Core Insights - Legend Biotech is presenting six poster presentations on CARVYKTI at the upcoming Tandem Meetings, showcasing its efficacy, safety, and real-world outcomes in treating multiple myeloma [1][4]. Group 1: CARVYKTI Efficacy and Safety - CARVYKTI has treated over 10,000 patients globally, generating substantial clinical and real-world evidence for its use in multiple myeloma treatment [2]. - The therapy demonstrates consistent and durable efficacy and safety, particularly when administered earlier in the treatment journey, leading to meaningful quality-adjusted survival gains [3][4]. - CARVYKTI is the first and only BCMA-targeted CAR-T cell therapy approved for patients with multiple myeloma who have undergone at least one prior line of therapy, and it is now available in 14 countries [4]. Group 2: Poster Presentations Overview - The six poster presentations will cover various aspects of CARVYKTI, including quality-adjusted survival analysis, management of neurologic events, and the impact of bridging therapy on treatment outcomes [5][6]. - Specific topics include the characterization of neurologic events, the relationship between bridging therapy response and safety outcomes, and long-term progression-free survival benefits [5][6]. Group 3: Industry Context - Multiple myeloma is an incurable blood cancer with an estimated 35,000 new diagnoses and over 12,000 deaths in the U.S. in 2024, highlighting the critical need for effective treatments like CARVYKTI [58]. - Legend Biotech is positioned as a leader in cell therapy, focusing on maximizing patient access and therapeutic potential of CARVYKTI while expanding its pipeline of innovative treatments [59].

Core Insights - Johnson & Johnson announced positive topline results from the Phase 3 MajesTEC-9 study, demonstrating that TECVAYLI monotherapy reduced the risk of disease progression or death by 71% and the risk of death by 40% in a patient population largely refractory to existing therapies [1][5][6] Group 1: Study Results - The MajesTEC-9 study confirmed superior progression-free survival (PFS) and overall survival (OS) with TECVAYLI compared to standard care as early as second line therapy [1][2] - The study involved patients who were predominantly refractory to anti-CD38 monoclonal antibodies (85%) and lenalidomide (79%), with over 90% being refractory to their last line of therapy [4][5] - TECVAYLI's safety profile was manageable, with no new safety concerns identified, and the Independent Data Monitoring Committee recommended unblinding the study based on the strength of the data [5][6] Group 2: Treatment Context - Multiple myeloma is characterized by high relapse rates and a significant unmet need for additional therapies, particularly for patients refractory to commonly used treatments [2][3] - The results from MajesTEC-9 build on previous findings from the MajesTEC-3 study, which showed significant benefits of TECVAYLI in combination with DARZALEX FASPRO for patients who were naïve or sensitive to anti-CD38 therapy [2][3] Group 3: Future Implications - The results from the MajesTEC-9 study position TECVAYLI as a potential new standard of care for multiple myeloma treatment, particularly for patients experiencing their first relapse [3][6] - Johnson & Johnson continues to innovate in the multiple myeloma space, aiming to redefine treatment options and improve outcomes for patients at all stages of the disease [6][8]

Core Insights - Johnson & Johnson has submitted a Type II variation application to the European Medicines Agency (EMA) for an indication extension of TECVAYLI® (teclistamab) in combination with DARZALEX® (daratumumab SC) for treating adult patients with relapsed/refractory multiple myeloma (RRMM) who have received at least one prior therapy [1][2] Group 1: Clinical Study and Results - The application is supported by data from the Phase 3 MajesTEC-3 study, which showed a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) compared to standard treatment [1][2] - The MajesTEC-3 study enrolled 587 patients and demonstrated an 83.4% reduction in the risk of disease progression or death compared to standard regimens at nearly three years follow-up (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.12-0.23; P<0.0001) [2][4] - More than 90% of patients who remained progression-free at six months continued to be progression-free at three years [2] Group 2: Treatment Efficacy and Safety - Teclistamab and daratumumab SC work in a complementary manner by targeting both BCMA and CD38, enhancing immune-mediated responses earlier in treatment [2] - The combination regimen showed similar rates of Grade 3/4 treatment-emergent adverse events (TEAE) compared to standard care (95.1% vs. 96.6%) [2] - The most common Grade 3/4 events were cytopenia and infection, with infections observed in 96.5% of patients receiving teclistamab and daratumumab SC [2] Group 3: Regulatory and Market Position - The FDA has granted Breakthrough Therapy Designation for the teclistamab and daratumumab SC combination, expediting its development and regulatory review [2] - Johnson & Johnson aims to redefine treatment possibilities in multiple myeloma by using the right medicines early and combining them for optimal outcomes [3] Group 4: Background on Multiple Myeloma - Multiple myeloma is an incurable blood cancer affecting plasma cells, with over 35,000 new diagnoses in the EU in 2022 [8] - Patients experience frequent relapses, and remissions become progressively shorter with each line of therapy [8]

