Xenon Pharmaceuticals Inc. · NASDAQ:XENE
Xenon Pharmaceuticals — Investor Presentation (September 2026)
43 slides from Xenon Pharmaceuticals's investor presentation, September 2026
Slide 1: Investor Presentation: Corporate Overview
Investor Presentation CORPORATE OVERVIEW SEPTEMBER 2026 NASDAQ: XENE xenon-pharma.com
Slide 2: Forward Looking Statement/Safe Harbor
Forward Looking Statement/Safe Harbor This slide presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995
Slide 3: About Xenon Pharmaceuticals
About Xenon Pharmaceuticals • Neuroscience-focused biopharmaceutical company and leader in small molecule, ion channel drug discovery and development • Robust pipeline of therapeutic candidates targeting potassium and sodium channels across various indications • Lead molecule, azetukalner (AZK), is
Slide 4: Xenon's Strategy
Xenon’s Strategy Building a fully-integrated neuroscience company committed to discovery, development and commercialization of life-changing medicines for patients in need Approval and Launch of AZK Broaden AZK Opportunity Advance Early-Stage in Epilepsy to Neuropsychiatry Pipeline • NDA submitted Q
Slide 5: Neuroscience-Focused Pipeline
Neuroscience-Focused Pipeline Therapeutic Area Pre-clinical Phase 1 Phase 2 Phase 3 NDA XENON PROGRAMS Azetukalner (AZK) KV7 Potassium Channel Opener FOS Submitted Q3 2026 PGTCS MDD BPD XEN1701 NaV1.7 Sodium Channel Inhibitor Pain XEN1720 NaV1.7 Sodium Channel Inhibitor Pain XEN1120 KV7 Potassium Ch
Slide 6: Azetukalner in Epilepsy
Azetukalner in Epilepsy
Slide 7: AZK's Potential for a Differentiated Profile in Epilepsy
AZK’s Potential for a Differentiated Profile in Epilepsy Robust Clinical Data Well-Documented Safety Profile • Compelling double-blind efficacy data in FOS • 1,500+ patient years of data in FOS patients, patients from two PBO-controlled studies with some dosed for more than 5 years • Durable long-te
Slide 8: Significant Epilepsy Burden in U.S.
Significant Epilepsy Burden in U.S. Fourth most common neurological condition with substantial unmet medical needs and limited innovation Estimated Diagnosed Adult Epilepsy Patient Ongoing Treatment Challenges in Epilepsy Population in the U.S. Inadequate Seizure Complicated Treatment Limited Opport
Slide 9: Treatment Decisions Are Highly Individualized and Complex
Treatment Decisions Are Highly Individualized and Complex Treatment goal aims to optimize efficacy while managing tolerability Diagnosed Epilepsy Patient • Levetiracetam and lamotrigine are commonly used in early lines of treatment • Monotherapy switching in second line driven by desire for better s
Slide 10: Phase 3 X-TOLE2 Study: Results Summary
Phase 3 X-TOLE2 Study: Results Summary Results included in NDA submitted in Q3 2026 PRIMARY ENDPOINT WAS MET: Highly statistically significant, dose-dependent reduction from baseline in median monthly FOS frequency (MPC) over the 12-week treatment period vs. placebo Responder rate 50: Statistically
Slide 11: Phase 3 X-TOLE2 Clinical Study in FOS
Phase 3 X-TOLE2 Clinical Study in FOS Multicenter, randomized, double-blind, placebo-controlled clinical study to evaluate the clinical efficacy, safety, and tolerability of AZK as adjunctive treatment in adults diagnosed with FOS Primary objective: Up to 9.5 weeks 12-week DBP 6-year OLE • Evaluate
Slide 12: X-TOLE2: Statistically Significant, Dose-Dependent Reduction in Seizures
