Introduce Kevin Lind, Chief Executive Officer of Longboard Pharmaceuticals. Kevin, thanks so much for joining. Fresh off a really interesting analyst event yesterday. So maybe give us first, you know, a quick snapshot of Longboard for those who are less familiar with the company, and then some of the highlights from yesterday. Yeah. Hey, thanks, Josh, and thanks to everybody for being here, and thanks for joining yesterday, and thanks for having us. So Longboard Pharmaceuticals was spun out of Arena Pharmaceuticals in 2020, designed to take some neurological assets forward. The premise behind Arena, behind Longboard is greater selectivity, greater specificity. Going after well-known targets can, and potentially should, translate into clinically and commercially differentiated products. The medicinal chemistry team there did a phenomenal job with etrasimod and ralinepag, and we're excited about bexicaserin and LP659. So we probably won't talk about 659 much today, so I'll just hit it on the front end. LP659 is an S1P receptor modulator, targeting neurological conditions. It's the sister compound to etrasimod. Etrasimod is on the market for ulcerative colitis. It's in development for Crohn's and atopic dermatitis. We have a centrally acting molecule. Etrasimod is peripherally restrictive. 659 's completed its phase I SAD, and moving into its phase I MAD early next year. But, I think we'll probably spend more of the time on bexicaserin, and I think that's where most of the investors are spending time, and we just had a great R&D day yesterday. I'm not sure the stock price liked the R&D day. I thought it was great. But, let me give you a second on what we were trying to accomplish yesterday. So, if you think about how folks can make money, how investors can make money with a phase II asset, it's really, what's the value of the asset after phase three, and what's the probability of success? And so what we were trying to do was walk through the commercial landscape and show that we think we have a multi-billion-dollar drug pretty easily. And so one part of it is, Epidiolex, which is an FDA-approved drug. It's approved in three of many DEEs, is going to be approximately a billion-dollar drug six years after launch. But it's priced at about 1/3 of Fintepla, so there's a lot of pricing room, and if you actually look at the prior auth between Fintepla and Epidiolex, there really isn't that much of a difference. If you go payer by payer, line item by line item, there really isn't that much difference. So there's a lot of pricing room that Epidiolex left on the table. So even if you take 2X that, six years after launch, that's a $2 billion drug. Then add in some credit potentially for breakthrough designation in all DEEs, which we think is a very large market. Add in some of the work we're doing right now to unlock the global market, particularly Europe, which I think they were a little slower behind. Add in the fact that we have composition of matter out into 2041. We think we have the opportunity for a very large multi-billion-dollar market product, assuming it gets approved. The other way investors kind of figure out valuation of where a company should be is the probability of success, right? You kinda take, here's what it should be worth after phase III, and then here's where you're trading, and presumably, probability of success and time value of money comes into it. What we were trying to articulate yesterday is that the phase III trial design was really designed to minimize the variability from the PACIFIC Study, our phase II study, which had unprecedented data, and take out as many variables as possible to push that probability of success up. We were trying to articulate the fact that TID is commercially viable. We have a direct path to a BID path, to an BID approval, because our shining star is to have the best commercial launch in the space. But if we had come out yesterday and said, "Hey, guess what? We're gonna do BID in the phase III," I think investors would have said, "Oh, my gosh, that's a new variable. How do I price that in?" If you think about the inclusion criteria, the exclusion criteria, if you think about the way we are counting the seizures and what the primary endpoint is, you think about what the patient populations are, it was all designed to lower that variability, to make it feel to us like we've given the probability of success, the best chance to be acceptable to everyone. And so obviously, we've got to run the study. The drug is in development. We don't know if it's gonna work, but that was really what we were trying to accomplish yesterday, was really kind of demonstrate where we thought both those levers are, because hopefully then people can do their own math to say, "You know, I think the probability of success is this. I think the peak sale potential is this, and therefore, I feel like this price is either fair or not fair." We've got a lot of different. Sorry, so I. Things to touch on, but no, that's great. Yeah. That's great. I thought it was a very informative event yesterday. Why don't we double-click on. Yeah. The Epidiolex pricing point? Mm-hmm. Right? Because to your point, when they priced Epidiolex, it was with the lens of unlocking the off-label population, the other DEEs that for you will be, in theory, on label. E ssentially, they left, you know, $2 billion+ per year just by that simple decision. You know, how do you think about, again, the ability for you to just kind of maybe be more aligned with Fintepla, given the precedent that Epidiolex has set? Yeah, I think. Look, I wasn't in the room at GW when the team made the decision on pricing, but I, I've heard rumors, whether it's true or not, that they were really worried about generic cannabidiol. 