Core Viewpoint - Karyopharm Therapeutics Inc. is set to report its first quarter 2025 financial results on May 12, 2025, 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 cancer development [3]. - The company's lead product, XPOVIO® (selinexor), is an oral exportin 1 (XPO1) inhibitor that has received approval in the U.S. for three oncology indications and has also been approved in various international markets, including Europe and China [3]. - Karyopharm has a focused pipeline targeting multiple high unmet need cancers, including multiple myeloma, endometrial cancer, myelofibrosis, and diffuse large B-cell lymphoma (DLBCL) [3].

Core Viewpoint - Antengene Corporation Limited has successfully expanded the approval and commercial presence of its drug XPOVIO® (selinexor) in multiple APAC markets, including Indonesia, enhancing its position in the biopharmaceutical industry focused on innovative cancer treatments [2][4]. Group 1: Product Approval and Indications - XPOVIO® is the first and only approved XPO1 inhibitor in Indonesia, with its New Drug Application (NDA) approved for three indications related to multiple myeloma and diffuse large B-cell lymphoma [1][2]. - The drug has been approved for multiple indications in ten markets across the APAC region, including health insurance coverage in China, Taiwan, Australia, Singapore, and South Korea [1][3]. Group 2: Market Potential and Expansion - The ASEAN region, with a population exceeding 600 million and steady economic growth, presents significant potential for biomedical development, driven by an aging population and increasing disease burden [4]. - Antengene is actively working to expand its presence in APAC markets to introduce more innovative medicines, aiming to improve healthcare levels and benefit patients in need [4]. Group 3: Mechanism of Action and Development - XPOVIO® is the world's first orally-available, selective XPO1 inhibitor, which promotes the accumulation of tumor suppressor proteins and down-regulates oncogenic proteins, delivering antitumor effects through multiple pathways [6][7]. - Antengene is developing various combination regimens of XPOVIO® for additional indications, including myelofibrosis and endometrial cancer, and is conducting multiple clinical studies in China [5][7]. Group 4: Company Overview and Pipeline - Antengene is a leading commercial-stage R&D-driven global biopharmaceutical company focused on innovative therapeutics for hematologic malignancies and solid tumors, with a vision of "Treating Patients Beyond Borders" [9]. - Since 2017, Antengene has built a pipeline of 9 oncology assets, obtained 31 investigational new drug (IND) approvals, and submitted 10 NDAs in various Asia Pacific markets [10].

Core Viewpoint - Karyopharm Therapeutics Inc. will implement a 1-for-15 reverse stock split to increase the per-share market price of its common stock, aiming to regain compliance with Nasdaq listing requirements [1][9]. Group 1: Reverse Stock Split Details - The reverse stock split will take effect at 5:00 p.m. Eastern Time on February 25, 2025, and trading on a split-adjusted basis will begin on February 26, 2025 [1][2]. - The number of issued and outstanding shares will decrease from approximately 126.2 million to approximately 8.4 million shares, and authorized shares will reduce from 800 million to 53.33 million [3]. - Proportional adjustments will be made to equity incentive plans, outstanding equity awards, and convertible notes in accordance with their terms [3]. Group 2: Shareholder Impact - No fractional shares will be issued; instead, stockholders entitled to a fractional share will receive a cash payment [4]. - Stockholders holding shares electronically will not need to take action to receive post-split shares, while those with shares through banks or brokers will have their positions adjusted accordingly [5]. Group 3: Company Overview - Karyopharm Therapeutics is a commercial-stage pharmaceutical company focused on novel cancer therapies, particularly oral compounds addressing nuclear export dysregulation [7]. - The company's lead product, XPOVIO® (selinexor), is approved in the U.S. and marketed in multiple oncology indications, with regulatory approvals in various international markets [7].

