Xenon Completes Enrollment of 380 Patients in Phase 3 Azetukalner Study

Phase 3 Azetukalner Program in Epilepsy & Depression: Phase 3 X-TOLE2 study of azetukalner in focal onset seizures has completed enrollment with 380 patients randomized, and final data are being collected to support the topline data readout anticipated in March 2026. Patient baseline characteristics and the open-label extension rollover rate in X-TOLE2 are consistent with the Phase 2b X-TOLE study. Xenon recently presented 48-month data from the ongoing X-TOLE OLE study of azetukalner in patients with FOS at the American Epilepsy Society meeting. These data highlighted the long-term efficacy and safety of azetukalner, with reductions in monthly FOS frequency of over 90% from double-blind period baseline among participants treated greater than or equal to48 months. Seizure freedom for any greater than or equal to12, greater than or equal to24, greater than or equal to36, and greater than or equal to48-month consecutive duration was attained by 38.2%, 25.2%, 19.8%, and 10.7% of participants treated for greater than or equal to48 months, respectively. These data, along with an update on Xenon's progress preparing for potential commercialization of azetukalner, were also highlighted in a webinar for investors in December 2025. Phase 3 X-TOLE3 study of azetukalner in FOS continues to enroll and is intended to support regulatory submissions outside the United States. In support of a potential regulatory submission in Japan, Xenon has completed an ethnobridging study and shared the results in a recent meeting with Japan's Pharmaceutical and Medical Devices Agency. Xenon has aligned with PMDA to enroll approximately 60 of the planned 360 X-TOLE3 participants in Japan. Enrollment of non-Japanese participants in X-TOLE3 is expected to complete in 2026. Phase 3 X-ACKT study of azetukalner in Primary Generalized Tonic-Clonic Seizures continues to enroll and is intended to support regulatory submissions for an additional epilepsy indication. Phase 3 X-NOVA2 and X-NOVA3 studies are ongoing as the first two of three planned Phase 3 clinical studies evaluating azetukalner in patients with major depressive disorder. Topline data from X-NOVA2 are expected in H1 2027. Phase 3 X-CEED study evaluating azetukalner in patients with bipolar depression I or II is underway. Broader Pipeline Opportunity: Phase 1 Single Ascending Dose/Multiple Ascending Dose study in healthy adult participants is underway for XEN1701 targeting the sodium channel NaV1.7. 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. Study completion is expected in 2026 to support initiating a Phase 2 proof-of-concept study in acute pain. NaV1.7 is an important target for pain based on strong human genetic validation and may represent a new class of pain medicines without the limitations of opioids. Phase 1 SAD/MAD study in healthy adult participants is underway for XEN1120 targeting KV7. Preliminary Phase 1 data from the SAD portion of the study suggest that XEN1120 has reached drug concentrations that are consistent with pain reductions in preclinical models. Study completion is expected in 2026 to support initiating a Phase 2 proof-of-concept study in acute pain. IND-enabling studies are ongoing for the Company's NaV1.1 program for the treatment of Dravet syndrome. Pre-clinical data suggest that targeting NaV1.1 could potentially address the underlying cause and symptoms of Dravet syndrome. In collaboration with Neurocrine Biosciences, a Phase 1 study is ongoing for NBI-921355, an investigational, selective inhibitor of voltage-gated sodium channels NaV1.2 and NaV1.6 in development for the potential treatment of certain types of epilepsy.