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]

Core Insights - Xenon Pharmaceuticals is entering a significant period with multiple clinical catalysts, including the completion of patient randomization in the Phase 3 X-TOLE2 study of azetukalner, with topline data expected in early 2026 [1][2] - The company has appointed Tucker Kelly as Chief Financial Officer to enhance its strategic finance capabilities ahead of the azetukalner launch [1][9] - Financial results for Q3 2025 show a net loss of $90.9 million, an increase from $62.8 million in Q3 2024, primarily due to higher research and development expenses [13][23] Clinical Development - The Phase 3 X-TOLE2 study of azetukalner in focal onset seizures (FOS) has completed patient enrollment with 380 patients randomized, and topline data is anticipated in early 2026 [7][14] - Ongoing Phase 3 studies include X-NOVA2 and X-NOVA3 for major depressive disorder (MDD) and X-CEED for bipolar depression (BPD), with recruitment continuing [6][16] - Azetukalner is a selective Kv7 potassium channel opener, currently in late-stage clinical development for epilepsy and neuropsychiatric disorders [3][17] Financial Overview - As of September 30, 2025, the company reported cash, cash equivalents, and marketable securities totaling $555.3 million, down from $754.4 million at the end of 2024 [13] - Research and development expenses for Q3 2025 were $77.1 million, compared to $57.0 million in Q3 2024, reflecting increased costs associated with ongoing clinical studies [13][23] - General and administrative expenses rose to $19.3 million in Q3 2025 from $16.7 million in Q3 2024, primarily due to higher professional and consulting fees [13][23] Pipeline and Future Plans - The company is advancing its early-stage pipeline, including two first-in-human Phase 1 studies for lead molecules targeting Nav1.7 and Kv7 for pain management [5][12] - A Phase 1 study for NBI-921355, a sodium channel inhibitor in collaboration with Neurocrine Biosciences, is also underway [8] - Xenon plans to present new long-term safety and efficacy data at the upcoming American Epilepsy Society meeting in December 2025 [7]

Xenon Pharmaceuticals Conference Call Summary Company Overview - **Company**: Xenon Pharmaceuticals (NasdaqGM:XENE) - **Focus**: Neuroscience-focused biopharmaceutical company specializing in small molecule ion channel drug discovery and development [3][4][6] Key Points Pipeline and Development - **Lead Molecule**: Azetucaner, a KV7 channel opener, is in phase III development for epilepsy and depression, representing the most advanced potassium channel modulator in late-stage clinical development [3][4][8] - **Indications**: Azetucaner is being developed for four distinct indications: focal onset seizures, primary generalized tonic-clonic seizures, major depressive disorder, and bipolar depression [4] - **Early-Stage Pipeline**: The company is advancing a robust early-stage pipeline targeting both potassium and sodium channels, particularly KV7 and NAV1.7 for pain management [5][11] Pain Management Focus - **Pain Programs**: Xenon is focusing on developing KV7 potentiators and NAV1.7 inhibitors as non-opioid approaches for pain treatment [5][24] - **Clinical Trials**: Both lead compounds, XEN1120 (KV7) and XEN1701 (NAV1.7), are currently in phase I clinical studies [59][54] Scientific Insights - **Pain Signaling Pathway**: Pain signals originate in tissues and travel through dorsal root ganglion neurons to the spinal cord, where they are processed and relayed to the brain [16][17] - **Mechanism of Action**: KV7 channels regulate neuronal excitability, while NAV1.7 channels are critical for action potential initiation. Modulating these channels could significantly impact pain signaling [18][20][24] Genetic Validation - **NAV1.7 Target**: Loss of function mutations in the SCN9A gene (encoding NAV1.7) lead to congenital insensitivity to pain, validating NAV1.7 as a compelling target for pain treatment [33][53] - **Receptor Occupancy**: Recent findings suggest that 75% to 85% receptor occupancy of NAV1.7 is sufficient for pain relief, contrasting with previous beliefs that near 100% was necessary [38][64] Competitive Landscape - **Current Pain Treatments**: Existing options like NSAIDs and opioids have significant limitations, including risks of addiction and poor tolerability. There is a strong demand for non-opioid alternatives [57][60] - **Physician Insights**: Clinicians express a desire for mechanism-based innovations that can provide effective pain relief without the risks associated with current treatments [58][59] Future Plans - **Clinical Development**: Plans to initiate phase II proof-of-concept studies for both lead compounds next year [59] - **Ongoing Research**: Continued exploration of additional KV7 and NAV1.7 compounds to expand the pipeline and address various pain conditions [59][54] Additional Important Insights - **Collaboration and Expertise**: Xenon has established collaborations with major biopharmaceutical companies and has built a strong internal team focused on ion channel drug discovery [8][10] - **Preclinical Data**: Promising preclinical data supports the efficacy of KV7 openers in both acute and chronic pain models, indicating potential for significant therapeutic impact [30][31] This summary encapsulates the key points discussed during the conference call, highlighting Xenon Pharmaceuticals' strategic focus on pain management through innovative ion channel modulation.

