Karyopharm Therapeutics (KPTI) closed the last trading session at $9.4, gaining 58% over the past four weeks, but there could be plenty of upside left in the stock if short-term price targets set by Wall Street analysts are any guide. The mean price target of $14.67 indicates a 56.1% upside potential.The mean estimate comprises six short-term price targets with a standard deviation of $5.32. While the lowest estimate of $6.00 indicates a 36.2% decline from the current price level, the most optimistic analys ...

Summary of Karyopharm Therapeutics Special Meeting Company Overview - **Company**: Karyopharm Therapeutics, Inc. (NasdaqGS: KPTI) - **Meeting Date**: February 18, 2026 - **Participants**: Richard Paulson (President, CEO, and Director), Michael Mano (Chief Legal Officer), Lori Macomber (Chief Financial Officer), Brendan Strong (Senior Vice President of Investor Relations) [1][2][3] Key Proposals Discussed 1. **Proposal One**: - Adoption and approval of an amendment to the restated certificate of incorporation to increase the number of authorized shares of capital stock from **58,333,333** to **111,000,000**. - Increase the number of authorized shares of common stock from **53,333,333** to **106,000,000** [7][9]. 2. **Proposal Two**: - Approval to adjourn the special meeting to a later date if necessary for further solicitation of proxies in case of insufficient votes for Proposal One [7][10]. Voting Results - A quorum was established with **18,310,283** shares of common stock entitled to vote present [5][6]. - Both proposals were approved based on preliminary voting results: - Proposal One to increase authorized shares was approved. - Proposal Two to allow for adjournment was also approved [9][10]. Important Notes - The meeting was conducted in a virtual format, allowing stockholders to participate similarly to an in-person meeting [2]. - Forward-looking statements were made, with a disclaimer regarding reliance on these statements due to potential differences in actual results [4]. - The final vote results will be documented in a Form 8-K to be filed within four business days after the meeting [10]. Additional Information - Stockholders were encouraged to submit questions related solely to the proposals during the meeting, but no questions were raised [7][8]. - The meeting concluded with gratitude expressed to shareholders for their participation and support [10].

Financial Performance - As of December 31, 2025, the company had an accumulated deficit of $1.8 billion and net losses of $196.0 million, $76.4 million, and $143.1 million for the years ended December 31, 2025, 2024, and 2023, respectively[22]. - Total revenue recognized in 2025 was $146.1 million, which included $114.9 million from XPOVIO net product revenue and $31.2 million from license revenue[22]. - The company had $63.7 million in cash, cash equivalents, and investments as of December 31, 2025, raising substantial doubt about its ability to continue as a going concern within one year[22]. Strategic Focus - The strategy focuses on maximizing the commercial value of XPOVIO in multiple myeloma and expanding its use across therapy lines in the relapsed/refractory setting[23]. - The company aims to preserve capital and enhance its balance sheet to execute core objectives while managing capital resources effectively[23]. Clinical Pipeline and Trials - The clinical pipeline is prioritized to target cancers with high unmet needs, including myelofibrosis and endometrial cancer, with a focus on advancing late-stage clinical programs[23]. - Selinexor and eltanexor are being evaluated in multiple late-stage clinical trials for hematological and solid tumor malignancies, with ongoing investigator-sponsored trials[32]. - The pivotal Phase 3 SENTRY Trial for selinexor has completed enrollment with 353 JAKi-naive patients, and top-line data is expected to be reported in March 2026[39]. - The SENTRY-2 Trial is enrolling approximately 58 patients, with a primary endpoint of SVR35 at week 24[42]. - In the MF-035 Trial, 67% of selinexor treated patients achieved SVR25 or greater compared to 38% in the physician's choice group[45]. - The ESSENTIAL Trial showed that 27% of patients achieved SVR35 after at least 24 weeks of selinexor treatment[46]. - The XPORT-EC-042 Trial aims to enroll approximately 276 patients with TP53 wild-type tumors, with a primary endpoint of progression-free survival[53]. - The SIENDO Trial evaluated selinexor as maintenance therapy, with a primary endpoint of progression-free survival from randomization[54]. - The median overall survival in the ESSENTIAL Trial was 35 months, compared to a historical survival of 13 to 14 months in this population[46]. - In the SIENDO Trial, selinexor-treated patients had a median progression-free survival (PFS) of 5.7 months compared to 3.8 months for placebo, representing a 50% improvement[55]. - Updated data from the SIENDO Trial showed selinexor-treated patients with TP53 wild-type advanced or recurrent endometrial cancer had a median PFS of 28.4 months versus 5.2 months for placebo, with a hazard ratio (HR) of 0.44[56]. - The BOSTON Trial demonstrated a median PFS of 13.9 months for the XVd Arm compared to 9.5 months for the Vd Arm, indicating a 47% increase in PFS[61]. - In the BOSTON Trial, the overall response rate (ORR) for the XVd Arm was 76.4% compared to 62.3% for the Vd Arm[61]. - The STORM Trial