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 ...

Jefferies Global Healthcare Conference 3 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 multip ...

Karyopharm Therapeutics (KPTI) Conference Summary Company Overview - Karyopharm Therapeutics is an innovation-driven commercial stage oncology company focusing on myelofibrosis and endometrial cancer treatments [3][4] Key Points on Myelofibrosis - The company is conducting two transformative Phase 3 studies: one for myelofibrosis and another for endometrial cancer, with top-line data expected by the end of 2025 or early 2026 [2][4] - The potential peak opportunity for myelofibrosis treatment is projected to exceed $1 billion [5] - The ongoing Phase 3 program targets JAK naive patients, with a focus on the efficacy of selinexor in combination with ruxolitinib [5][6] - Selinexor has shown promising results in heavily pretreated patients, demonstrating significant spleen volume reduction and symptom improvement [6][16] - The combination therapy has achieved a 79% SVR 35 rate compared to the 30-35% rate seen with ruxolitinib alone [16][28] - The durability of response is notable, with a 100% probability of maintaining spleen volume reduction among patients achieving SVR 35 [18] - The company emphasizes the importance of modifying the underlying disease and improving patient outcomes through innovative treatment approaches [34] Key Points on Endometrial Cancer - Karyopharm is leveraging the p53 wild type biomarker in endometrial cancer, which is present in approximately 50% of patients [38][39] - Selinexor has demonstrated a median progression-free survival (PFS) of 28.4 months in p53 wild type patients, significantly outperforming placebo [40] - The ongoing Phase 3 trial for endometrial cancer will evaluate selinexor as a monotherapy in a maintenance setting, with a planned enrollment of 276 patients [41] Additional Insights - The company has established commercialization capabilities to rapidly launch treatments upon receiving positive data [9][10] - The focus on innovative therapies aims to transform treatment standards in both myelofibrosis and endometrial cancer, enhancing patient outcomes [44] - The management team expresses confidence in the potential of selinexor to address unmet needs in oncology, particularly in challenging patient populations [11][12] Conclusion - Karyopharm Therapeutics is positioned for significant advancements in oncology with its innovative treatments for myelofibrosis and endometrial cancer, backed by promising clinical data and a strong commercialization strategy [44]

作 者丨季媛媛 编 辑丨张星 图 源丨摄图网 当创新药行业的领军企业恒瑞医药在港股市场首日上市即收涨25%时，A股和H股市场上的创 新药板块也呈现出显著的上涨趋势。回顾整个创新药板块的市场表现，尽管在5月26日经历了 一定程度的回调，但整体来看， 创新药板块依旧是今年表现最为出色的子板块之一 ，其成绩 令人鼓舞。 根据Wind数据，截至5月26日10时30分， 恒生行业指数中的医疗保健业，年初至今涨幅已超 30% 。其中，三生制药年初至今涨幅高达210.86%、远大医药涨幅达94.17%、科伦博泰生物- B涨幅达87.88%、诺诚健华涨幅达69.28%、乐普生物-B涨幅达64.12%。另外，港股概念板块 中的未盈利生物科技指数年初至今涨幅超39%。其中，德琪医药-B年初至今涨幅达456.92%、 和铂医药-B涨幅达358.60%、加科思-B涨幅达244.88%、康宁杰瑞制药-B涨幅超148%。 面 对 市 场 表 现 ， 许 多 行 业 专 家 坦 率 表 示 ： 医 药 领 域 ， 特 别 是 创 新 药 物 ， 已 经 从 " 寒 冬"迈向"暖春"，进入了一个新的政策扶持和发展的周期。 长江证券分析认为， ...

创新药：爆款，突围，与自证 编者按：创新药行业正迎来政策扶持、产业升级与业绩回暖的"三重共振"，资本市场估值逻辑加速重 构，"熊市思维"下的传统评估方式已难适用。21世纪经济报道将持续聚焦行业热点——从BD交易模式 到全球化竞争策略，从高估值背后的风险到政策波动的应对，推出系列报道专题《创新药：爆款，突 围，与自证》，深入解读创新药企如何在变革中穿越周期，重塑价值坐标，定义行业新未来，此篇为第 一篇。 21世纪经济报道记者季媛媛 上海报道 当创新药行业的领军企业恒瑞医药在港股市场首日上市即收涨25%时，A股和H股市场上的创新药板块 也呈现出显著的上涨趋势。回顾整个创新药板块的市场表现，尽管在5月26日经历了一定程度的回调， 但整体来看，创新药板块依旧是今年表现最为出色的子板块之一，其成绩令人鼓舞。 根据Wind数据，截至5月26日10时30分，恒生行业指数中的医疗保健业，年初至今涨幅已超30%。其 中，三生制药年初至今涨幅高达210.86%、远大医药涨幅达94.17%、科伦博泰生物-B涨幅达87.88%、诺 诚健华涨幅达69.28%、乐普生物-B涨幅达64.12%。另外，港股概念板块中的未盈利生物科技指数年初 ...