'Cause remember, the drug had no patent protection. It was orphan drug designation. Sure, yeah. You could walk down the street and go get generic cannabidiol at various places. So I think that is the rumor that's kind of stuck around for a while. Whether it's true or not, I'll never know. I think that that was probably the decision which, again, I think it allowed it to unlock some of that additional value, because I'm not sure they knew where prior auth was gonna come out. And so then you see the prior auth that came out after Fintepla got approved, which was after, and Fintepla priced at three X that price. And so again, there's a significant amount of room there, and we're not even talking about the other recent DEE drugs, ZTALMY, that got launched in the space, which is priced even higher than Fintepla. So you know, lots more work to do on pricing between now and launch. Lots more work to do with the payers, lots more work to do along the way, but I think we take tremendous comfort in the fact that there is that ability to potentially play with price. One of the things that I found most interesting about the discussion. Because for me, as I think about the seizure market, and I've been following it for over a decade, you know, we kinda hear about 100,000 patients with these rare seizures, so maybe even 200,000, and yet the sales of the drugs, you know, like, the best drugs are potentially able to get to a billion and not much beyond that. What I heard in terms of, you know, why that's the case, is that there are a lot of good drugs for seizures, but there hasn't really been that one great drug priced as a great drug. Mm-hmm. Maybe you can talk a little bit about that dynamic, and should we be thinking about bexicaserin as that one great drug? What are the characteristics for that kind of a product to emerge? Yeah, thanks for that. I think, you know, the interesting thing about the DE space is that polytherapy is the norm. So you almost have to remove the partial onset seizure drugs from your thoughts on as an analog. You know, I've been involved in the epilepsy space for over 10 years as well. And so, you know, the challenge with the partial onset seizure drug is you have 20 generic ASMs you've gotta go fight your way through on pharmacy and, and all those other things. From our perspective with the DE patients, they're on three to four concomitant anti-seizure medications already. So it's not like we're fighting our way in. We're taking patients who are not well-controlled on probably clobazam, that's about half of the patients in the U.S. Epidiolex is about 1/3 of the patients in the U.S., at least at the major sites that we're studying it in. And then one to two anti-seizure medications that's been generic for a long time, that's probably not doing that much. And so all we have to do is go to those physicians when those patients are coming in and say. "Hey, we think patients should be on a 5-HT2C. They probably should be on a cannabidiol, if it- they can tolerate it, and they can see effect, and one to two anti-seizure generic medications." And so that gives us this great ability to have a quick pickup along the way because we're not fighting our way through. And remember, these unfortunately these patients are incredibly sick, and they're in this- they're in the ER a lot. They're getting hospitalized a lot. They're having 20, 30 seizures a month, hundreds of seizures a year. It's not like they can't see additional benefit. They're not generally getting seizure-free. So there's a tremendous unmet need along the way. And so I think with a safe, easy to add on to current standard of care drug, which is what we're focused on, that also demonstrates good efficacy, I think we do have that opportunity to really become part of that standard of care going forward. You know, as the treatment landscape evolves and, you know, you're pursuing the strategy that you are, do you think you can approximate market share of Epidiolex? What would it take to do that? You know, I think we talked about it yesterday. We did a survey. I think Epidiolex, depending on the physician. So we asked 100 physicians who were familiar with recent anti-seizure medications and treated these DEEs. It was about 1/3 to 40% were on there. So again, they kind of... It's why I tried to triangulate back to six years after launch, you end up with a $1 billion drug for Epidiolex. Adjust for pricing, that's kind of how we feel comfortable. The survey we did showed physicians thought that TID formulation would be about 42% market share, which sounds in that same range. You know, again, we have this shining star that is, we wanna have the best launch in the space, and so that gets to making sure we get BID. And that's an additional six-ish%, which could mean close to 50% of these patients, which is something we hope, right? And I think it's potentially doable. Does it imply that 50% of patients are well managed and wouldn't need bexicaserin? Like, what's the obstacle to unlocking even more of the market? Yeah, I think. So if you go back to the slide yesterday, they said may or may not. There's a group of physicians that say may or may not, and I had lunch with commercial team, commercial folks that after the [audio distortion] say, "I