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Use eyedropper tool to select colors from the expanded color palette: NASDAQ: XENE xenon-pharma.com Corporate Overview 2026 J.P . MORGAN HEALTHCARE CONFERENCE JANUARY 2026
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Forward Looking Statement/Safe Harbor This slide presentation and the accompanying oral commentary contain 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 and Canadian Securities laws) that involve risks, uncertainties and assumptions. If the risks or uncertainties ever materialize or the assumptions prove incorrect, our results may differ materially from those expressed or implied by such forward- looking statements. All statements other than statements of historical fact could be deemed forward-looking and include statements regarding the timing of and potential results from clinical studies; the potential efficacy, safety profile, future development plans in current and anticipated indications, addressable market, regulatory success and commercial potential of our and our partners’ product candidates; the efficacy of our clinical study designs; our ability to successfully develop and achieve milestones in our azetukalner and other pipeline and development programs, including the anticipated filing of INDs and NDAs; the timing and results of our interactions with regulators, including the timing of any NDA submission; our ability to successfully develop and obtain regulatory approval of azetukalner and our other product candidates; anticipated timing of topline data readout from our clinical studies of azetukalner; and our expectation that we will have sufficient cash to fund operations into 2027. These forward-looking statements are based on current assumptions that involve risks, uncertainties and other factors that may cause the actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical studies may not demonstrate safety and efficacy of any of our or our collaborators’ product candidates; promising results from pre-clinical development activities or early clinical study results may not be replicated in later clinical studies; our assumptions regarding our planned expenditures and sufficiency of our cash to fund operations may be incorrect; our ongoing discovery and pre-clinical efforts may not yield additional product candidates; any of our or our collaborators’ product candidates, including azetukalner, may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; regulatory agencies may impose additional requirements or delay the initiation or completion of clinical studies; the impact of market, industry, and regulatory conditions on clinical study enrollment; the impact of competition; the impact of expanded product development and clinical activities on operating expenses; the impact of new or changing laws and regulations; the impact of unstable economic conditions in the general domestic and global economic markets; adverse conditions from geopolitical events; as well as the other risks identified in our filings with the U.S. Securities and Exchange Commission and the securities commissions in British Columbia, Alberta, and Ontario. These forward- looking statements speak only as of the date hereof and we assume no obligation to update these forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements. Xenon and the Xenon logo are registered trademarks or trademarks of Xenon Pharmaceuticals Inc. in the US, Canada, and elsewhere. All other trademarks belong to their respective owner. 2JPM 2026
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height About Xenon Pharmaceuticals 3 AZETUKALNER (AZK) is the most advanced potassium channel modulator in late-stage clinical development across multiple indications and the only KV7 program with 800+ patient-years of efficacy & safety data • 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, is a highly potent KV7 channel opener in Phase 3 development in epilepsy and depression • Strong financial position – $555.3 million in cash, cash equivalents and marketable securities (as of September 30, 2025) and anticipated cash runway to fund operations into 2027 JPM 2026 Azetukalner is an investigational drug that has yet to be approved by the FDA