Financial Data and Key Metrics Changes - Total revenue for Q4 2024 was $30.5 million, down from $33.7 million in Q4 2023, primarily due to lower milestone-related revenue from licensing agreements [51] - Total revenue for the full year was $145.2 million, compared to $146 million in 2023 [52] - U.S. XPOVIO net product revenue for Q4 2024 was $29.3 million, up from $25.1 million in Q4 2023, and for the full year, it was $112.8 million compared to $112 million in 2023 [52] - The gross-to-net discount for XPOVIO was 33.3% for Q4 2024 and 30.9% for the full year, compared to 23.5% and 22.3% in the same periods in 2023 [52] - R&D expenses for Q4 2024 were $33.3 million, down from $39.4 million in Q4 2023, while for the full year, R&D expenses were $143.2 million compared to $138.8 million in 2023 [53] - SG&A expenses for Q4 2024 were $27.2 million, down from $30.7 million in Q4 2023, and for the full year, SG&A expenses were $115.4 million compared to $131.9 million in 2023 [54] Business Line Data and Key Metrics Changes - XPOVIO net product revenue for Q4 2024 was $29.3 million, consistent with Q3 2024 and up 16% compared to Q4 2023 [40] - For the year, XPOVIO net product revenue was $112.8 million, up from $112 million in 2023, despite increased competition [41] - 60% of XPOVIO sales came from the community setting, indicating strong demand despite competition [42] Market Data and Key Metrics Changes - The company expects to grow XPOVIO net product revenue in 2025 and reduce expenses while advancing clinical programs [9] - The peak revenue potential for Selinexor in myelofibrosis is estimated at approximately $1 billion in the U.S. alone if approved [15] Company Strategy and Development Direction - The company aims to redefine the standard of care in myelofibrosis and endometrial cancer, focusing on advancing Phase 3 clinical trials [9][60] - The strategy includes cost reduction initiatives and resource allocation towards pivotal clinical trials [8][55] - The company is preparing for a potential launch of Selinexor in combination with Ruxolitinib in myelofibrosis, targeting a rapid market entry [46] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming Phase 3 trial data for myelofibrosis and endometrial cancer, viewing these as transformative opportunities [60] - The company remains focused on maintaining a profitable commercial organization while navigating a competitive landscape [41][58] - Management highlighted the importance of being well-capitalized to support ongoing operations and clinical trials [110] Other Important Information - The company exited 2024 with cash and investments of $109.1 million, down from $192.4 million at the end of 2023 [56] - Guidance for 2025 includes total revenue of $140 million to $155 million, with U.S. XPOVIO net product revenue projected between $115 million and $130 million [56] Q&A Session Summary Question: Can you provide insights on the myelofibrosis Phase 3 trial and the expected TSS reduction for statistical significance? - Management indicated that a delta of three to four points in TSS would be meaningful, with previous trials showing statistical significance with smaller differences [64][66] Question: What drove the recent FDA discussions regarding the endometrial cancer study? - The FDA recommended focusing on the pMMR patient population due to the evolving standard of care with new therapies, which led to modifications in the trial design [70][73] Question: How is enrollment progressing in the endometrial cancer trial? - Enrollment is on track with approximately 276 patients expected, and top-line results are anticipated in mid-2026 [105] Question: Can you elaborate on the cash runway guidance relative to the Phase 3 studies? - The company is exploring various financing options to extend its cash runway while maintaining a profitable revenue-generating business [110][111] Question: What are the characteristics of the dMMR population not eligible for checkpoint inhibitors? - The dMMR patients are typically excluded due to comorbidities rather than tumor characteristics, and no unique features were identified [115]