Company Overview - Arcellx is actively engaging with investors at the 67th Annual ASH Meeting in Orlando, Florida, highlighting its leadership under Rami Elghandour as Chairman and CEO [1] - The company is focusing on the evolving landscape of multiple myeloma, which is a significant area of interest for stakeholders [2] Clinical Development - Dr. Krina Patel presented the latest results from the iMMagine-1 Registrational Phase II study at the ASH Medical Congress, indicating ongoing advancements in clinical trials [3] - Following Dr. Patel's presentation, Dr. Chris Heery, the Chief Medical Officer, will moderate a physician panel to discuss further insights [3]

Clinical Trial Updates - Phase 3 SENTRY试验的顶线数据预计在2026年3月公布[8, 25] - Phase 3 XPORT-EC-042子宫内膜癌试验的顶线数据预计在2026年中期公布[8, 67] - 评估SPd治疗复发性多发性骨髓瘤患者的3期全球研究(XPORT-MM-031/EMN29)的顶线数据预计在2026年上半年公布[70, 73] - SENTRY (XPORT-MF-034) 是一项针对JAKi初治骨髓纤维化患者，Selinexor联合Ruxolitinib的3期试验，已于2025年9月完成患者招募，共353名患者[23, 24] Commercial Performance - 2025年第三季度，美国XPOVIO净产品收入为3200万美元，比2024年第三季度的2950万美元增长8.5%[37] - 公司重申2025年全年净产品收入指导范围为1.1亿美元至1.2亿美元[37, 54] - 社区环境持续驱动约60%的美国整体净产品收入[37] Financial Highlights - 2025年第三季度总收入为4400万美元，高于2024年第三季度的3880万美元[51] - 预计现有流动资金，在计入2025年10月8日宣布的融资交易的影响后，足以支持公司计划运营至2026年第二季度[53] - 研发和SG&A费用预计为2.35亿美元至2.45亿美元[54] Myelofibrosis Market Opportunity - Selinexor联合Ruxolitinib疗法在美国市场可能达到每年约10亿美元的净销售额峰值[41, 43] - 约75%的患者有意愿接受联合治疗[42]

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]

Core Insights - The European Commission has approved an indication extension for DARZALEX® (daratumumab) subcutaneous formulation in combination with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma patients [1][3] - The Phase 3 CEPHEUS study demonstrated significant improvements in minimal residual disease (MRD)-negativity rate, progression-free survival, and complete response rates compared to standard care [1][4] Company Overview - Janssen-Cilag International NV, a subsidiary of Johnson & Johnson, has been a leader in multiple myeloma treatment for over 20 years, with daratumumab becoming a foundational therapy used in over 618,000 patients globally [6][7] - The company aims to provide access to daratumumab-based regimens for all patient populations, regardless of age or fitness, marking a critical step towards achieving a functional cure for multiple myeloma [3][6] Clinical Study Findings - The CEPHEUS study involved 395 patients with newly diagnosed multiple myeloma who were ineligible for stem cell transplantation, comparing daratumumab-VRd to standard VRd [4][5] - At a median follow-up of 59 months, the MRD-negativity rate was 60.9% for daratumumab-VRd versus 39.4% for VRd, with a significant odds ratio of 2.37 [1][4] - The study also reported a 43% reduction in the risk of progression or death with daratumumab-VRd compared to VRd, with median progression-free survival not reached for daratumumab-VRd [1][4] Safety Profile - The safety profile of daratumumab-VRd aligns with known safety profiles for daratumumab SC and VRd, with common Grade 3/4 adverse events including neutropenia (44.2% vs 29.7% for VRd) and thrombocytopenia (28.4% vs 20.0% for VRd) [2][4]