Hello, everyone, and welcome to Oppenheimer's thirty-fourth Annual Healthcare Conference. I'm Jay Olson, one of the biotech analysts at Oppenheimer, and I want to thank you all for joining us. It's my pleasure to welcome Longboard Pharmaceuticals to our conference, and it's an honor to introduce Kevin Lind, President and Chief Executive Officer. If you have any questions during our discussion, please feel free to submit them using the Q&A function. With that, we'll get started. Thank you so much for joining us, Kevin. Hey, thank you for having us. Yeah, it's our pleasure. Maybe just to get started, for those who aren't fully familiar with the Longboard story, could you give us a brief overview of the company and some background on bexicaserin? Sure. Before I get started, I do want to note we'll be making some forward-looking statements today. Actual results and events may differ materially from Longboard's expectations. For more information on these forward-looking statements, including factors that could cause the actual events or results to differ, please refer to our S-1 filings with the SEC. Longboard was spun out of Arena in 2020 to focus on the development of the neurological assets in Arena's pipeline. We're concentrated on the development of two product candidates, bexicaserin, or LP352, which is a 5-HT2C super agonist in development for the reduction of seizures in patients with DEEs, and LP659, which is an S1P receptor modulator in development for rare neuroinflammatory disorders. We went public in March 2021, and have spent the last three years building out what we believe is a premier neurology-based team. In January of this year, we announced positive top-line phase Ib/2a data from bexicaserin from the PACIFIC Study, and we're in the process of preparing for our global Phase III program for bexicaserin. We think bexicaserin has the potential to improve treatment for patients taking the current drugs being used in the DEE space, and potentially expand into additional patients that have very few novel treatment options today. As many of you are aware, there's a tremendous unmet need for new and better treatments in the DEE space, with the average patient suffering hundreds to thousands of seizures each year on top of best polytherapy today. Bexicaserin was designed to be very selective to 5-HT2C. We believe that this selectivity provides bexicaserin with characteristics that may result in it having potential safety and efficacy profile that physicians and their patients are looking for. We plan to have an end of phase II meeting with the FDA as soon as possible, and provide more guidance on our phase III program later this year. We also plan to have SAD data for 659 in the first half of 2024. So it's gonna be a busy year for us. All right. Well, we'll certainly look forward to an exciting year. You closed out last year with a lot of excitement around the data from your PACIFIC Study. Congratulations on those results, which showed efficacy across different epilepsy types. Before we dig into the data, could you just remind us about the study design and the rationale behind the study, and what you were hoping to learn from the study? Yeah. So, the rationale was we wanted to look at Dravet and LGS, where the 5-HT2C mechanism of action has been implicated to have an impact on seizure reduction. But we also know anecdotally and through data that's been presented along the way, that the mechanism of action could work more broadly than just Dravet and LGS. So what we did was we had a 52-participant study, had to have 4 or more motor seizures per month. We randomized it 4 to 1. Patients could be on up to 4 concomitant meds, including cannabidiol, and we looked at Dravet patients, we looked at Lennox-Gastaut patients, and we looked at DEE other patients. Interestingly, the DEE other patients were not just from one or two DEEs, but from a number of the various DEEs out there. So there are over 20 DEEs. DEEs, for those who aren't familiar, I forgot to address this earlier, are developmental and epileptic encephalopathies, and these are patients that typically have seizures that are refractory. They have developmental disability, and they have an abnormal EEG. So we enrolled 40 adults, 12 pediatric participants. We're looking forward to studying younger participants in the phase III. Most of these drugs that are approved for DEEs are down to age 2. A couple of them are down to age 1. The 43 participants were in the U.S., 10 participants were from Australia. We wanted to interact with a few of the key KOLs in Australia. In terms of what we saw, we saw a 53.3% median reduction in seizures from baseline, compared to 20.8% for placebo, and we saw a 72% reduction from baseline in Dravet patients, 48.1% in Lennox-Gastaut, and 61.2% reduction in DEE other. Excellent. Well, congrats again on that impressive efficacy that it was demonstrated in that study. Could you just maybe share your thoughts on what drove those positive results? And how do these data in Dravet and LGS compare to other drugs in this space, like Fintepla or Epidiolex? Yeah. Hey, thanks for that. So we believe the data for our successful PACIFIC Study were profound. But as a reminder, what we've