Xenon Pharmaceuticals Conference Call Summary Company Overview - **Company**: Xenon Pharmaceuticals (NasdaqGM:XENE) - **Focus**: Development of innovative therapies for epilepsy, psychiatry, and pain management Key Themes Discussed 1. **Lead Program - Azetukalner in Epilepsy** - Near-term phase 3 data expected in early 2026 from the fully enrolled EXTOL-two program [2][4] - Positive phase 2b data showing best efficacy in focal onset seizure studies with a severe patient population [6][7] - High confidence in phase 3 readout due to consistent inclusion-exclusion criteria and experienced clinical sites [10][11] 2. **Expansion into Psychiatry** - Ongoing phase 3 trials for major depressive disorder (MDD) and recently initiated trials for bipolar depression [2][3] - Phase 2 proof of concept study (ExNOVA) showed clear separation between active and placebo with a three-point difference on clinical scales [25][26] 3. **Emerging Early-Stage Portfolio in Pain** - Two phase 1 assets targeting NaV1.7 and Kv7, with plans to advance to phase 2 proof of concept studies in 2026 [3][50] - NaV1.7 target based on genetic studies showing patients with loss of function do not feel pain [36][37] Important Data and Insights - **Azetukalner Efficacy**: Placebo-adjusted efficacy in phase 2b ranged from teens to low 30s in monthly seizure reduction [9] - **Commercial Strategy**: Engaging with the epilepsy community and preparing for a successful launch with a Chief Commercial Officer and medical science liaisons in place [14][16] - **Market Opportunity**: Approximately 1 million patients in the U.S. with focal onset seizures are not achieving good seizure control [18] Competitive Landscape - **Market Dynamics**: Acknowledgment of multiple existing drugs in the focal onset seizure market, but belief in the unique profile of Azetukalner to differentiate from competitors [34][35] - **Regulatory Path**: Plans to file NDA next year, with Exfil and Exfil II studies included in the filing package [12][13] Pipeline Developments 1. **NaV1.7 and Kv7 Programs** - NaV1.7 in phase I study with a focus on achieving high receptor occupancy and safety [39][40] - Kv7 program showing potential analgesic effects similar to opioids [50] 2. **NaV1.1 for Dravet Syndrome** - Development of an oral small molecule to potentiate NaV1.1 channels, aiming to protect against seizures and improve survival in animal models [51][53] - Plans to initiate human clinical trials next year [54] Financial Position - **Cash Reserves**: Over $500 million in cash at the end of the last quarter, expected to sustain operations into 2027 [55]

Financial Data and Key Metrics Changes - Cash, cash equivalents, and marketable securities totaled $555.3 million as of September 30, 2025, down from $754.4 million as of December 31, 2024 [31][32] - The company anticipates having sufficient cash to fund operations into 2027 based on current operating plans [31][32] Business Line Data and Key Metrics Changes - The phase 3 XTOL-2 study of Ezetikelner for focal onset seizures has randomized 380 patients, exceeding the original goal of 360 [6][14] - The company is focused on completing the XTOL-2 study to deliver top-line data in early 2026 [14][33] Market Data and Key Metrics Changes - The company is expanding Ezetikelner's therapeutic opportunities beyond epilepsy into neuropsychiatric indications, including major depressive disorder and bipolar depression [5][20] - The XCEED trial for bipolar I and II depression is underway, with a primary efficacy endpoint based on the change from baseline in the MADRS score [21] Company Strategy and Development Direction - The company aims to file its first NDA for Ezetikelner in the U.S. following positive top-line data from the XTOL-2 study [5][33] - There is a strong focus on advancing earlier stage programs, including Nav1.7 and KV7 ion channel programs, which are now in phase 1 studies [22][24] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism for a positive outcome from the XTOL-2 study, which they believe will support the NDA submission for Ezetikelner [10][12] - The company is preparing for commercialization and anticipates a significant increase in operational expenses in 2026 as they prepare for a potential launch in 2027 [57] Other Important Information - The company has made targeted investments to prepare for commercialization and has a healthy balance sheet to support multiple registration programs [31][57] - The new Chief Financial Officer, Tucker Kelly, brings extensive experience in corporate strategy and financial planning, which will be valuable for the company's future growth [29][30] Q&A Session Summary Question: What should be expected in the top-line data release regarding efficacy and safety? - Management indicated that the top-line data will include key efficacy endpoints and overall comments on safety and tolerability, similar to previous releases [36][37] Question: What was the screen failure rate for XTOL-2? - Management stated that the screen failure rate trended as expected, with reasons for dropouts being consistent with prior experiences [38][39] Question: How does the efficacy of Ezetikelner compare to other therapies? - Management emphasized that while efficacy is important, the overall profile, including tolerability and ease of use, will drive prescribing decisions [42][43] Question: What is the rationale for using MADRS in the XCEED trial? - The decision to use MADRS was based on precedents in bipolar studies, as it has been commonly used for assessing depressive symptoms in this population [47][48] Question: What are the expectations for the early-stage pipeline? - Management expects to provide updates on the phase 1 studies for XEN1701 and XEN1120 in early 2026, with a focus on safety and tolerability [52][53]

