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]

Jefferies Global Healthcare Conference June 5, 2025 Forward-looking Statements and Other Important Information This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's beliefs about the market opportunity and annual peak revenue opportunities for selinexor; expectations with respect to commercialization efforts; the ability of selinexor to treat patients with multiple ...

Incyte (INCY) Update Summary Company Overview - Incyte Corporation is focusing on the long-term growth of its Jakafi franchise beyond 2029, addressing concerns about its sustainability and future growth drivers [2][3]. Core Industry Focus - The primary focus is on essential thrombocythemia (ET) and myeloproliferative neoplasms (MPNs), particularly the role of the KALR mutation in these diseases [5][30]. Key Points and Arguments Clinical Data Presentation - The meeting presented the first clinical data related to a new treatment for ET, specifically targeting the KALR mutation [1][2]. - The data discussed is expected to drive growth in the NPN franchise and is a result of extensive research programs conducted over the years [3]. Disease Overview - ET is a rare disease with an incidence of approximately 1 in 100,000 and a prevalence of at least 30 per 100,000 [10]. - The median age of presentation is typically in the 60s, but younger patients, particularly females, are also affected [11]. - Disease progression primarily leads to myelofibrosis, with acute leukemia also being a risk [12]. Current Treatment Landscape - Current treatments for high-risk ET patients include hydroxyurea and interferon, which do not modify the disease or provide a cure [16][21]. - There is a significant unmet need for new therapies, as the last new treatment was approved in 2005 [19][20]. KALR Mutation Insights - The KALR mutation is present in about 30% of ET patients and is associated with a higher risk of disease progression [12][14]. - Patients with KALR mutations tend to have higher platelet counts and are less likely to respond to standard treatments [15][19]. New Treatment: INCA-3989 - INCA-3989 is a first-in-class monoclonal antibody targeting the mutant KALR oncogene, designed to inhibit the JAK-STAT signaling pathway associated with the mutation [46][49]. - The treatment shows selectivity for mutant cells while sparing normal cells, potentially allowing for the expansion of wild-type hematopoietic stem cells [50][51]. Phase I Study Results - The Phase I study included 49 patients with high-risk ET, demonstrating significant reductions in platelet counts and normalization of blood parameters [58][76]. - The study reported no dose-limiting toxicities (DLTs) and a favorable safety profile, with 65% of patients able to discontinue previous therapies [60][88]. Biomarker and Clinical Outcomes - Early results indicate a reduction in the KALR variant allele frequency (VAF) in patients, correlating with clinical responses [82][86]. - The treatment has shown potential for disease modification, which could impact the long-term progression of ET and reduce the risk of transformation to myelofibrosis or acute leukemia [88]. Additional Important Insights - The meeting highlighted the importance of addressing patient anxiety related to chronic diseases, noting that effective treatment can lead to shorter office visits and improved patient satisfaction [68]. - The data presented suggests that INCA-3989 could represent a transformative approach in treating mutant KALR ET patients, with implications for future clinical practice [89].

Summary of Karyopharm Therapeutics (KPTI) Conference Call Company Overview - **Company**: Karyopharm Therapeutics (KPTI) - **Key Products**: Selinexor (XPOVIO) - **Focus Areas**: Oncology, specifically multiple myeloma and myelofibrosis Key Points Commercial Performance and Product Dynamics - **Q1 Demand Growth**: KPTI reported a 5% year-over-year demand growth for XPOVIO in Q1, despite a one-time impact of $5 million from atypical returns related to high-dose selinexor [3][4] - **Real-World Utilization**: The company is focusing on increasing the utilization of selinexor in both community and academic settings, with a particular emphasis on lower doses [4][5] - **Community Treatment**: Selinexor is primarily used in the community setting for multiple myeloma patients, positioned in the second to fourth line of treatment [5][6] Growth Drivers and Future Outlook - **T Cell Engaging Therapies**: KPTI is generating data to support the use of selinexor in conjunction with T cell engaging therapies, which are becoming more prevalent in earlier treatment lines [9][10] - **Myelofibrosis Opportunity**: The ongoing SENTRI trial is evaluating selinexor in combination with ruxolitinib, with promising early data showing a 79% SVR 35 rate at week 24 compared to 30-35% for ruxolitinib alone [12][13][15] - **Durability of Response**: The company reported a 100% durability of response for patients achieving SVR 35 or TSS 50, indicating sustained benefits from treatment [17] Clinical Trials and Data - **Phase III Trials**: KPTI is focused on executing its Phase III trials for both myelofibrosis and endometrial cancer, with the latter leveraging a biomarker (p53 wild type) for patient selection [45][46] - **Endpoint Changes**: The transition from TSS 50 to absolute TSS is seen as a more sensitive measure for symptom improvement, gaining positive feedback from investigators and regulators [28][29] Safety and Tolerability - **Antiemetic Use**: KPTI has incorporated dual antiemetics in its Phase III trials to mitigate nausea and vomiting, achieving over 85% compliance and lower rates of these side effects [36][38] - **Safety Profile**: The safety profile of selinexor is evolving positively, with improvements noted in gastrointestinal side effects [17][38] Commercial Strategy - **Market Positioning**: KPTI aims to target all frontline myelofibrosis patients, leveraging existing commercial infrastructure to facilitate rapid uptake among physicians [41][42] - **Unmet Need**: Research indicates a significant unmet need in the myelofibrosis market, with 75% of physicians willing to adopt therapies that address key disease hallmarks [42] Financial Discipline - **Operational Focus**: KPTI is maintaining a disciplined approach to operational expenditures, concentrating resources on Phase III readouts and shutting down non-essential programs [48][49] Additional Insights - **Endometrial Cancer Landscape**: The company anticipates that selinexor will address a sizable unmet need in patients with p53 wild type tumors, with enrollment for the Phase III trial progressing well [46][47] - **Future Readouts**: KPTI is positioned for significant upcoming data readouts that could transform treatment paradigms in both myelofibrosis and endometrial cancer [49]