[PART I. FINANCIAL INFORMATION](index=3&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) This section provides Xenon Pharmaceuticals Inc.'s unaudited condensed consolidated financial statements and related notes for the periods ended June 30, 2025, and December 31, 2024 [Item 1. Financial Statements](index=3&type=section&id=Item%201.%20Financial%20Statements) This section presents Xenon Pharmaceuticals Inc.'s unaudited condensed consolidated financial statements and detailed notes for the periods ended June 30, 2025, and December 31, 2024 [Condensed Consolidated Balance Sheets](index=3&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This section presents the company's condensed consolidated balance sheets, detailing assets, liabilities, and shareholders' equity as of June 30, 2025, and December 31, 2024 | Metric | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | Change (in thousands) | | :-------------------------------- | :----------------------------- | :------------------------------- | :-------------------- | | Total Assets | $674,281 | $798,139 | $(123,858) | | Total Liabilities | $40,303 | $43,236 | $(2,933) | | Total Shareholders' Equity | $633,978 | $754,903 | $(120,925) | | Cash and cash equivalents | $135,381 | $142,712 | $(7,331) | | Marketable securities (current) | $352,164 | $484,193 | $(132,029) | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=4&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) This section presents the company's condensed consolidated statements of operations and comprehensive loss for the three and six months ended June 30, 2025, and 2024 | Metric | Three Months Ended June 30, 2025 (in thousands) | Three Months Ended June 30, 2024 (in thousands) | Change (in thousands) | | :------------------------------------ | :-------------------------------------------- | :-------------------------------------------- | :-------------------- | | Collaboration revenue | $— | $— | $— | | Research and development | $74,985 | $49,702 | $25,283 | | General and administrative | $19,244 | $19,402 | $(158) | | Net loss | $(84,706) | $(57,924) | $(26,782) | | Net loss per common share (Basic and diluted) | $(1.07) | $(0.75) | $(0.32) | | Metric | Six Months Ended June 30, 2025 (in thousands) | Six Months Ended June 30, 2024 (in thousands) | Change (in thousands) | | :------------------------------------ | :------------------------------------------ | :------------------------------------------ | :-------------------- | | Collaboration revenue | $7,500 | $— | $7,500 | | Research and development | $136,185 | $93,952 | $42,233 | | General and administrative | $38,282 | $34,193 | $4,089 | | Net loss | $(149,753) | $(105,855) | $(43,898) | | Net loss per common share (Basic and diluted) | $(1.90) | $(1.36) | $(0.54) | [Condensed Consolidated Statements of Shareholders' Equity](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Shareholders%27%20Equity) This section presents the company's condensed consolidated statements of shareholders' equity for the six months ended June 30, 2025, and 2024 | Metric | December 31, 2024 (in thousands) | June 30, 2025 (in thousands) | | :-------------------------- | :------------------------------- | :--------------------------- | | Common shares | $1,456,836 | $1,469,196 | | Additional paid-in capital | $199,149 | $213,892 | | Accumulated deficit | $(899,470) | $(1,049,223) | | Other comprehensive income | $(1,612) | $113 | | Total shareholders' equity | $754,903 | $633,978 | - Net loss for the six months ended June 30, 2025, was **$(149.8) million**, contributing to the accumulated deficit[14](index=14&type=chunk) - Stock-based compensation expense for the six months ended June 30, 2025, was **$25.9 million**[14](index=14&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) This section presents the company's condensed consolidated statements of cash flows for the six months ended June 30, 2025, and 2024 | Cash Flow Activity | Six Months Ended June 30, 2025 (in thousands) | Six Months Ended June 30, 2024 (in thousands) | Change (in thousands) | | :-------------------------------- | :------------------------------------------ | :------------------------------------------ | :-------------------- | | Net cash used in operating activities | $(125,885) | $(77,339) | $(48,546) | | Net cash provided by investing activities | $116,770 | $65,999 | $50,771 | | Net cash provided by financing activities | $1,216 | $— | $1,216 | | Decrease in cash and cash equivalents | $(7,331) | $(11,909) | $4,578 | | Cash and cash equivalents, end of period | $135,381 | $136,734 | $(1,353) | [Notes to Condensed Consolidated Financial Statements](index=8&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) This section provides detailed notes explaining the company's financial position, performance, and accounting policies - Xenon Pharmaceuticals Inc. is a neuroscience-focused biopharmaceutical company dedicated to drug discovery, clinical development, and commercialization of therapeutics[16](index=16&type=chunk) - The company had an accumulated deficit of **$1,049.2 million** and a net loss of **$149.8 million** for the six months ended June 30, 2025[17](index=17&type=chunk) - Cash, cash equivalents, and marketable securities totaled **$624.8 million** as of June 30, 2025, expected to fund current operations for at least the next 12 months[19](index=19&type=chunk) - A prior period error was corrected, reclassifying **$1.5 million** of accretion of discounts on marketable securities from investing to operating activities for the six months ended June 30, 2024[23](index=23&type=chunk) - The company recognized **$7.5 million** in collaboration revenue for the six months ended June 30, 2025, due to a milestone payment from Neurocrine Biosciences for NBI-921355 entering a Phase 1 study[39](index=39&type=chunk) - As of June 30, 2025, the unrecognized stock-based compensation expense related to unvested stock options was **$115.3 million**, expected to be recognized over 2.8 years[35](index=35&type=chunk) - Future potential regulatory milestone payments to 1st Order Pharmaceuticals for azetukalner could be up to **$6.0 million**[42](index=42&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=17&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses Xenon Pharmaceuticals Inc.'s financial condition, results of operations, liquidity, and capital resources, highlighting operating losses and R&D investments [Overview](index=18&type=section&id=Overview) This section provides a strategic overview of Xenon Pharmaceuticals Inc.'s neuroscience-focused biopharmaceutical pipeline and clinical development programs - Xenon Pharmaceuticals Inc. is a neuroscience-focused biopharmaceutical company advancing an ion channel product portfolio for epilepsy and depression[51](index=51&type=chunk) - Azetukalner, a Kv7 potassium channel opener, is in late-stage clinical development for multiple indications including focal onset seizures (FOS), primary generalized tonic-clonic seizures (PGTCS), major depressive disorder (MDD), and bipolar depression (BPD)[52](index=52&type=chunk) - Phase 3 X-TOLE2 clinical study of azetukalner in FOS has completed patient recruitment, with topline data anticipated in early 2026 - Phase 3 X-NOVA2 and X-NOVA3 clinical trials evaluating azetukalner in MDD are underway and screening patients - Phase 3 X-CEED clinical study evaluating