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Indications Preclinical Phase 1 Phase 2 Phase 3 Azetukalner KV7 Potassium Channel Opener FOS PGTCS MDD BPD XEN1701 NaV1.7 Sodium Channel Inhibitor Pain XEN1120 KV7 Potassium Channel Opener Pain Early-Stage Ion Channel Modulators KV7 Potassium Channel Openers Epilepsy, pain, neuropsychiatry NaV1.7 Sodium Channel Inhibitors Pain NaV1.1 Sodium Channel Openers Dravet syndrome NBI-921355 - Neurocrine Biosciences NaV1.2/1.6 Inhibitor Epilepsy Xenon’s Neuroscience-Focused Pipeline FOS: Focal onset seizures; PGTCS: Primary generalized tonic-clonic seizures; MDD: Major depressive disorder; BPD: Bipolar depression Purple: epilepsy; Green: depression; Orange: pain; Grey: multiple 4 XENON PROGRAMS PARTNERED PROGRAMS This chart displays pipeline drug candidates currently undergoing clinical and pre-clinical testing in a variety of disease indications. The safety and efficacy of these investigational drug candidates have not been fully evaluated, and they have not yet been approved for use by any regulatory authorities. Topline X-TOLE2 data expected March 2026 JPM 2026
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Azetukalner’s Significant Potential Across Epilepsy & Neuropsychiatry 5 Ease-of-Use • Once-daily dosing and no required titration, enabling potential for rational polypharmacy • No meaningful DDIs or anticipated monitoring requirements Robust Clinical Efficacy • Highly compelling double-blind efficacy data in FOS patients, durable long-term seizure freedom data as demonstrated in the ongoing OLE • Clinically meaningful activity in depression and significant reductions in anhedonia observed in MDD patients Well-Documented Safety Profile • More than 800 patient years of data in FOS patients, with some dosed for more than 5 years • Potentially differentiated profile in MDD patients, with no notable weight gain or sexual dysfunction observed Novel Mechanism • Highly potent KV7.2/7.3 potassium channel opener with no activity on GABAA Source: 1. “Long-Term Safety and Efficacy of Azetukalner, a Novel, Potent KV7 Potassium Channel Opener, in Adults With Focal Epilepsy: ≥48-Month Interim Analysis of the Ongoing 7-Year X-TOLE Open-Label Extension.” 2025 Annual Meeting of the American Epilepsy Society (AES). 2. French JA et al. JAMA Neurol.2023;80(11):1145-1154.ccJPM 2026 5
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Use eyedropper tool to select colors from the expanded color palette: Azetukalner & Epilepsy Market Opportunity
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE 0.8 M 2.6 M 3.0 M 2.6 M 0.4 M 0.1 M 0.2 M 1.6 M 0.3 M 0.8 M 1.8 M 0.3 M 0.9 M Patients (Millions) Estimated Diagnosed Adult Epilepsy Patient Population (2020) Sources: Xenon-sponsored market research; Mula, et al, Effect of drug treatment changes and seizure outcomes on depression and suicidality in adults with drug-resistant focal epilepsy, Epilepsia, December 11, 2023 Significant Global Epilepsy Burden • Epilepsy is the fourth most common neurological condition • Hallmark symptoms include: – focal seizures that start in one brain hemisphere (either aware or unaware) – generalized seizures the most common of which are tonic-clonic/convulsive seizures • Despite the availability of multiple ASMs, a substantial unmet medical need exists – up to 50% of epilepsy patients require additional treatment options • Rates of comorbid depression exist in up to 50% of epilepsy patients 7 FOS represent the largest segment of the epilepsy population Approximately 80% of adult patients with generalized epilepsy experience PGTCS Key: U.S. EU4 + UK Japan Adults with Epilepsy Adults with Focal Onset Seizures Adults with Undefined/Combination Epilepsy Adults with Generalized Seizures JPM 2026
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 X-TOLE Phase 2b Clinical Study in Focal Onset Seizures 8 Topline results reported in October 2021 and subsequent analyses and OLE data presented at AES meetings Randomization 2:1:1:2 AZK 25 mg QD* AZK 20 mg QD* AZK 10 mg QD* Placebo QD* Final 6-Week Follow-up (if not entering OLE) Open-Label Extension (20 mg QD*) Screening Baseline Up to 4 weeks 8-weeks 8-week double-blind period (DBP) 7-year open-label extension (OLE) Phase 2b Study and 7-year OLE *Administered as a once-daily capsule with food with no titration period.