Financial Performance - For the nine months ended September 30, 2025, the company recognized revenue of $7.5 million, compared to nil for the same period in 2024[57]. - The company incurred a net loss of $240.6 million for the nine months ended September 30, 2025, compared to a net loss of $168.6 million for the same period in 2024[58]. - As of September 30, 2025, the company had an accumulated deficit of $1,140.1 million[58]. - Collaboration revenue for the nine months ended September 30, 2025, was $7.5 million, a significant increase from $0 in the same period in 2024[77]. - Net cash used in operating activities was $197.6 million for the nine months ended September 30, 2025, compared to $127.0 million for the same period in 2024, reflecting increased expenses[88]. - For the nine months ended September 30, 2025, net cash provided by financing activities was $3.6 million, compared to nil for the same period in 2024[91]. Research and Development - The Phase 3 X-TOLE2 study of azetukalner in focal onset seizures has completed patient enrollment with 380 patients randomized, with topline data anticipated in early 2026[56]. - The company is advancing azetukalner for multiple indications, including major depressive disorder and bipolar depression, with ongoing Phase 3 studies[56]. - A Phase 1 study for NBI-921355, a selective inhibitor of voltage-gated sodium channels, is underway as part of a collaboration with Neurocrine Biosciences[57]. - The company expects research and development expenses to increase substantially as it continues to invest in product candidates and clinical studies[66]. - Direct external costs related to azetukalner increased by $13.1 million (44.3%) for the three months and $41.5 million (54.5%) for the nine months ended September 30, 2025, compared to the same periods in 2024[78]. - The company expects to incur significant expenses and increasing operating losses for the foreseeable future as it prepares for the potential commercial launch of azetukalner[84]. Expenses - Research and development expenses increased by $20.1 million (35.2%) for the three months and $62.3 million (41.3%) for the nine months ended September 30, 2025, compared to the same periods in 2024[78]. - General and administrative expenses rose by $2.6 million (15.4%) for the three months and $6.7 million (13.1%) for the nine months ended September 30, 2025, compared to the same periods in 2024[79]. - The company anticipates an increase in general and administrative expenses as it expands its operating activities and prepares for commercialization[69]. Cash and Securities - As of September 30, 2025, the company had cash and cash equivalents and marketable securities of $555.3 million[81]. - As of September 30, 2025, the company had U.S. dollar denominated cash and cash equivalents and marketable securities of $497.3 million and Canadian dollar denominated cash and cash equivalents and marketable securities of CAD$79.6 million[95]. - A 100 basis point increase in interest rates would have resulted in approximately a $2.7 million decrease in the fair value of the company's marketable securities as of September 30, 2025[98]. Foreign Currency Risk - The company is exposed to foreign currency exchange rate risk, particularly with transactions denominated in Canadian dollars[96]. - The company does not currently hedge its exposure to foreign currency exchange rates, assuming the risk of future gains or losses[97]. Strategic Focus - The company is focused on maintaining existing collaborations and establishing new ones, which may generate milestone payments and royalties[90]. - The company is expanding its research and development and initiating pre-commercial and commercial activities, which will impact headcount growth and associated costs[90]. - The company plans to prepare for the potential commercial launch of azetukalner and invest significantly in its development[63]. Other Information - There have been no material changes in the company's significant contractual obligations as of September 30, 2025, compared to those disclosed in the Annual Report on Form 10-K[92]. - As of October 30, 2025, the company had 77,275,005 common shares issued and outstanding, along with various outstanding warrants and stock options[93].