said all along is physicians, patients, and caregivers are looking for safe, easy-to-add-on therapies that provide additional efficacy. Efficacy is interesting, but even in indications like Dravet and LGS, where there are multiple approved therapies for those individual diagnoses, there's a tremendous unmet need, with patients on average still having 10-20 seizures per week. In our PACIFIC Study, we tested bexicaserin versus placebo in that broad DEE population and saw that 53% seizure reduction from baseline in patients that were on top of current standard of care, meaning on top of 3-4 concomitant anti-seizure medications. And the data included certain medications that were previously unavailable when previous studies were conducted. So the fact that we saw a seizure reduction of 72% in Dravet, and that 48% in LGS, and 61% in other DEEs, in a study that really seemed to simulate real world experience, was exciting to physicians and others because bexicaserin appeared, in this small study, to show evidence of a potential safety and efficacy profile that could offer patients benefit in Dravet and LGS, where there are multiple approved molecules like, Fintepla and Epidiolex, but also in that broader DEE patient population, where there aren't approved novel therapies. Okay, great, and so that's super helpful. I know that investors were extremely excited about these results, as shown by your stock price reaction. But what about KOLs? Can you share some KOL feedback with us that you may have received so far? Yeah, look, the KOLs are still really looking for additional treatment options, and they're excited by the results. I've been incredibly pleased because they enthusiastically wanna be engaged in our global phase III program, and the data reinforced that you can study DEEs broadly from an efficacy and safety perspective. The community feels this unanimously. Patient advocates do as well. There's really this desire to be able to use these molecules a little more broadly, and so they're asking how they can help inform the broader community of the opportunity for a molecule like bexicaserin. So that was what was so exciting to us about interacting with the KOLs, particularly the PIs who are involved in the study, but also a lot of the PIs who wanna be a part of the global phase III program. Okay, understood. And then, when you talk to caregivers and clinicians in the community setting, what do they consider most clinically meaningful? And any insights on how bexie could potentially change treatment practices? Yeah, so this is a complicated question, and it really depends on the individual patient and family. So patients with DEEs have multiple medical and developmental issues. To most families and KOLs, the seizures and SUDEP, or SUDEP being sudden unexpected death from epilepsy, those are certainly the most acute concern, right? Those are the things that are causing them to go into the ER. Those are the things that can cause death. The seizures really are of concern. For investors, reducing seizures matters because it's probably the most objective outcome to measure in our studies, and will likely be our endpoints in our pivotal studies. But to get to your original question, in addition to seizure reduction, if you talk to the caregivers, there are other issues like cognition and sleep that register as high needs, too. So what we're trying to do is really think about how do we get this molecule approved, which will likely be on seizure outcomes, but then look at some of these additional matter outcomes that may matter to parents. Some of them we might not be able to address in a short phase III program. Some of these we might only address if we really treat early. It's hard to imagine using any anti-seizure medication that you are going to somehow profoundly cause a child who's wheelchair-bound to get up and walk, right? That's probably a little too late to intervene. But that is the promise, is to get in early, cause the seizure reduction that is hopefully going to cause less developmental disability down the road. Whether or not we can study it in our phase IIIs is to be determined, but is definitely important to the parents beyond just, "I'd like to take my kid's seizures from 20 seizures a week down." Does that make sense? Yeah, that makes perfect sense. And I guess as we try to extrapolate more broadly for bexie and look across other DEEs, are there any phenotypic similarities of other DEEs with LGS? And why do you think treating these types of epilepsy has remained such an unmet need? Yeah, so I think the challenge has to do with how the spaces continue to evolve over time, right? So if you think about it, neither Fintepla nor Epidiolex had composition of matter, and we were learning along the way what truly is DEE versus not. And so if it made sense to start with a narrow, homogeneous population like Dravet. For folks with Dravet, 80%-90% have an SCN1A mutation. I still don't understand what the other 10%-20% have. It's a little bit strange, but that's kind of where the science started. Lennox-Gastaut has no underlying genetic cause. If you were to whole genome sequence all those Lennox-Gastaut patients, some would probably end up being Dup15qs. Some