Xenon Pharmaceuticals, Inc. Q2 FY2024 earnings call

1. Continued execution across Phase 3 azetukalner epilepsy studies, with top-line results from X-TOLE2 in focal onset seizures anticipated in the second half of 2025. Positive results could enable submission of NDA for commercialization. 2. Preparation for azetukalner MDD program, with Phase 3 protocol finalized and filed with FDA, study initiation expected in the second half of 2024. Results from Phase 2 X-NOVA trial presented at ASCP meeting showed potential differentiated profile. 3. Expansion of pipeline with multiple development track candidates targeting potassium and sodium channels. Nominating lead candidates for Kv7 and Nav1.7, with plans for IND-enabling studies. 4. Progress in collaboration with Neurocrine Biosciences for epilepsy treatments, including ongoing Phase 2 study of NBI-921352 and next lead candidate in IND-enabling studies.

1. X-TOLE2 top-line data for focal onset seizures anticipated in the second half of 2025. 2. Anticipate having sufficient cash to fund operations into 2027. 3. Expect to initiate first of three Phase 3 clinical trials in MDD in the second half of 2024. 4. Aim to file multiple INDs or equivalent submissions in 2025.

Q: On X-TOLE2, demographics and enrollment timing.

A: Demographics tracked blinded, not publicly shared yet. X-TOLE2 top-line data guidance is second half of 2025, with patient screening completion leading to top-line data.

Q: On MDD trial design, ex-U.S. sites and anhedonia.

A: First MDD Phase 3 study to focus on U.S. sites initially, ex-U.S. sites may be added later. Azetukalner's profile with unique mechanism, rapid onset, and favorable safety vs standard of care, including benefit on anhedonia.

Q: On pace of enrollment for X-TOLE2, competitive pressures, and regions.

A: Enrollment has ebb and flow, no competitive pressure observed. X-TOLE2 used similar regions as X-TOLE, with 60% of X-TOLE enrollment from Europe and 40% from U.S.

Q: On next-generation Kv7 asset.

A: Multiple diverse chemistry candidates in IND-enabling studies, not specifically aiming to improve on azetukalner's attributes but to diversify therapeutically into various indications.

Q: On Nav1.7 development in pain.

A: Early work includes healthy volunteer studies, with both acute and chronic development opportunities possible but premature to fully flesh out plan.

Q: On PGTCS study timeline and expectations.

A: No guidance yet on X-ACKT, PGTCS studies slower than FOS due to lower seizure burden and fewer patients, powered based on previous studies.

Q: On Nav1.8 program and broader seizure-related indications.

A: 352 in SCN8A Phase 2 trial, next lead candidate is dual Nav1.2/1.6 inhibitor, which would be evaluated in epilepsy studies if advanced.

Q: On X-ACKT efficacy and dose.

A: Powered based on successful previous studies, dose of 25 mg chosen based on field experience with other successful drugs in similar indications.