Xenon Pharmaceuticals Inc Q3 2025 Earnings Call Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Tessa Romero - JPMorgan Chase & Co - Analyst : Hi, Ian. Welcome to the team again, Tucker. Are you able to disclose where your screen failure rate ultimately landed for X-TOLE2? Generally, when screenouts occurred, were they for reasons as expected from prior experience? And then, my second question is just, how far behind do you think the results of X-NOVA2 will be from X-TOLE2? Think it makes it into 2026? Thank you. Ian Mortimer - Xenon Pharmaceuticals Inc - President, Chief Executive Officer, Interim Chief Financial Officer, Director Thanks, Tessa. Again, I'm happy to start. And then, Chris can add his perspective. When we talk about -- just want to be clear on some definitions up front, we will, at the appropriate time, give the screen and baseline failure rate. We have that as a combined number. So those are patients that may have dropped out during the screening period, as well as the baseline period prior to randomization. Again, with an ongoing study, we don't go into very specific details across a number of different parts of the study, including this. But I would say that it's trended and tracked as we would have expected in the Phase 3 program. Chris can go through, probably, some of the reasons that you lose patients due to either baseline seizure burden or BMI or compliance with (inaudible) or a variety of things that people drop out during the screen and baseline period before randomization. Chris, do you want to do that? And then, I'm happy to address the second question, which is just the timing of X-NOVA2.

Question: Joseph Thome - Cowen and Company LLC - Analyst : Hi, there. Good afternoon. Thank you for taking my question. Maybe on the Phase 3 epilepsy study, can you talk a little bit about your expectation for the change in Cenobamate use in the Phase 3 versus the Phase 2, given that that's been on the market obviously a little bit longer now; and, maybe, how should we think about that when we see response rates in the placebo and the active arms or the discontinuation rates due to (inaudible)? Is that going to be a consideration? And then, maybe just one on the MDD. Can you talk a little bit about why you don't have an interim analysis in the MDD studies? Is this a consideration with the third Phase 3 that would start, given that you did incorporate one in the bipolar study? Ian Mortimer - Xenon Pharmaceuticals Inc - President, Chief Executive Officer, Interim Chief Financial Officer, Director Chris, why don't I start on the Cenobamate question. I can share maybe some of our thoughts on preclinical data there, as well, that may be relevant. And then, you can add your perspective, as well as answer the question on the interim analysis on MDD. Joe, yeah, we expect that Cenobamate usage. And so we saw some Cenobamate usage in X-TOLE in the Phase 2 study. But, remember, around that time, Cenobamate was just going through getting approvals and then being available commercially so we do expect Cenobamate usage to be higher in the Phase 3 study than we saw in Phase 2. We're just going to have to see what those data tell us when we unblind. Obviously, in our Phase 2 program, because patients are on one, two, or three background anti-seizure medicines and there's lots of these drugs available, there's actually a huge number of permutations of different combinations of background medications that it becomes quite difficult to tease all that apart. But I think that as we get deeper into the Phase 3 analysis, I think you've raised an interesting question that we've been thinking about, as well. I can share with you some preclinical data that maybe gets to your question a little bit of a different way, which is, we've looked at Azetukalner in our preclinical epilepsy models in combination with all of the commonly used mechanisms and medications, including Cenobamate, and whether we combine Azetukalner with Cenobamate or (inaudible) or (inaudible) or (inaudible), sodium valproate -- like, we've looked at a whole bunch, we've looked at a panel -- we don't see, when you add the two drugs together, you get a benefit of efficacy. We don't see changes necessarily from the tolerability perspective. So I think we feel we've, at least based on our Phase 2 data -- is Azetukalner, based on the novel mechanism and the profile, we think plays really well with others. I'm not sure that's going to change in Phase 3 but we'll know better when we unblind the data. Chris, I don't know if you have anything to add on the Cenobamate side; and then, maybe you can address the MDD question. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 03, 2025 / 9:30PM, XENE.OQ - Q3 2025 Xenon Pharmaceuticals Inc Earnings Call