Xenon Pharmaceuticals Inc Q2 2025 Earnings Call Transcript

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

Question: Tessa Romero - JPMorgan Chase & Co - Analyst : Congrats on the progress here from us. So for X-TOLE2, when would you expect all the patients to be randomized here? What was your patient recruitment split US versus ex US? And can you comment on how many sites you ultimately enrolled at for X-TOLE-2? And how many of them you used in X-TOLE?

Question: Tessa Romero - JPMorgan Chase & Co - Analyst : Ian, Chris, have you seen any compassionate use interest?

Question: Brian Abrahams - RBC Capital Markets Inc - Analyst : Hi, good afternoon. Thanks for taking my question and congrats on all the progress. So I realize for X-TOLE2, you still need to finalize randomization. But I'm curious if we should be sort of thinking about this potentially, the study size in the end being larger than the 360 originally planned, sort of depending on how things go with the final screens and randomization. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. AUGUST 11, 2025 / 8:30PM, XENE.OQ - Q2 2025 Xenon Pharmaceuticals Inc Earnings Call And then I guess along those lines, some of our analyses had shown that Phase 2 to Phase 3 translatability in focal tends to be pretty good with limited diminishment of the delta in seizure reduction. So I guess I'm curious if you could maybe speak to your latest assumptions for what the delta could be and what the dropout rate could be for the study as we think about powering.

Question: Brian Abrahams - RBC Capital Markets Inc - Analyst : Thank you very much. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. AUGUST 11, 2025 / 8:30PM, XENE.OQ - Q2 2025 Xenon Pharmaceuticals Inc Earnings Call

Question: Brian Skorney - Robert W. Baird & Co Inc - Analyst : On 1701, can you talk a little bit about the molecules profile? Do the preclinical models in the PK and bioavailability can do so to once daily or more frequent dosing? Can it be developed in an IV formulation? And how are you thinking about the first clinical pain model to serve as proof of concept here as opposed to operative pain severe pain model or more along the lines of a moderate pain indication?

Question: Brian Skorney - Robert W. Baird & Co Inc - Analyst : Got it, Ian. Thanks so much.

Question: Jason Gerberry - Bofa Merrill Lynch Asset Holdings Inc - Analyst : Hey guys, thanks for taking my questions. Just another X-TOLE2 question now that enrollment's complete. And in terms of like the blinded demographics, I'm just curious to the extent, maybe severity if you've had a chance to assess that look similar to X-TOLE1. I know a competitor in the space ended up enrolling less severe patients and we're just kind of wondering if that's perhaps company specific or maybe an industry trend. And then with your BPD study, do you anticipate a high degree of site overlap with MDD? I'm just wondering if there's an opportunity for accelerated enrollment of the BPD study. And then just lastly, I think there was comments that with these healthy volunteer pain studies that there'd be some sort of induced challenge to assess efficacy parameters. I know that there's some debate around the utility of those, but I'm just kind of curious if that's something that you'll be assessing in those Phase 1 pain studies. Thanks.

Question: Jason Gerberry - Bofa Merrill Lynch Asset Holdings Inc - Analyst : Got it. Thank you.

Question: Andrew Tsai - Jefferies LLC - Analyst : Hey, good afternoon. Congrats on the enrollment completion and thanks for the update. So on bipolar depression, it sounded as if there is an interim built into the study. So, when could that interim occur in your view and what kind of efficacy separation over placebo do you want to see at that interim? And ultimately can this study be counted as a supporting pivot? Thank you.

Question: Andrew Tsai - Jefferies LLC - Analyst : Thank you.

Question: Cory Kasimov - Evercore Inc - Analyst : Guys, thanks for taking the questions. I guess two from me, first, on the competitive front, curious how you see the potential read-through from Biohaven's pending MDD readout that's expected at some point in the second half over to azetukalner X-NOVA MDD program. I guess maybe on that front it would help if you can just remind us of the key differences between the two assets. And then second question is for Darren. Darren, good to be covering you again, recognizing it's early days, and I know there's a lot of excitement about a new mechanism of action with this kind of overall profile in the medical community, but I'm curious how you're thinking about some of the key headwinds and just general nuances of the epilepsy market that you'll have to deal with upon approval and launch. Thank you.

Question: Cory Kasimov - Evercore Inc - Analyst : Great, very helpful. Thank you.

Question: Basma Radwan, Ph.D. - Leerink Partners LLC - Analyst : Hi, good afternoon. Thank you for taking our question. This is Basma on for Marc. Could you please provide some color on the difference between the type 1 and type 2 bipolar depression and whether would you expect that azetukalner would be more effective in one patient population versus the other? And also, can you please let us know if you're assessing mania as a secondary endpoint of the trials or not? That's it for us. Thank you.

Question: Basma Radwan, Ph.D. - Leerink Partners LLC - Analyst : That's great. Thank you. That's very helpful.

Question: Joseph Thome - Cowen and Company LLC - Analyst : Congrats on progress and thank you for taking my question. Congrats on progress and thank you for taking my question. Maybe on the Kv7 for pain, Obviously, flupirtine showed some anti-pain activity, but it ended up seeing some liver toxic signals. So I guess, how confident are you that you can de-risk potential liver toxicity pre-clinically through avoiding any sort of toxic metabolite generation, kind of what have you seen there? And then, have any of the quality-of-life measures that you've collected for azetukalner related to pain at all? And last, just a kind of upkeep question, when we see the topline release, what level of detail will we see? Will we also see seizure freedom rates in addition to reduction in the seizures? Thank you.

Question: Paul Choi - Goldman Sachs Group Inc - Analyst : Hi, thanks for squeezing me in, maybe for either Ian or Chris to start. Now that you've completed enrollment in the Phase 3, could you maybe give us your latest thoughts on just how you're thinking about the potential difference in dose response for the 15 and 25 mg doses versus the dose response we saw in the Phase 2? And as part of your filing strategy, is the plan to definitely go with both doses or just maybe the minimally efficacious dose, maybe that is the first question? And then second, on the Nav1.7 program, once you establish proof of concept, would you contemplate exploring combinations with a Nav1.8? I think one of your competitors in the space is examining that, just your thoughts on potentially looking at dual targeted therapies here. Thank you.