would probably end up being SCN2As, SCN8As. We know there are plenty of these patients with dual diagnoses, okay? What we know from what we've seen with other 5-HT2Cs is Fintepla is approved in Dravet and Lennox-Gastaut, and we know anecdotally it's being used broader than just those two indications. They're obviously running a phase III in CDD, which is CDKL5. So to us, it doesn't feel like the mechanism of action of 5-HT2C is specific to one underlying genetic cause, because if it only worked in SCN1A, it probably wouldn't work in CDKL5. That was the premise that we brought to the Pacific study, that LGS is really not that different from DEE. There's never really been an approved DEE indication, but if you look at what the ILAE has written as a DEE indication, it's very similar to Lennox-Gastaut. So if Lennox-Gastaut is an approvable indication, why shouldn't DEE be an approved indication? If the patients tend to have seizures that are treatment-resistant, developmental disability, and an abnormal EEG. That's all we're trying to do, is adjust what is an approved indication in LGS, which has no underlying genetic cause, and just broaden it to include some of these other patients, particularly in the indications where the N is probably too small to justify clinical studies. That's what we've seen. You have multiple drugs approved for Dravet because the patient population is large enough. You have multiple drugs approved for Lennox-Gastaut because the patient population is large enough. There's nothing for Ring 20. There's nothing for Ring 14. There's nothing for Dup15q. It just doesn't seem fair, because if I had a child with a DEE, I would go to my provider, and I would say, "You're going to call my child Lennox-Gastaut, so I have access to all these medications," and I would actually have a whole genome sequence done on my child, and no one besides me would ever see what that diagnosis is. Because God forbid, they come out with Dup15q, and I no longer have access to the medications that are available for a patient who has Lennox-Gastaut. It just doesn't seem fair. Agreed, and totally understood. I want to follow up on something you mentioned earlier in terms of combining- Yeah ... different treatment options. So do you think that bexie can easily be added on top of current medications like cannabidiol or other standards of care to provide an incremental benefit, and are there any pharmacological synergies you would expect? Yeah, really interesting question. So, the exciting part about PACIFIC is, we did include some medications that are newer. So the Fintepla data was generated at a time when they excluded cannabidiol. So our data, we're excited about because we think it's on top of current standard of care. And the average patient was on 3-4 medications in our study. So, that's actually a good thing because we think that data is extrapolatable to a phase three. We'll see. And, I don't know if there's any pharmacologic synergies we would expect. We haven't seen it. It's an amazing question, though, because frankly, we've had generic ASMs around for 20 years, and no one's ever run the analysis to show is Keppra synergistic with any other ASM. At some point, we should probably generate that data. It's probably not a Longboard thing. But, as of right now, we haven't seen anything that says we're synergistic or antagonistic to one of the other standard of care meds. Okay. So that, that's super helpful. And I guess with all of that as a backdrop, as you look ahead to the, to the potential launch of bexicaserin, where do you see the initial commercial opportunity? Yeah. So there's a tremendous unmet need for new medications across all the DEEs, and given that polytherapy is the norm, the value proposition in our mind is really about demonstrating that safe, easy to add on to the current treatment paradigm. Unfortunately, these kids are pretty refractory, and multiple mechanisms of action are needed to reduce seizures. So we believe bexicaserin has the potential to be the 5-HT2C of choice. We could see a world where a DEE patient is on, you know, multiple generic anti-seizure medications, and we're just added on top. We are expecting patients to cycle through over time. So when we talk about a phase III program for bexicaserin, we've talked about a fast-to-market strategy in one homogenous population that probably is in Dravet. That's probably the initial indication we would get approved for while we're working on what's that broad indication, if it's allowed via the FDA and other regulatory agencies, or whether we'll do multiple phase IIIs in individual indications. So it's really a question of how do we come up with the best plan to get to the market quickly and then broaden out over time? As a reminder, we've got composition of matter, plus patent term adjustments and patent term extensions to get out to 2041. So if we can't get a new DEE indication, that's fine. We can just hit multiple indications along the way, and that's kind of what we're telling investors to imagine as a base case, is start with the Dravet, and then assume we will run simultaneously a Lennox-Gastaut study and likely a third indication at the same time. Okay. All right. That makes