azetukalner in BPD I and BPD II depression has been initiated - A Phase 1 study is underway for NBI-921355, a selective Nav1.2 and Nav1.6 inhibitor, as part of the collaboration with Neurocrine Biosciences for epilepsy[55](index=55&type=chunk)[56](index=56&type=chunk) - Early-stage pipeline includes XEN1120 (Kv7 channel opener for pain) in Phase 1, XEN1701 (Nav1.7 development candidate for pain) in Phase 1, and a Nav1.1 lead candidate expected to enter IND-enabling studies in 2025 for Dravet Syndrome[60](index=60&type=chunk) [Financial Operations Overview](index=19&type=section&id=Financial%20Operations%20Overview) This section summarizes Xenon Pharmaceuticals Inc.'s financial performance, including revenue sources, net losses, and expected increases in operating expenses - Revenue is primarily derived from collaboration and licensing agreements; no product sales have been generated to date[58](index=58&type=chunk) - The company incurred net losses of **$149.8 million** for the six months ended June 30, 2025, and had an accumulated deficit of **$1,049.2 million**[57](index=57&type=chunk) - Operating expenses are expected to increase substantially due to continued investment in R&D, clinical trials, regulatory approvals, manufacturing, and preparations for potential commercial launch of azetukalner[61](index=61&type=chunk)[65](index=65&type=chunk)[68](index=68&type=chunk) - Collaboration revenue of **$7.5 million** was recognized for the six months ended June 30, 2025, from a milestone payment related to NBI-921355's progression into a Phase 1 clinical study[56](index=56&type=chunk)[62](index=62&type=chunk) [Critical Accounting Policies and Significant Judgments and Estimates](index=23&type=section&id=Critical%20Accounting%20Policies%20and%20Significant%20Judgments%20and%20Estimates) This section outlines the critical accounting policies and significant judgments and estimates used in preparing the financial statements - The condensed consolidated financial statements are prepared in conformity with GAAP, requiring significant estimates and assumptions[72](index=72&type=chunk) - Critical accounting policies include revenue recognition, research and development costs, and stock-based compensation[73](index=73&type=chunk) - No material changes in critical accounting policies and significant judgments and estimates occurred during the six months ended June 30, 2025[74](index=74&type=chunk) [Results of Operations](index=23&type=section&id=Results%20of%20Operations) This section details the company's financial results for the three and six months ended June 30, 2025, and 2024, including revenue, expenses, and net loss | Metric | Three Months Ended June 30, 2025 (in thousands) | Three Months Ended June 30, 2024 (in thousands) | Change (in thousands) | | :-------------------------------- | :-------------------------------------------- | :-------------------------------------------- | :-------------------- | | Collaboration revenue | $— | $— | $— | | Research and development expenses | $74,985 | $49,702 | $25,283 | | General and administrative expenses | $19,244 | $19,402 | $(158) | | Interest income | $7,199 | $10,837 | $(3,638) | | Foreign exchange gain | $1,698 | $10 | $1,688 | | Loss before income taxes | $(85,332) | $(58,257) | $(27,075) | | Metric | Six Months Ended June 30, 2025 (in thousands) | Six Months Ended June 30, 2024 (in thousands) | Change (in thousands) | | :-------------------------------- | :------------------------------------------ | :------------------------------------------ | :-------------------- | | Collaboration revenue | $7,500 | $— | $7,500 | | Research and development expenses | $136,185 | $93,952 | $42,233 | | General and administrative expenses | $38,282 | $34,193 | $4,089 | | Interest income | $15,282 | $22,192 | $(6,910) | | Foreign exchange gain | $1,733 | $177 | $1,556 | | Loss before income taxes | $(149,952) | $(105,776) | $(44,176) | - Direct external costs for azetukalner increased by **$28.3 million** for the six months ended June 30, 2025, driven by ongoing Phase 3 clinical trials in epilepsy and MDD, and start-up costs for the Phase 3 BPD program[77](index=77&type=chunk) - Personnel-related R&D costs increased by **$12.8 million** for the six months ended June 30, 2025, due to higher headcount supporting late-stage development[77](index=77&type=chunk) - Interest income decreased by **$6.9 million** for the six months ended June 30, 2025, due to a lower average balance of marketable securities and lower average market yields[80](index=80&type=chunk) - Foreign exchange gains increased by **$1.6 million** for the six months ended June 30, 2025, due to Canadian dollar fluctuations and higher Canadian dollar cash balances[80](index=80&type=chunk) [Liquidity and Capital Resources](index=26&type=section&id=Liquidity%20and%20Capital%20Resources) This section discusses the company's cash position, cash flow activities, and capital resources, assessing its ability to fund future operations - As of June 30, 2025, the company had **$624.8 million** in cash, cash equivalents, and marketable securities, which are expected to fund operating expenses and capital expenditure requirements for at least the next 12 months[81](index=81&type=chunk)[86](index=86&type=chunk) - Net cash used in operating activities increased to **$125.9 million** for the six months ended June 30, 2025, from **$77.3 million** in the prior year, primarily due to higher R&D and G&A expenses[88](index=88&type=chunk) - Net cash provided by investing activities increased to **$116.8 million** for the six months ended June 30, 2025, from **$66.0 million** in the prior year, mainly due to a decrease in net purchases of marketable securities[89](index=89&type=chunk) - Net cash provided by financing activities was **$1.2 million** for the six months ended June 30, 2025, primarily from stock option exercises[90](index=90&type=chunk) - As of August 7, 2025, the company had **77,105,799 common shares outstanding**, along with **over 14 million potentially dilutive securities**[93](index=93&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=29&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) This section details Xenon Pharmaceuticals Inc.'s exposure to market risks, including foreign currency and interest rate sensitivity, and their potential financial impact [Foreign currency risk](index=29&type=section&id=Foreign%20currency%20risk) This section describes the company's exposure to foreign currency exchange rate fluctuations, particularly with Canadian dollars - The company is exposed to foreign currency exchange rate risk, particularly with Canadian dollars, as it holds CAD-denominated assets and incurs significant expenses in CAD[95](index=95&type=chunk)[96](index=96&type=chunk) - As of June 30, 2025, the company held **CAD$84.1 million** in Canadian dollar denominated cash and cash equivalents and marketable securities[95](index=95&type=chunk) - The company does not currently hedge its foreign currency exposure and does not believe a **10% increase or decrease** in the U.S. dollar's value relative to the Canadian dollar would materially affect operating results[97](index=97&type=chunk) [Interest rate sensitivity](index=29&type=section&id=Interest%20rate%20sensitivity) This section assesses the company's interest rate sensitivity, primarily related to its cash, cash equivalents, and marketable securities - Interest rate sensitivity is primarily attributable to the company's **$624.8 million** in cash, cash equivalents, and marketable securities as of June 30, 2025[98](index=98&type=chunk) - A **100 basis point (1%) increase** in interest rates would result in an approximate **$3.3 million decrease** in the fair value of marketable securities[98](index=98&type=chunk) - The company does not use derivative financial instruments to manage interest rate exposure[98](index=98&type=chunk) [Item 4. Controls and Procedures](index=29&type=section&id=Item%204.