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]

Core Insights - Karyopharm Therapeutics Inc. announced that its abstract on selinexor monotherapy for myelofibrosis has been selected for presentation at the 2025 European Hematology Association Annual Meeting [1][2] - The data from the Phase 2 XPORT-MF-035 trial indicates that selinexor shows clinical activity in heavily pretreated myelofibrosis patients, demonstrating spleen volume reduction, hemoglobin stabilization, and symptom improvement [2][4] Summary by Sections Company Overview - Karyopharm Therapeutics is a commercial-stage pharmaceutical company focused on developing novel cancer therapies, particularly through its lead compound, XPOVIO (selinexor), which is a first-in-class oral exportin 1 (XPO1) inhibitor [4][11] - The company has received regulatory approvals for XPOVIO in multiple oncology indications in the U.S. and various international markets, including Europe and China [5][11] Clinical Trial Insights - The XPORT-MF-035 trial involved 24 patients, randomized 1:1 to receive either selinexor monotherapy or physician's choice treatment, with selinexor administered at 80 mg weekly for the first two cycles, then reduced to 60 mg [4] - Key findings from the trial include: - 67% of selinexor-treated patients achieved a spleen volume reduction of 25% or more compared to 38% in the physician's choice group [4] - 33% of selinexor patients achieved a spleen volume reduction of 35% or more versus 13% in the physician's choice group [4] - Patients on selinexor had higher mean hemoglobin levels and lower rates of red blood cell transfusions compared to those on physician's choice [4] Safety and Adverse Events - The most common treatment-emergent adverse events (TEAEs) in the selinexor arm included decreased weight (50%), asthenia (42%), and nausea (33%) [4] - Serious adverse reactions were reported in 52% of patients in the BOSTON trial, with a treatment discontinuation rate of 19% due to adverse reactions [9]

Financial Performance - Karyopharm Therapeutics reported quarterly losses of $2.77 per share, which was better than the analyst consensus estimate of losses of $4.16 per share [1] - The company reported quarterly sales of $30.02 million, missing the analyst consensus estimate of $35.24 million [1] Clinical Trial Update - The Phase 3 SENTRY trial in patients with JAKi-naïve myelofibrosis has passed its pre-specified futility analysis and continues as planned without modifications [2] - New data in hard-to-treat myelofibrosis patients showed spleen volume reduction, symptom improvement, hemoglobin stabilization, and evidence of disease modification with selinexor monotherapy [2] Sales Guidance and Market Reaction - Karyopharm affirmed FY2025 sales guidance of $140.00 million to $155.00 million, compared to market estimates of $149.32 million [3] - Following the earnings announcement, Karyopharm shares fell 15.6% to trade at $5.17 [3] Analyst Ratings and Price Targets - Baird analyst Michael Ulz maintained an Outperform rating and lowered the price target from $54 to $42 [8] - Barclays analyst Peter Lawson maintained an Overweight rating and raised the price target from $5 to $10 [8] - RBC Capital analyst Brian Abrahams maintained an Outperform rating and lowered the price target from $34 to $33 [8]

– New Randomized Phase 2 Monotherapy Data from XPORT-MF-035 Trial in a Hard-to-Treat Patient Population Further Strengthens Conviction in Selinexor's Potential in Combination with Ruxolitinib in JAKi-Naïve Myelofibrosis in Ongoing Phase 3 SENTRY Trial –– Phase 3 SENTRY Trial Passed Planned Futility Analysis; Trial is Approximately 80% Enrolled with Target Enrollment Expected in June/July 2025 –– Demand for XPOVIO® (selinexor) Increased 5% in the First Quarter of 2025 Compared to the First Quarter of 2024; T ...

-- Conference Call Scheduled for Monday, May 12, 2025, at 4:30 p.m. ET --NEWTON, Mass., May 8, 2025 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced it will report first quarter 2025 financial results on Monday, May 12, 2025. Karyopharm's management team will host a conference call and audio webcast at 4:30 p.m. ET on Monday, May 12, 2025, to discuss the financial results and other company updates.To acc ...