sense. And you've spoken a couple of times about the importance of safety and tolerability. So maybe just, I guess, from the PACIFIC Study, what are the key points of safety and tolerability for differentiation of bexi versus other ASMs? And can you just talk about the discontinuation rate, most common reasons for discontinuation, and how to mitigate discontinuations in your next study? Sure. So we were incredibly pleased with the safety data generated in the PACIFIC Study. We didn't run echocardiograms as part of the study, and the most common AEs observed were somnolence, decreased appetite, GI issues, et cetera. Everyone's been talking about the discontinuation rate, because the percentage was a little high. The N was actually not that high. The main reasons for discontinuation were due to CNS and GI AEs. Of note, the majority of discontinuations occurred in the titration period. The discontinuation rate for patients that achieved the maintenance dose was just under 5%, which we thought was really good. The discontinuation rate was a bit higher from a percentage perspective in the titration phase window. Now, if we don't do anything to address that in phase III, it shouldn't have an impact on efficacy. Patients in the titration phase are usually not counted as part of the efficacy population, so you would just solve it by over-enrolling patients. Now, that's not a great thing. We don't wanna churn patients. We don't wanna have any child go into the study knowing that there's a likelihood they would discontinue along the way. It's not, it's not the right thing to do. But we did think we were able to solve the issue. So we recognized early on in the study that as physicians got more experienced with bexicaserin, they were able to understand the AEs that we're seeing and how to handle them before moving to the next dose. So as the study continued, we saw the discontinuation rate stabilize. Importantly, 86% of the bexicaserin treated participants were able to achieve and maintain the top 12 mg dose TID. So we were able to move all 9 of the placebo patients through the titration period and onto the maintenance dose because we learned along the way. So we think we've got it dialed in for the phase III, but there are a couple of things we could do if we needed to. Does that answer your question? Yeah. Yeah, that, that's perfect. Appreciate that additional color there. And I know you said earlier that you were planning your end of phase II meeting. Is there any guidance you can give to investors in terms of the timeline for that meeting, and when you could potentially initiate a phase III study, and when investors should expect to see the phase III study results? Yeah. So, you know, we've had the data for about a month. We're obviously moving very quickly. Typically, companies take about six months to go from data to end of phase II m eeting. Obviously, we want to be as good as everybody else or slightly better. In this case, because we're thinking about splitting the world into a fast-to-market strategy and a broad indication strategy, that might change a little bit. I wanna make sure we give ourselves the best chance to have the conversation with the agency on broad. We think we have the right molecule to help address that and potentially change it for all the drugs that are going to come after us, because we can't keep doing this. You can't end up with 20 drugs approved for LGS and no drugs approved for Dup15q. It's just not the right thing. So we wanna make sure that while we're giving guidance to folks that we wanna do as well as everyone else or slightly better, this one might take a little bit longer. Our goal is to have the phase III start as rapidly as possible in that fast-to-market strategy, and then move along at a very crisp pace. So as we think about that end of phase II, I really don't wanna give guidance along the way, but we really are obviously incredibly motivated to move as quickly as possible, not just for investors, not just for ourselves, but frankly, you know, who really doesn't understand this is the patient advocacy and the caregiver community. They expect us to start the study tomorrow, and so they're calling on a daily basis saying, Hey, when can we get going? Okay, fair enough. And then, you mentioned earlier the pros and cons of developing each indication in a serial approach as opposed to in parallel. When you do have your end of phase II meeting, will you be asking for a kind of basket study approach, or will you do individual studies for each indication? ... So, you know, that's really beyond. Well, we can ask for whatever we want. What we get back is beyond our control. It's why we're telling investors, plan on a Dravet study, a Lennox-Gastaut study, and a third indication study, all running simultaneously. We understand what those generally look like. There are plenty of analogs out there that we could essentially cut and paste. These studies typically are 100-150 participants. These studies generally cost around $30 million-$40 million each. So the amount of money we raised recently should give us the ability to run three of these studies simultaneously and feel very confident about it. It's highly unlikely we would do a