X-TOLE2: Statistically Significant, Dose-Dependent Reduction in Seizures Change from baseline in seizure frequency RR50 PBO AZK AZK 15 mg 25 mg 0% 60% 54.8% p=0.00000008 -10% 50% -10.4% 37.6% -20% 40% p=0.003 Responders (%) MPC (%) 42.7% -30% 30% placebo-adjusted MPC 20.8% -34.5% 20% -40% p=0.00007
Slide 13: X-TOLE2: Dose-Dependent Reductions in Weekly FOS Frequency
X-TOLE2: Dose-Dependent Reductions in Weekly FOS Frequency Observed as Early as Week 1 Change in Seizure Frequency at Week 1 PBO AZK AZK 15 mg 25 mg 0% -10% -20% -19.3% MPC (%) -30% -33.3% -40% (p=0.08) -50% -45.2% ** -60% **p<0.01 Reductions in weekly FOS frequency sustained through DBP AZK: azetuk
Slide 14: X-TOLE2: Summary of TEAEs
X-TOLE2: Summary of TEAEs Treatment-Emergent Adverse Events Serious Adverse Events Most common TEAEs across TEAEs resulted in Incidence of SAEs was low and Any TEAE occurred in: all AZK groups included: discontinuation in: similar across AZK groups: • 62.4% in PBO • Dizziness (20.5%) • 3.2% in PBO
Slide 15: X-TOLE2: Additional Safety Findings & Safety Summary
X-TOLE2: Additional Safety Findings & Safety Summary Additional Safety Findings Summary of Safety and Tolerability • No severe allergic rashes (SJS, DRESS) occurred • No signals of retinal pigment epithelium or macular abnormalities • AZK was generally well-tolerated with a dose-dependent • No signa
Slide 16: Phase 2b X-TOLE Clinical Study in FOS
Phase 2b X-TOLE Clinical Study in FOS Multicenter, randomized, double-blind, placebo-controlled clinical study to evaluate the clinical efficacy, safety, and tolerability of AZK as adjunctive treatment in adults diagnosed with FOS 8-week DBP Up to 4 AZK 25 mg QD* 7-year OLE Primary objective: weeks
Slide 17: Phase 2b X-TOLE: Statistically Significant, Dose-Dependent Reduction in Seizures
Phase 2b X-TOLE: Statistically Significant, Dose-Dependent Reduction in Seizures Change from baseline in seizure frequency RR50 AZK AZK AZK Placebo 10 mg 20 mg 25 mg 60% *** 54.5% 0% 50% *** -10% 43.1% Responders (%) 40% MPC (%) -20% -18.2% * 28.3% -30% 30% -33.2% -40% 20% 14.9% * -50% -46.4% 10% **
Slide 18: X-TOLE OLE: Robust Long-Term Efficacy and Seizure Freedom
X-TOLE OLE: Robust Long-Term Efficacy and Seizure Freedom MPC in monthly FOS frequency for overall population and those treated for Seizure freedom rates (100% seizure reduction) ≥48 months in OLE for participants treated for ≥48 months 50 40 38.2% 30 25.2% 19.8% 20 10.7% 10 0 ≥12 Months ≥24 Months
Slide 19: X-TOLE and X-TOLE OLE: Safety and Tolerability Data
X-TOLE and X-TOLE OLE: Safety and Tolerability Data X-TOLE Double-blind Period X-TOLE OLE • AZK was generally well-tolerated in this study with adverse events consistent • AZK was generally well-tolerated in the OLE with commonly prescribed ASMs • Long-term safety in the OLE is comparable Most commo
Slide 20: Placebo-Adjusted MPCs for All AZK Doses in X-TOLE and X-TOLE2
Placebo-Adjusted MPCs for All AZK Doses in X-TOLE and X-TOLE2 AZK (10 mg) AZK (15 mg) AZK (15 mg) AZK (20 mg) AZK (25 mg) AZK (25 mg) AZK (25 mg) X-TOLE (8 wks) X-TOLE2 (8 wks) X-TOLE2 (12 wks) X-TOLE (8 wks) X-TOLE (8 wks) X-TOLE2 (8 wks) X-TOLE2 (12 wks) 0% -5% Placebo-Adjusted MPC (%) -10% -15% -
Slide 21: Next Steps for AZK in Epilepsy
Next Steps for AZK in Epilepsy Path NDA to Commercialization Submission Opportunities for Growth • NDA submitted to FDA in Q3 2026 • Phase 3 X-TOLE3 study ongoing to support regulatory • NDA submission includes data from two RCTs: submissions outside the U.S., including Japan X-TOLE, X-TOLE2 • Phase
Slide 22: A Focused HCP Strategy to Drive Branded ASM Adoption at Launch
