Xenon Pharmaceuticals (XENE) investor relations material

Key clinical data and program updates

• Azetukalner (AZK) is the only Kv7 channel opener in development with long-term efficacy and safety data, showing over 800 patient-years of exposure and robust, dose-dependent, placebo-adjusted efficacy in focal onset seizures, with up to 52.8% median reduction and rapid onset by Week 1.

• 48-month open-label extension data show a 90.9% median reduction in seizure frequency, with 38% of patients treated for at least 48 months achieving 12 months of seizure freedom.

• Seizure freedom can be regained after breakthrough seizures, with mean regained freedom lasting 18.9 months, supporting continued AZK use.

• Safety profile remains consistent over 48 months, with most common adverse events being dizziness, headache, and somnolence; serious adverse events were infrequent and balanced across groups.

• Phase 3 X-TOLE2 study is fully enrolled, with top-line data expected in early 2026; AZK is also being studied in primary generalized tonic-clonic seizures and neuropsychiatric indications.

Commercial and market readiness

• AZK's differentiated profile—novel mechanism, no titration, fast onset, and minimal drug-drug interactions—resonates with epileptologists and general neurologists, supporting broad adoption.

• Market research shows AZK is viewed favorably for its ease of use, safety, and potential to become the preferred branded ASM for general neurologists.

• Early investments in commercial infrastructure, payer engagement, and experienced leadership are underway to ensure a successful launch.

• The commercial team is leveraging advanced technologies and mapping the patient journey to optimize access, adherence, and long-term retention.

• AZK targets a significant unmet need in epilepsy, with FOS representing the largest segment and high rates of comorbid depression among patients.

Physician and patient perspectives

• Clinicians report patients achieving seizure freedom for the first time, significantly improving independence and quality of life.

• AZK's mood-neutral or mood-positive potential is highly valued, given the high prevalence of depression in epilepsy and the negative impact of some ASMs on mood.

• The lack of titration and monitoring requirements reduces burden on both patients and providers, addressing a key unmet need in epilepsy management.

• Both patients and healthcare providers report challenges with titration, including increased clinic visits, complexity, and emotional burden.

• Ongoing collection of patient-reported outcomes on depression and anxiety in phase 3 will further inform AZK's impact on comorbidities.