Core Insights - Completion of patient recruitment for Phase 3 X-TOLE2 study of azetukalner marks a significant milestone, with topline data expected in early 2026, indicating potential for the first commercial product for the company [1][2] - The company is advancing multiple Phase 3 programs for azetukalner in neuropsychiatric disorders, including major depressive disorder (MDD) and bipolar depression (BPD) [2][3] - The company appointed Darren Cline as Chief Commercial Officer to lead the commercial strategy for the anticipated launch of azetukalner [1][9] Clinical Development - Azetukalner is a selective Kv7 potassium channel opener, currently in late-stage clinical development for epilepsy and neuropsychiatric disorders [3][18] - The Phase 3 X-TOLE2 study for focal onset seizures (FOS) has completed patient recruitment, while X-CEED for BPD has recently been initiated [6][17] - Ongoing Phase 1 studies for Nav1.7 and Kv7 candidates are targeting pain management, with the potential for broader therapeutic applications [13][18] Financial Performance - As of June 30, 2025, the company reported cash and cash equivalents of $624.8 million, down from $754.4 million at the end of 2024, indicating a need for careful cash management as clinical trials progress [14] - Research and development expenses for Q2 2025 were $75.0 million, an increase from $49.7 million in Q2 2024, primarily due to ongoing clinical trials for azetukalner [14][23] - The net loss for Q2 2025 was $84.7 million, compared to $57.9 million in the same period of 2024, reflecting increased operational costs associated with clinical development [14][23] Upcoming Milestones - The company anticipates topline results from the Phase 3 X-TOLE2 study in early 2026, which could lead to regulatory submissions and potential product approval [2][6] - Multiple abstracts related to the company's epilepsy programs have been accepted for presentation at the 36th International Epilepsy Congress in late August 2025 [6] - The company plans to host R&D webinars focusing on early-stage pipeline programs, with the first scheduled for October 2, 2025 [13]

Core Viewpoint - Xenon Pharmaceuticals reported a narrower loss per share in Q1 2025 compared to estimates, while also generating modest revenue from collaborations, indicating ongoing development in its pipeline despite financial challenges [1][2]. Financial Performance - The company reported a loss of 83 cents per share for Q1 2025, which is an improvement from the loss of 94 cents estimated by Zacks and a loss of 62 cents in the same quarter last year [1]. - Revenues for the first quarter were $7.5 million, slightly below the Zacks Consensus Estimate of $8 million, with no revenues reported in the year-ago quarter [2]. - Research and development (R&D) expenses increased by 38.1% year over year to $61.2 million, primarily due to costs associated with late-stage epilepsy studies and the initiation of a phase III study for major depressive disorder (MDD) [4]. - General and administrative expenses rose to $19 million, up 28.4% year over year, attributed to increased personnel-related costs [5]. - As of March 31, 2025, the company had cash, cash equivalents, and marketable securities totaling $691.1 million, down from $754.4 million at the end of 2024, which is expected to fund ongoing clinical developments through 2027 [6]. Pipeline Developments - Xenon's lead candidate, azetukalner, is undergoing late-stage studies for focal onset seizures (FOS), with two phase III studies (X-TOLE2 and X-TOLE3) evaluating different doses [8]. - The first top-line data readout from the X-TOLE2 study is now anticipated in early 2026, delayed from the previously expected second half of 2025 [8]. - The company is also evaluating azetukalner for primary generalized tonic-clonic seizures in a phase III study and has initiated a phase III study for MDD following a successful phase II study [9]. - Plans for a late-stage bipolar depression program are set to begin by mid-2025, addressing significant unmet medical needs [10]. - The company is advancing multiple preclinical candidates targeting various indications, with plans to file an investigational new drug application for its Nav1.7 candidate, XEN1701, in Q3 2025 [11].