A Focused HCP Strategy to Drive Branded ASM Adoption at Launch Prescriber 2L+ Disease Priorities at Universe Managers Launch All Epileptologists 7,000 – 9,000 HCPs ~4,500 HCPs prioritized at launch (~2,400) Epileptologists Own >80% of all branded new General Neurologists patient starts and scripts A
Slide 23: Market Research Supports Potential for Broad Physician Appeal
Market Research Supports Potential for Broad Physician Appeal Epilepsy Specialists1 General Neurologists1 Perceptions of Unfavorable Favorable Unfavorable Favorable “Product X” Novel Mechanism of Action Ease of Use2 “Product X” Dosing Flexibility to Balance Efficacy and Safety Manageable Safety Prof
Slide 24: Phase 3 X-TOLE3 Clinical Trial in FOS
Phase 3 X-TOLE3 Clinical Trial in FOS X-TOLE3 is ongoing with study design identical to X-TOLE2; intended to support regulatory submissions outside the U.S., with enrollment outside Japan expected to complete in 2026 Primary objective: • Evaluate effect of AZK vs. PBO on MPC Up to 9.5 weeks 12-week
Slide 25: Phase 3 X-ACKT Clinical Trial in PGTCS
Phase 3 X-ACKT Clinical Trial in PGTCS PGTCS opportunity for a broad-spectrum agent with activity across seizure types; enrollment is ongoing in single, multicenter, placebo-controlled Phase 3 trial to support registration Up to 9.5 weeks 6-year OLE Primary objective: 12-week DBP • Assess effect of
Slide 26: Azetukalner in Neuropsychiatry
Azetukalner in Neuropsychiatry
Slide 27: MDD Is a Highly Prevalent Mental Health Disorder
MDD Is a Highly Prevalent Mental Health Disorder Depression Accounts for Greatest Disability Among • In 2022, the MDD diagnosed prevalent All Central Nervous System Disorders population in the U.S. was approximately 21 million adults – ~55% treated with pharmacotherapy – 1 in 3 patients are inadequa
Slide 28: Opportunity to Improve MDD Treatment Paradigm
Opportunity to Improve MDD Treatment Paradigm Treatment Considerations MDD Lines of Therapy 1st Line • Physicians typically use SSRI multiple SSRIs/SNRIs, prior to progressing to branded therapy 2nd Line • Poorly managed patients may Switch SSRI SNRI + NDRI seek alternative MOAs in 3L+ • Opportunity
Slide 29: X-NOVA Phase 2 Proof-of-Concept Clinical Study in MDD
X-NOVA Phase 2 Proof-of-Concept Clinical Study in MDD Conducted a Phase 2 proof-of-concept, randomized, double-blind, placebo-controlled, multicenter study to evaluate the safety, tolerability, and efficacy of AZK in major depressive disorder (MDD) 4 weeks 6-week DBP Primary objective: • Montgomery-
Slide 30: X-NOVA: Primary Efficacy Endpoint (MADRS)
X-NOVA: Primary Efficacy Endpoint (MADRS) Change in MADRS Total Scores at Week 6 (mITT) 0 MADRS Total Score Change From Baseline -2 -4 PBO AZK 20 mg -6 (n=54) (n=53) -8 MADRS total score -10 p<0.05 change from baseline -13.90 -16.94 at Week 6, LS mean -12 -14 Difference vs. PBO -3.04 Placebo -16 Aze
Slide 31: X-NOVA: Pre-Specified Endpoint Improvement in Depressive Symptoms
X-NOVA: Pre-Specified Endpoint Improvement in Depressive Symptoms Change in HAM-D17 Total Score at Week 6 (mITT) AZK placebo 20 mg (n=54) (n=53) HAM-D17 total score change from -10.18 -13.26 baseline at Week 6 (LS mean) Difference vs PBO -3.08 p-value 0.042* AZK was administered as a once-daily caps
Slide 32: X-NOVA: Secondary Efficacy Endpoint
X-NOVA: Secondary Efficacy Endpoint Change in SHAPS Total Score at Week 6 (mITT) SHAPS Total Score Change From Baseline 0 AZK -1 PBO 20 mg -2 (n=54) (n=53) -3 SHAPS total score -4 change from baseline -5.30 -7.77 -5 at Week 6 (LS mean) -6 Difference vs -7 -2.46 placebo -8 Placebo Azetukalner 10 mg -
