revenue Guidance: **$140 Million to $155 Million**[1](index=1&type=chunk) - Updates U.S. XPOVIO Net Product Revenue Guidance: **$110 Million to $120 Million**[1](index=1&type=chunk) - The Company is exploring financing transactions and strategic alternatives to extend its cash runway and maximize value[1](index=1&type=chunk) [CEO Commentary](index=1&type=section&id=CEO%20Commentary) CEO Richard Paulson discussed financing efforts and the nearing completion of Phase 3 SENTRY trial enrollment, with top-line data expected March 2026 - Company is seeking potential financing and strategic alternatives to extend cash runway and enhance liquidity[2](index=2&type=chunk) - Phase 3 SENTRY trial in myelofibrosis is in its final weeks of enrollment, with top-line data anticipated in **March 2026**[2](index=2&type=chunk) [XPOVIO Commercial Performance](index=1&type=section&id=XPOVIO%20Commercial%20Performance) This section details XPOVIO's Q2 2025 commercial performance, including U.S. net product revenue growth and demand drivers [XPOVIO Commercial Performance Overview](index=1&type=section&id=XPOVIO%20Commercial%20Performance%20Overview) Karyopharm reported a 6% increase in U.S. XPOVIO net product revenue to $29.7 million in Q2 2025 compared to Q2 2024, with consistent demand driven primarily by the community setting (approximately 60% of revenue) | Metric | Q2 2025 | Q2 2024 | YoY Change | | :----------------------- | :-------- | :-------- | :--------- | | U.S. Net Product Revenue | $29.7 million | $28.0 million | +6.1% | | Royalty Revenue | $1.6 million | N/A | +28% | - Demand for XPOVIO was consistent year-over-year, with the community setting contributing approximately **60% of overall net product revenue**[3](index=3&type=chunk) [Research and Development (R&D) Highlights](index=2&type=section&id=Research%20and%20Development%20(R%26D)%20Highlights) Key updates on Karyopharm's clinical development programs for myelofibrosis, endometrial cancer, and multiple myeloma are provided [Myelofibrosis Program](index=2&type=section&id=Myelofibrosis%20Program) The Phase 3 SENTRY trial is nearing full enrollment, with new patient screening expected to close this week, and preliminary safety data suggests potential improvements in adverse events - Phase 3 SENTRY trial (XPORT-MF-034) is nearing full enrollment, with new patient screening expected to close this week, and top-line data anticipated in **March 2026**[6](index=6&type=chunk)[8](index=8&type=chunk) - Preliminary blinded aggregate safety data from the first 61 patients in SENTRY may suggest improvements in both hematologic and non-hematologic treatment emergent adverse events[6](index=6&type=chunk) - Phase 2 SENTRY-2 trial (XPORT-MF-044) continues enrollment for JAKi-naïve myelofibrosis patients with moderate thrombocytopenia and plans to amend the protocol to include patients with platelet counts above 100,000[6](index=6&type=chunk) [Endometrial Cancer Program](index=2&type=section&id=Endometrial%20Cancer%20Program) Enrollment is ongoing for the Phase 3 XPORT-EC-042 trial, evaluating selinexor as a maintenance monotherapy in patients with TP53 wild-type advanced or recurrent endometrial cancer, with top-line data expected in mid-2026 - Enrollment continues in the Phase 3 XPORT-EC-042 trial for selinexor as maintenance-only therapy in TP53 wild-type advanced or recurrent endometrial cancer[5](index=5&type=chunk)[9](index=9&type=chunk) - Top-line data from the event-driven XPORT-EC-042 trial is expected in **mid-2026**[9](index=9&type=chunk) [Multiple Myeloma Program](index=3&type=section&id=Multiple%20Myeloma%20Program) Enrollment for the Phase 3 XPORT-MM-031 trial was completed in Q4 2024, evaluating an all-oral combination of selinexor, pomalidomide, and dexamethasone, with top-line data expected in the first half of 2026 - Enrollment of approximately **120 patients** in the Phase 3 XPORT-MM-031 trial was completed in the fourth quarter of 2024[7](index=7&type=chunk) - The trial evaluates the all-oral combination of selinexor 40 mg, pomalidomide, and dexamethasone (SPd40) in patients with previously treated multiple myeloma[7](index=7&type=chunk) - Top-line data from the event-driven XPORT-MM-031 trial is expected in the **first half of 2026**[10](index=10&type=chunk) [Anticipated Catalysts and Operational Objectives](index=3&type=section&id=Anticipated%20Catalysts%20and%20Operational%20Objectives) This section outlines key upcoming milestones and operational objectives for Karyopharm's myelofibrosis, endometrial cancer, and multiple myeloma programs [Myelofibrosis