Xenon Pharmaceuticals Inc. · NASDAQ:XENE
Xenon Pharmaceuticals — 2025 J.P. Morgan Healthcare Conference
25 slides from Xenon Pharmaceuticals's conference presentation, Jan 13, 2025
Slide 1: 2025 J.P. Morgan Healthcare Conference
2025 J.P. Morgan Healthcare Conference Corporate Overview P R E S E N T E D B Y: I A N M O R T I M E R , P R E S I D E N T & C E O , X E N O N P H A R M A C E U T I C A L S JANUARY 13, 2025 NASDAQ: XENE www.xenon-pharma.com
Slide 2: Forward Looking Statement/Safe Harbor
Forward Looking Statement/Safe Harbor This slide presentation and the accompanying oral commentary contain forward-looking statements that involve risks, uncertainties and assumptions. If the risks or uncertainties ever materialize or the assumptions prove incorrect, our results may differ materiall
Slide 3: About Xenon Pharmaceuticals
About Xenon Pharmaceuticals ▪ Neuroscience-focused biopharma company and leader in small molecule, ion channel drug discovery and development ▪ Azetukalner, our highly potent, selective Kv7 channel opener, represents the most advanced, clinically validated potassium channel modulator in late-stage c
Slide 4: Xenon’s Neuroscience-Focused Pipeline
Xenon’s Neuroscience-Focused Pipeline Clinical Trial/Partner Pre-Clinical Phase 1 Phase 2 Phase 3 Azetukalner (Potassium Channel Opener) Epilepsy: Focal Onset Seizures (FOS) X-TOLE2 Epilepsy: Focal Onset Seizures (FOS) X-TOLE3 Epilepsy: Primary Generalized Tonic-Clonic Seizures (PGTCS) X-ACKT Major
Slide 5: Overview of Azetukalner in Epilepsy
Overview of Azetukalner in Epilepsy X-TOLE, X-TOLE2, X-TOLE3, AND X-ACKT CLINICAL TRIALS 5
Slide 6: Significant Global Epilepsy Burden
Significant Global Epilepsy Burden Estimated Diagnosed Adult Epilepsy Patient Population (2020) Key: U.S. Epilepsy is the fourth most common 1.8 M EU4 + UK neurological condition 3.0 M Japan Hallmark symptoms include: 1.6 M • focal seizures that start in one brain Patients (Millions) Approximately 8
Slide 7: X-TOLE Phase 2b Clinical Trial in Focal Onset Seizures
X-TOLE Phase 2b Clinical Trial in Focal Onset Seizures Topline results reported in October 2021 and subsequent ad hoc analyses and OLE data presented at AES meetings 7
Slide 8: Compelling Phase 2b Efficacy Results
Compelling Phase 2b Efficacy Results Azetukalner (XEN1101) was administered as a once-daily capsule with food with no titration period. Statistically significant and dose dependent reduction in seizures Source: “Phase 2b Efficacy and Safety of XEN1101, a Novel Potassium Channel Modulator, in Adults
Slide 9: Robust Long-Term Efficacy Results in X-TOLE OLE
Robust Long-Term Efficacy Results in X-TOLE OLE MPC in Monthly FOS Frequency During DBP and OLE Patients receiving 1–2 ASMs at OLE Dose: 20 mg QD baseline experienced higher monthly MPC reductions in FOS frequency from baseline at OLE study month 36 (100% seizure reduction, n=67), compared to those
Slide 10: Impressive Seizure Freedom in the X-TOLE OLE
Impressive Seizure Freedom in the X-TOLE OLE Participants (n=147) Treated for >36 Months in the OLE 50% 45% 40% 35% 32.7% Responders (%) 30% 25% 20.4% 20% 15% 10.2% 10% 5% 0% Participants, n 48 30 15 >12 Months >24 Months >36 Months Any Consecutive Months of 100% Seizure Reduction Nearly 1 in 3 pati
Slide 11: X-TOLE: Safety and Tolerability Data
X-TOLE: Safety and Tolerability Data ▪ X-TOLE Double-Blind Period • Azetukalner was generally well-tolerated in this study with adverse events consistent with other commonly prescribed ASMs • The most common reported treatment emergent adverse events (TEAEs) across all azetukalner dose groups were d