reported an ORR of 26% for selinexor in combination with dexamethasone, with a median duration of response (DOR) of 4.4 months[66]. - The EMN29 Trial enrolled 117 patients to evaluate selinexor in combination with pomalidomide and dexamethasone versus elotuzumab, with primary endpoint being PFS[69]. - The EMN29 Trial's design was amended to reduce target enrollment from 222 to approximately 120 patients due to slower than expected patient enrollment[71]. - The STOMP Trial indicated a median PFS of 18.4 months for the SPd regimen, influencing the design of the EMN29 Trial[71]. - The SADAL Trial demonstrated an ORR of 29% for selinexor in patients with relapsed or refractory DLBCL, with a complete response (CR) rate of 13% and a median duration of response (DOR) of 9.3 months[74]. - The XPORT-DLBCL-030 Trial is currently in Phase 2, evaluating the combination of selinexor and R-GDP, with primary endpoint being progression-free survival (PFS)[76]. Partnerships and Agreements - The company received an upfront cash payment of $75 million from Menarini in December 2021 and an additional $3.5 million in April 2023 under the Menarini Agreement[84]. - From 2022 to 2025, Menarini reimbursed the company for 25% of development expenses up to $15 million per year, totaling $15 million in reimbursements for the year ended December 31, 2025[84]. - The Amended Antengene Agreement provided the company with an upfront payment of $11.7 million in June 2020, with additional milestone payments and tiered royalties based on net sales in the Antengene Territory[87]. - The company entered into an exclusive distribution agreement with FORUS for XPOVIO in Canada, receiving an upfront payment of $5 million and eligible for double-digit royalties on net sales[88]. - The company has retained exclusive production rights for XPOVIO while FORUS is responsible for regulatory filings in Canada[88]. Intellectual Property - As of February 5, 2026, the company holds 53 patents in the U.S. and has 13 pending patent applications, along with 189 granted patents and 79 pending applications in foreign jurisdictions[93][94]. - The patent portfolio includes significant coverage for selinexor, with two U.S. patents expiring in July 2032 and July 2033, and additional patents expiring no earlier than August 2035[99]. - The company has filed applications for Supplementary Protection Certificates in Europe for selinexor, with some applications granted and others pending[99]. - The patent term for selinexor has been extended by 342 days in the U.S., 150 days in Korea, and 5 years in Taiwan, with an extension in Australia from July 26, 2032, to March 8, 2037[100]. Competitive Landscape - The company faces competition from major pharmaceutical and biotechnology companies, with several other XPO1 inhibitors in clinical development globally[105][106]. - The competitive landscape includes multiple therapies for myelofibrosis, with only four JAK inhibitors currently approved, and ongoing clinical trials for alternative treatments[113][114]. - The treatment landscape for endometrial cancer has evolved significantly since 2023, with new combination therapies available, but no specific targeted FDA-approved therapies for TP53 wild-type cases[115]. - XPOVIO is the only XPO1 inhibitor with marketing approval, competing against various treatment types for multiple myeloma[116]. - XPOVIO is competing in the multiple myeloma market against established therapies such as IMiDs and PIs, with new bispecific T-cell engagers like TECVAYLI® approved in October 2022 and others expected in 2026 and beyond[117]. Sales and Marketing - The sales team consists of approximately 60 field-based employees focused on educating healthcare providers about XPOVIO, with plans for potential expansion to support future product launches[121]. - The KaryForward® patient support program assists eligible patients with insurance coverage issues, offering copay cards that reduce prescription costs to as low as $5.00[123]. Manufacturing and Supply Chain - XPOVIO's manufacturing relies on third-party contract manufacturers, with all global supplies produced in the U.S. to ensure quality and reliability[124]. - The company maintains sufficient inventory levels to exceed two-year forecasts for XPOVIO, minimizing supply disruption risks[126]. - Regulatory compliance is critical, with substantial time and financial resources required for drug development and approval processes[128]. Regulatory Environment - The FDA's approval process includes multiple steps, such as preclinical studies, IND submission, and clinical trials, which must comply with stringent regulations[131]. - The FDA requires sponsors to submit amendments for new protocols or changes to existing protocols before implementation[138]. - Clinical trials may be suspended or terminated if participants are exposed to unacceptable health risks or due to evolving business objectives[139]. - Foreign clinical trials must comply with FDA regulations and GCP standards to be considered valid for U.S. marketing approval[140]. - The FDA will not accept foreign trial data as the sole basis for approval unless specific conditions are met, including applicability to the U.S. population[141]. - Sponsors must register and disclose clinical trial information on clinicaltrials.gov, with results required to be disclosed within two years post-completion[143]. - The FDA has issued