don't care about the likely to prescribe. I care about you hitting the may or may not," because those are the ones that are kind of up for grabs. Now, the challenge in epilepsy is that physicians have been burned in the past with certain molecules that have great promise, and then they have side effects along the way, they have challenges along the way. So if you think about oncology, I think oncology, aesthetics business, you have very, very fast adopters of new medication, right? There's a reason to be a fast adopter. Then you have other therapeutic areas like pulmonary arterial hypertension, where we are in Arena, and it is a very slow adopting market. I can't tell you without offending the epilepsy space where they come out, but I'm not sure they're the fastest adopters along the way. That might be appropriate, but we definitely have had the conversation with community that clinical trials need to be part of the go-forward plan for every patient. It's not there today. Oncology, if you know you have cancer, you're going to be a part of a clinical study. Epilepsy, that's not the case. I think that speaks a little bit to the physicians because these patients are having SUDEP. They're dying. These patients are having significant developmental damage done because physicians aren't moving aggressively. I think there's more work to be done there, but I wouldn't say that they're the fastest adopters. I thought the rationale for carving out Dravet syndrome as a separate phase III was to let that one kind of move faster. Mm-hmm. To get to market faster, but seems like the timelines for Dravet are gonna be similar to the LGS and other DE. What is the rationale then for carving out Dravet as a separate trial? Yeah, so, you know, everything is multifactorial, so I can't get into all twenty or we'll be here for, you know, the rest of the day. I will say, when we met with the FDA, we weren't sure what they were gonna say. I think we were very open and honest with the investor community. We didn't know what they were gonna say about DE. And so we had proposed a Dravet study, and we had proposed DEE study, knowing that, you know, we really believed the right thing to do was DEE. When we got into the conversation with them, it kind of made no sense to pull it out. I will tell you, if I had pulled it out, I would spend the next couple of years with investors, with investors asking us a question that I don't actually think is the right question. I don't think it's relevant, but I think of a bunch of investors would've said, "How are you gonna compete with Fintepla in Dravet if you haven't done that specific study?" Right. I don't think that's the right question. I don't think it's the right answer, but we might as well just do it. I think the other thing is, we did wanna be careful that one arm of the study or one subset of the study didn't provide incredibly superior returns in terms of benefit that could have caused questions to our overall argument, right? Our overall argument is Lennox-Gastaut is no different than DEE. And I get that pulling Dravet out is a little bit talking out of both sides of our mouth, but given the way the 5-HT2C appear to work in SCN1A mutations, which is Dravet, predominantly, it should be all of Dravet. It just felt easier, simpler, safer, to pull that out into a separate study. Now, we knew we could start that study sooner. I don't know which one's gonna read out faster. I probably scared some investors yesterday by walking through all the scary things about enrolling that study, but, you know, I come from the credit side of the business, where you share the risk. I think we're gonna be able to enroll without problems, but I did walk people through why it's not a straightforward study to enroll, but I think we'll be just fine there. Did you consider adding a Fintepla, like, open-label arm as a comparator and to facilitate enrollment, and, and why did you not? Yeah, I think. We could have. You know, there's a big question we have right now around risk and reward. The conversations we had with the FDA were so incredibly positive that, you know, I think when we thought about it, I'm not sure how relevant Fintepla is going to be at the time of launch. So why do we want to include that risk? Why do we want to include some unknown variables along the way? I think those are absolutely great questions. If we were seeing Fintepla was gonna be 90% of the Dravet market, I'd have to do that. I think where they are today, we can sit back and look at it a little bit further before we make that call. Got it. For the LGS and other DEE trial, I didn't see if you had a separate LGS analysis, 'cause I think that was initially part of maybe the strategy to give yourself two shots on goal to win. Do you still have that? There really is need. It needs to be the full trial. I think as we talk about it today and going forward, and as we talk about it with the FDA, we have to speak with one voice, which is the right thing to do, is to study DEE. Got it. Now, having said that, anybody who's ever seen FDA response will see everything is it's a matter of review. Like, you've never seen a question that doesn't come back with, "But it will be a matter of review." If we did have to go down that path of parsing out individual DEE subtypes, it would be a matter of review, but I think the right thing for all of us is to move on from LGS, which I think, as you heard yesterday, was a great diagnosis 60 years ago when we had EEG monitors, and that was it. But