Xenon Pharmaceuticals, Inc. Q3 FY2024 earnings call

• Significant progress in azetukalner's clinical programs, with Phase 3 epilepsy and MDD programs ongoing. • Long-term data from X-TOLE open-label extension study shows patients on azetukalner for over 3 years with seizure freedom and improved quality of life. • Pipeline expansion with multiple Kv7 candidates and Nav1.7 sodium channel program; IND-enabling work underway for early-stage candidates. • Matt Ronsheim joined as COO to oversee R&D and commercialization. • Active engagement with medical community at events like American Epilepsy Society Meeting and Psych Congress to highlight azetukalner's potential.

No specific financial performance for product segments with absolute terms and revenue contribution % provided in the transcript.

• Anticipated top line data from X-TOLE2, a Phase 3 epilepsy study, in the second half of 2025. • Plan to initiate Phase 3 MDD program before the end of 2024. • Anticipate filing INDs or equivalents for early-stage candidates in 2025. • Sufficient cash to fund operations into 2027.

• Uncertainty in clinical trial outcomes, including potential variability in efficacy results. • Competition in ion channel therapeutics development, which could impact market position. • Regulatory challenges in obtaining approvals for azetukalner and other candidates.

Q: Could you provide color on enrollment dynamics in Phase 3 epilepsy program and how MDD investigator-sponsored study relates to Phase 3 pivotal program?

A: Ian Mortimer stated they're comfortable with Phase 3 epilepsy program progress, with top line data from X-TOLE2 expected in second half of 2025. On MDD, the investigator-sponsored study is small and not read-through to their own Phase 3 program, which will have three Phase 3 trials with 20-mg dose of azetukalner.

Q: When can we expect to learn more about lead Nav1.7 candidate's clinical profile and what a proof-of-concept study for Nav1.7 could look like?

A: Ian Mortimer said they're incorporating learnings into Nav1.7 program but not sharing all details publicly. Initial study will be first-in-human SAD/MAD, with proof-of-concept study potentially in bunionectomy.

Q: What are assumptions for placebo rate in X-TOLE 2 and 3 studies and how is placebo risk controlled?

A: Ian Mortimer mentioned they used data from X-TOLE study to model placebo rates, with powering based on actual data. Chris Kenney added they mitigate placebo risk by targeting experienced sites and using electronic diaries.

Q: What are key elements of 36-month data from X-TOLE OLE and confidence in safety profile?

A: Ian Mortimer said the 36-month data will show consistency in seizure reduction and seizure freedom rates. Safety profile is consistent over time with no new safety concerns observed.

Q: Thoughts on bringing azetukalner into pediatric development and unique aspects of pediatric studies?

A: Ian Mortimer stated there are agreed-upon pediatric plans with regulators, with work on formulation and juvenile toxicology ongoing, and studies to be conducted in younger cohorts over time.

Q: Confidence in food effect patent and label language for dosing close to meal time?

A: Sherry Aulin said they're comfortable with the food effect patent, and dosing with food near evening meal is part of Phase 3 development, expected to be on label.

Q: Pursuit of acute vs chronic pain indications for Nav1.7 and thoughts on Nav1.8 inhibitors?

A: Ian Mortimer said Nav1.7 target isn't limited to acute or chronic, with focus on proof-of-concept in bunionectomy. No formal Nav1.8 program as focus is on Nav1.7 due to stronger genetics and less competitive space.

Q: X-TOLE3's role in data strategy for NDA filing and European filing?

A: Ian Mortimer said X-TOLE2 is prioritized for NDA filing in U.S., with X-TOLE3 important for European filing and overall safety database.

Q: Impact if X-TOLE2 efficacy effect size diminishes relative to X-TOLE?

A: Chris Kenney and Ian Mortimer noted X-TOLE data is compelling, and even if X-TOLE2 data differs, the totality of data package (including open-label and other attributes) supports azetukalner's value proposition.

Q: Strategy for MDD program in terms of trial staggering?

A: Ian Mortimer said Phase 3 MDD studies will be run in parallel with a natural stagger, with focus on initiating X-NOVA2 before end of 2024.

Q: Differentiation of early-stage Kv7 candidates from azetukalner and IP portfolio?

A: Ian Mortimer said early-stage Kv7 candidates are novel structures with different IP, having chemical diversity but no specific focus on changing azetukalner's profile yet.

Q: Cadence and readouts for ion channel portfolio?

A: Ian Mortimer said early-stage candidates like Kv7 and Nav1.7 will transition into human clinical development in 2025, with updates to follow as first-in-human studies progress.