Financial Performance - Cash, cash equivalents, and marketable securities were $555.3 million as of September 30, 2025, down from $754.4 million as of December 31, 2024[13] - Net loss for Q3 2025 was $90.9 million, compared to a net loss of $62.8 million for the same period in 2024[18] - Revenue for the nine months ended September 30, 2025, was $7,500,000, compared to $0 for the same period in 2024[24] - Net loss for the nine months ended September 30, 2025, was $240,649,000, compared to a net loss of $168,645,000 in 2024, indicating a 42.7% increase in losses[24] - Basic and diluted net loss per common share for the nine months ended September 30, 2025, was $(3.05), compared to $(2.17) for the same period in 2024[24] - Comprehensive loss for the nine months ended September 30, 2025, was $238,560,000, compared to $167,232,000 in 2024, representing a 42.6% increase[24] Expenses - Research and development expenses for Q3 2025 were $77.1 million, an increase of $20.1 million compared to $57.0 million in Q3 2024[13] - General and administrative expenses for Q3 2025 were $19.3 million, up from $16.7 million in Q3 2024, reflecting an increase of $2.6 million[18] - Research and development expenses increased to $213,239,000 for the nine months ended September 30, 2025, up from $150,922,000 in 2024, representing a 41.4% increase[24] - General and administrative expenses rose to $57,564,000 for the nine months ended September 30, 2025, compared to $50,899,000 in 2024, a 13.1% increase[24] - Total operating expenses for the nine months ended September 30, 2025, were $270,803,000, up from $201,821,000 in 2024, reflecting a 34.2% increase[24] Clinical Development - The Phase 3 X-TOLE2 study of azetukalner in focal onset seizures has completed patient enrollment with 380 patients randomized, with topline data expected in early 2026[7] - The company is conducting three Phase 3 clinical studies evaluating azetukalner for major depressive disorder, with approximately 450 patients per study[12] - The Phase 1 studies for Nav1.7 and Kv7 pain programs are currently underway, focusing on developing non-opioid treatments for pain[12] Cash Flow and Financial Strategy - Xenon anticipates having sufficient cash to fund operations into 2027 based on current operating plans[13] - Other income for Q3 2025 was $6.1 million, down from $10.6 million in Q3 2024, primarily due to lower interest income[18] - Other income for the nine months ended September 30, 2025, was $23,132,000, down from $32,935,000 in 2024, a decrease of 29.6%[24] - Other comprehensive income included an unrealized gain on available-for-sale securities of $2,089,000 for the nine months ended September 30, 2025, compared to $1,413,000 in 2024[24] Leadership Changes - The company appointed Tucker Kelly as Chief Financial Officer to lead finance strategy ahead of the anticipated commercialization of azetukalner[10]

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]