%20Controls%20and%20Procedures) This section evaluates Xenon Pharmaceuticals Inc.'s disclosure controls and procedures, confirming their effectiveness and reporting no material changes in internal control [Evaluation of disclosure controls and procedures](index=29&type=section&id=Evaluation%20of%20disclosure%20controls%20and%20procedures) This section details the management's evaluation and conclusion on the effectiveness of disclosure controls and procedures - Management, including the CEO and CFO, concluded that disclosure controls and procedures were **effective**, in design and operation, at the reasonable assurance level as of June 30, 2025[99](index=99&type=chunk) [Changes in internal control over financial reporting](index=29&type=section&id=Changes%20in%20internal%20control%20over%20financial%20reporting) This section reports on any material changes in internal control over financial reporting during the period - There were **no material changes** in internal control over financial reporting during the period ended June 30, 2025[100](index=100&type=chunk) [Inherent limitation on the effectiveness of internal control](index=29&type=section&id=Inherent%20limitation%20on%20the%20effectiveness%20of%20internal%20control) This section acknowledges the inherent limitations on the effectiveness of any internal control system - The effectiveness of any internal control system is subject to inherent limitations and can only provide reasonable, not absolute, assurances[101](index=101&type=chunk) [PART II. OTHER INFORMATION](index=30&type=section&id=PART%20II.%20OTHER%20INFORMATION) This section provides additional information, including legal proceedings, risk factors, other disclosures, and exhibits [Item 1. Legal Proceedings](index=30&type=section&id=Item%201.%20Legal%20Proceedings) This section confirms Xenon Pharmaceuticals Inc. is not currently involved in legal proceedings expected to materially adversely affect its business or financial condition - The company is not presently a party to any legal proceedings that are reasonably expected to have a **material adverse effect** on its business, financial condition, operating results, or cash flows[102](index=102&type=chunk) - Litigation, regardless of outcome, can adversely impact the company due to defense and settlement costs, and diversion of management resources[102](index=102&type=chunk) [Item 1A. Risk Factors](index=30&type=section&id=Item%201A.%20Risk%20Factors) This section details significant risks and uncertainties that could materially harm Xenon Pharmaceuticals Inc.'s business, financial condition, and operating results [Risks Related to Our Financial Condition and Capital Requirements](index=30&type=section&id=Risks%20Related%20to%20Our%20Financial%20Condition%20and%20Capital%20Requirements) This section outlines risks associated with the company's financial condition, including operating losses, funding needs, and potential dilution - The company has incurred significant operating losses since inception, with an accumulated deficit of **$1,049.2 million** as of June 30, 2025, and expects to continue incurring losses for the foreseeable future[104](index=104&type=chunk) - Additional funding will be required to develop product candidates and fund operations, which may not be available on acceptable terms, potentially forcing delays or termination of programs[109](index=109&type=chunk)[112](index=112&type=chunk) - Raising additional capital through equity or convertible securities would cause **dilution to existing shareholders** and could cause the market price of common shares to fall[115](index=115&type=chunk) - The company is subject to foreign currency exchange rate risk, particularly with Canadian dollars, and does not currently hedge this exposure, which could impact operating results[119](index=119&type=chunk) [Risks Related to Our Business and Industry](index=34&type=section&id=Risks%20Related%20to%20Our%20Business%20and%20Industry) This section details risks inherent to the company's business and the biotechnology industry, including competition, growth management, and data security - The biotechnology and pharmaceutical industries are highly competitive, with many competitors possessing greater financial resources and expertise, potentially reducing Xenon's commercial opportunities[120](index=120&type=chunk)[122](index=122&type=chunk) - The company has no prior experience in completing Phase 3 clinical trials, obtaining regulatory approval, or independently commercializing products, making assessment of future commercialization difficult[125](index=125&type=chunk) - Managing growth, including increasing headcount and expanding operations, presents difficulties and could divert management attention and financial resources[136](index=136&type=chunk)[137](index=137&type=chunk) - Evolving global data privacy and security laws (e.g., EU GDPR, UK GDPR, CCPA, My Health My Data Act, Protecting Americans' Data from Foreign Adversaries Act) require substantial compliance costs and any failure could harm business and operations[138](index=138&type=chunk)[139](index=139&type=chunk)[140](index=140&type=chunk)[141](index=141&type=chunk) - The company's business and operations could suffer from information security incidents (e.g., cybersecurity breaches, system failures), leading to loss of intellectual property, business disruptions, and significant liabilities[143](index=143&type=chunk) - International operations expose the company to risks such as differing regulatory requirements, reduced intellectual property protection, economic instability, and foreign currency fluctuations[145](index=145&type=chunk) - Xenon was a Passive Foreign Investment Company (PFIC) for 2024 and may be in 2025, which could result in **adverse tax consequences** for U.S. holders of its common shares[147](index=147&type=chunk)[149](index=149&type=chunk) [Risks Related to the Discovery, Development and Commercialization of Our Product Candidates](index=46&type=section&id=Risks%20Related%20to%20the%20Discovery%2C%20Development%20and%20Commercialization%20of%20Our%20Product%20Candidates) This section covers risks associated with the discovery, development, and commercialization of product candidates, including clinical trial success and regulatory approvals - The company's business substantially depends on the successful development, regulatory approval, and commercialization of azetukalner, which is subject to numerous risks including clinical trial success, regulatory processes, and market acceptance[165](index=165&type=chunk)[166](index=166&type=chunk) - Clinical trials may fail to adequately demonstrate the safety and efficacy of product candidates, leading to delays, termination of development, or a more restrictive label, materially harming the business[175](index=175&type=chunk)[176](index=176&type=chunk)[191](index=191&type=chunk) - Difficulties