Core Insights - Karyopharm Therapeutics reported a quarterly loss of $0.24 per share, better than the Zacks Consensus Estimate of a loss of $0.26, and an improvement from a loss of $0.36 per share a year ago, resulting in an earnings surprise of 7.69% [1] - The company achieved revenues of $30.54 million for the quarter ended December 2024, surpassing the Zacks Consensus Estimate by 0.83%, although this represents a decline from year-ago revenues of $33.75 million [2] - Karyopharm has surpassed consensus EPS estimates four times over the last four quarters and topped consensus revenue estimates three times during the same period [2] Earnings Outlook - The immediate price movement of Karyopharm's stock will largely depend on management's commentary during the earnings call and the company's earnings outlook [3][4] - The current consensus EPS estimate for the upcoming quarter is -$0.23 on revenues of $40.39 million, and for the current fiscal year, it is -$0.71 on revenues of $172.21 million [7] Industry Context - The Medical - Drugs industry, to which Karyopharm belongs, is currently ranked in the top 35% of over 250 Zacks industries, indicating a favorable outlook compared to the bottom 50% [8] - The performance of Karyopharm's stock may also be influenced by the overall industry outlook, as empirical research shows a strong correlation between near-term stock movements and trends in earnings estimate revisions [5][8]

• Welcome Fourth Quarter and Full Year 2024 Financial Results & Business Update February 19, 2025 On Today's Call 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 • Financial Results and Guidance Lori Macomber, Chief Financial Officer and Treasure ...

