XENE

• Corporate Strategic Goal: Xenon is transitioning from a clinical-stage biotechnology company to a fully integrated neuroscience company focused on delivering novel therapies for epilepsy, neuropsychiatric indications, and pain. The company maintains three core focus areas: (1) preparing the new drug application (NDA) for azetucalner (AZK) for focal onset seizures (FOS) and advancing launch preparations; (2) expanding AZK development into additional epilepsy and neuropsychiatry indications; and (3) advancing the company's pipeline of non-opioid pain therapies.

• AZK (Focal Onset Seizures) Development & Regulatory Update: The company completed a successful, collaborative in-person pre-NDA meeting with the U.S. FDA, with full alignment on NDA package components. The NDA submission remains on track for Q3 2026. Positive Phase 3 XTOL2 trial results have been presented at two major epilepsy conferences, with additional presentations planned for the September 2026 European Epilepsy Congress (EEC) and December 2026 American Epilepsy Society (AES) meeting. Key XTOL2 data includes: the best placebo-adjusted seizure reduction efficacy reported for any pivotal FOS trial to date; rapid dose-dependent seizure reduction starting at Week 1; dose-dependent improvements in responder rates (including 100% seizure freedom) that build over time; and a generally well-tolerated safety profile consistent with prior studies. Open-label extension data show a 91% reduction in monthly seizure frequency and almost 40% of patients remained seizure-free for at least 12 months after 48 months of treatment, in a heavily treatment-resistant population.

• AZK Expansion Clinical Development: Five additional Phase 3 trials of AZK are ongoing: the XTOL3 study (to support ex-U.S. regulatory submissions for FOS), the EXACT study (for primary generalized tonic-clonic seizures to expand the epilepsy indication), and the ExNova II, ExNova III, and EXCEED studies (for major depressive disorder (MDD) and bipolar depression (BPD)). Enrollment in the three neuropsychiatry trials remains on track, with top-line data from ExNova II (MDD) expected in H1 2027.

• Pain Pipeline Progress: Two Phase 1 studies of pain candidates (XEN1120 targeting KV7, XEN1701 targeting NAV1.7) are nearing completion, and generated data to date supports initiation of Phase 2 proof-of-concept studies in acute pain for both programs. The company recently initiated a Phase 1 trial for a second NAV1.7 candidate, XEN1720, creating multiple shots on goal for this genetically validated pain target. For XEN1701, the company confirmed that it achieves both peripheral and central nervous system exposure (consistent with its therapeutic hypothesis) at levels predicted to deliver efficacy based on modeling and human genetic data. For XEN1120, data to date confirms target engagement in both peripheral and central compartments at levels consistent with preclinical pain reduction models. The partnered preclinical NAV1.1 program for Dravet syndrome is in IND-enabling studies, and the partnered MBI 921355 program (for epilepsy, with Neurocrine) continues to advance through a Phase 1b trial with data expected in 2027.

• Commercial Preparation: The company continues to build out its commercial team and refine its launch strategy for AZK, pending FDA approval. Market research shows strong enthusiasm from both epilepsy specialists and general neurologists for AZK's differentiated profile (novel mechanism, rapid onset, once-daily dosing with no titration, favorable tolerability), and the company expects earlier adoption by general neurologists than is typical for new epilepsy therapies. The company is building out its payer engagement team (to be fully deployed by early 2027) and developing patient and provider support services to overcome historical access barriers.

• AZK NDA submission for FOS remains on track for Q3 2026
• Top-line data from the ExNova 2 Phase 3 trial of AZK for major depressive disorder is expected in the first half of 2027; no updated guidance is provided for ExNova 3 or EXCEED trial readouts, which will follow ExNova 2
• Phase 1 studies for XEN1120 and XEN1701 are on track to be completed in 2026
• The company's current $1.2 billion cash balance is sufficient to fund all planned operations into 2029
• No changes to prior pipeline timelines were announced; there were no upward or downward revisions to existing guidance

No segment-level financial performance data (absolute revenue or revenue contribution percentage) was disclosed in this earnings call. The only financial figure provided was total cash, cash equivalents, and marketable securities of $1.2 billion as of the end of Q2 2026.