in patient enrollment for clinical trials could significantly delay or prevent successful completion, increasing costs and jeopardizing regulatory approval[179](index=179&type=chunk)[181](index=181&type=chunk) - The regulatory approval processes of the FDA, EMA, and other foreign jurisdictions are lengthy, expensive, and unpredictable, with no guarantee of timely approval or approval at all[196](index=196&type=chunk) - Product liability lawsuits, arising from clinical testing or commercialization, could result in substantial liabilities exceeding insurance coverage and require limitations on commercialization[203](index=203&type=chunk)[204](index=204&type=chunk) - The company lacks its own sales, marketing, and distribution capabilities, requiring significant investment or reliance on third parties, which may not be successful or favorable[207](index=207&type=chunk)[208](index=208&type=chunk) - Approved product candidates will be subject to ongoing regulatory obligations and review, potentially leading to significant additional expenses, delays, and restrictions[211](index=211&type=chunk)[214](index=214&type=chunk) - Future product candidates containing controlled substances will face additional regulatory requirements, potential delays, and adverse public perception[216](index=216&type=chunk)[220](index=220&type=chunk) - Unfavorable third-party coverage and reimbursement practices, along with pricing regulations, may adversely affect demand and profitability for approved products[222](index=222&type=chunk)[224](index=224&type=chunk) - Healthcare reforms in the U.S. and other jurisdictions, including drug pricing initiatives (e.g., Inflation Reduction Act), could increase commercialization costs and affect product prices[228](index=228&type=chunk)[229](index=229&type=chunk)[233](index=233&type=chunk) - Disruptions at government agencies (e.g., FDA staffing/funding shortages) could delay product development, approval, or commercialization[238](index=238&type=chunk)[239](index=239&type=chunk) [Risks Related to Our Dependence on Third Parties](index=65&type=section&id=Risks%20Related%20to%20Our%20Dependence%20on%20Third%20Parties) This section addresses risks arising from the company's reliance on third parties for development, manufacturing, and clinical trials - The successful development and commercialization of partnered products and product candidates are dependent on the research, development, and marketing efforts of collaborators (e.g., Neurocrine Biosciences), over whom the company has limited control[240](index=240&type=chunk) - Failure to establish new collaborations or maintain existing alliances could adversely affect the ability to develop product candidates and commercialize products, potentially increasing cash expenditures and requiring additional financing[243](index=243&type=chunk)[245](index=245&type=chunk) - Reliance on third parties for manufacturing product candidates increases the risk of insufficient quantities, raw material issues, quality control problems, and potential delays in clinical trials or commercialization[245](index=245&type=chunk)[246](index=246&type=chunk) - Third-party manufacturers may face difficulties in scaling up production or optimizing manufacturing processes, leading to increased costs and delayed commercialization[252](index=252&type=chunk) - Reliance on third parties (e.g., CROs, academic institutions) to conduct pre-clinical studies and clinical trials means less control over timing and cost, and potential delays or data rejection if they fail to meet contractual duties or regulatory requirements[253](index=253&type=chunk)[254](index=254&type=chunk)[255](index=255&type=chunk) [Risks Related to Intellectual Property](index=70&type=section&id=Risks%20Related%20to%20Intellectual%20Property) This section details risks concerning the company's intellectual property, including patent protection, infringement claims, and trade secret safeguarding - The company may be unsuccessful in obtaining or maintaining adequate patent protection for its product candidates, or issued patents may be found invalid or unenforceable, failing to provide competitive advantage[261](index=261&type=chunk)[263](index=263&type=chunk) - Protecting intellectual property rights globally is expensive and challenging, as foreign laws may offer less protection, making it difficult to prevent infringement in certain countries[265](index=265&type=chunk) - Claims that the company's product candidates infringe third-party intellectual property rights could result in costly litigation, require substantial time and money, and potentially prevent or delay development/commercialization[274](index=274&type=chunk)[278](index=278&type=chunk) - Unfavorable outcomes in intellectual property litigation could limit research and development activities, commercialization efforts, or lead to significant liabilities[280](index=280&type=chunk)[281](index=281&type=chunk) - Breaching license agreements could result in the **loss of critical license rights**, materially harming the business[284](index=284&type=chunk) - Inability to prevent unauthorized disclosure of trade secrets and proprietary information could compromise the company's competitive position[285](index=285&type=chunk) - Changes in U.S. or foreign patent law could increase uncertainties and costs in patent prosecution and enforcement, impairing the ability to protect product candidates[288](index=288&type=chunk) - Failure to obtain patent term extensions under the Hatch-Waxman Act or similar foreign legislation could shorten exclusive marketing rights and reduce revenue[290](index=290&type=chunk)[291](index=291&type=chunk) - Inadequate trademark protection could hinder name recognition in target markets and adversely affect the business[293](index=293&type=chunk)[295](index=295&type=chunk) [Risks Related to Ownership of Our Common Shares](index=78&type=section&id=Risks%20Related%20to%20Ownership%20of%20Our%20Common%20Shares) This section outlines risks associated with owning the company's common shares, including market price volatility, dilution, and governance differences - The market price of the company's common shares may be volatile due to various factors, including clinical trial results, regulatory announcements, competitor actions, and general market conditions, potentially leading to substantial losses for purchasers[296](index=296&type=chunk)[297](index=297&type=chunk) - Future sales and issuances of common shares or securities convertible into common shares would cause **dilution to existing shareholders** and could cause the market price to fall[298](index=298&type=chunk)[300](index=300&type=chunk) - The company is governed by Canadian corporate and securities laws, which may affect shareholder rights differently than U.S. laws and could delay or discourage acquisitions[301](index=301&type=chunk)[303](index=303&type=chunk) - U.S. civil liabilities may be difficult to enforce against the company or its non-U.S. directors and officers due to their location and governing laws[304](index=304&type=chunk) - The company is at risk of securities class action litigation, which could result in substantial costs and diversion of management's attention[305](index=305&type=chunk) - Management has broad discretion over the use of cash, and ineffective application could adversely affect results of operations and common share value[306](index=306&type=chunk) - The company does not anticipate paying any cash dividends on its common shares in the foreseeable future, meaning capital appreciation is the sole source of gain for investors[307](index=307&type=chunk) [General Risk Factors](index=82&type=section&id=General%20Risk%20Factors) This section covers general risk factors, including unstable market conditions and compliance costs with corporate governance regulations - Unstable market and economic conditions, including global credit disruptions, inflation, and banking sector instability, may seriously and adversely affect the company's business and financial condition[311](index=311&type=chunk) - The company incurs significant and ongoing costs due to compliance with corporate governance laws and regulations (e.g., Dodd-Frank, Sarbanes-Oxley, CBCA, SEC rules) and evolving ESG matters[312](index=312&type=chunk)[314](index=314&type=chunk) [Item 5. Other Information](index=83&type=section&id=Item%205.