it doesn't make sense as we move forward with genetic diagnosis, structural diagnosis, acquired diagnoses, where you just don't see slow spike and wave on the EEG, but everything else is similar. Got it. You know, there's a lot of time and effort and focus spent on titration and kind of working through some of the early titration challenges, which you did successfully. But then in the phase three, you're gonna start at six versus three milligrams, which seems to kind of be going in the other direction of pushing the titration more aggressively. So how did you kinda decide on that? What gives you the confidence that's not gonna pose any tolerability issues? Yeah, so we looked at it in a couple. So a couple things. First of all, based on how the statistical plan was in PACIFIC, discontinuations during titration didn't have an impact on efficacy. We're still working our way through the final statistical analysis plan. That might change. I still fundamentally believe if you give one patient one dose of drug and they don't have a seizure, it's not appropriate to call them seizure-free. It doesn't make sense, right? But as we thought about it. Look, it's really around discontinuations, which doesn't have an impact on efficacy. It's in PACIFIC. I think the more important thing is when we did the analysis, and you could imagine, we spent a lot of time on this, the first initial dose wasn't the problem. It was that physician saying, "I really wanna see how much I can reduce the seizures. I'm going to aggressively push that patient from six to nine, and then nine to 12." And that was really where we saw the challenges. We think we've got it sorted. We think we sorted it with the placebo patients in PACIFIC. We got all nine placebo patients onto drug just by having a conversation and having a two-week titration window. We've made it a three-week titration window, just giving a little more comfort and time. The patients who did get on six, 86% of them did get up to 12, but we just felt like there were a couple physicians. It was the first patient in at each site, the physician was really excited about pushing that dose, and we just had to have that conversation with them, and it's why all those discontinuations were in LGS. Because the first patients we got in were LGS, because that was the first patients the physicians knew they wanted to put in the study. Then they had the DEEs, 'cause we went back to them and asked them, "Hey, we know you've got DEE patients," but they had to go through the roster a whole second time, and then same with Dravet." So I think we've got it sorted, or not. And, yeah, we're feeling good about it. I think we did look at three, and here's the thing. If we were really developing these drugs not for the FDA in a regulated environment, you'd dose them based on plasma levels, but you can't do that in a phase three. You'd break the blind, right? You don't really want to have that as a commercial product because then you gotta go bring these patients in for blood draws, and you gotta do these plasma. But plasma levels is very appropriate to look at for response. Maybe on the topic of the BID. Mm-hmm Dosing and while advancing with TID, because I think many of us thought it would be BID in the phase three. I guess, first question, what's your confidence that you have the right BID formulation? Yep. Yeah, so we feel incredibly confident because it's essentially PACIFIC. So we removed the variable, right? We're not. If I had said, we're gonna take bexicaserin and go from three times a day to two times a day, I would be spending the next two years articulating why we feel comfortable with it. We removed that variable. Bexicaserin from PACIFIC is bexicaserin in the phase III. TID is the same from PACIFIC and from the phase III. Is the formulation the same between BID and TID? The data we presented at AES a year ago shows that BID and TID look similar with the exact same formulation. One you just take. So 12 mg 3x a day is our top dose. That translates into a total dose of 36 mg per day. If you give that dose at 18 and 18, or you give it TID, you give it 12, 12 and 12, same thing, same exact formulation. Now, we did have an XR. We do have an XR. We could work on that. We had a conversation. There's been a bunch of questions on this. I was probably the most bullish in the, on the team on BID because that shining star is to have the best launch in, in the space. We had a conversation with the FDA, and the FDA looked at us and said, "We want this drug to win." I think I can say that safely. I always hate putting words in the FDA's mouth, so I hope that the FDA, if you're listening, you don't take this the wrong way. Essentially, they said, you know, "Do you feel lucky on BID?" And then they actually referenced Clint Eastwood. And so if you put those together, it feels a little reckless to essentially tell the FDA, "Yeah, we're gonna disregard your advice." We want this to be a collaborative, positive interaction. We proposed some ideas to them. We can do it as part of BID as part of the open-label extension. We can finish enrolling certain sites, because obviously you don't wanna have too many patients come from one site and start a whole new study. We can wait until the Dravet and or the DEE study finish enrolling and run and keep those sites up and running, where they're actually finding patients and moving quickly and do a study, or we can do XR. We have a viable path forward that we've already discussed with the FDA. But it was a