Financial Performance - As of December 31, 2024, the company had an accumulated deficit of $1.6 billion and net losses of $76.4 million for the year ended December 31, 2024, compared to $143.1 million in 2023[24]. - Total revenue for 2024 was $145.2 million, which included $112.8 million from XPOVIO net product revenue and $32.4 million from license revenue[24]. - The company had $108.7 million in cash, cash equivalents, and investments as of December 31, 2024, with a requirement to maintain at least $25.0 million at all times[24]. Clinical Development and Trials - The clinical pipeline is focused on advancing lead programs in myelofibrosis, endometrial cancer, and multiple myeloma, targeting cancers with high unmet needs[25]. - The SENTRY Trial for selinexor in myelofibrosis is expected to enroll 350 patients, with top-line data anticipated in the second half of 2025[40]. - Selinexor received Orphan Drug Designation from the FDA for myelofibrosis in May 2022 and Fast Track Designation in July 2023[39]. - The unique mechanism of action of SINE compounds may provide therapeutic benefits across a broad range of cancer types, potentially serving as a backbone therapy in combination treatments[32]. - The company is strategically prioritizing late-stage clinical programs while pausing certain early-stage pipeline programs[34]. - In the Phase 1 SENTRY Trial, 92% of efficacy evaluable patients achieved SVR35 at week 24, with 79% of intent to treat patients also achieving this endpoint[42]. - The median duration of SVR35 and TSS50 was 32 weeks and 51 weeks, respectively, with the most common treatment-emergent adverse events being nausea (79%) and anemia (64%) for the 60 mg dose group[43]. - The SENTRY-2 Trial is currently enrolling 58 patients to evaluate selinexor as a monotherapy, with a primary endpoint of SVR35 at week 24[44]. - In the ongoing Phase 2 ESSENTIAL Trial, 27% of patients treated for at least 24 weeks achieved SVR35, with a median overall survival of 35 months compared to a historical survival of 13 to 14 months[45]. - The EC-042 Trial aims to enroll approximately 276 patients with TP53 wild-type tumors, with primary endpoint of progression-free survival and key secondary endpoint of overall survival[49][51]. - The FDA recommended modifications to the EC-042 Trial to focus on TP53 wild-type and pMMR tumors, with top-line data expected in mid-2026[50][51]. - In the SIENDO Trial, selinexor-treated patients had a median progression-free survival of 28.4 months compared to 5.2 months for placebo, representing a hazard ratio of 0.44[55]. - The most common grade 3-4 treatment-emergent adverse events in the SIENDO Trial included neutropenia (20%) and nausea (13%) with a discontinuation rate of 10.5% due to adverse events[54][55]. - Selinexor treatment led to a significant reduction in plasma levels of proinflammatory cytokines, consistent with its proposed mechanism of action[45]. Regulatory and Compliance - The company is engaged in discussions with the FDA regarding the evolving treatment landscape for advanced or recurrent endometrial cancer, particularly concerning checkpoint inhibitors[50]. - The FDA's approval process includes multiple steps, such as preclinical studies and clinical trials, before a product can be marketed[130]. - Clinical trials must comply with Good Clinical Practice (GCP) standards, including independent ethics committee approval and informed consent from subjects[138]. - The FDA may not accept data from foreign clinical trials unless they meet specific conditions, including applicability to the U.S. population and compliance with GCP regulations[139]. - Sponsors are required to register and disclose clinical trial information on clinicaltrials.gov, with results to be disclosed within two years post-completion[141]. - The FDA can issue notices of non-compliance for failure to submit required clinical trial information, with potential penalties of up to $10,000 per day[142]. - The FDA requires sponsors to develop and submit a diversity action plan for each Phase 3 clinical trial to encourage diverse patient enrollment[154]. - The FDA conducts annual inspections of clinical trial sites to ensure compliance with GCP and data integrity[156]. Competitive Landscape - The company faces competition from major pharmaceutical and biotechnology companies, as well as smaller firms with significant resources[108]. - XPOVIO competes with currently marketed products and investigational therapies in the oncology market[113]. - The current standard of care for myelofibrosis includes four approved JAK inhibitors, with ongoing clinical trials for new treatments[114]. - The treatment landscape for endometrial cancer has evolved, with new combination therapies available since 2023[116]. - XPOVIO is the only XPO1 inhibitor approved for multiple myeloma, competing with various therapies including IMiDs and monoclonal antibodies[117]. - The FDA approved TECVAYLI in October 2022 and two additional bispecifics in August 2023, indicating a growing competitive landscape in multiple myeloma treatments[117]. - CARVYKTI and Abecma were approved in April 2024 for earlier lines of multiple myeloma treatment, expanding the treatment options available[117]. Commercialization and Partnerships - The company received an upfront cash payment of $75 million from Menarini in December 2021 for the licensing agreement related to selinexor[86]. - The Amended Menarini Agreement expanded the territory for selinexor commercialization to include all countries in Africa and several Middle Eastern countries[85]. - The company is entitled to receive tiered royalties ranging from mid-teens to mid-twenties based on future net sales of selinexor in the Expanded Menarini Territory[86]. - Antengene has exclusive rights to develop and commercialize selinexor and eltanexor in several Asia-Pacific regions[87]. Manufacturing and Supply Chain - The company relies on third-party contract manufacturers for the production of XPOVIO, ensuring a consistent supply chain[124]. - The manufacturing strategy aims to direct more financial resources towards the commercialization and development of products[127]. - The company plans to continue outsourcing manufacturing and distribution to maintain high-quality standards while focusing on product development[127]. Intellectual Property - As of February 14, 2025, the company held 48 patents in the U.S. and had 178 granted patents in foreign jurisdictions[96]. - The selinexor patent portfolio includes two U.S. patents expiring in July 2032 and July 2033, with additional patents expiring in August 2035[19]. - Eltanexor patent portfolio consists of four issued U.S. patents and will expire no earlier than 2034[19]. - The PAK4/NAMPT inhibitors patent portfolio includes seven issued U.S. patents and 25 issued foreign patents, expiring no earlier than 2034[19]. - Biomarkers related to XPO1 inhibitors have a pending U.S. patent application that will expire in 2040[99]. - The company has filed for patent term extensions in multiple jurisdictions, including 342 days in the U.S. and 5 years in Taiwan[102].

