Xenon Pharmaceuticals FY Conference Summary Company Overview - **Company**: Xenon Pharmaceuticals (NasdaqGM:XENE) - **Event**: 44th Annual J.P. Morgan Healthcare Conference - **Date**: January 12, 2026 - **Key Presenters**: Ian Mortimer (President and CEO), Chris Kenny (Chief Medical Officer), Darren Kline (Chief Commercial Officer), Tucker Kelly (CFO) [1][2] Core Focus Areas Lead Molecule: Azetukalner - **Indications**: Developed for epilepsy and neuropsychiatry - **Clinical Development**: Most advanced potassium channel modulator in late-stage clinical development with over 800 patient years of efficacy and safety data [3][4] - **Dosing**: Once-daily dosing with no titration required, which is a significant advantage over other CNS drugs [5] Epilepsy Market Insights - **Prevalence**: Epilepsy is the fourth most common neurological condition, with a lifetime risk of 1 in 26 [6] - **Patient Population**: Approximately 3 million Americans have epilepsy, with focal onset seizures representing about 60% of the market [6][7] - **Unmet Need**: About half of epilepsy patients are not receiving adequate treatment, indicating a significant market opportunity for azetukalner [7][8] Clinical Trial Updates - **Phase IIb Trial (X-TOLE)**: Randomized 325 subjects, showing a 52.8% reduction in seizures at the highest dose (25 mg) with significant statistical significance (P < 0.05) [9][10] - **Open-Label Extension**: Patients showed over 90% reduction in seizure burden over 48 months, with nearly 40% achieving 12 months of seizure freedom [13][15] - **Phase III Trials**: Two parallel trials (X-TOLE2 and X-TOLE3) for focal onset seizures, with the first readout expected in March 2026 [19][20] Neuropsychiatry Development - **Major Depressive Disorder (MDD)**: A smaller phase II study showed a clear dose response with rapid onset of efficacy, leading to ongoing phase III trials [22][27] - **Bipolar Depression**: New study (EXCED) initiated to address this significant unmet need [27] Early-Stage Pipeline - **Nav1.7 Program**: Focused on a novel analgesic targeting pain pathways, currently in phase I clinical trials [28][29] - **Genetic Insights**: The program leverages genetic findings related to the SCN9A gene, which is linked to pain perception [29][30] Strategic Objectives - **Integration**: Aim to become a fully integrated biopharma company, focusing on discovering, developing, and commercializing proprietary molecules [36][38] - **Market Positioning**: Emphasis on building a strong commercial team with deep epilepsy experience to ensure successful product launch [55][56] Key Takeaways - **Market Opportunity**: Significant unmet medical needs in both epilepsy and neuropsychiatry present a strong market opportunity for azetukalner [8][27] - **Clinical Confidence**: Robust clinical data supports the efficacy and safety of azetukalner, positioning it as a potential first-line treatment in its categories [18][19] - **Future Outlook**: Successful outcomes in ongoing trials could lead to a substantial expansion of Xenon's portfolio and market presence in the coming years [59][62]

Core Insights - Xenon Pharmaceuticals Inc. is advancing its Phase 3 portfolio, particularly focusing on azetukalner for epilepsy and neuropsychiatry, with significant milestones expected in the near future [1][2] Phase 3 Azetukalner Program in Epilepsy & Depression - The topline data for the X-TOLE2 Phase 3 study of azetukalner in focal onset seizures (FOS) is anticipated in March 2026, followed by a New Drug Application (NDA) submission in the second half of 2026 [4] - Five additional Phase 3 studies of azetukalner are ongoing, targeting various indications in epilepsy and neuropsychiatry, with topline data from the X-NOVA2 study in major depressive disorder (MDD) expected in the first half of 2027 [4][5] - The X-TOLE2 study has completed enrollment with 380 patients, and the data collected will support the upcoming topline readout [5] Broader Pipeline Opportunity - Azetukalner is a novel KV7 potassium channel opener, currently in late-stage clinical trials for epilepsy, MDD, and bipolar depression (BPD), representing a significant advancement in treatment options [7][10] - The company is also developing early-stage candidates targeting NaV1.7 and KV7 for pain management, with preliminary Phase 1 data expected in 2026 to support Phase 2 studies [11][12] About Epilepsy and Focal Onset Seizures - Epilepsy affects approximately 3 million adults in the U.S., with focal onset seizures being a common form that presents a substantial unmet medical need due to the inadequacy of existing treatments for many patients [9]