%20Other%20Information) This section provides additional information not covered elsewhere, specifically addressing Rule 10b5-1 trading plans [Rule 10b5-1 Trading Plans](index=83&type=section&id=Rule%2010b5-1%20Trading%20Plans) This section reports on the adoption or termination of Rule 10b5-1 trading plans by directors or officers - No director or officer adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement during the last fiscal quarter[315](index=315&type=chunk) [Item 6. Exhibits](index=84&type=section&id=Item%206.%20Exhibits) This section lists all exhibits filed as part of the Form 10-Q, including corporate governance documents, employment agreements, and certifications - Exhibits include corporate articles, by-laws, an employment agreement, and certifications from the Chief Executive Officer and Chief Financial Officer[318](index=318&type=chunk) - Certifications 32.1 and 32.2 are not deemed filed with the Securities and Exchange Commission[317](index=317&type=chunk) [SIGNATURES](index=85&type=section&id=SIGNATURES) This section contains the official signatures of authorized officers, confirming the submission of the Quarterly Report on Form 10-Q - The report was signed by Ian Mortimer as President and Chief Executive Officer, and Interim Chief Financial Officer, on **August 11, 2025**[321](index=321&type=chunk)

[Executive Summary](index=1&type=section&id=1.%20Executive%20Summary) Xenon Pharmaceuticals reported Q2 2025 financial results and business updates, highlighting significant clinical progress and pipeline advancements [Second Quarter 2025 Financial Results & Business Update](index=1&type=section&id=1.1%20Second%20Quarter%202025%20Financial%20Results%20%26%20Business%20Update) Xenon Pharmaceuticals reported its financial results for the second quarter ended June 30, 2025, alongside a comprehensive business update, highlighting significant progress in its clinical development programs and early-stage pipeline - Xenon Pharmaceuticals Inc. reported financial results for Q2 2025 and provided a business update[3](index=3&type=chunk) [CEO Statement](index=1&type=section&id=1.2%20CEO%20Statement) CEO Ian Mortimer announced completed patient recruitment for azetukalner's Phase 3 X-TOLE2 study, with early 2026 results expected, and highlighted progress in other Phase 3 and early-stage programs - Patient recruitment for Phase 3 X-TOLE2 study of azetukalner is complete, with topline results expected in early 2026[4](index=4&type=chunk) - Phase 3 programs for azetukalner are underway in bipolar depression (X-CEED) and major depressive disorder (X-NOVA)[4](index=4&type=chunk) - Two first-in-human studies are ongoing within the Kv7 and Nav1.7 early-stage programs, targeting epilepsy, depression, and pain[4](index=4&type=chunk) [Business Highlights and Clinical Development](index=1&type=section&id=2.%20Business%20Highlights%20and%20Clinical%20Development) This section details Xenon's clinical development progress for azetukalner across epilepsy and neuropsychiatric programs, alongside early-stage pipeline advancements and corporate updates [Azetukalner Clinical Development](index=1&type=section&id=2.1%20Azetukalner%20Clinical%20Development) Azetukalner, a Kv7 potassium channel opener, is Xenon's most advanced clinical asset, with significant progress across its Phase 3 programs for epilepsy and neuropsychiatric disorders, including completed recruitment for a pivotal epilepsy study and initiation of multiple studies for depression - Azetukalner is a novel, highly potent, selective Kv7 potassium channel opener in late-stage clinical development for multiple indications[5](index=5&type=chunk) [Epilepsy Programs](index=1&type=section&id=2.1.1%20Epilepsy%20Programs) The Phase 3 X-TOLE2 study for focal onset seizures (FOS) has completed patient recruitment, with topline data expected in early 2026, while enrollment continues for the X-TOLE3 FOS study and the X-ACKT study for primary generalized tonic-clonic seizures (PGTCS) - Phase 3 X-TOLE2 clinical study of azetukalner in FOS has completed patient recruitment; topline data anticipated in early 2026[7](index=7&type=chunk)[8](index=8&type=chunk) - Phase 3 X-TOLE3 clinical study in FOS and X-ACKT clinical study in PGTCS continue to enroll patients[8](index=8&type=chunk)[13](index=13&type=chunk) - Four abstracts related to epilepsy were accepted for presentation at the 36th International Epilepsy Congress (IEC)[13](index=13&type=chunk) [Neuropsychiatric Programs](index=2&type=section&id=2.1.2%20Neuropsychiatric%20Programs) Xenon has initiated Phase 3 clinical trials for azetukalner in major depressive disorder (MDD) with X-NOVA2 and X-NOVA3, and in bipolar depression (BPD) with the X-CEED study - X-NOVA2 and X-NOVA3, the first two of three planned Phase 3 clinical trials for azetukalner in MDD, are underway and screening patients[7](index=7&type=chunk)[13](index=13&type=chunk) - X-CEED, the first of two planned Phase 3 clinical studies for azetukalner in BPD I and BPD II depression, has been initiated[7](index=7&type=chunk)[13](index=13&type=chunk) [Early-Stage Pipeline: Next-Generation Ion Channel Modulators](index=2&type=section&id=2.2%20Early-Stage%20Pipeline%3A%20Next-Generation%20Ion%20Channel%20Modulators) Xenon is actively expanding its early-stage portfolio, leveraging expertise in potassium and sodium channel therapeutics with a goal to file multiple INDs in 2025, including Phase 1 studies for Kv7 and Nav1.7 channel openers for pain, and IND-enabling studies for a Nav1.1 candidate for Dravet Syndrome - Xenon aims to file multiple INDs (or equivalent) in 2025, leveraging expertise in potassium and sodium channel therapeutics[9](index=9&type=chunk) - Phase 1 studies are underway for XEN1120 (Kv7 channel opener) and XEN1701 (Nav1.7 development candidate) for pain[7](index=7&type=chunk)[13](index=13&type=chunk) - Nav1.1 lead candidate is expected to enter IND-enabling studies in 2025, targeting Dravet Syndrome[13](index=13&type=chunk) [Partnered Program](index=2&type=section&id=2.3%20Partnered%20Program) A Phase 1 study is ongoing for NBI-921355, a selective inhibitor of voltage-gated sodium channels Nav1.2 and Nav1.6, developed in collaboration with Neurocrine Biosciences for certain types of epilepsy - A Phase 1 study is underway for NBI-921355, a selective inhibitor of Nav1.2 and Nav1.6, in collaboration with Neurocrine Biosciences for epilepsy[10](index=10&type=chunk) [Corporate Updates](index=2&type=section&id=2.4%20Corporate%20Updates) Xenon appointed Darren Cline as Chief Commercial Officer to lead the company's transition to a commercial-stage entity in anticipation of azetukalner's launch, and also plans to host R&D webinars focusing on its early-stage pipeline - Darren Cline was appointed Chief Commercial Officer to lead the commercial build and anticipated launch of azetukalner[7](index=7&type=chunk)[11](index=11&type=chunk) - Xenon plans to host multiple R&D webinars, with the first on October 2, 2025, focusing on pain treatments targeting Nav1.7 and Kv7[13](index=13&type=chunk) [Second Quarter Financial Performance](index=2&type=section&id=3.