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].

NEWTON, Mass., Feb. 24, 2025 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that it will implement a 1-for-15 reverse stock split of the issued shares of the Company's common stock ("Reverse Stock Split"), effective at 5:00 p.m. Eastern Time on February 25, 2025. The Reverse Stock Split was approved by the Company's stockholders at the Company's Special Meeting of Stockholders held on January 30, 2025, ...

Karyopharm Therapeutics Inc. (NASDAQ:KPTI) Q4 2024 Earnings Call February 19, 2025 8:00 AM ET Company Participants Brendan Strong - SVP, IR Richard Paulson - President and CEO Reshma Rangwala - CMO & Head of Research Sohanya Cheng - CCO & Head of Business Development Lori Macomber - EVP, CFO, & Treasurer Conference Call Participants Colleen Kusy - Baird Maury Raycroft - Jefferies Unidentified Analyst - Barclays Jonathan Chang - Leerink Partners Unidentified Analyst - RBC Capital Markets Ed White - H.C. Wain ...

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].

Core Insights - Karyopharm Therapeutics is focused on redefining the treatment paradigm for myelofibrosis with the Phase 3 SENTRY trial evaluating selinexor in combination with ruxolitinib, with top-line data expected in the second half of 2025 [1][2] - The company has made key leadership changes, appointing Lori Macomber as CFO and Brendan Strong as SVP of Investor Relations and Corporate Communications [1][20] - Preliminary unaudited total revenue for 2024 is estimated at approximately $145 million, with U.S. XPOVIO net product revenue expected to be around $113 million [1][12] Company Objectives and Strategy - The primary strategic goal for 2025 is to deliver transformative results from the SENTRY trial, aiming to establish selinexor as the first all-oral combination therapy for myelofibrosis [2][15] - The company is committed to high-quality clinical trial execution and is on track to complete enrollment in the SENTRY trial by the first half of 2025 [2][21] Financial Performance - Demand for XPOVIO remained consistent in 2024 compared to 2023, with growth in the second half of the year offsetting earlier declines due to increased competition [5] - The company expects total revenue of approximately $30 million for Q4 2024 and $145 million for the full year, with U.S. XPOVIO net product revenue projected at $29 million for Q4 and $113 million for the full year [12][20] Clinical Development Highlights - The SENTRY trial has updated its co-primary endpoint to absolute mean change in total symptom score (Abs-TSS) and increased the sample size to approximately 350 patients to enhance statistical power [4][19] - Updated clinical data from the Phase 2 trials of selinexor in combination with pomalidomide and dexamethasone showed a median progression-free survival of 18.4 months [5][11] Regulatory and Market Expansion - Karyopharm has expanded global patient access for selinexor with favorable reimbursement decisions in multiple countries, increasing approvals to over 45 countries [5][12] - The company is engaged with the FDA regarding the evolving treatment landscape in endometrial cancer and plans to provide updates on its Phase 3 XPORT-EC-042 trial in early 2025 [8][17] Pipeline and Future Catalysts - The company is preparing for a rapid launch of selinexor following the SENTRY trial results and aims to maintain its commercial foundation in the competitive multiple myeloma market [2][21] - Key upcoming milestones include reporting topline results from the SENTRY trial and updates on the XPORT-MM-031 trial [21][22]