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    • Visit us at AES 2024

    The Azetukalner Epilepsy Phase 3 Program Is Launched And Enrolling

    X‑TOLE2 and X‑TOLE3 are two identical Phase 3 clinical trials evaluating azetukalner as an adjunctive treatment in focal onset seizures1,2

    LEARN MORE

    X-ACKT is a Phase 3 clinical trial evaluating azetukalner as an adjunctive treatment in primary generalized tonic-clonic seizures3

    LEARN MORE

    In 2024, we are planning to initiate a Phase 3 azetukalner program in major depressive disorder, based on topline data from our azetukalner Phase 2 X-NOVA clinical trial.

    Connect with Us at the American Epilepsy Society (AES) Annual Meeting in Los Angeles, California

    Stop by Booth #1721 to learn more about azetukalner and our neurology pipeline.

    Saturday, December 7  Noon - 6:00 PM
    Sunday, December 8  10:00 AM - 4:00 PM
    Monday, December 9  10:00 AM - 2:00 PM.

    AES Annual Meeting | December 6-10, 2024

    The AES Annual Meeting brings together healthcare providers, scientists, advocates, industry, and other professionals dedicated to better outcomes for people with epilepsy.

    Take a look through our AES 2024 poster presentations.

    AES 2024 poster presentation information

    Long-Term Safety and Efficacy of Azetukalner, a Novel, Potent Kv7 Potassium Channel Opener in Adults With Focal Epilepsy: Update From the Ongoing 7-Year Open-Label Extension of X-TOLE | Jacqueline French, Roger Porter, Emilio Perucca, Martin Brodie, Cynthia Harden, Jenny Qian, Constanza Luzon Rosenblut, Christopher Kenney, Gregory N. Beatch

    VIEW POSTER

    Is the Mental Health Burden of Epilepsy Under-Recognized in Patients Reporting Focal Onset Seizures? A Patient-Reported Outcomes Study | Joanne M. Wagner, Bhagyashree Oak, Brittany Smith, Amod Athavale, Jeffrey R. Skaar, Alvin Ong, Cynthia Harden

    VIEW POSTER

    A Targeted Literature Review of Comorbidity Burden in Focal Epilepsy | Alvin Ong, Zarmina Khankhel, Darrin Benjumea, Grace Goldsmith-Martin, Agata Los, Dan Thornton

    VIEW POSTER

    For a complete list of Xenon conference posters and presentations, please visit our Publications page.

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    Azetukalner — a Novel, Potent Kv7 Potassium Channel Opener5,6

    Potassium channels play a major role in the control of neuronal excitability and represent a promising treatment target for epilepsy.7,8




    Potential Mechanism of Action (MOA)*

    Kv7 Channels Have a Critical Role in Neuronal Firing9-11

    *Azetukalner is in Phase 3 clinical investigation and has not been approved by the US FDA or other regulatory bodies.

    K+ channels repolarize membranes to end the action potential9

    Kv7 channels9

    • Are translated from the KCNQ gene family (Q1–Q5)
    • Exert important inhibitory control over neuronal firing
    • Control unwanted burst and spontaneous firing that can lead to seizures

    Azetukalner is being studied as a once-daily capsule taken with food with no titration.12

    View our clinical trial brochure for azetukalner in focal onset seizures and primary generalized tonic-clonic seizures to learn more.

    VIEW BROCHURE
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    Phase 3 Focal Onset Seizures: X-TOLE2 & X-TOLE3

    Study Design1,2

    X‑TOLE2 and X‑TOLE3 are two identical Phase 3, multicenter, randomized, double-blind, placebo-controlled trials to evaluate the clinical efficacy, safety, and tolerability of azetukalner as adjunctive treatment in adults aged ≥18 years diagnosed with FOS who are taking 1 to 3 ASMs.

    Approximately 360 eligible subjects will be randomized 1:1:1 (azetukalner 25 mg : 15 mg : placebo taken QD with food) per trial.

    ASM, antiseizure medication; FOS, focal onset seizures.

    Screening/baseline period: Up to 9.5 weeks duration to assess the frequency of seizures.

    Double-blind period (DBP): 12 weeks duration. There is no titration period.

    Follow-up period: 8 weeks duration after the last dose of study drug for subjects who do not complete the 12-week DBP or who complete the DBP but do not enter the OLE study.

    azetukalner is administered as a once-daily capsule with food with no titration required.3

    On completion of the double-blind period in X‑TOLE2 or X‑TOLE3, eligible patients may enter an open-label extension study for up to three years.13

    Primary efficacy endpoint

    Median percent change in monthly focal seizure frequency from baseline to DBP of azetukalner compared to placebo.1,2

    For additional information, including inclusion and exclusion criteria, visit the X‑TOLE2 and X‑TOLE3 clinical trial pages.

