证 券 研 究 报 告 赛道百花齐放，潜力靶点或迎新突破 ——癫痫药物行业深度报告 证券分析师： 张静含 A0230522080004 凌静怡 A0230522060001 2025.6.17 投资案件 www.swsresearch.com 证券研究报告 2 ◼ 癫痫是神经系统常见疾病，患者人数众多。根据《柳叶刀-公共卫生》数据统计：2021年，全球有 5170万人患有癫痫，年龄标准化患病率为658/10万人。据中国抗癫痫协会数据，中国约有900万左 右的癫痫患者，其中500-600万是活动性癫痫患者，同时每年新增加癫痫患者约40万，在中国癫痫 已经成为神经科仅次于头痛的第二大常见病。 ◼ 癫痫的发病机制复杂多样，存在较大治疗缺口。癫痫发病机制复杂多样，包括离子通道异常、中枢 神经系统兴奋性/抑制性神经递质分泌不平衡、神经环路异常，以及神经炎症和神经胶质细胞异常等， 抗癫痫发作药物（ASMs）是目前最重要和最基本的治疗手段，但疗效有限、副作用明显等问题依然 影响着癫痫患者的治疗效果。我国癫痫病人经单药序贯或多药联合治疗后，仍有30%的癫痫患者发 作无法得到有效控制，治疗存在着较大缺口。 ◼ 抗癫痫药物在研管 ...

Summary of Xenon Pharmaceuticals Conference Call Company Overview - **Company**: Xenon Pharmaceuticals - **CEO**: Ian Mortimer Industry Context - **Industry**: Epilepsy treatment - **Market Size**: Approximately 3 million Americans have epilepsy, with 60% experiencing focal onset seizures, translating to about 2 million patients. 30-50% of these patients do not achieve good seizure control, indicating a significant market opportunity for new treatments [30][31]. Key Points and Arguments Clinical Trials and Drug Development - **Phase III Studies**: Xenon is conducting two Phase III clinical trials named XTOL-2 and XTOL-3, designed to mirror the successful Phase II study in terms of size, inclusion criteria, and dosing [6][7][9]. - **Efficacy Data**: The Phase II data for Ezetucalner showed robust efficacy, with a placebo-adjusted efficacy that is the best seen in focal onset seizures. The drug has a high power of over 99% at the primary endpoint in Phase III [4][9]. - **Enrollment Challenges**: There has been a slight delay in enrollment for XTOL-2, but the company is confident in completing enrollment in the coming months, with data expected in early 2026 [15][17]. Safety and Efficacy Profile - **Long-term Data**: Over 150 patients have been on the drug for more than three years, with a one in three chance of being seizure-free for 12 months or more. This is significant given the baseline characteristics of patients who had previously failed multiple treatments [22][23]. - **Adverse Events**: The safety profile is consistent with other anti-seizure medications, with common CNS adverse events like dizziness and fatigue. No significant issues related to pigmentation or urinary retention have been observed, addressing concerns from previous drugs in the same class [25][27][28]. Market Opportunity and Competitive Landscape - **Polypharmacy**: The treatment landscape for epilepsy often involves polypharmacy, with many patients not achieving adequate seizure control. Ezetucalner is positioned as a second or third-line treatment option [32][33]. - **Comparison with Competitors**: Ezetucalner offers advantages over competitors like XCOPRI, including no titration required and early onset of efficacy. XCOPRI is projected to generate $400-$450 million in sales this year, with expectations of reaching $1 billion by the end of the decade [34][35][36]. Future Directions - **Major Depressive Disorder (MDD)**: Xenon is also exploring Ezetucalner for MDD, with a Phase III program initiated. Initial data from a small investigator-sponsored study showed some treatment effects, but the company is focusing on its larger Phase III studies for more definitive results [37][41]. - **Pipeline Development**: The company is excited about its drug development pipeline, including new targets for pain and other syndromes, with plans for investor webinars to discuss these developments [52][53]. Additional Important Insights - **Regulatory Interactions**: Ongoing interactions with the FDA have not indicated any changes in the regulatory landscape, and the company expects more engagement as it approaches the NDA submission [19]. - **Patient Feedback**: Positive anecdotal feedback from physicians indicates that patients are experiencing improved quality of life, including increased independence and social interactions due to better seizure control [24]. This summary encapsulates the key points discussed during the conference call, highlighting the company's strategic focus, clinical trial progress, market positioning, and future opportunities.

Financial Data and Key Metrics Changes - The company recognized revenue of $7.5 million during Q1 2025, related to a milestone payment from a collaboration with Neurocrine [24] - Cash and cash equivalents totaled $691.1 million as of March 31, 2025, down from $754.4 million as of December 31, 2024 [24][25] - The company anticipates having sufficient cash to fund operations into 2027, supporting multiple registrational programs [25][26] Business Line Data and Key Metrics Changes - The Phase 3 epilepsy program, particularly the EXTOL-two study, is nearing the end of patient recruitment, with top-line results expected early next year [5][14] - The company is expanding its clinical development work in psychiatry, with ongoing enrollment in the Phase 3 MDD study X NOVA two and plans to initiate X NOVA three and a study in bipolar depression by mid-year [8][22] - The early-stage pipeline is gaining momentum, with multiple regulatory filings expected this year for first-in-human trials across various ion channel targets [9][10] Market Data and Key Metrics Changes - The company has received positive feedback from the epilepsy community regarding the need for new efficacious therapies, highlighting the potential of Ezetucalendar [7][16] - The company presented data at the American Academy of Neurology conference, showcasing the burden of illness for people living with epilepsy and the unmet needs in treatment [16][17] Company Strategy and Development Direction - The company is focused on advancing its neuroscience pipeline, with a particular emphasis on the Zetu calendar for epilepsy and its potential applications in neuropsychiatry [4][13] - The company aims to transition from a clinical-stage to a commercial organization, with plans for NDA submissions following positive Phase 3 results [26] - The strategy includes leveraging extensive knowledge in developing potassium and sodium channel therapeutics to broaden the pipeline [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the conduct and quality of the EXTOL-two study, despite slight delays, and emphasized the importance of the upcoming top-line data readout [14][42] - The management highlighted the excitement within the medical community regarding Ezetucalendar's potential to address unmet needs in epilepsy and neuropsychiatric disorders [7][22] - The company is entering a catalyst-rich period, with significant milestones expected in the near future [13] Other Important Information - The company plans to host multiple R&D webinars to showcase early-stage programs and engage with healthcare providers and patient communities [12] - The management noted that the Phase 3 program for MDD will not change based on the results of the investigator-sponsored study, maintaining the current entry criteria [50][51] Q&A Session Summary Question: Timeline for NDA filing after top-line epilepsy data - The company indicated that it typically takes about six months from top-line data to NDA filing, with critical clinical data being on the path [28] Question: Patient recruitment status for EXTOL-two - The company is nearing completion of patient recruitment for EXTOL-two, with variability in screening and randomization expected [33][35] Question: Reasons for slight timeline slippage for EXTOL-two - Management views the delay as minor and does not anticipate significant competitive impacts, noting that most clinical sites focus on one study at a time [42][44] Question: Inclusion of bipolar I and II patients in studies - The company decided to include both types based on advice from key opinion leaders, focusing on the depression aspect of both conditions [88][90] Question: Efficacy assessment for NAV1.1 in Dravet syndrome - The company plans to assess both seizure reduction and potential disease modification in its clinical development for NAV1.1 [64]