six notices of non-compliance for failure to submit required clinical trial information, with potential penalties of up to $10,000 per day[144]. - Expanded access allows investigational drugs to be used outside of clinical trials for patients with serious conditions when no alternatives exist[145]. - The Right to Try Act allows certain patients to access investigational products post-Phase I trials without FDA permission[147]. - The FDA requires sponsors to develop and submit diversity action plans for Phase 3 clinical trials to encourage diverse patient enrollment[155]. - The FDA issued draft guidance in June 2023 aimed at modernizing GCPs to facilitate more efficient clinical trials[156]. - The FDA's 2024 guidance indicates that companion diagnostic devices used in clinical trials are generally considered investigational unless already approved, requiring compliance with IDE regulations[162]. - The PMA process for in vitro companion diagnostics can take several years, with a standard application fee of $540,783 and a small business fee of $135,196 for federal fiscal year 2025[166]. - The FDA mandates that medical devices, including diagnostics, must be marketed only for approved uses, and manufacturers must comply with Quality System Regulation[167]. - The Pediatric Research Equity Act requires pediatric data for products intended for use in children, with initial Pediatric Study Plans due within 60 days of an EOP2 meeting[170]. - The FDA can grant Fast Track designation for products addressing unmet medical needs, allowing for greater interaction and rolling review of applications[174]. - Breakthrough Therapy designation may be granted if preliminary evidence shows substantial improvement over existing therapies, facilitating more efficient clinical trial designs[175]. - Priority Review designation shortens the FDA's review time from ten months to six months for products that significantly improve safety or effectiveness[177]. - The accelerated approval pathway allows drugs to be approved based on surrogate endpoints, with a requirement for post-approval confirmatory studies[179]. - New legislation in December 2022 allows the FDA to require confirmatory trials to be underway before granting accelerated approval and mandates progress reports every six months[183]. - The FDA's application fee for NDA submission in federal fiscal year 2025 is $4,310,002, with an annual program fee of $403,889 per eligible prescription product[187]. - The standard review time for an initial NDA is 12 months, while a supplemental application takes 10 months[187]. - The FDA conducts a preliminary review within 60 days of receipt to determine if the application is sufficiently complete for substantive review[188]. - A Complete Response Letter (CRL) indicates that the application will not be approved in its current form, outlining deficiencies that may require substantial additional testing[198]. - The FDA may require a Risk Evaluation and Mitigation Strategy (REMS) to ensure the benefits of a product outweigh its risks[194]. - The FDA has ten months from the filing date to complete its initial review of a standard application, with a potential three-month extension for new information[189]. - The FDA may refer applications to an advisory committee for review, although it is not bound by their recommendations[193]. - Post-approval, drugs are subject to ongoing regulation, including recordkeeping and reporting of adverse experiences[201]. - The FDA may withdraw approval if compliance with regulatory requirements is not maintained after market entry[203]. - The FDA published draft guidance in October 2023 regarding non-promotional communication of unapproved uses to healthcare providers, which was finalized on January 6, 2025[205]. - The FDA has established a ten-year phase-in process for the Drug Supply Chain Security Act, requiring manufacturers to implement electronic systems for tracing prescription drugs by November 2023[207]. - The FDA provides a five-year regulatory exclusivity period for new drugs containing a new chemical entity, preventing ANDA or 505(b)(2) applications until this period expires[213]. - A three-year exclusivity period is granted if the NDA includes reports of new clinical trials essential for approval, protecting changes to previously approved drug products[214]. - The FDA must review certain generic drug applications within eight months if there are three or fewer approved drugs listed in the Orange Book, expediting the approval process[215]. - The Paragraph IV certification allows ANDA sponsors to challenge existing patents, potentially delaying FDA approval for up to 30 months if a lawsuit is filed[219]. - Orphan Drug Designation encourages the development of products for rare diseases affecting fewer than 200,000 individuals in the U.S.[221]. - Section 505(b)(2) NDAs can expedite FDA approval by allowing reliance on previous findings of safety and efficacy for similar products[208]. - The FDA may require additional studies to support changes from approved products under Section 505(b)(2)[210]. - The FDA's designation of therapeutic equivalence allows for substitution of generic drugs without clinician or patient consent, impacting market dynamics[212]. - Companies may face significant penalties, including fines and injunctions, for improper promotion of drug products, affecting their commercial operations[209].