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE Source: “Phase 2b Efficacy and Safety of XEN1101, a Novel Potassium Channel Modulator, in Adults with Focal Epilepsy (X-TOLE).” 2022 Annual Meeting of the American Epilepsy Society (AES). Statistically Significant and Dose Dependent Reduction in Seizures Observed in Phase 2b X-TOLE Study 9 14.9% 28.3% 43.1% 54.5% 0% 10% 20% 30% 40% 50% 60% Placebo AZK AZK AZK 10 mg 20 mg 25 mg % Responders * *** *** -18.2% -33.2% -46.4% -52.8% -60% -50% -40% -30% -20% -10% 0% AZK 10 mg AZK 20 mg AZK 25 mg Median % change (MPC) Placebo * *** *** Change from baseline in seizure frequency Responder rate (RR50) Azetukalner was administered as a once-daily capsule with food with no titration period. *p<0.05, ***p<0.001 *p<0.05, ***p<0.001 JPM 2026
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE Rapid Onset of Efficacy in Double-Blind Period (DBP) 10 Marked reduction in median FOS frequency at Week 1 for all doses compared with placebo Source: “Rapid Onset of Efficacy of XEN1101, a Novel Potassium Channel Opener, in Adults with Focal Epilepsy: Results from a Phase 2b Study (X-TOLE).” 2022 Annual Meeting of the American Epilepsy Society (AES). 28.1% 43.5% (p<0.05) 47.1% (p<0.05) 53.6% (p<0.001) 0% 10% 20% 30% 40% 50% 60% Placebo AZK AZK AZK 10 mg 20 mg 25 mg % Responders (Weekly FOS Frequency) AZK 10 mg AZK 20 mg AZK 25 mgPlacebo 0 2 4 6 8 Week 0% -20% -40% -60% -80% -100% Responders (RR50) based on percent change from baseline for Week 1 in weekly FOS frequency in DBP Change from baseline in FOS frequency in DBP *Azetuklaner was administered as a once-daily capsule with food with no titration period. JPM 2026 Median % change (MPC)
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE 11 After the DBP, all participants received 20 mg azetukalner at start of OLE as a once-daily capsule with food and no titration period. Data cutoff: October 6, 2025. Monthly seizure rate was calculated for 28 days per month. Sample sizes for each month varied for the 131 participants treated for ≥48 months in the OLE due to non-compliance with daily seizure diary entries. DBP: double-blind period; FOS: focal onset seizures; mo: month; MPC, median percent change; OLE, open-label extension. Source: “Long-Term Safety and Efficacy of Azetukalner, a Novel, Potent KV7 Potassium Channel Opener, in Adults With Focal Epilepsy: ≥48-Month Interim Analysis of the Ongoing 7-Year X-TOLE Open-Label Extension.” 2025 Annual Meeting of the American Epilepsy Society (AES). Robust Long-Term Efficacy Results in X-TOLE OLE • 90.9% reduction in monthly FOS frequency from DBP baseline at OLE month 48 • Higher monthly reductions in FOS frequency in participants receiving 1-2 ASMs at DBP baseline (n=60, 100%) vs. those receiving 3 ASMs (n=69, 81.8%) (data not shown) MPC in monthly FOS frequency for overall OLE population and those participants treated for ≥48 months in OLE JPM 2026
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE 12 Data cutoff: October 6, 2025. Monthly seizure rate was calculated for 28 days per month. OLE: open-label extension. Source: “Long-Term Safety and Efficacy of Azetukalner, a Novel, Potent KV7 Potassium Channel Opener, in Adults With Focal Epilepsy: ≥48-Month Interim Analysis of the Ongoing 7-Year X-TOLE Open-Label Extension.” 2025 Annual Meeting of the American Epilepsy Society (AES). Impressive Seizure Freedom in the X-TOLE OLE Seizure freedom rates for any consecutive ≥12, ≥24, ≥36, and ≥48 months in OLE participants treated for ≥48 months (n=131) JPM 2026 Any consecutive months of 100% seizure reduction Responders n = 50 33 26 14
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Keep content within provided margin guidelines: 12.5” width Please do not move or change the size of the Title box Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE Safety and Tolerability Data • Azetukalner was generally well-tolerated in this study with adverse events consistent with commonly prescribed ASMs – The most common reported treatment emergent adverse events (TEAEs) across all azetukalner dose groups were dizziness (24.6%), somnolence (15.6%) and fatigue (10.9%), as compared to the placebo group which reported dizziness (7.0%), somnolence (7.0%) and fatigue (5.3%) – The most common TEAEs leading to discontinuation across all azetukalner dose groups were dizziness (4.7%), balance disorder (2.4%), dysarthria (1.9%) and gait disturbance (1.9%) – Serious adverse events (SAE) incidence was low and balanced across groups (3.3% across all azetukalner dose groups as compared to 2.6% in the placebo group) • Azetukalner was generally well tolerated in OLE, long- term safety in the OLE is comparable with the safety observed in the DBP • As of October 6, 2025, the OLE has generated >775 patient-years of safety data exposure X-TOLE Double-Blind Period X-TOLE Open-Label Extension Sources: “Phase 2b Efficacy and Safety of XEN1101, a Novel Potassium Channel Modulator, in Adults with Focal Epilepsy (X-TOLE).” 