Slide 33: X-NOVA: Safety and Tolerability Data
X-NOVA: Safety and Tolerability Data AZK was generally well-tolerated with similar rates of overall adverse events reported across all treatment arms Treatment-Emergent Adverse Events • The most commonly reported TEAEs in the AZK 20 mg group included dizziness (17.9%), somnolence (10.7%), headache (
Slide 34: Phase 3 Clinical Studies in Major Depressive Disorder
Phase 3 Clinical Studies in Major Depressive Disorder Phase 3 MDD program consists of three multi-center, placebo-controlled clinical trials with plan to submit sNDA supported by efficacy data from two positive Phase 3 MDD trials Primary objective: • Change from baseline in HAM-D17 Up to 4 weeks 1-y
Slide 35: Limited Options to Address Lifelong Nature of Bipolar Depression
Limited Options to Address Lifelong Nature of Bipolar Depression Hallmark of bipolar disorder is its cyclical pattern, where individuals alternate between mania/hypomania and depression, often with periods of normal in between Estimated U.S. bipolar disorder prevalence Percent of patients by disease
Slide 36: Phase 3 Clinical Studies in Bipolar Depression
Phase 3 Clinical Studies in Bipolar Depression Phase 3 BPD program consists of two multi-center, placebo-controlled clinical trials in patients with bipolar I or II depression (BPD) Primary objective: Up to 4 weeks 1-year OLE • Change from baseline in MADRS score at week 6 6-week DBP Secondary objec
Slide 37: Clinical Programs for Pain
Clinical Programs for Pain
Slide 38: Prevalence and Treatment Paradigms Across Pain Types
Prevalence and Treatment Paradigms Across Pain Types Acute Pain Chronic Nociceptive Pain* Neuropathic Pain NSAIDs; Neuromodulators Neuromodulators 1L NSAIDs, Opioid 1L/2L 1L 1L (e.g., diclofenac, diazepam, Cymbalta) (e.g., TCAs, anticonvulsants, Cymbalta) acetaminophen analgesics (e.g., diclofenac,
Slide 39: Maturing Pipeline of Novel Phase 1 Programs in Pain
Maturing Pipeline of Novel Phase 1 Programs in Pain Leveraging Xenon’s deep ion channel expertise to develop promising drug candidates that target sodium and potassium channels Na V 1.7 Programs K V 7 Program • Phase 1 SAD/MAD studies underway for two NaV1.7 candidates: • Phase 1 SAD/MAD study under
Slide 40: The Human Genetics of NaV1.7 in Pain
The Human Genetics of NaV1.7 in Pain • Loss-of-function mutations in SCN9A (the gene encoding NaV1.7) can cause congenital indifference to pain (CIP) – individuals who are otherwise healthy but cannot feel pain • Gain-of-function mutations in SCN9A can lead to extreme pain disorders, such as inherit
Slide 41: XEN1701 Performance in IEM Mouse Model
XEN1701 Performance in IEM Mouse Model XEN1701 demonstrates target engagement at In vivo activity correlates to free brain low total plasma concentrations concentrations across Xenon's lead compounds 75-90% receptor occupancy 1.0 IEM Aconitine Flinching XEN1701 1.0 IEM Aconitine Flinching (Fraction
Slide 42: Upcoming Milestones
Upcoming Milestones Catalyst-rich period as AZK progresses toward U.S. approval and broader pipeline delivers key clinical data Q3 2026 AZK NDA in Epilepsy Q3 2026 Ph3 X-NOVA2 H2 2026 Q1 2027 Mar-Sep Submitted Enrollment H2 2026 Ph3 X-TOLE3 Phase 3 X-NOVA2 Ph3 Topline Data Complete Enrollment to Top
Slide 43: For more information
For more information INVESTORS@XENON-PHARMA.COM
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