Financial Data and Key Metrics Changes - Total revenue for Q4 2025 was $34.1 million, an increase of 11.8% compared to Q4 2024 [51] - For the full year 2025, total revenue was $146.1 million, a slight increase from 2024 [51] - U.S. XPOVIO net product revenue for Q4 2025 was $32.1 million, an increase of 9.6% compared to Q4 2024 [52] - For the full year, U.S. XPOVIO net product revenue was $114.9 million, an increase of 1.9% from 2024 [52] - The company reported a net loss of $102.2 million, or $5.71 per share on a GAAP basis in Q4 2025 [60] - The full year net loss was $196 million, or $17.93 per diluted share for 2025 [60] 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 [36] - The company expects to guide towards $115 to $130 million of Xpovio net product revenue in 2026 [36] - License and other revenue was $2 million in Q4 and $31.2 million for the full year 2025 [53] Market Data and Key Metrics Changes - Demand for Xpovio was consistent year-over-year in 2025, with the community setting driving approximately 60% of total U.S. sales [37] - The company is targeting approximately 4,000 newly diagnosed patients with intermediate to high-risk myelofibrosis [45] Company Strategy and Development Direction - Karyopharm is focused on expanding its oncology franchise, particularly in myelofibrosis and endometrial cancer [7][8] - The company is preparing for pivotal data readouts from its late-stage clinical programs, with significant opportunities in myelofibrosis and endometrial cancer [63] - The strategy includes evaluating a range of financing and strategic options to maintain flexibility and align capital decisions with value creation [12] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming data readout from the phase three SENTRY trial in March, which is expected to address an unmet need in myelofibrosis [9][26] - The company is managing its business with discipline, focusing on near-term value-creating milestones while maintaining flexibility [64] - Management emphasized the importance of executing well and generating high-quality data to define the next phase of the company [64] Other Important Information - The company ended the year with $64.1 million in cash, cash equivalents, restricted cash, and investments, compared to $109.1 million as of December 31, 2024 [61] - The full year 2025 included $15 million of R&D reimbursement from Menarini, which will not be received in future years [53] Q&A Session Summary Question: Can you discuss the differences in exposure and activity between the 40 mg and 60 mg doses? - Management indicated that the 60 mg dose showed a clear benefit-risk profile compared to the 40 mg dose, with maximized efficacy in the 60 mg group [70] Question: What are your thoughts on Novartis' recent plans in myelofibrosis? - Management noted that the continued investment in the myelofibrosis space highlights the unmet need and significant market value [74] Question: Can you elaborate on the strategy for eltanexor and other MPNs? - Management stated that eltanexor is a second-generation XPO1 inhibitor with potential applications beyond myelofibrosis, including other MPNs [78] Question: What updates can you provide on the blinded safety data? - Management confirmed that no updates have been made beyond previously disclosed data, and they are looking forward to the upcoming data readout [85] Question: How do you view the potential for symptomatic improvement in your trials? - Management emphasized the goal of achieving statistical significance for both spleen volume reduction and symptomatic improvement [104]

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].