2022 Annual Meeting of the American Epilepsy Society (AES). Long-Term Safety and Efficacy of Azetukalner, a Novel, Potent KV7 Potassium Channel Opener, in Adults With Focal Epilepsy: ≥48-Month Interim Analysis of the Ongoing 7- Year X-TOLE Open-Label Extension.” 2025 Annual Meeting of the American Epilepsy Society (AES). 13JPM 2026
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 X-TOLE2 and X-TOLE3 Phase 3 Clinical Trials in FOS • Phase 3 epilepsy program in focal onset seizures and primary generalized tonic-clonic seizures is underway • Plan to submit NDA supported by efficacy data from Phase 2b study (X-TOLE) and first Phase 3 study (X-TOLE2) • Conducting two identical multi-center, placebo-controlled Phase 3 FOS trials (target n = 360 in each study) 14 Phase 3 X-TOLE2 FOS topline data expected March 2026 followed by anticipated NDA submission H2 2026 AZK 25 mg QD* AZK 15 mg QD* Placebo QD* 12-week double-blind period (DBP) 3-year open-label extension (OLE) Final 8-Week Follow-up (if not entering OLE) Open-Label Extension (25 mg QD*) • Primary Objective: assess effect of azetukalner vs placebo on reducing focal onset seizure frequency • Secondary Objectives: include assessing the effect of azetukalner vs placebo on RR50, early treatment effect as measured at week 1, and PGI-C Randomization 1:1:1 Screening and Baseline Up to 9.5 weeks *Administered as once-daily capsule with food with no titration period.
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 X-ACKT Phase 3 Clinical Trial in PGTCS • Significant unmet need remains in PGTCS despite available treatment options and an opportunity remains for a broad-spectrum agent with activity across seizure types • Conducting a single, multi-center, placebo-controlled Phase 3 trial to support registration (n = ~160) 15 AZK 25 mg QD* Placebo QD* 12-week double-blind period (DBP) 3-year open-label extension (OLE) Final 8-Week Follow-up (if not entering OLE) Open-Label Extension (25 mg QD*) • Primary Objective: assess effect of azetukalner vs placebo on reducing frequency of primary generalized tonic-clonic seizures • Secondary Objectives: include assessing the effect on azetukalner vs placebo on RR50, seizure freedom and PGI-C Randomization 1:1 Screening and Baseline Up to 9.5 weeks *Administered as once-daily capsule with food with no titration period. Participants aged ≥12 years and <18 years will receive either azetukalner 15mg, azetukalner 25 mg, or placebo; participants aged ≥18 years will receive either azetukalner 25 mg or placebo.
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Use eyedropper tool to select colors from the expanded color palette: Expanding Azetukalner in Neuropsychiatry
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 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 azetukalner in major depressive disorder (MDD) 17 Phase 2 topline data from X-NOVA study announced in November 2023 AZK 20 mg QD* AZK 10 mg QD* placebo QD* 6-week double-blind period (DBP) 4 weeks 4-Week Follow-up • Primary Objective: Montgomery- Åsberg Depression Rating Scale (MADRS) score change through week 6 • Key Secondary Objective: Snaith- Hamilton Pleasure Scale (SHAPS) score change through week 6 Randomization 1:1:1 Screening 4 weeks *Administered as once-daily capsule with food with no titration period.
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Please do not move or change the size of the Subtitle box Keep content within provided margin guidelines: 4.9” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 X-NOVA Primary Efficacy Endpoint Change in MADRS Total Scores at Week 6 (mITT) MADRS: Montgomery-Åsberg Depression Rating Scale; LSMean (SEM) shown; mITT: modified intent to treat; population included all randomized participants who received at least 1 dose of study treatment and at least 1 post randomization MADRS score 18 *p<0.05 A clear dose response and a clinically meaningful, but not statistically significant, 3.04 difference in MADRS at week 6 in the 20 mg group placebo (N=54) AZK 20 mg (N=53) ΔMADRS from baseline at Wk 6 (LS mean) -13.90 -16.94 Difference vs placebo -3.04 p-value 0.135 Azetukalner was administered as a once-daily capsule with food with no titration period.