comment, "Do you feel lucky?" So more to come on this. I think the answer is, we are going to. The beauty of breakthrough designation is that we can have a conversation with the FDA over time to sort our way through that. We look forward to coming back to you, but I don't want to do it in an iterative process. We'll come back to you with something that we think makes sense, that the FDA feels good about. Because, again, I think the FDA also, if I hopefully don't put words in their mouth, said that they realize in a pediatric population, doses are gonna get missed. We didn't have that problem in PACIFIC. We had very high compliance. But in the real world, it's gonna happen. One last point on TID, very much commercially viable. These kids are under 24-hour care. It is not hard to give them a dose at the middle of the day. We're not overly stressed about it. If you looked at our R&D day yesterday, again, 42% market share if we have two-TID, but we want to get that last piece. How do you ensure such high compliance in the phase three as you had in PACIFIC, given the TID dosing? Yeah, you know, you spend a lot of time with the parents. You know that it's not that big of a deal. I think the other part is, I think you go to good sites that articulate the promise and the challenges as well to these parents, so that the parents know what they're in for, and the parents know what's expected of them. Because we would hate to have parents kind of be flippant. We need them to count seizures the right way. We need them to count seizures consistently. There's a lot that goes into patient selection. It's why we have such a massive hand-holding effort around our studies. So you, during the presentation, talked about some data sets you may be able, in theory, to generate, right? Because we're gonna be waiting a couple of years to, you know, for the trials to run, execute, and read out. How do you think about maybe with any, whatever more granularity you can provide, you know, why should investors hang around over the next year and a half, you know, as we're just kinda waiting for the enrollment updates? I remember having that conversation six or seven months ago, and I think we did pretty well with breakthrough designation. For me, I think that it would be highly unlikely for us to go two years without data. Now, will we have data that you think is valuable, and that person thinks valuable, and that person thinks valuable? I don't know, because I can't tell you what you're gonna think is valuable. Will we have data that we think helps further elucidate the value of our product, helps on the commercial side, helps with probability of success, helps with enrollment, helps with physicians, all those sorts of things? Absolutely. I just can't promise you this exact study will read out here, because frankly, I don't want to tell our competitors where we're going. There's a lot of really exciting stuff we can do, but if I give them a heads-up, then either they're gonna counter-detail or there's just too much other stuff going. But I guarantee you, we are, y ou know, I like being able to, you know, beat up on the shorts as much as anybody. I think we're looking for a CDKL5 [dell] update from Fintepla later this year. Anything in particular you're looking for to help inform prospects for bexicaserin? Yeah, look, I hope that it works. I hope that it helps those CDKL5 patients. Obviously, all these kids need better therapies. They need help. I think if Fintepla works, it's another argument for why the 5 -HT2 C mechanism of action is a broad, anti-seizure medication. So it's not just in SCN1A patients. It, obviously, the bexicaserin data and Fintepla approval in, Lennox-Gastaut supports, there. I really hope it works there. The handful of patients that were, you know, got CDKL5, or that have CDKL5, that got, Fintepla prior, and they've been published, the data looks really good, so I hope they can replicate it. I think that's a good thing for all of us. I think we had seen Fintepla work quite well in Dravet, not so well in LGS. I don't know, like, how do you think about CDKL5 relative to those two? I'm not gonna make a guess on it. I think the handful of patients, the ten-ish patients that they have, I think Devinsky's patients were there, looks very good. Okay. So, I'm hoping for them to have great data. That would be a great win for that patient population. Where... You know, as we think about the various unmet needs, Dravet, LGS, and then the other DEEs, where do you think your earliest, fastest, and ultimately strongest traction will be? Our fastest, strongest traction will be in DEE. There's massive unmet need. It's not just all the genetic disorders that we put on the page yesterday. It's also the structural, it's the acquired. I think Dr. Dlugos did a great job articulating why he thinks it's gonna be much bigger than even we can put on paper. I think then, you know, LGS, massive unmet needs still. I'm not worried about Dravet, but I think there are some, you know, really nice molecules on the market. But again, these patients aren't seizure-free. We're rooting for Stoke. I would love to see an genetic modifying drug really win there because it would be very valuable. Interestingly, about Stoke, about half the patients were on fenfluramine. That's great. If they add Stoke onto best standard of care, that is a really good win for us. The takeaway is polytherapy is the norm, and these kids need new medication. There is massive unmet need. Absolutely. I think we're.