Financial Performance - Preliminary unaudited total revenue for 2024 is expected to be approximately $145 million, with U.S. XPOVIO net product revenue estimated at $113 million[1]. - Cash, cash equivalents, and investments as of December 31, 2024, were approximately $109 million, expected to fund operations into the first quarter of 2026[13]. - The company expects to reduce selling, general, and administrative expenses significantly in 2024, focusing resources on research and development[12]. - Karyopharm's ability to continue as a going concern is under substantial doubt, highlighting financial uncertainties[30]. Clinical Trials and Research - The Phase 3 SENTRY trial evaluating selinexor in combination with ruxolitinib for myelofibrosis is on track to report top-line data in the second half of 2025, with enrollment expected to be completed in the first half of 2025[2][3]. - The updated clinical data from the Phase 2 trials showed a median progression-free survival of 18.4 months for the SPd regimen in multiple myeloma patients[5]. - Karyopharm plans to provide updates on its endometrial cancer program in the first quarter of 2025, continuing patient enrollment in the Phase 3 XPORT-EC-042 trial[9][16]. - KPT-9274 received two Rare Pediatric Disease Designations from the FDA for treating Rhabdomyosarcoma and Ewing sarcoma, with plans for out-licensing or partnerships[12]. Product Development and Market Access - Karyopharm expanded global patient access for selinexor in 2024, achieving favorable reimbursement decisions in over 45 countries[4]. - Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. for three oncology indications and has received regulatory approvals in various international markets, including Europe and China[28]. - Karyopharm is focused on developing therapies for multiple high unmet need cancers, including multiple myeloma and diffuse large B-cell lymphoma (DLBCL)[28]. Adverse Reactions and Safety - 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[25]. - The treatment discontinuation rate due to adverse reactions in the BOSTON trial was 19%[25]. - In the STORM trial, fatal adverse reactions occurred in 9% of patients, with a 27% treatment discontinuation rate due to adverse reactions[25]. - The most common adverse reactions (≥20%) in patients with multiple myeloma receiving XVd include fatigue, nausea, and decreased appetite[25]. - In the SADAL trial for DLBCL, fatal adverse reactions occurred in 3.7% of patients within 30 days, with serious adverse reactions in 46% of patients[26]. Leadership and Strategic Changes - Key leadership changes include the appointment of Lori Macomber as Chief Financial Officer and Brendan Strong as Senior Vice President of Investor Relations[3][12]. Risks and Forward-Looking Statements - Karyopharm's forward-looking statements include expectations regarding commercialization efforts and the clinical development plans for selinexor[29]. - The company faces risks related to the commercialization of XPOVIO and the successful completion of clinical development phases for its drug candidates[30].

Core Insights - Karyopharm Therapeutics reported total revenue of $145 million for the full year 2024, with U.S. XPOVIO® (selinexor) net product revenue of $113 million, showing slight growth compared to 2023 [5][18][19] - The company anticipates top-line data from the Phase 3 SENTRY trial in the second half of 2025 and aims to complete enrollment in the first half of 2025 [2][4] - Karyopharm has updated its Phase 3 XPORT-EC-042 trial for endometrial cancer, increasing the sample size to 276 and expecting top-line data in mid-2026 [4][10] Financial Performance - For the fourth quarter of 2024, total revenue was $30.5 million, down from $33.7 million in the same quarter of 2023 [18] - U.S. net product revenue for Q4 2024 was $29 million, compared to $25 million in Q4 2023, indicating consistent demand for XPOVIO [5][19] - The company reported a net loss of $30.8 million for Q4 2024, an improvement from a net loss of $41.8 million in Q4 2023 [27][28] Research and Development Highlights - The Phase 3 SENTRY trial's co-primary endpoint has been updated to absolute mean change in total symptom score (Abs-TSS), with a sample size increase to approximately 350 patients [4][6] - In endometrial cancer, the trial will focus on TP53 wild-type tumors, which represent about 50% of all endometrial cancer cases [2][10] - Karyopharm continues to enroll patients in the Phase 3 XPORT-EC-042 trial and expects to pursue regulatory approval based on the strength of the data [10][14] Future Outlook - The company projects total revenue for 2025 to be between $140 million and $155 million, with U.S. XPOVIO net product revenue expected to be between $115 million and $130 million [16] - Karyopharm plans to maintain its commercial foundation in the competitive multiple myeloma market and drive increased revenues from XPOVIO [15] - The company aims to report preliminary data from the Phase 2 SENTRY-2 trial in the first half of 2025 and top-line results from the Phase 3 SENTRY trial in the second half of 2025 [15]

Core Viewpoint - Karyopharm Therapeutics Inc. is set to report its fourth quarter and full year 2024 financial results on February 19, 2025, 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 product, 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 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].