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 [26]. - 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, U.S. XPOVIO net product revenue was $114.9 million, an increase of 1.9% from 2024 [26]. - Gross to net provisions for XPOVIO were 26.9% in Q4 and 31.2% for the full year 2025 [26]. - The company reported a net loss of $102.2 million, or $5.71 per share in Q4 2025, and a net loss of $196 million, or $17.93 per diluted share for the full year 2025 [32]. 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 deliver revenue growth in 2026, guiding towards $115 million-$130 million [18]. - The community setting continues to drive approximately 60% of total U.S. sales for Xpovio [18]. Market Data and Key Metrics Changes - In the myelofibrosis market, the only treatment options currently available are JAK inhibitors, with ruxolitinib being the standard of care for the past 15 years [21]. - There are approximately 20,000 patients living with myelofibrosis in the U.S., representing a multibillion-dollar marketplace, with about 6,000 newly diagnosed patients each year [22]. Company Strategy and Development Direction - Karyopharm is focusing on expanding its oncology franchise, particularly in myelofibrosis and endometrial cancer, with pivotal data expected in March and mid-2026, respectively [4][5]. - The company aims to establish a new standard of care in frontline myelofibrosis by combining selinexor with ruxolitinib, addressing the unmet need in the market [21][24]. - The strategy includes evaluating a range of financing and strategic options to maintain flexibility and align capital decisions with value creation [5]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming data readouts from pivotal trials, which could significantly expand the role of the oncology franchise [35]. - The company is managing its business with a clear focus on near-term value-creating milestones while maintaining flexibility in capital allocation [35]. Other Important Information - Research and development expenses for Q4 2025 were $27.7 million, a decrease of 17% from Q4 2024, driven by lower personnel costs and focused clinical trial expenses [29]. - Selling, general, and administrative expenses were $22.8 million for the quarter, a decrease of 16% compared to Q4 2024 [29]. Q&A Session Summary Question: Can you discuss the differences in exposure and activity between the 40 mg and 60 mg doses? - Management indicated that the 60 mg dose showed a clear benefit-risk profile compared to the 40 mg dose, with maximized efficacy in the 60 mg group [38][39]. Question: What are the implications of Novartis' new plans in myelofibrosis? - Management noted that Novartis' investment in myelofibrosis highlights the unmet need in the market, and Karyopharm aims to establish itself as the standard of care pending positive data [41][44]. Question: What is the strategy for eltanexor and other myeloproliferative neoplasms (MPNs)? - Eltanexor is a second-generation XPO1 inhibitor with potential applications in other MPNs, and the company is excited about expanding beyond myelofibrosis [46][47][48]. Question: Can you provide updates on the blinded safety data and any changes in discontinuation rates? - Management confirmed that no updates have been made beyond previously disclosed data, and they are looking forward to the upcoming data readout [52][55].

Fourth Quarter 2025 Financial Results & Business Update February 12, 2026 On Today's Call • Welcome Brendan Strong, SVP, Investor Relations • Overview Richard Paulson, President and Chief Executive Officer • Pipeline Update Dr. Reshma Rangwala, Chief Medical Officer and Head of Research • Commercial Highlights and Myelofibrosis Commercial Opportunity Sohanya Cheng, Chief Commercial Officer and Head of Business Development • Financial Results and Guidance Lori Macomber, Chief Financial Officer and Treasurer ...