• Clinical development risk: Success in preclinical and early-stage clinical research does not guarantee positive results in late-stage proof-of-concept or Phase 3 trials, and final regulatory approval of AZK or any pipeline candidate is not guaranteed
• Competitive risk: The epilepsy market already has over 20 approved therapies, and potential fast-follower competitors in the KV7 opener class for focal seizures could impact commercial adoption, though management notes multiple therapies in the same mechanistic class have historically coexisted successfully
• Trial design uncertainty: There are multiple accepted approaches to Phase 2 acute pain trial design, and the company's chosen design may not deliver a clear readout of efficacy
• Enrollment uncertainty: Delays in patient enrollment for ongoing Phase 3 trials could push back data readout timelines
• Market access risk: Payer receptivity to premium pricing for AZK is still being evaluated, and unfavorable pricing or coverage decisions could limit commercial adoption

Q: What notable outcomes came from the FDA pre-NDA meeting for AZK, what safety signals have been observed for the lead NAV1.7 candidate XEN1701, and what is the rationale for advancing a second NAV1.7 candidate XEN1720 now? / A: The pre-NDA meeting was productive and collaborative, with all key topics addressed and no major outstanding issues; the NDA package is straightforward and the company remains on track to submit in Q3 2026. For XEN1701, all safety data collected to date supports moving forward to Phase 2 proof-of-concept; no dose-limiting cardiovascular adverse events have been observed that would alter development plans, and the company has confirmed the candidate achieves target levels of both peripheral and central nervous system exposure. XEN1720 has a differentiated chemistry and profile compared to XEN1701, with improvements in selectivity, potency, and biodistribution that address historical limitations of NAV1.7 candidates; advancing multiple candidates increases the chance of success for this high-value target, and development of XEN1701 remains unchanged.

Q: What is the publication strategy for additional XTOL2 Phase 3 data, and what additional analyses will be released publicly? / A: Top-line efficacy and safety data has already been released and presented at two major conferences, with additional subgroup and secondary analysis data to be presented at the upcoming EEC and AES conferences. The company is working toward peer-reviewed publication of the full XTOL2 dataset, which is considered critical for provider acceptance. Additional analyses in process include outcomes for the subset of patients who were on or had failed prior treatment with cenobamate, which will be released publicly in the future.

Q: What data on pain pipeline candidates will be shared later this year, when will acute pain indications be finalized, and what is the timeline for the EXCEED bipolar depression trial? / A: The company will share a full update on the completed Phase 1 data for XEN1120 and XEN1701 once the studies are fully unblinded, and will outline the rationale for moving to Phase 2. Final trial designs and specific acute pain indications (expected to be standard models like bunionectomy or abdominoplasty) will be announced in the coming months once finalized. The EXCEED trial started after ExNova 2, and enrollment is not far enough along to provide a firm readout timeline; it will read out after the H1 2027 ExNova 2 data release.

Q: How is the company thinking about payer receptivity to AZK pricing, and how will commercial strategy change if a KV7 fast-follower competitor enters the market? / A: It has been almost 10 years since the last new FOS therapy was approved, and initial payer conversations have been very positive, with payers recognizing the significant unmet need and AZK's differentiated profile. Pricing work is ongoing, but management expects to be able to set a price that reflects AZK's clinical value while maintaining broad patient access. As the first-to-market KV7 opener, Xenon has set a high bar with AZK's strong dose-response and favorable tolerability profile; management notes that multiple therapies in the same mechanistic class have historically coexisted successfully in the epilepsy market, and AZK's first-mover position and differentiated profile leave it well-positioned for commercial success.

Q: How does the company plan to drive earlier adoption by general neurologists, and what efforts are being made to improve their experience with AZK? / A: AZK's unique attributes (novel mechanism, ease of use, favorable efficacy and safety profile, and strong long-term seizure freedom data) make it particularly appealing to general neurologists, who have historically been slow to adopt new epilepsy therapies. The company is focusing on overcoming traditional barriers to adoption, including developing innovative support services for providers to help with prior authorization, and improving patient access at retail pharmacies. These services are expected to help speed adoption compared to historical new epilepsy drug launches.