Xenon Pharmaceuticals (XENE) Goldman Sachs 45th Annual Global Healthcare Conference summary

Strategic focus and pipeline overview

• Deep expertise in CNS ion channels underpins a pipeline targeting epilepsy, depression, and pain indications.

• Lead asset ezetucalner (formerly XEN1101) shows strong efficacy in epilepsy, with over 600 patient-years of exposure and some patients achieving 12 months seizure freedom.

• Indication expansion includes major depressive disorder (MDD), with proof-of-concept data showing rapid onset and efficacy on multiple depression scales.

• Discovery pipeline targets Kv7, Nav1.1 (for Dravet syndrome), and Nav1.7 (pain), with candidate selection ongoing and IND filings expected from 2025 onward.

• Cash runway extends into 2027, fully funding late-stage epilepsy and MDD programs.

Clinical development and data highlights

• Ezetucalner demonstrated statistically significant seizure reduction at all doses in phase II-B epilepsy trials, with rapid onset and best-in-class efficacy.

• In MDD, phase II X-NOVA study showed dose response and rapid onset, with statistical significance on HAMD-17 and anhedonia scales, though primary endpoint narrowly missed significance due to sample size.

• Phase III MDD trials will use HAMD-17 as the primary endpoint, 1:1 randomization, and stricter inclusion criteria to enroll more severe patients.

• Three phase III studies planned in MDD, with risk mitigation strategies including site selection and third-party adjudication.

• X-TOLE 2 epilepsy trial enrollment expected to complete late 2024 or early 2025, with top-line data 6–8 months after last patient screened.

Commercial and competitive positioning

• Ezetucalner offers a differentiated profile in both epilepsy and MDD, with rapid onset, efficacy, and minimal sexual dysfunction or weight gain.

• Anhedonia benefit is a key differentiator in MDD, addressing an unmet need not met by SSRIs/SNRIs.

• In epilepsy, positioned for third-line or later use, with potential to address depressive symptoms in difficult-to-treat patients.

• Commercial launch planned in the U.S. with a focused field team; ex-U.S. partnership strategy anticipated.

• Competitive landscape monitored, but ezetucalner is the only potassium channel modulator with robust efficacy and long-term safety data, supporting a leadership position.