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Please do not move or change the size of the Subtitle box Keep content within provided margin guidelines: 4.9” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 X-NOVA Pre-Specified Endpoint Improvement in Depressive Symptoms Change in HAM-D17 Total Score at Week 6 (mITT) HAM-D17: Hamilton Depression Rating Scale was assessed at screening, baseline, and Week 6; mITT: modified intent to treat; population included all randomized participants who received at least 1 dose of study treatment and at least 1 post randomization MADRS score; p-value nominal 19 Improvement in depressive symptoms assessed by HAM-D17 total scores was significantly different at week 6 placebo (N=54) AZK 20 mg (N=53) HAM-D17 total score change from baseline at Wk 6 (LS mean) -10.18 -13.26 Difference vs placebo -3.08 p-value 0.042 Azetukalner (XEN1101) was administered as a once-daily capsule with food with no titration period.
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Please do not move or change the size of the Subtitle box Keep content within provided margin guidelines: 4.9” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 X-NOVA Secondary Efficacy Endpoint Change in SHAPS Total Score at Week 6 (mITT) SHAPS: Snaith-Hamilton Pleasure Scale; LSMean (SEM) shown; p-value nominal 20 Anhedonia symptom improvement: significantly different change in SHAPS at week 6in 20 mg group placebo (N=54) AZK 20 mg (N=53) SHAPS total score change from baseline at Wk 6 (LS mean) -5.30 -7.77 Difference vs placebo -2.46 p-value 0.046 Azetukalner (XEN1101) was administered as a once-daily capsule with food with no titration period.
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Please do not move or change the size of the Subtitle box Keep content within provided margin guidelines: 4.9” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 X-NOVA: Safety and Tolerability Data • The most commonly reported TEAEs in the azetukalner 20 mg group included dizziness (17.9%), somnolence (10.7%), headache (8.9%), and disturbance in attention (8.9%), as compared to the placebo group, which reported dizziness (7.3%), somnolence (1.8%), headache (12.7%), and disturbance in attention (0%) • Rates of discontinuation were similar across all treatment arms and rates of discontinuation due to TEAEs were low with three patients in the azetukalner 20 mg group (5.4%), as compared to two patients in the placebo group (3.6%) • No SAEs were reported in the two azetukalner treatment groups, and there were two patients (3.6%) in the placebo group who experienced a treatment-emergent SAE • Azetukalner was not associated with notable weight gain; patients did not report notable sexual dysfunction Azetukalner was generally well-tolerated with similar rates of overall adverse events reported across all treatment arms 21
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE AZK 20 mg QD* placebo QD* 6-week double-blind period (DBP) 8-Week Follow-up (if not entering OLE) Open-Label Extension (20 mg QD*) JPM 2026 Phase 3 Clinical Studies in Major Depressive Disorder • Phase 3 MDD program consists of three multi-center, placebo-controlled clinical trials (N=~450 in each study) • Plan to submit sNDA supported by efficacy data from two positive Phase 3 MDD trials 22 Phase 3 X-NOVA2 and X-NOVA3 studies in MDD are ongoing; X-NOVA2 topline data expected H1 2027 • Primary Objective: change from baseline in HAM-D17 score at week 6 • Key Secondary Objectives: include change from baseline in HAM-D17 score at week 1; change from baseline in SHAPS score at week 6; and change from baseline in CGI-S at week 6 Randomization 1:1 Screening and Baseline Up to 4 weeks *Administered as once-daily capsule with food with no titration period.
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 Phase 3 Clinical Studies in Bipolar Depression • Phase 3 BPD program consists of two multi-center, placebo-controlled clinical trials (n=~400 in each study) in patients with bipolar I or II depression (BPD) 23 X-CEED, first of two Phase 3 studies in BPD, is ongoing Randomization 1:1 AZK 20 mg QD* placebo QD* Screening and Baseline Up to 4 weeks 6-week double-blind period (DBP) 8-Week Follow-up (if not entering OLE) Open-Label Extension (20 mg QD*) 1-year open-label extension (OLE) • Primary Objective: change from baseline in MADRS score at week 6 • Key Secondary Objectives: include change from baseline in MADRS score at week 1; change from baseline in SHAPS score at week 6; and change from baseline in CGI-S at week 6 *Administered as once-daily capsule with food with no titration period.