Milestones](index=3&type=section&id=Myelofibrosis%20Milestones) The company expects to close new patient screening for the Phase 3 SENTRY trial this week, with top-line data anticipated in March 2026 - New patient screening for the Phase 3 SENTRY trial is expected to close this week[8](index=8&type=chunk) - Top-line data from the Phase 3 SENTRY trial is expected in **March 2026**[8](index=8&type=chunk) [Endometrial Cancer Milestones](index=3&type=section&id=Endometrial%20Cancer%20Milestones) Karyopharm plans to continue enrolling patients in the Phase 3 XPORT-EC-042 trial, with top-line data from this event-driven trial expected in mid-2026 - Continue to enroll patients into the Phase 3 XPORT-EC-042 trial[9](index=9&type=chunk) - Top-line data from the event-driven XPORT-EC-042 trial is expected in **mid-2026**[9](index=9&type=chunk) [Multiple Myeloma Milestones](index=3&type=section&id=Multiple%20Myeloma%20Milestones) The company will continue to follow patients enrolled in the Phase 3 XPORT-MM-031 trial, with top-line data from this event-driven trial expected in the first half of 2026 - Continue to follow patients that are enrolled in the Phase 3 XPORT-MM-031 (EMN29) trial[10](index=10&type=chunk) - Top-line data from the event-driven XPORT-MM-031 trial is expected in the **first half of 2026**[10](index=10&type=chunk) [2025 Financial Outlook & Liquidity](index=3&type=section&id=2025%20Financial%20Outlook%20%26%20Liquidity) Karyopharm's full-year 2025 financial guidance and liquidity position are discussed, including ongoing efforts to explore strategic alternatives [Full-Year 2025 Guidance](index=3&type=section&id=Full-Year%202025%20Guidance) For full-year 2025, Karyopharm projects total revenue of $140 million to $155 million, with U.S. XPOVIO net product revenue contributing $110 million to $120 million, and combined R&D and SG&A expenses estimated between $240 million and $250 million | Metric | 2025 Guidance Range | | :----------------------------- | :------------------ | | Total Revenue | $140 million to $155 million | | U.S. XPOVIO Net Product Revenue | $110 million to $120 million | | R&D and SG&A Expenses | $240 million to $250 million | - Maintain the Company's commercial foundation in the increasingly competitive multiple myeloma marketplace and drive increased XPOVIO revenues[10](index=10&type=chunk) - Continue to support global launches by partners following regulatory and reimbursement approvals for selinexor in ex-U.S. territories[10](index=10&type=chunk) [Liquidity and Strategic Alternatives](index=4&type=section&id=Liquidity%20and%20Strategic%20Alternatives) Karyopharm anticipates its current liquidity will fund operations until October 2025, or into January 2026 excluding certain obligations, while actively exploring financing and strategic alternatives - Existing liquidity is expected to fund planned operations to the maturity of its senior convertible notes due **October 2025**[12](index=12&type=chunk) - Excluding the **$24.5 million** Remaining 2025 Notes maturity and its **$25.0 million** minimum liquidity covenant, the Company expects it would have sufficient liquidity to fund planned operations into **January 2026**[12](index=12&type=chunk) - The Company, with the assistance of its advisors, is exploring potential financing and strategic alternatives to enhance liquidity and maximize value[12](index=12&type=chunk) [Second Quarter 2025 Financial Results](index=4&type=section&id=Second%20Quarter%202025%20Financial%20Results) A detailed analysis of Karyopharm's Q2 2025 financial performance, covering revenue, operating expenses, net loss, and cash position [Revenue Analysis](index=4&type=section&id=Revenue%20Analysis) Total revenue for Q2 2025 was $37.9 million, down from $42.8 million in Q2 2024, primarily due to a non-recurring license-related revenue recognized in Q2 2024, while U.S. net product revenue increased to $29.7 million | Revenue Type | Q2 2025 (Millions) | Q2 2024 (Millions) | YoY Change | | :---------------------- | :----------------- | :----------------- | :--------- | | Total Revenue | $37.9 | $42.8 | -$4.9 (-11.4%) | | Net Product Revenue | $29.7 | $28.0 | +$1.7 (+6.1%) | | License and Other Revenue | $8.2 | $14.8 | -$6.6 (-44.6%) | - The decrease in license and other revenue was primarily attributable to **$6.0 million** of non-recurring license-related revenue recognized during the second quarter of 2024[14](index=14&type=chunk) [Operating Expenses](index=4&type=section&id=Operating%20Expenses) Operating expenses decreased in Q2 2025 compared to Q2 