%20Second%20Quarter%20Financial%20Performance) This section details Xenon's Q2 2025 financial results, including cash position, R&D expenses, G&A expenses, other income, and net loss [Cash Position and Runway](index=2&type=section&id=3.1%20Cash%20Position%20and%20Runway) Xenon's cash, cash equivalents, and marketable securities totaled **$624.8 million** as of June 30, 2025, a decrease from **$754.4 million** at December 31, 2024, with the company anticipating this cash position will fund operations into 2027 Cash and Marketable Securities (in thousands of U.S. dollars) | Metric | June 30, 2025 | December 31, 2024 | Change | | :------------------------------------------ | :------------ | :------------------ | :----- | | Cash and cash equivalents and marketable securities (current) | $487,545 | $626,905 | $(139,360) | | Marketable securities (long-term) | $137,297 | $127,496 | $9,801 | | **Total Cash and Marketable Securities** | **$624,842** | **$754,401** | **$(129,559)** | - Based on current operating plans, Xenon anticipates having sufficient cash to fund operations into 2027[12](index=12&type=chunk) [Research and Development Expenses](index=3&type=section&id=3.2%20Research%20and%20Development%20Expenses) Research and development expenses significantly increased to **$75.0 million** for Q2 2025, up **$25.3 million** from **$49.7 million** in Q2 2024, primarily due to ongoing azetukalner Phase 3 clinical trials in epilepsy and MDD, start-up costs for the BPD trial, and increased personnel-related costs Research and Development Expenses (in thousands of U.S. dollars) | Period | Q2 2025 | Q2 2024 | Change (YoY) | | :----- | :------ | :------ | :----------- | | R&D Expenses | $74,985 | $49,702 | +$25,283 | - The increase was primarily attributable to ongoing azetukalner Phase 3 clinical trials in epilepsy and MDD, start-up costs for the BPD clinical trial, and increased personnel-related costs[18](index=18&type=chunk) [General and Administrative Expenses](index=3&type=section&id=3.3%20General%20and%20Administrative%20Expenses) General and administrative expenses remained relatively stable at **$19.2 million** for Q2 2025, compared to **$19.4 million** for the same period in 2024 General and Administrative Expenses (in thousands of U.S. dollars) | Period | Q2 2025 | Q2 2024 | Change (YoY) | | :----- | :------ | :------ | :----------- | | G&A Expenses | $19,244 | $19,402 | $(158) | [Other Income](index=3&type=section&id=3.4%20Other%20Income) Other income decreased by **$2.0 million** to **$8.9 million** for Q2 2025, down from **$10.8 million** in Q2 2024, mainly due to lower interest income, partially offset by an increase in foreign exchange gain Other Income (in thousands of U.S. dollars) | Period | Q2 2025 | Q2 2024 | Change (YoY) | | :----- | :------ | :------ | :----------- | | Other Income | $8,897 | $10,847 | $(1,950) | - The decrease was primarily attributable to lower interest income, partially offset by an increase in foreign exchange gain[18](index=18&type=chunk) [Net Loss](index=3&type=section&id=3.5%20Net%20Loss) The net loss for Q2 2025 increased to **$84.7 million**, compared to **$57.9 million** for the same period in 2024, primarily driven by higher research and development expenses and lower interest income Net Loss (in thousands of U.S. dollars, except per share amounts) | Metric | Q2 2025 | Q2 2024 | Change (YoY) | | :-------------------------- | :------ | :------ | :----------- | | Net Loss | $(84,706) | $(57,924) | $(26,782) | | Net Loss per Common Share | $(1.07) | $(0.75) | $(0.32) | - The increase in net loss was primarily attributable to higher research and development expenses driven by the azetukalner program, increased personnel-related costs, and lower interest income[18](index=18&type=chunk) [Detailed Clinical Program Descriptions](index=3&type=section&id=4.%20Detailed%20Clinical%20Program%20Descriptions) This section provides in-depth details on the design and primary endpoints of azetukalner's Phase 3 clinical programs for epilepsy, major depressive disorder, and bipolar depression [Azetukalner Phase 3 Epilepsy Program Details](index=3&type=section&id=4.1%20Azetukalner%20Phase%203%20Epilepsy%20Program%20Details) Xenon's Phase 3 epilepsy program for azetukalner includes three clinical trials for focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS), which are randomized, double-blind, placebo-controlled studies evaluating **15 mg or 25 mg** of azetukalner as adjunctive treatment, with the primary endpoint being the median percent change in monthly seizure frequency - The Phase 3 epilepsy program includes three clinical trials for FOS and PGTCS, designed after the Phase 2b X-TOLE trial[15](index=15&type=chunk) - X-TOLE trials for FOS evaluate **15 mg or 25 mg of azetukalner** in approximately **360 patients**, with the primary endpoint being median percent change in monthly seizure frequency[15](index=15&type=chunk) - X-ACKT for PGTCS evaluates **25 mg of azetukalner** in approximately **160 patients**, with a similar primary efficacy endpoint[15](index=15&type=chunk) [Azetukalner Phase 3 MDD X-NOVA Program Details](index=3&type=section&id=4.2%20Azetukalner%20Phase%203%20MDD%20X-NOVA%20Program%20Details) The Phase 3 MDD program for azetukalner consists of three multicenter, randomized, double-blind, placebo-controlled trials, each evaluating **20 mg** of azetukalner as monotherapy in approximately **450 patients** with moderate-to-severe MDD, with the primary efficacy endpoint being the change from baseline in HAM-D17 score at week 6 - The Phase 3 MDD program includes three multicenter, randomized, double-blind, placebo-controlled clinical trials[16](index=16&type=chunk) - Studies evaluate **20 mg of azetukalner** as monotherapy in approximately **450 patients** with moderate-to-severe MDD[16](index=16&type=chunk) - The primary efficacy endpoint is the change from baseline in the HAM-D17 score at week 6[16](index=16&type=chunk) [Azetukalner Phase 3 BPD X-CEED Program Details](index=3&type=section&id=4.3%20Azetukalner%20Phase%203%20BPD%20X-CEED%20Program%20Details) Xenon's Phase 3 BPD program for azetukalner involves two multicenter, randomized, double-blind, placebo-controlled clinical trials, assessing **20 mg** of azetukalner as monotherapy in approximately **400 patients** with bipolar depression (BPD) I or II, with the primary efficacy endpoint being the change from baseline in the MADRS score at week 6 - The Phase 3 BPD program includes two multicenter, randomized, double-blind, placebo-controlled clinical trials[17](index=17&type=chunk) - Studies evaluate **20 mg of azetukalner** as monotherapy in approximately **400 patients** with BPD I or II[17](index=17&type=chunk) - The primary efficacy endpoint is the change from baseline in the MADRS score at week 6[17](index=17&type=chunk) [Company Overview and Investor Information](index=3&type=section&id=5.