Company Overview - Xenon Pharmaceuticals Inc. is a neuroscience-focused biopharmaceutical company dedicated to drug discovery, clinical development, and commercialization of therapeutics for patients in need [3] - The company is advancing its lead molecule, azetukalner, which is a selective Kv7 potassium channel opener currently in Phase 3 clinical trials for epilepsy, major depressive disorder (MDD), and bipolar depression (BPD) [3] - Additionally, Xenon is developing an early-stage portfolio of potassium and sodium channel modulators, including Kv7 and Nav1.7 programs in Phase 1 development for pain treatment [3] Upcoming Financial Results - Xenon Pharmaceuticals will report its third quarter 2025 financial results and provide a business update after the close of U.S. financial markets on November 3, 2025 [1] - A conference call and webcast will take place on the same day at 4:30 pm Eastern Time (1:30 pm Pacific Time) [2] Contact Information - Colleen Alabiso is the Senior Vice President of Corporate Affairs, and can be reached at (617) 671-9238 [5] - Media inquiries can be directed to media@xenon-pharma.com, while investor inquiries can be sent to investors@xenon-pharma.com [5]

Core Insights - Xenon Pharmaceuticals Inc. has appointed Tucker Kelly as Chief Financial Officer, bringing extensive strategic and commercial finance expertise to the company as it prepares for the commercialization of its lead candidate, azetukalner [1][2] Company Overview - Xenon Pharmaceuticals is a neuroscience-focused biopharmaceutical company dedicated to drug discovery, clinical development, and commercialization of therapeutics for patients in need [4] - The company is advancing azetukalner, a selective Kv7 potassium channel opener, currently in Phase 3 clinical trials for epilepsy, major depressive disorder, and bipolar depression [5] Leadership Appointment - Tucker Kelly has over 25 years of experience in corporate and financial strategy for life sciences companies, previously serving as Executive Vice President, CFO, and Treasurer at Deciphera Pharmaceuticals [2] - His role at Deciphera included overseeing the company's growth and strategic financial planning, culminating in a $2.4 billion acquisition by Ono Pharmaceuticals in 2024 [2] Compensation Details - In connection with his appointment, Mr. Kelly was granted an option to purchase 225,000 common shares at an exercise price of $41.90, with shares vesting over four years [3] - Additionally, he received 30,000 restricted share units (RSUs) that will vest over four years, subject to his continued service with the company [3]

Core Viewpoint - The investor webinar focuses on Xenon Pharmaceuticals' Kv7 and Nav1.7 programs aimed at pain treatment, highlighting the company's leadership in ion channel drug development [1][4]. Company Overview - Ian Mortimer serves as the President and CEO of Xenon Pharmaceuticals and is moderating the session [1]. - The company has a strong pipeline and a history of positioning itself as a leader in ion channel drug development [4]. Key Personnel - Dr. Jim Empfield, Executive Vice President of Drug Discovery, will discuss Xenon's history and its advancements in drug development [3][4]. - Dr. JP Gilbert, Senior Director of Biology, and Dr. Chris Kenney, Chief Medical Officer, are also part of the speaking team [3].

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 - Xenon Pharmaceuticals Inc. is hosting an investor webinar on October 6, 2025, to discuss its early-stage programs targeting Kv7 and Nav1.7 as potential non-opioid treatments for pain [1][2]. Company Overview - Xenon Pharmaceuticals is a neuroscience-focused biopharmaceutical company engaged in drug discovery, clinical development, and commercialization of therapeutics for patients in need [4]. - The company's lead molecule, azetukalner, is a selective Kv7 potassium channel opener currently in Phase 3 clinical trials for epilepsy, major depressive disorder (MDD), and bipolar depression (BPD) [4]. - Xenon is also advancing a portfolio of potassium and sodium channel modulators, including Kv7 and Nav1.7 programs in Phase 1 development for pain treatment [4]. Webinar Details - The webinar will take place from 11:30 AM to 12:30 PM Eastern Time, and participants can submit questions via chat or email [2]. - A live webcast will be available on the "Investors" section of Xenon's website, with a replay posted after the event [3].