Xenon Pharmaceuticals Inc Wells Fargo 21st Annual Healthcare Conference

Tucker, thank you. Great. Thanks for having us, Ben.

Yeah, no. We are an ion channel drug discovery and development company, and on our way to becoming a commercial company. Our lead asset is called azetukalner. We completed the second of our registration studies earlier this year, the X-TOLE2 trial, in focal onset seizures. And we've got it to filing this month an NDA. It'll be the company's first, that'll allow us to commercialize here in the U.S. A really incredible medicine that's got an unmet need in focal onset seizures, and really allows us to make that transition from being a discovery and development organization on through to commercial here in the U.S.

Beyond that, we are looking to expand opportunities for azetukalner in neuropsychiatry, and we have got a really exciting earlier stage pipeline of phase I assets in pain, another Kv7 mechanism drug, which is the same as azetukalner for epilepsy, as well as a NaV1.7 inhibitor as well. Those are both in phase I studies in SAD/MAD. We are going to achieve the goal, hopefully, this time next year, late 2027, of becoming a fully integrated biopharma company, and with a real exciting pipeline behind it.

We do. We have got a team of a couple dozen people in Athens, Greece this week. The conference is just finishing up. It is the major medical meeting for epilepsy, as you said, in Europe, and then AES is the one here in the States. Yeah, we had a really great presence at AES. Feedback from the team that I have gotten has been really incredibly positive. We had six posters and presentation. We had an oral presentation, which was an encore presentation of the phase III data from X-TOLE2 that Dr. Jacqueline French presented, and some really great feedback on the panel discussion there. It is always great to kind of broaden the understanding and awareness of the drug.

We get some great feedback from Dr. French and some of the other KOLs who are on the panel, giving some updates and anecdotal evidence that they have from their patients about how well they can do on azetukalner. It is a novel mechanism. It has got a lot of ease-of-use attributes, and it is going to be a really important addition to the armamentarium for these physicians. We had a variety of other posters as well. We had one on the mechanism, the Kv7 mechanism for azetukalner, and how that can combine with other ASMs. Oftentimes, for patients who are not well controlled, they are on polypharmacy, so they are typically on multiple anti-seizure medications, SV2A blockers, sodium channel inhibitors, but there is no other Kv7 potassium channel modulators out there.

We showed that the synergy in combination with potassium channels, with SV2A inhibitors, sodium channels can be really profound for patients as well. We talked about things like ease of use. One of the other benefits of azetukalner is that it is a drug that doesn't need to be titrated. We have doses from 10 milligrams up to 25, but all of them are at efficacious doses, and that's unlike a lot of other anti-seizure medications. We had some data talking about the patient and physician experience, where patients get really nervous if they're on a drug that requires titration. They're very scared of having another breakthrough seizure. It's a really traumatic event for them, and so the idea that they're on a subtherapeutic dose of a drug can be really challenging.

I think it really highlighted the unmet need for azetukalner, the novel mechanism, the benefits of the ease of use that it comes with it, and then again, these kind of anecdotal stories from the clinicians who've worked with the drug in their hands and how impactful it's been for their patients.

Yeah. ASM anti-seizure medication labels are pretty standard in terms of what the indication is. It'll be for kind of broadly for focal onset seizures. It wouldn't be relegated to a particular line of therapy or prior exposure. But as you said, beyond that, we're hoping to have four doses. We studied in the two registrational trials, the phase IIb. There we studied three doses, 10, 15, and 25. 10, 15 Oh, sorry. 10, 20, and 25. In the phase III study, we had 15 and 25 milligrams. So we've got a really robust data set across four different doses, and what we see is that across all four doses, we've got good efficacy. So there's a very strong correlation between exposure and efficacy. Our best efficacy is at 25 milligrams, where it's the best placebo-adjusted efficacy in FOS that we've seen in a clinical study.

We've got really good efficacy down at 10 milligrams, and we also have the A profile, which changes as you increase dose as well. You see more CNS-related adverse events at 25 milligrams. You see much lower rates and very comparable to what we saw in the placebo arm in the phase II-B study at 10 milligrams. Our goal is to get all four of those doses on label. We think that that's going to provide a lot of optionality for clinicians to try and find the right dose for the right patient. We do know there's a BMI to exposure relationship, so if you're a really slight patient, you probably don't need to be on 25 milligrams of azetukalner. You can probably get good efficacy and moderate any of the side effects at a lower dose.

For patients who've got really difficult-to-treat seizures, or maybe are heavier, then maybe 25 is good. In practice, I think what we hear is that a lot of physicians may start at 15 milligrams. In fact, that's one of the things that Dr. French commented on at the EC conference, is that in her experience, she probably will start patients at 15 and then move them up as needed, versus starting them at 25 and bringing them back down. For us, commercially, it won't make a difference. We're looking to do flat pricing. I think this gives the physicians a lot of choice as far as how they manage their patients without an economic impact on us. We've got good, strong data across those two studies to show that we've got good support for each of those doses.