Brendan Strong, SVP, Investor Relations Opening Remarks Richard Paulson, President and Chief Executive Officer Phase 3 SENTRY Topline Results March 24, 2026 On Today's Call Welcome Phase 3 SENTRY Topline Results Dr. Reshma Rangwala, Chief Medical Officer and Head of Research Myelofibrosis Treatment Landscape Dr. John Mascarenhas, Principal Investigator of Phase 3 SENTRY Trial; Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and ...

Prelude Therapeutics Conference Call Summary Company Overview - Prelude Therapeutics is a precision oncology company with a differentiated pipeline targeting clinically validated pathways [2][3] - The company announced a strategic shift in its portfolio, pausing the SMARCA2 selective degrader program to focus on JAK2 V617F and KAT6A programs [3][4] Key Programs and Developments JAK2 V617F Program - The JAK2 V617F program has received IND clearance, with plans to initiate clinical trials in 2026 [4] - The program targets myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) [11][12] - The JAK2 mutation is present in over 90% of PV cases and about half of ET and MF cases [11] - Prelude's approach aims to develop a mutant-selective inhibitor that spares normal bone marrow function, addressing limitations of first-generation JAK2 inhibitors [13][14] KAT6A Program - Prelude is developing a KAT6A degrader, which is expected to have a better safety profile by selectively targeting KAT6A while sparing KAT6B [38][40] - The KAT6A degrader aims to provide deeper responses by eliminating the protein rather than just inhibiting it [39] - The IND for the KAT6A program is expected to be filed by mid-2026 [44] Mutant CALR Degrader - Prelude is also working on a mutant CALR degrader, which targets a specific fraction of ET and MF patients [46] - This program aims to utilize a degrader conjugate payload to effectively kill disease-initiating cells with minimal receptor occupancy [46][47] - The company has built expertise in developing these conjugates through a collaboration with AbCellera [48] Strategic Partnerships - Prelude has entered a business development deal with Incyte for the JAK2 V617F program, which includes an option for Incyte to acquire the program [5][29] - This partnership is expected to extend the company's financial runway into the second quarter of 2027, with $106 million in cash reported [53] Financial Position - Prelude reported $106 million in cash, which is projected to last until the second quarter of 2027, not including potential additional funding from Incyte [53] Clinical Development Plans - The clinical development plan for the JAK2 program includes a parallel design for both myelofibrosis and polycythemia vera, allowing for rapid development [23][24] - The company aims to enroll patients who may not be eligible for other JAK2 inhibitors, enhancing the trial's potential for meaningful data [25][26] Competitive Landscape - Prelude's JAK2 inhibitor is differentiated from competitors by its selective targeting of the mutant form of the enzyme, which is expected to improve efficacy and safety [18][21] - The KAT6A degrader is positioned to outperform existing KAT6 inhibitors by offering better efficacy and reduced side effects, particularly neutropenia [42][44] Conclusion - Prelude Therapeutics is strategically focusing on its JAK2 V617F and KAT6A programs while leveraging partnerships to enhance its financial position and clinical development capabilities [3][29][53]

