Xenon Pharmaceuticals Inc. Q3 FY2025 earnings call

• Completed randomization in Phase III X-TOLE2 study of azetukalner with 380 patients, exceeding the original goal of 360, on track for top line data readout in early 2026. • Broaden therapeutic opportunities for azetukalner into neuropsychiatric indications like major depressive disorder and bipolar depression with ongoing Phase III studies (X-NOVA2, X-NOVA3, X-CEED). • Expand pipeline with early-stage Nav1.7, Kv7, and Nav1.1 ion channel programs, with Nav1.7 and Kv7 modulators moving into Phase I studies. • Highlighted long-term efficacy and safety data of azetukalner in epilepsy, including 48-week open-label extension data to be presented at AES.

No detailed breakdown of product segments by absolute revenue and contribution % provided in the transcript. Focus is on progress across azetukalner epilepsy program, neuropsychiatric expansion, and early-stage ion channel programs.

• Anticipate sufficient cash to fund operations into 2027. • Expect top line data readout for X-TOLE2 in early 2026. • Plan to file NDA for azetukalner in the U.S. with positive X-TOLE2 data. • Aim to initiate Phase II proof-of-concept studies for early-stage Nav1.7 and Kv7 programs next year.

• Uncertainties in clinical trial results, including variability in patient enrollment and study outcomes. • Regulatory challenges in obtaining approvals for new indications. • Competition from other companies developing similar therapies. • Operational risks related to scaling up commercialization and managing multiple clinical programs.

Q: Could you set the stage for the top line data release, including what would be rate limiting to filing if positive?

A: Ian and Chris discussed that top line data would include key efficacy endpoints and safety/tolerability, with efficacy results from X-TOLE2 being critical for NDA filing, and much of the NDA work already ongoing.

Q: What's the screen failure rate for X-TOLE2 and timing of X-NOVA2?

A: Screen failure rates trended as expected, with insufficient seizures being a major reason; timing of X-NOVA2's top line data not yet guided, but extrapolating from Phase II, it could take 2-2.5 years.

Q: Differences in bipolar I and II in X-CEED trial and use of MADRS vs HAM-D?

A: X-CEED includes both BPD I and II, with screen failure rates related to seizure criteria; MADRS used in BPD due to precedents in bipolar studies, while HAM-D was used in MDD.

Q: Enrollment in X-TOLE2 and data disclosure for early-stage programs?

A: Enrollment exceeded target due to patient interest, with success in early-stage programs being based on achieving sufficient exposure and safety/tolerability to move to Phase II.

Q: Impact of competitor readouts on azetukalner and operating costs into 2026?

A: More innovation in epilepsy is good, but azetukalner sets a high bar with its attributes; operating costs will increase in 2026 to prep for launch in 2027.