%20Company%20Overview%20and%20Investor%20Information) This section provides an overview of Xenon Pharmaceuticals, details conference call information, includes a safe harbor statement, and lists contact information [About Xenon Pharmaceuticals Inc.](index=4&type=section&id=5.1%20About%20Xenon%20Pharmaceuticals%20Inc.) Xenon Pharmaceuticals is a neuroscience-focused biopharmaceutical company dedicated to drug discovery, clinical development, and commercialization, with its lead molecule, azetukalner, in Phase 3 trials for epilepsy, MDD, and BPD, complemented by an early-stage pipeline of potassium and sodium channel modulators for pain - Xenon Pharmaceuticals is a neuroscience-focused biopharmaceutical company[19](index=19&type=chunk) - Azetukalner, a Kv7 potassium channel opener, is in Phase 3 clinical trials for epilepsy, MDD, and BPD[19](index=19&type=chunk) - The company is also advancing an early-stage portfolio of Kv7 and Nav1.7 programs in Phase 1 development for pain[19](index=19&type=chunk) [Conference Call Information](index=3&type=section&id=5.2%20Conference%20Call%20Information) Xenon hosted a conference call and webcast on August 11, 2025, at 4:30 pm ET to discuss its second quarter 2025 results, with replay access available on the Investors section of the company's website - Xenon hosted a conference call and webcast on August 11, 2025, at 4:30 pm ET to discuss Q2 2025 results[14](index=14&type=chunk) - A listen-only webcast can be accessed on the Investors section of the Xenon website, with a replay available[14](index=14&type=chunk) [Safe Harbor Statement](index=4&type=section&id=5.3%20Safe%20Harbor%20Statement) This section contains forward-looking statements regarding clinical trial timing and results, product candidate efficacy, regulatory success, and commercial potential, cautioning readers about inherent risks and uncertainties that could cause actual results to differ materially from projections - The press release contains forward-looking statements regarding clinical trials, product efficacy, regulatory approvals, and commercial potential[20](index=20&type=chunk) - These statements are subject to risks and uncertainties, including potential failures in clinical trials, incorrect assumptions on funding, and regulatory delays[20](index=20&type=chunk) - Readers are cautioned not to place undue reliance on forward-looking statements, and the company assumes no obligation to update them[20](index=20&type=chunk) [Contacts](index=5&type=section&id=5.4%20Contacts) Contact information for investor relations and media inquiries is provided for Xenon Pharmaceuticals Inc - Contact details for Investor Relations (Chad Fugere) and Corporate Affairs (Colleen Alabiso) are provided[22](index=22&type=chunk) [Condensed Consolidated Financial Statements](index=6&type=section&id=6.%20Condensed%20Consolidated%20Financial%20Statements) This section presents Xenon's condensed consolidated balance sheets and statements of operations and comprehensive loss for the reported periods [Condensed Consolidated Balance Sheets](index=6&type=section&id=6.1%20Condensed%20Consolidated%20Balance%20Sheets) The balance sheet shows a decrease in total assets and shareholders' equity from December 31, 2024, to June 30, 2025, primarily driven by a reduction in cash and marketable securities, while total liabilities also saw a slight decrease Condensed Consolidated Balance Sheets (in thousands of U.S. dollars) | Metric | June 30, 2025 | December 31, 2024 | | :------------------------------------------ | :------------ | :------------------ | | Cash and cash equivalents and marketable securities (current) | $487,545 | $626,905 | | Other current assets | $12,707 | $8,359 | | Marketable securities, long-term | $137,297 | $127,496 | | Other long-term assets | $36,732 | $35,379 | | **Total assets** | **$674,281** | **$798,139** | | Accounts payable and accrued liabilities | $31,588 | $34,221 | | Other current liabilities | $1,459 | $1,369 | | Other long-term liabilities | $7,256 | $7,646 | | **Total liabilities** | **$40,303** | **$43,236** | | **Shareholders' equity** | **$633,978** | **$754,903** | | **Total liabilities and shareholders' equity** | **$674,281** | **$798,139** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=6.2%20Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The statements show an increased net loss for both the three and six months ended June 30, 2025, primarily driven by higher research and development expenses, with revenue remaining at zero for the quarter but showing **$7.5 million** for the six-month period in 2025 Condensed Consolidated Statements of Operations and Comprehensive Loss (in thousands of U.S. dollars, except per share amounts) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Revenue | $— | $— | $7,500 | $— | | Research and development | $74,985 | $49,702 | $136,185 | $93,952 | | General and administrative | $19,244 | $19,402 | $38,282 | $34,193 | | **Total operating expenses** | **$94,229** | **$69,104** | **$174,467** | **$128,145** | | Loss from operations | $(94,229) | $(69,104) | $(166,967) | $(128,145) | | Other income | $8,897 | $10,847 | $17,015 | $22,369 | | Net loss | $(84,706) | $(57,924) | $(149,753) | $(105,855) | | Net loss per common share: Basic and diluted | $(1.07) | $(0.75) | $(1.90) | $(1.36) | | Weighted average common shares outstanding: Basic and diluted | 78,953,445 | 77,671,128 | 78,820,474 | 77,632,864 |

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 Insights - Xenon Pharmaceuticals Inc. will report its second quarter 2025 financial results and provide a business update on August 11, 2025, after U.S. market close [1] - The company focuses on developing therapeutics for neurological conditions, particularly through its ion channel product portfolio [3] Financial Reporting - The financial results and business update will be available after the close of U.S. financial markets on August 11, 2025 [1] - A live webcast of the presentation will be accessible on the company's website, with a replay available post-event [2] Company Overview - Xenon Pharmaceuticals is dedicated to discovering and developing life-changing therapeutics, with a focus on high unmet medical needs such as epilepsy and depression [3] - The company is advancing Azetukalner, a selective Kv7 potassium channel opener, which is in late-stage clinical development for multiple indications [3]

Core Points - Xenon Pharmaceuticals Inc. has been added to the Russell 3000® and Russell 2000® Indexes as part of the annual reconstitution effective June 27, 2025 [1] - The Russell 3000® Index tracks the performance of the largest 3,000 U.S. stocks by market capitalization, while the Russell 2000® Index measures the performance of the 2,000 smallest companies within the Russell 3000® Index [2] - Approximately $10.6 trillion in assets are benchmarked against Russell U.S. indexes, making them widely used by investment managers and institutional investors [3] Company Overview - Xenon Pharmaceuticals is a neuroscience-focused biopharmaceutical company dedicated to discovering, developing, and delivering life-changing therapeutics [4] - The company is advancing an ion channel product portfolio to address high unmet medical needs, including epilepsy and depression [4] - Azetukalner, a novel and highly potent selective Kv7 potassium channel opener, is the most advanced clinically validated potassium channel modulator in late-stage clinical development for multiple indications [4]