Karyopharm Therapeutics Conference Summary Company Overview - Karyopharm Therapeutics is a U.S.-based, innovation-focused, commercial-stage oncology company specializing in areas of high unmet need, particularly in multiple myeloma and myelofibrosis [5][6] - The lead compound, Selinexor (XPOVIO), is already commercialized for multiple myeloma and approved in over 50 countries [5] Key Developments - Karyopharm is excited about two upcoming Phase III trials: one for myelofibrosis and another for endometrial cancer, with results for the myelofibrosis trial (SENTRY) expected in March 2026 [5][6] - The SENTRY trial aims to establish a new standard of care using Selinexor in combination with Ruxolitinib [6] Scientific Rationale - Selinexor is an XPO1 inhibitor that modulates various pathways relevant to myelofibrosis, including the NF-kappa B pathway and tumor suppressors like P53 [9][10] - The Phase I study showed that 79% of patients achieved a spleen volume reduction of 35% (SVR35) at week 24 when treated with Selinexor and Ruxolitinib, compared to 30%-35% with Ruxolitinib alone [12] Safety Profile - The safety profile of Selinexor in combination with Ruxolitinib appears manageable, with lower rates of nausea and vomiting compared to previous studies [18][20] - Only 7% of patients discontinued treatment due to adverse events in the Phase III study, indicating a favorable safety profile [18] Clinical Insights - Dr. Claire Harrison, a leading expert in myelofibrosis, emphasized the need for treatments that provide deeper and more durable responses than current JAK inhibitors [26] - The combination of Selinexor and Ruxolitinib is expected to be well-tolerated, with manageable side effects, particularly nausea [32][66] Trial Design and Endpoints - The SENTRY trial involves a two-to-one randomization of 353 patients to receive either Selinexor plus Ruxolitinib or Ruxolitinib plus placebo [40] - Primary endpoints include SVR35 and absolute total symptom score (TSS), with a focus on achieving a statistically significant improvement over Ruxolitinib alone [41][46] Baseline Characteristics - The baseline TSS in the SENTRY trial is higher than in previous trials, which may enhance the likelihood of demonstrating a meaningful treatment effect [52][54] - Dr. Harrison noted that a higher baseline TSS could lead to more accurate assessments of treatment efficacy [54] Future Expectations - A successful outcome in the SENTRY trial would likely lead to the combination being used as a first-line treatment for myelofibrosis patients [63] - The community of physicians is eager for new treatment options, and there is a strong interest in the results of the SENTRY trial [69] Additional Considerations - The trial's design excludes fatigue from the primary endpoints, which has been a challenge in previous studies [44] - The combination therapy is expected to improve hemoglobin levels, which is a critical prognostic factor in myelofibrosis [60] This summary encapsulates the key points discussed during the Karyopharm Therapeutics conference, highlighting the company's focus on innovative treatments for myelofibrosis and the anticipated impact of the SENTRY trial results.

Summary of Celldex Therapeutics Conference Call Company Overview - **Company**: Celldex Therapeutics (NasdaqCM:CLDX) - **Date**: November 13, 2025 - **Key Speakers**: Anthony Marucci (CEO), Tibor Keler (CSO), Diane Young (CMO) Key Points Industry and Product Focus - The discussion primarily revolves around Celldex's ongoing clinical trials and data related to their drug Barzolvolimab, particularly in the context of Chronic Spontaneous Urticaria (CSU), Prurigo Nodularis (PN), and Atopic Dermatitis (AD) [3][4][34] Clinical Data Highlights - **CSU Phase Two Data**: - A 76-week phase two study showed a **41% complete response rate** seven months after stopping Barzolvolimab, indicating a durable remission [3][4] - This response rate is comparable to Xolair and higher than Dupixent, suggesting significant efficacy [3][4] - **Competitor Comparison**: - Xolair's effects diminish within weeks after cessation, while Ruxolitinib's long-term effects remain unclear. Dupixent shows modest efficacy [4][5] - **Mast Cell Dynamics**: - Data indicates that mast cells return to normal levels after treatment, but the long-term effects on disease modification are still being evaluated [6] Future Studies and Trials - **OLE (Open Label Extension)**: - The OLE is designed to gather additional follow-up data and explore retreatment options post-approval [7][8] - **Upcoming Trials**: - Ongoing phase two studies for PN and AD are expected to yield results in the second half of 2026. The PN trial involves 120 patients and focuses on itch reduction and lesion healing [17][21][34] - **CDX-622 Development**: - CDX-622, a bispecific targeting mast cells and TSLP, is in phase one trials with promising pharmacokinetics and no immunogenicity observed [28][29] Market Position and Strategy - **Competitive Landscape**: - Celldex aims to position Barzolvolimab as a competitive option against existing treatments like Dupixent, focusing on improving itch reduction and lesion healing [19][20] - **Pipeline Expansion**: - The company is considering various indications for CDX-622, including severe asthma and food allergies, based on ongoing data [31][32] Upcoming Catalysts - Key upcoming milestones include: - Phase three study initiation for cold urticaria and symptomatic dermographism by the end of 2025 - Phase two readouts for cold urticaria and symptomatic dermographism in Q1 2026 - Completion of CSU phase three accrual by summer 2026 - Data releases for AD and PN in the second half of 2026 [34][36] Enrollment and Study Progress - Enrollment for the ongoing EMBARK studies is proceeding well, with expectations to complete by summer 2026 [36][37] Additional Insights - The discussion emphasizes the importance of understanding mast cell roles in various conditions, which could lead to innovative treatment strategies and improved patient outcomes [20][22]

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]