    Find out how to become a clinical trial investigator and enroll your patients in X‑TOLE 2/3 by contacting X‑TOLE@xenon‑pharma.com

    For additional information, including inclusion and exclusion criteria, visit the X‑TOLE2 and X‑TOLE3 clinical trial pages.

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    Phase 3 Primary Generalized Tonic-Clonic Seizures: X-ACKT

    Study Design3

    X-ACKT is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of azetukalner as adjunctive treatment in adults aged ≥12 years with a seizure frequency of ≥3 PGTCS during the last 8 weeks of the baseline period and taking 1 to 3 ASMs.

    Approximately 160 eligible subjects will be randomly assigned 1:1 (azetukalner 25 mg : placebo taken QD with food).

    ASM, antiseizure medication; PGTCS, primary generalized tonic-clonic seizures.

    Screening/baseline period: Up to 9.5 weeks duration to assess the frequency of seizures.

    Double-blind period (DBP): 12 weeks duration. There is no titration period.

    Follow-up period: 8 weeks duration after the last dose of study drug for subjects who do not complete the 12-week DBP or who complete the DBP but do not enter the OLE study.

    Azetukalner is administered as a once-daily capsule with food with no titration required. Subjects aged ≥12 years and <18 years will receive either azetukalner 15 mg, azetukalner 25 mg, or placebo; subjects aged ≥18 years will receive either azetukalner 25 mg or placebo.3

    On completion of the double-blind period in X-ACKT, eligible patients may enter an open-label extension study for up to three years.13

    Primary efficacy endpoint

    Median percent change in monthly PGTCS frequency from baseline through the DBP of azetukalner versus placebo.3

    For additional information, including inclusion and exclusion criteria, visit the X-ACKT clinical trial page.

    Find out how to become a clinical trial investigator and enroll your patients in X-ACKT by contacting X‑ACKT@xenon‑pharma.com

    For additional information, including inclusion and exclusion criteria, visit the X-ACKT clinical trial page.

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    For More Information

    Find out more about our azetukalner Epilepsy Phase 3 program by contacting medicalaffairs@xenon-pharma.com.

    References

    1. NCT05614063: A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE2). NIH U.S. National Library of Medicine ClinicalTrials.gov. Accessed December 2, 2024. Study Details | A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures | ClinicalTrials.gov
    2. NCT05716100: A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3). NIH U.S. National Library of Medicine ClinicalTrials.gov. Accessed December2, 2024. Study Details | A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3) | ClinicalTrials.gov
    3. NCT05667142: A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures (X-ACKT). NIH U.S. National Library of Medicine ClinicalTrials.gov. Accessed December 2, 2024. Study Details | A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures | ClinicalTrials.gov
    4. Annual Meeting: World's Premier Neurology Meeting | AAN. American Academy of Neurology. Accessed February 21, 2024. https://www.aan.com/events/annual-meeting.
    5. Dean R, Lin S, Bankar G, et al. Preclinical In Vitro and In Vivo Comparison of the Kv7 Activator XEN1101 with Ezogabine. American Epilepsy Society 2020 Symposium. December 4-8, 2020, Seattle, WA.
    6. Xenon Pharmaceuticals Inc. Data on file MA08/2023.
    7. Xenon Pharmaceuticals Inc. Data on file CC08/2022.
    8. Porter RJ, Kenney C, Harden C, Sherrington R. The Unmet Need in Epilepsy: The Therapeutic Potential of Potassium Channel Modulators. American Epilepsy Society 2021 Symposium. December 3, 2021, Chicago, IL.
    9. Xenon Pharmaceuticals Inc. Data on file CC08/2023.
    10. Xenon Pharmaceuticals Inc. Data on file CC09/2023.
    11. Badawy RA, Harvey AS, Macdonell RA. Cortical hyperexcitability and epileptogenesis: understanding the mechanisms of epilepsy - part 1. J Clin Neurosci. 2009;16(3):355-365. doi:10.1016/j.jocn.2008.08.026
    12. French JA, Porter RJ, Perucca E, et al. Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults With Focal Epilepsy A Phase 2b Randomized Clinical Trial. JAMA Neurol. 2023;80(11):1145-1154. doi:10.1001/jamaneurol.2023.3542
    13. NCT05718817: An Open-label Study of XEN1101 in Epilepsy (X-TOLE4) NIH U.S. National Library of Medicine ClinicalTrials.gov. Accessed December 2, 2024. Study Details | An Open-label Study of XEN1101 in Epilepsy | ClinicalTrials.gov
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