Xenon Pharmaceuticals (XENE) investor relations material

Key program updates and milestones

• Lead molecule azetukalner is advancing in epilepsy, neuropsychiatry, and pain, with a focus on unblinding the first phase III epilepsy trial (X-TOLE2) in early 2026.

• Three phase III epilepsy trials are running in parallel: X-TOLE2 and X-TOLE3 (focal onset seizures) and X-ACKT (primary generalized tonic-clonic seizures), with X-TOLE2 fully enrolled and data expected in early 2026.

• For major depressive disorder, three phase III trials are planned, with two (X-NOVA2, X-NOVA3) underway and a third in bipolar depression (X-CEED) recently initiated; MDD studies are expected to take 2–2.5 years to complete.

• Pain portfolio includes two molecules (XEN1701 for Nav1.7 and XEN1120 for Kv7) in phase I, with phase II proof-of-concept studies targeted for 2027.

• Annual press release in January will outline 2026 milestones and provide updated guidance.

Clinical trial design and positioning

• X-TOLE2 and X-TOLE3 are identically designed, with X-TOLE2 focused on U.S. sites and X-TOLE3 on ex-U.S.; both are required for EMA submission.

• Phase III epilepsy trials mirror phase II in inclusion criteria and design, with high statistical power and expectations of reproducibility.

• Azetukalner's profile includes a novel mechanism, rapid onset, no titration, and favorable tolerability, aiming for earlier-line use in epilepsy.

• In psychiatry, differentiation is based on novel mechanism, rapid onset, impact on anhedonia, and a distinct adverse event profile.

• Bipolar depression trial (X-CEED) includes both bipolar I and II, with interim analysis for potential resizing; timelines expected to be longer than MDD studies.

Market opportunity and regulatory outlook

• U.S. epilepsy market includes about 1 million patients with unmet needs for new mechanisms; azetukalner is positioned for broad use, including less severe cases.

• NDA submission for epilepsy is planned for 2026, with potential approval in 2027; both X-TOLE2 and X-TOLE3 data will support ex-U.S. filings.

• All anti-seizure medications are typically scheduled; final DEA scheduling for azetukalner will depend on phase III data.

• Pain program leverages unique ion channel expertise, with phase I studies focused on achieving target receptor occupancy and phase II studies to start in acute pain settings before expanding to chronic pain.

• Proof-of-concept pain studies are expected to yield patient data in 2027, with rapid execution anticipated once phase I is complete.