2024, with reductions in cost of sales, R&D expenses due to lower personnel and clinical trial costs, and SG&A expenses from cost reduction initiatives | Expense Type | Q2 2025 (Millions) | Q2 2024 (Millions) | YoY Change | | :---------------- | :----------------- | :----------------- | :--------- | | Cost of Sales | $1.1 | $1.5 | -$0.4 (-26.7%) | | R&D Expenses | $32.8 | $38.4 | -$5.6 (-14.6%) | | SG&A Expenses | $28.5 | $31.1 | -$2.6 (-8.4%) | - R&D expense decrease was due to a reduction in personnel costs and stock-based compensation, coupled with lower clinical trial and related costs[16](index=16&type=chunk) - SG&A expense decrease was primarily due to the realization of previously implemented cost reduction initiatives[17](index=17&type=chunk) [Other Income (Expense) & Net Loss](index=4&type=section&id=Other%20Income%20(Expense)%20%26%20Net%20Loss) Karyopharm reported a net loss of $37.3 million in Q2 2025, a significant shift from net income in Q2 2024, largely due to changes in interest income/expense and the absence of a prior year gain on debt extinguishment | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | YoY Change | | :------------------------------ | :----------------- | :----------------- | :--------- | | Net (Loss) Income | -$37.3 | $23.8 | -$61.1 | | Basic Net (Loss) Income Per Share | -$4.32 | $2.26 | -$6.58 | | Diluted Net Loss Per Share | -$4.32 | -$2.97 | -$1.35 | | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | YoY Change | | :------------------------------ | :----------------- | :----------------- | :--------- | | Interest Income | $0.6 | $1.9 | -$1.3 (-68.4%) | | Interest Expense | $11.2 | $8.9 | +$2.3 (+25.8%) | | Gain on Extinguishment of Debt | $0.0 | $44.7 | -$44.7 | | Other (expense) income, net | -$2.2 | $14.3 | -$16.5 | - Interest expense increased due to a full quarter of interest on the term loan and convertible debt issued in the second quarter of 2024[18](index=18&type=chunk) - The change in other (expense) income, net, is attributable to recurring non-cash fair value remeasurements related to 2024 refinancing transactions, and the absence of a **$44.7 million** gain on extinguishment of debt from Q2 2024[19](index=19&type=chunk) [Cash Position](index=5&type=section&id=Cash%20Position) As of June 30, 2025, Karyopharm's cash, cash equivalents, restricted cash, and investments totaled $52.0 million, a decrease from $109.1 million as of December 31, 2024 | Metric | June 30, 2025 (Millions) | December 31, 2024 (Millions) | Change | | :---------------------------------------------- | :----------------------- | :--------------------------- | :----- | | Cash, Cash Equivalents, Restricted Cash & Investments | $52.0 | $109.1 | -$57.1 | [Conference Call Information](index=5&type=section&id=Conference%20Call%20Information) Details regarding Karyopharm's conference call to discuss Q2 2025 financial results and business updates are provided [Conference Call Details](index=5&type=section&id=Conference%20Call%20Details) Karyopharm hosted a conference call on August 11, 2025, at 8:00 a.m. ET to discuss Q2 2025 financial results, the 2025 financial outlook, and other business updates - Conference call held on **August 11, 2025, at 8:00 a.m. Eastern Time**, to discuss Q2 2025 financial results, 2025 financial outlook, and business updates[22](index=22&type=chunk) - Access details for dial-in and live audio webcast, along with accompanying slides, were provided[22](index=22&type=chunk) [About XPOVIO (selinexor)](index=5&type=section&id=About%20XPOVIO%20(selinexor)) This section provides a description of XPOVIO (selinexor), its approved indications, and important safety information [Product Description and Indications](index=5&type=section&id=Product%20Description%20and%20Indications) XPOVIO is a first-in-class, oral XPO1 inhibitor approved in the U.S. for multiple myeloma and DLBCL, with international approvals in over 50 territories - XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds for the treatment of cancer, functioning by selectively binding to and inhibiting the nuclear export protein XPO1[23](index=23&type=chunk)[30](index=30&type=chunk) - Approved in the U.S. for multiple myeloma: (i) in combination with VELCADE® (bortezomib) and dexamethasone (XVd) after at least one prior therapy; (ii) in combination with dexamethasone (Xd) in adult patients with heavily pre-treated multiple myeloma[23](index=23&type=chunk)[24](index=24&type=chunk) - Approved under accelerated approval in adult patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy[23](index=23&type=chunk)[25](index=25&type=chunk) - Received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada, marketed by partners[23](index=23&type=chunk)[30](index=30&type=chunk) [Important Safety Information](index=6&type=section&id=Important%20Safety%20Information) Important safety information for XPOVIO includes common adverse reactions such as fatigue and nausea, significant Grade 3-4 laboratory abnormalities like thrombocytopenia, and warnings for various toxicities - Most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting[27](index=27&type=chunk) - Grade 3-4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia[27](index=27&type=chunk) - Most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection[32](index=32&type=chunk) - Warnings and Precautions include monitoring for thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, embryo-fetal toxicity, and cataract[28](index=28&type=chunk) - Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception[28](index=28&type=chunk) - For specific populations, advise not to breastfeed during lactation[29](index=29&type=chunk) [About Karyopharm Therapeutics](index=7&type=section&id=About%20Karyopharm%20Therapeutics) An overview of Karyopharm Therapeutics Inc., its mission, lead compound XPOVIO, and focused pipeline [Company Overview](index=7&type=section&id=Company%20Overview) Karyopharm Therapeutics Inc. is a commercial-stage pharmaceutical company focused on pioneering novel cancer therapies by addressing nuclear export dysregulation, with its lead compound XPOVIO approved in the U.S. for three oncology indications and globally in over 50 territories - Karyopharm Therapeutics Inc. is a commercial-stage pharmaceutical company dedicated to pioneering novel cancer therapies by addressing nuclear export dysregulation, a fundamental mechanism of oncogenesis[30](index=30&type=chunk) - Karyopharm's lead compound, XPOVIO® (selinexor), a first-in-class, oral exportin 1 (XPO1) inhibitor, is approved in the U.S. for three oncology indications and has received regulatory approvals in various indications in **50 ex-U.S. territories and countries**[30](index=30&type=chunk) - Karyopharm has a focused pipeline targeting indications in multiple high unmet need cancers, including multiple myeloma, endometrial cancer, myelofibrosis, and diffuse large B-cell lymphoma (DLBCL)[30](index=30&type=chunk) [Forward-Looking Statements](index=7&type=section&id=Forward-Looking%20Statements) This section outlines Karyopharm's forward-looking statements and the inherent risks and uncertainties that may impact future results [Forward-Looking Statements and Risks](index=7&type=section&id=Forward-Looking%20Statements%20and%20Risks) Karyopharm's forward-looking statements regarding 2025 financial guidance, cash runway, strategic alternatives, commercialization, and clinical development are subject to numerous risks and uncertainties that may cause actual results to differ materially - Forward-looking statements include guidance on 2025 total revenue, U.S. net product revenue, R&D and SG&A expenses; expected cash runway and liquidity; exploration of strategic alternatives and financing transactions; expectations for commercialization efforts; and expectations for clinical development plans and potential regulatory submissions of selinexor[31](index=31&type=chunk) - Such statements are subject to numerous important factors, risks, and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from current expectations[31](index=31&type=chunk) - Risks include the ability to successfully commercialize XPOVIO, successful completion of clinical development phases, regulatory approval, stock price appreciation, adoption of XPOVIO, timing and costs of commercialization, clinical trial results, FDA decisions, ability to enroll patients, unplanned expenditures, going concern doubt, competitor development, COVID-19 impact, and intellectual property protection[31](index=31&type=chunk)[33](index=33&type=chunk) [Condensed Consolidated Financial Statements](index=9&type=section&id=Condensed%20Consolidated%20Financial%20Statements) Presents Karyopharm's condensed consolidated statements of operations and balance sheets for Q2 2025 and comparative periods [Condensed Consolidated Statements of Operations](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) The Condensed Consolidated Statements of Operations show a net loss of $37.3 million for Q2 2025, compared to a net income of $23.8 million for Q2 2024, with total revenue and operating expenses both decreasing | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | | :-------------------------------------- | :------------------------------- | :------------------------------- | | Product revenue, net | $29,681 | $28,032 | | License and other revenue | $8,248 | $14,754 | | **Total revenue** | **$37,929** | **$42,786** | | Cost of sales | $1,051 | $1,465 | | Research and development | $32,788 | $38,371 | | Selling, general and administrative | $28,477 | $31,070 | | **Total operating expenses** | **$62,316** | **$70,906** | | Loss from operations | $(24,387) | $(28,120) | | Interest income | $613 | $1,930 | | Interest expense | $(11,228) | $(8,949) | | Gain on extinguishment of debt | — | $44,702 | | Other (expense) income, net | $(2,210) | $14,296 | | **Net (loss) income** | **$(37,252)** | **$23,792** | | Basic net (loss) income per share | $(4.32) | $2.26 | | Diluted net loss per share | $(4.32) | $(2.97) | | Metric (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------------- | :----------------------------- | :----------------------------- | | Product revenue, net | $50,735 | $54,038 | | License and other revenue | $17,209 | $21,874 | | **Total revenue** | **$67,944** | **$75,912** | | Cost of sales | $2,352 | $3,376 | | Research and development | $67,406 | $73,796 | | Selling, general and administrative | $55,829 | $60,619 | | **Total operating expenses** | **$125,587** | **$137,791** | | Loss from operations | $(57,643) | $(61,879) | | Interest income | $1,613 | $4,086 | | Interest expense | $(22,222) | $(14,833) | | Gain on extinguishment of debt | — | $44,702 | | Other (expense) income, net | $17,614 | $14,492 | | **Net (loss) income** | **$(60,714)** | **$(13,570)** | | Basic net (loss) income per share | $(7.11) | $(1.72) | | Diluted net loss per share | $(7.11) | $(7.16) | [Condensed Consolidated Balance Sheets](index=10&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) The Condensed Consolidated Balance Sheets show total assets of $104.9 million as of June 30, 2025, a decrease from $164.4 million at December 31, 2024, with total stockholders' deficit increasing to $(238.9) million | Metric (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------------------------------- | :------------ | :---------------- | | Cash, cash equivalents and investments | $51,697 | $108,712 | | Restricted cash | $350 | $338 | | Accounts receivable | $32,932 | $30,766 | | Other assets | $19,900 | $24,602 | | **Total assets** | **$104,879** | **$164,418** | | Convertible senior notes due 2025 | $24,484 | $24,426 | | Convertible senior notes due 2029 | $62,684 | $68,345 | | Senior secured term loan | $95,816 | $94,603 | | Deferred royalty obligation | $73,499 | $73,499 | | Other liabilities | $87,322 | $89,562 | | **Total liabilities** | **$343,805** | **$350,435** | | **Total stockholders' deficit** | **$(238,926)**| **$(186,017)** |

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]

Core Viewpoint - Karyopharm Therapeutics (KPTI) is expected to report a year-over-year decline in earnings and revenues for the quarter ended June 2025, with the consensus outlook indicating a loss of $3.80 per share and revenues of $40.08 million, reflecting a 26.7% and 6.3% decrease respectively [1][3]. Earnings Expectations - The upcoming earnings report could lead to a stock price increase if the actual results exceed expectations, while a miss could result in a decline [2]. - The consensus EPS estimate has been revised 2.21% lower in the last 30 days, indicating a reassessment by analysts [4]. Earnings Surprise Prediction - The Zacks Earnings ESP model suggests that Karyopharm has a positive Earnings ESP of +0.92%, indicating a likelihood of beating the consensus EPS estimate [12]. - The stock currently holds a Zacks Rank of 3, which supports the potential for an earnings beat [12]. Historical Performance - Karyopharm has a history of exceeding consensus EPS estimates, having beaten expectations in the last four quarters [14]. - In the last reported quarter, the company was expected to post a loss of $4.21 per share but actually reported a loss of -$2.77, resulting in a positive surprise of +34.20% [13]. Industry Context - In the Zacks Medical - Drugs industry, Ardelyx (ARDX) is expected to report a loss of $0.13 per share, indicating a significant year-over-year decline of 85.7%, with revenues projected at $84.64 million, up 15.6% from the previous year [18]. - Ardelyx's consensus EPS estimate has been revised 6.3% lower, resulting in a negative Earnings ESP of -6.18%, combined with a Zacks Rank of 4, making it difficult to predict an earnings beat [19].