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Use eyedropper tool to select colors from the expanded color palette: Pain Programs
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 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 that are otherwise healthy but cannot feel pain • Gain-of-function mutations in SCN9A can lead to extreme pain disorders, such as inherited erythromelalgia (IEM) or paroxysmal extreme pain disorder (PEPD), demonstrating that excessive NaV1.7 activity can drive pain 25 There is strong human genetic evidence to support Nav1.7 as a compelling target for pain drug development
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Keep content within provided margin guidelines: 5.5” height NaV1.7 Pain Program • Xenon has long history with NaV1.7 science and deep ion channel drug discovery expertise and is applying this knowledge to generate a pipeline of NaV1.7 molecules with differentiated profiles: – CNS penetrant to globally inhibit NaV1.7, better mimicking patient genetics – Demonstrates good free fraction and tissue distribution, achieving high levels of target engagement – Excellent potency and selectivity to safely achieve target therapeutic levels of NaV1.7 inhibition • NaV1.7 compound, XEN1701, in Phase 1 clinical study with a profile that has never been tested in clinic • Growing early-stage pipeline of numerous other compounds and distinct chemistries advancing IND- enabling studies 26JPM 2026
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Use eyedropper tool to select colors from the expanded color palette: Keep content within provided margin guidelines: 4.7” height Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Please do not move or change the size of the background banner XEN1701 Performance in IEM Mouse Model CNS penetrance, improved free fraction and good potency and selectivity demonstrate target engagement at low plasma exposures 27 0.01 0.1 1 10 100 1000 0.0 0.5 1.0 Plasma (μM) IEM Aconitine Flinching (Fraction in Pain) 2nd Gen (PF-771) XEN1701 2nd Gen (GDC-0310) 0.01 0.1 1 10 100 0.0 0.5 1.0 [Free Brain]/NaV1.7 EP IC50 IEM Aconitine Flinching (Fraction in Pain) XPC-1 XEN1701 XPC-2 XPC-3 75-90% receptor occupancy XEN1701 demonstrates target engagement at low total plasma concentrations In vivo activity correlates to free brain concentrations across Xenon's lead compounds JPM 2026
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Please do not move or change the size of the Subtitle box Keep content within provided margin guidelines: 4.9” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE NaV1.7 Program Status Advancing XEN1701, a NaV1.7 channel inhibitor in development for pain Phase 1 SAD/MAD* study underway in healthy participants Study completion expected in 2026 to support initiating a Phase 2 proof-of-concept study in acute pain Preliminary Phase 1 data from the SAD portion of the study suggest that XEN1701 has reached drug concentrations that are predicted to achieve receptor occupancies required for therapeutic activity based on human genetic data SAD: Single Ascending Dose; MAD: Multiple Ascending DoseJPM 2026 28
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Use eyedropper tool to select colors from the expanded color palette: Milestones
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Use eyedropper tool to select colors from the expanded color palette: Please try to avoid covering the logo Please do not move or change the size of the Title box Keep content within provided margin guidelines: 12.5” width Please do not move or change the size of the Subtitle box Keep content within provided margin guidelines: 4.9” height Copy and paste clinical trial logo from Icon library slide Center image inside shape DO NOT RESIZE JPM 2026 Potential Value-Creating Milestone Opportunities FOS: Focal onset seizures; PGTCS: Primary generalized tonic-clonic seizures; DBP: Double-blind period; MDD: Major depressive disorder; BPD: Bipolar depression; PoC: proof- of-concept 30 Azetukalner in Epilepsy Phase 3 studies ongoing in FOS (X-TOLE2/3) & PGTCS (X-ACKT) Azetukalner in Neuropsychiatry Phase 3 studies ongoing in MDD (X- NOVA2/3) and BPD (X-CEED) Early-Stage Programs Maturing pipeline, including multiple Phase 1 studies underway in pain • X-TOLE2: Topline data expected March 2026 with anticipated NDA submission in H2 2026 • X-TOLE3: Enrollment of non- Japanese participants expected to complete in 2026 • X-ACKT: Enrollment ongoing • X-NOVA2: Topline data expected H1 2027 • X-NOVA3 and X-CEED: Enrollment ongoing • XEN1701 (NaV1.7) and XEN1120 (KV7): Ph1 completion expected in 2026 to support Ph2 PoC studies in acute pain • NaV1.1 program: IND-enabling studies ongoing (Dravet syndrome) • Neurocrine collaboration: Ph1 study ongoing for NBI-921355 (NaV1.2/1.6 Inhibitor for certain types of epilepsy)
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Use eyedropper tool to select colors from the expanded color palette: INVESTORS@XENON-PHARMA.COM For more information