Core Insights - Xenon Pharmaceuticals has appointed Darren Cline as Chief Commercial Officer to lead the transition to a commercial-stage company with a focus on azetukalner, which is in Phase 3 trials for epilepsy and major depressive disorder [1][2][3] Company Overview - Xenon Pharmaceuticals is a neuroscience-focused biopharmaceutical company dedicated to developing therapeutics for high unmet medical needs, including epilepsy and depression [5][6] - Azetukalner is a novel Kv7 potassium channel opener, currently the most advanced potassium channel modulator in late-stage clinical development [6] Leadership Appointment - Darren Cline brings over 30 years of experience in the biopharmaceutical industry, with a strong background in commercial strategy and successful product launches, particularly in epilepsy [2][3] - His previous roles include President and CEO of Epygenix Therapeutics and Chief Commercial Officer at GW Pharmaceuticals, where he contributed to the commercialization of Epidiolex [2][3] Product Development - Azetukalner is being studied in Phase 3 trials for epilepsy and major depressive disorder, with plans to initiate a trial for bipolar depression this year [1][3] - The Phase 2b X-TOLE and open label extension data support azetukalner's potential as a significant new treatment option for epilepsy [3] Compensation Details - In connection with Mr. Cline's appointment, he was granted an option to purchase 185,800 common shares at an exercise price of $31.49, with a vesting schedule over four years [4]

Company Overview - Xenon Pharmaceuticals (XENE) shares have increased by approximately 8.7% over the past month, outperforming the S&P 500 [1] - The most recent earnings report is essential for understanding the key drivers behind this performance [1] Earnings Estimates - Fresh estimates for Xenon Pharmaceuticals have remained flat over the past month [2] VGM Scores - The company has a poor Growth Score of F, a Momentum Score of B, and a Value Score of F, resulting in an aggregate VGM Score of F [3] Outlook - Xenon Pharmaceuticals holds a Zacks Rank of 3 (Hold), indicating an expectation of in-line returns in the upcoming months [4] Industry Comparison - Xenon Pharmaceuticals is part of the Zacks Medical - Biomedical and Genetics industry, where Celldex Therapeutics (CLDX) has seen a gain of 6.6% over the past month [5] - Celldex reported revenues of $0.69 million for the last quarter, reflecting a year-over-year increase of 331.3% [5] - For the current quarter, Celldex is projected to report a loss of $0.86 per share, a decrease of 59.3% from the previous year [6]

Financial Data and Key Metrics Changes - The company ended Q1 with just under $700 million on the balance sheet, guiding that this cash runway extends into 2027, supporting an ambitious clinical program in epilepsy and psychiatry [72]. Business Line Data and Key Metrics Changes - The lead molecule, ZetuCalder, is in a Phase III epilepsy program, with data expected in early 2026. The company is also ramping up late-stage clinical programs in major depression and bipolar depression [3][6][5]. - The Phase III clinical trial for focal onset seizures (XTOL-two) is nearing completion of patient screening, maintaining consistency with the Phase II study [17][18]. Market Data and Key Metrics Changes - Approximately 3 million Americans have epilepsy, with 60% experiencing focal onset seizures. An estimated 30% to 50% of these patients do not achieve good seizure control, indicating a significant market opportunity for ZetuCalder [21][22]. Company Strategy and Development Direction - The company focuses on validated targets in neurology, particularly ion channels, to maintain a competitive advantage. The strategy includes building a commercial infrastructure in the U.S. while seeking partners for international markets [9][40][43]. - The company is advancing its early-stage pipeline, including molecules targeting KV7 and Nav1.7, with plans for clinical trials in the near future [74][76]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the efficacy of their lead product and highlighted the importance of clinical data in shaping future commercial strategies. They noted a data-rich period ahead with multiple clinical milestones expected [20][73]. - The management acknowledged the challenges in the regulatory landscape but emphasized their preparedness for filing an NDA based on the ongoing clinical trials [30][31]. Other Important Information - The company has made significant changes in its Phase III clinical trial design for major depression, including increasing sample size and adjusting primary endpoints to reduce variability and enhance data quality [45][50][51]. - The company is also exploring bipolar depression, leveraging existing safety data from previous studies to support this new indication [68][70]. Q&A Session Summary Question: Can you provide an update on trial execution and enrollment for XTOL-two? - The company is close to completing patient screening for XTOL-two, with data expected in early 2026 [17][18]. Question: How does the company plan to approach pricing for ZetuCalder? - The company believes it can price ZetuCalder competitively within the specialty neurology drug market, with a focus on indication-specific pricing strategies [20][22]. Question: What is the company's strategy for commercialization outside the U.S.? - The company plans to build commercial infrastructure in the U.S. and will seek partners for market access in international markets [40][43]. Question: How is the company addressing placebo responses in clinical trials? - The company is focusing on enrolling a more severe depressed population to minimize placebo effects and has implemented a one-to-one randomization strategy [54][66]. Question: What is the current status of the early-stage pipeline? - The company is advancing several early-stage programs, including those targeting KV7 and Nav1.7, with plans for clinical trials in the near future [74][76].

Company Overview - Xenon Pharmaceuticals Inc. is a neuroscience-focused biopharmaceutical company dedicated to discovering, developing, and delivering life-changing therapeutics for patients in need [2] - The company is advancing an ion channel product portfolio to address areas of high unmet medical need, including epilepsy and depression [2] - Azetukalner, a novel, highly potent, selective Kv7 potassium channel opener, is the most advanced, clinically validated potassium channel modulator in late-stage clinical development for multiple indications [2] Event Announcement - Xenon Pharmaceuticals will present at the Goldman Sachs 46th Annual Global Healthcare Conference in Miami, FL, from June 9-11, 2025 [1] - The fireside chat presentation is scheduled for June 10, 2025, from 3:20-3:55 PM Eastern Time, with Ian Mortimer, President and CEO, as the presenter [1] - A live audio webcast of the presentation will be available on the "Investors" section of Xenon's website and will be posted for replay following the event [1]

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.