Core Insights - Karyopharm Therapeutics reported its financial results for Q4 and full year 2025, highlighting significant revenue growth and upcoming clinical milestones for its lead product, XPOVIO (selinexor) [1][2] Financial Performance - Total revenue for Q4 2025 was $34.1 million, up from $30.5 million in Q4 2024, while full-year revenue reached $146.1 million compared to $145.2 million in 2024 [2][5] - U.S. net product revenue for XPOVIO was $32.1 million in Q4 2025, compared to $29.3 million in Q4 2024, and $114.9 million for the full year, up from $112.8 million in 2024 [2][5] - The company expects total revenue for 2026 to be between $130 million and $150 million, with U.S. XPOVIO net product revenue projected between $115 million and $130 million [1][2] Research and Development Highlights - The Phase 3 SENTRY trial for myelofibrosis is expected to report top-line data in March 2026, with the potential to introduce the first combination therapy in this area [1][3] - The Phase 3 XPORT-EC-042 trial for endometrial cancer is on track to report top-line data in mid-2026, focusing on a biomarker-driven patient population [1][3] - Enrollment in the Phase 3 XPORT-MM-031 trial for multiple myeloma was completed in Q4 2024, with top-line data anticipated in the second half of 2026 [1][3] Operational Objectives - The company aims to maintain its commercial foundation in the competitive multiple myeloma market and drive increased revenues for XPOVIO [2][3] - Karyopharm plans to support global launches of XPOVIO in ex-U.S. territories following regulatory approvals [2][3] Market Context - Myelofibrosis affects approximately 20,000 patients in the U.S., with significant unmet needs in treatment options [3] - Endometrial cancer is the most common gynecologic malignancy in the U.S., with rising incidence and mortality rates, highlighting the need for effective therapies [3][4]

Core Viewpoint - Karyopharm Therapeutics Inc. will report its fourth quarter and full year 2025 financial results on February 12, 2026, and will host a conference call to discuss these results and other updates [1]. Company Overview - Karyopharm Therapeutics Inc. is a commercial-stage pharmaceutical company focused on pioneering novel cancer therapies, particularly through oral compounds that address nuclear export dysregulation, a key mechanism in oncogenesis [3]. - The company's lead compound, XPOVIO (selinexor), is a first-in-class oral exportin 1 (XPO1) inhibitor approved in the U.S. for three oncology indications and has received regulatory approvals in over 50 territories, including the EU, UK (as NEXPOVIO), 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].

Financial Projections - Preliminary unaudited total revenue for full year 2025 is expected to be approximately $145 million, with U.S. XPOVIO net product revenue estimated at $115 million[1][4][8]. - Cash and cash equivalents as of December 31, 2025, were approximately $64 million, expected to fund operations into Q2 2026[8]. - The company is currently evaluating its preliminary financial information for Q4 and full year 2025, including expected cash runway and liquidity[28]. Clinical Trials and Research - The Phase 3 SENTRY trial in myelofibrosis completed enrollment with 353 patients, evaluating selinexor in combination with ruxolitinib[3][13]. - Top-line data from the Phase 3 SENTRY trial is expected in March 2026, which could redefine the standard-of-care in myelofibrosis[2][14]. - The Phase 3 XPORT-EC-042 trial in endometrial cancer is on track to report top-line data in mid-2026, focusing on a targeted patient population[2][10]. - The company modified the design of the Phase 3 XPORT-EC-042 trial to focus on patients with proficient and deficient mismatch repair status, increasing the sample size to approximately 276 patients[8][18]. Product and Market Development - Demand for XPOVIO remained consistent in 2025 compared to 2024, with approximately 60% of overall net product revenue driven by the community setting[4]. - Global patient access for selinexor expanded in 2025, with approvals in over 50 countries, including favorable reimbursement decisions in Spain and China[4]. - Karyopharm Therapeutics' lead compound, XPOVIO® (selinexor), is approved in the U.S. and marketed in three oncology indications, with regulatory approvals in over 50 territories including the EU and China[27]. Safety and Adverse Reactions - In the BOSTON trial, 6% of patients experienced fatal adverse reactions within 30 days of the last treatment, while serious adverse reactions occurred in 52% of patients[26]. - The treatment discontinuation rate due to adverse reactions in the BOSTON trial was 19%[26]. - In the STORM trial, 9% of patients experienced fatal adverse reactions, with serious adverse reactions occurring in 58% of patients[26]. - The discontinuation rate due to adverse reactions in the STORM trial was 27%[26]. - In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days and 5% within 60 days, with serious adverse reactions occurring in 46% of patients[26]. Strategic Outlook - Karyopharm anticipates 2026 to be a catalyst-rich year with significant opportunities for long-term value creation[2]. - The company completed strategic financing transactions to extend cash runway beyond the expected top-line readout of the Phase 3 SENTRY trial[8]. - Management emphasizes the importance of regulatory approvals and successful commercialization of XPOVIO and other drug candidates[29]. - Karyopharm is focused on developing therapies for multiple high unmet need cancers, including multiple myeloma and diffuse large B-cell lymphoma (DLBCL)[27]. Risks and Uncertainties - Karyopharm's forward-looking statements are subject to numerous risks and uncertainties that may cause actual results to differ materially from current expectations[28].