Slide 12: X-TOLE2 and X-TOLE3 Phase 3 Clinical Trials in FOS
X-TOLE2 and X-TOLE3 Phase 3 Clinical Trials in FOS ▪ 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 (N = ~360 in each study) ▪ Primary Objective: assess effect
Slide 13: X-ACKT Phase 3 Clinical Trial in PGTCS
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
Slide 14: Expanding Azetukalner in MDD
Expanding Azetukalner in MDD 14
Slide 15: X-NOVA Phase 2 Proof-of-Concept Clinical Trial in MDD
X-NOVA Phase 2 Proof-of-Concept Clinical Trial 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) ▪ Primary Objective: Montgomery-Åsberg De
Slide 16: Primary Efficacy Endpoint: Change in MADRS Total Scores at Week 6
Primary Efficacy Endpoint: Change in MADRS Total Scores at Week 6 (mITT) Azetukalner *p<0.05 Placebo 20 mg (N=54) (N=53) ΔMADRS from BL at Wk 6 -13.90 -16.94 (LS mean) Diff. vs Pbo -3.04 p-value 0.135 A clear dose response and a clinically meaningful 3.04 difference in MADRS at Week 6 in the 20 mg g
Slide 17: Pre-Specified Endpoint: Change in HAM-D17 Total Score at Week 6
Pre-Specified Endpoint Improvement in Depressive Symptoms: Change in HAM-D17 Total Score at Week 6 (mITT) Azetukalner 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. placebo -3.08 p-value 0.042 Improvement in depressive symptoms a
Slide 18: Secondary Efficacy Endpoint: Change in SHAPS Total Score at Week 6
Secondary Efficacy Endpoint: Change in SHAPS Total Score at Week 6 (mITT) Azetukalner Placebo 20 mg (N=54) (N=53) SHAPS total score change from baseline at Week 6 -5.30 -7.77 (LSMean) Difference vs. placebo -2.46 p-value 0.046 Anhedonia symptom improvement: significantly different change in SHAPS at
Slide 19: X-NOVA: Safety and Tolerability Data
X-NOVA: Safety and Tolerability Data ▪ Azetukalner was generally well-tolerated with similar rates of overall adverse events reported across all treatment arms • The most commonly reported TEAEs in the azetukalner 20 mg group included dizziness (17.9%), somnolence (10.7%), headache (8.9%) and distur
Slide 20: Phase 3 Clinical Studies in MDD
Phase 3 Clinical Studies in MDD ▪ 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 Phase 3 Studies ▪ Primary Objective: change from baseline in HAM-D17 s
Slide 21: Azetukalner: Significant Potential Across Epilepsy and MDD
Azetukalner: Significant Potential Across Epilepsy and MDD 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 significantly different red
Slide 22: Pipeline Programs
Pipeline Programs POTASSIUM & SODIUM CHANNEL SCIENCE 22
Slide 23: Xenon’s Ongoing Pre-Clinical and Product Life Cycle Work
Xenon’s Ongoing Pre-Clinical and Product Life Cycle Work ▪ Leveraging Xenon’s deep ion channel expertise to develop promising drug candidates that target sodium and potassium channels ▪ Anticipate filing multiple INDs (or equivalent) across Kv7 and Nav1.7 programs in 2025 ▪ Expect to nominate lead N
Slide 24: Potential Value-Creating Milestone Opportunities
Potential Value-Creating Milestone Opportunities Azetukalner Epilepsy Program • Phase 3 clinical trials (X-TOLE2/X-TOLE3) in FOS underway; X-TOLE2 topline data expected in 2H:2025 • Phase 3 clinical trial (X-ACKT) in PGTCS underway to support registration in additional epilepsy indication • NDA subm
Slide 25: For more information
For more information INVESTORS@XENON -PHARMA.COM 25
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