Myelofibrosis Opportunity - Karyopharm is focused on the transformative myelofibrosis opportunity in 2025, building on its foundation in multiple myeloma[4,10] - The peak annual revenue opportunity for selinexor in myelofibrosis is estimated to be up to approximately $1 billion[4,12] - In a Phase 1 trial, 78.6% of intent-to-treat patients achieved SVR35 (spleen volume reduction of 35% or more) at week 24 with selinexor 60 mg + ruxolitinib[24] - In the Phase 1 trial, the average improvement in Absolute TSS (Total Symptom Score) was 18.5, suggesting a positive outcome for the SENTRY Phase 3 trial[31,32] - Selinexor meaningfully decreased transfusion burden by approximately 50% compared to physician's choice in the XPORT-MF-035 trial[58] Endometrial Cancer Opportunity - Karyopharm is focusing the Phase 3 XPORT-EC-042 trial on patients with TP53wt EC (endometrial cancer) that are pMMR or dMMR and medically ineligible to receive a checkpoint inhibitor[74] - Data from the SIENDO trial showed an encouraging signal of long-term median PFS (progression-free survival) benefit of 28.4 months in the TP53 wild-type subgroup[78] - In the SIENDO Trial, the median PFS benefit was 39.5 months in the TP53 Wild-Type/pMMR Subgroup[81] Commercial and Pipeline Strategy - XPOVIO net product revenue in 2024 was approximately $113 million[11] - The company aims to maintain its profitable commercial foundation in the competitive multiple myeloma marketplace and drive increased XPOVIO revenue in 2025[91] - The company is actively enrolling patients in the Phase 3 SENTRY trial in myelofibrosis, with top-line data expected in late 2025/early 2026[4,39,40] - The company is actively enrolling patients in the Phase 3 XPORT-EC-042 trial in endometrial cancer, with top-line data anticipated in mid-2026[85,88]

Myelofibrosis Opportunity - Karyopharm is focused on the transformative myelofibrosis opportunity in 2025, with a peak annual revenue opportunity of up to approximately $1 billion[4, 12] - The company expects top-line data from the Phase 3 SENTRY trial of selinexor in myelofibrosis in late 2025/early 2026[4] - Data from a Phase 1 trial showed that 78.6% of intent-to-treat patients achieved SVR35 at week 24 with selinexor 60 mg + ruxolitinib[24] - In the Phase 1 trial, the average improvement in Absolute TSS (Abs-TSS) was 18.5, suggesting a positive outcome with Abs-TSS can be achieved in the SENTRY Phase 3 trial[33] Clinical Trial Data and Development - The Phase 2 XPORT-MF-035 trial showed that spleen volume reduction rates more than doubled with selinexor compared to physician's choice, with 33% achieving SVR35 compared to 13%[48, 49] - In the XPORT-MF-035 trial, patients who progressed on physician's choice (Rux) and received selinexor showed a meaningful spleen volume reduction[51] - Selinexor meaningfully decreased transfusion burden by approximately 50% in the XPORT-MF-035 trial[59] - The SENTRY (XPORT-MF-034) Phase 3 trial of selinexor in combination with ruxolitinib in JAKi naïve myelofibrosis has passed futility analysis and continues as planned, with top-line data expected in late 2025/early 2026[39, 41] Endometrial Cancer - Karyopharm is focusing the Phase 3 XPORT-EC-042 trial on patients with TP53wt EC that are pMMR or dMMR and medically ineligible to receive a checkpoint inhibitor[75] - Data from the SIENDO trial (ASCO 2024) showed an encouraging signal of long-term median PFS benefit of 39.5 months in the TP53 Wild-Type/pMMR subgroup[82]