Xenon Pharmaceuticals (XENE) Stifel 2024 Healthcare Conference summary

Key milestones and strategic focus

• 2025 is positioned as a pivotal year with major phase 3 data readouts in epilepsy and progress in depression trials.

• Three parallel phase 3 trials for azetukalner in epilepsy, including two for focal onset seizures and one for primary generalized tonic-clonic seizures.

• First phase 3 trial in major depressive disorder (MDD) to start by year-end, with two more to follow in a staggered fashion.

• Long-term efficacy and safety data for azetukalner to be presented at the American Epilepsy Society meeting.

• Multiple INDs expected in 2025 and 2026, with first-in-human studies to follow.

Clinical trial design and risk management

• Phase 3 epilepsy studies closely mirror phase 2b design, with increased sample size and extended double-blind period from 8 to 12 weeks.

• Placebo rates managed by careful geographic and site selection, leveraging experienced sites and electronic diaries.

• Over 99% power in high-dose group and over 90% in mid-dose for phase 3 epilepsy trials.

• NDA filing for epilepsy will be based on X-TOLE and X-TOLE2 data, with X-TOLE3 supporting safety.

• MDD phase 3 program increases patient severity criteria and reduces drug arms to lower placebo rates.

Pipeline and future directions

• Pipeline includes additional Kv7 drugs, NaV1.1 for Dravet syndrome, and NaV1.7 for pain, with INDs planned for 2025.

• NaV1.1 program shows potential for disease modification in developmental epileptic encephalopathies.

• NaV1.7 program aims to overcome historical challenges in selectivity and safety, with no preclinical tox observed so far.

• Proof-of-concept for pain will likely use bunionectomy studies rather than variable healthy volunteer models.

• Indication expansion for azetukalner is under evaluation, with updates expected in 2025.