Dravet, wait for data, get to an LGS, wait for data, get to something else. So that's what we're telling investors to underwrite is, assume three indications moving forward simultaneously in phase three. The sites are very similar. There's a tremendous amount of overlap. You don't have to replicate a lot of stuff. The physicians who are treating Dravet are also the physicians who are treating LGS, are also the physicians who are treating these other DEEs. Okay. If we get to the upside node, it will not just be Pacific supersized. We will likely have a fast-to-market strategy with Dravet, and then we'll have something else that is helping us on the broader indication, but probably has some bells and whistles put in. All right. Definitely appreciate your strategy there. And then, you did mention earlier the titration learnings from- Mm-hmm ... PACIFIC. Can you just talk about how you might leverage those learnings in phase III? And is there the potential to include a BID formulation in phase III? Yeah. So, we anticipate using a similar titration scheme in the adults and adolescents. We'll obviously incorporate weight-based dosing. We hope to get down to age 2. That's where the majority of the patients are, the younger kids, and that's where we hope to show the best benefit. We did learn a lot about dosing from Pacific, and we want to spend some time evaluating those learnings while we prepare the protocols and finalize the titration schedules. But in general, we were happy to see that majority of patients in Pacific were really able to reach the 12-milligram dose, and we think that the ability to dose optimize is a great differentiator for bexicaserin. We do intend to use a BID formulation for the phase III. TID is not an issue commercially. It's really just a convenience factor. Epidiolex is BID, so why not make it on the same schedule? And so we need to look through that, but we published some data at AES that we believe supports using the current formulation that was in Pacific, and just dosing twice a day. Bexicaserin's half-life is about 4.5-6 hours, and so a priori, you think it's right on the border of TID, BID. Based on that data we saw in that, 102 study that we published at AES, we think there's a viable path forward for just dosing it twice a day when you look at the CSF levels. Okay, that makes perfect sense. And then, I know there's an OLE portion of PACIFIC. Can you just tell us what you're looking for from that open-label extension, and when do you expect to share that? Yeah, we were happy to see great participation in the OLE. A hundred percent of the completing participants moved over into the OLE. Since it's an OLE, we can pull the data periodically, but we're really interested in how bexicaserin is doing long term. It's a 12-month OLE, so year-end 2024 is probably a good estimate at this time for making one of those data pulls. Okay. All right, we're getting into the lightning round here. So, can you just comment on the potential for reimbursement across different DEE indications? Yeah. Look, I think, given the fact we have composition of matter, that enables us to think strategically about how to best address the DEE community over time. These patients, unfortunately, are very, very challenged, and they are expensive. They're in and out of the ER, they're on polytherapy, they've got struggles. So we're gonna look at regulatory and pricing strategies to make sure that if bexicaserin is approved, we do our best to demonstrate that value. There's a significant range between Ztalmy at the high end and Epidiolex kind of lower, and I think it's gonna depend a little bit on what patient population we're really going after and how broad do we wanna go. Okay, that's super helpful. I wanna make sure we touch upon 659. Can you just maybe give us a quick update on the status of that molecule and how you're thinking about the development strategy? Yeah. So, LP659's an S1P receptor modulator, highly selective S1P1, little bit of activity on S1P5, no activity on two and three, which are generally considered bad actors, no activity on four, which is really more relevant for the derm as opposed to CNS. LP659 was developed at the same time as etrasimod, which was the cornerstone of the Pfizer acquisition of Arena. But LP659 was designed to be brain penetrant versus etrasimod was designed to be peripherally restrictive. So, we think LP659 was designed with a lot of those same great characteristics that should hopefully differentiate it over time. It's currently in a SAD study, and we expect to have top-line data in the first half of this year. Okay. All right. Well, I know we're just about out of time, if I could try to squeeze in one more question. Can you just share any thoughts on the potential for strategic partnerships, either with bexicaserin or LP659, and what kind of interest you're seeing in those molecules? Yeah. So first of all, can't say anything publicly about strategic interest, but, developing a drug in the DEE space gives us a tremendous opportunity to control our own destiny. We've seen other companies like Zogenix, GW, Marinus, successfully launch their DEE compounds. As a result, we're not really interested in partnering in the U.S. or Europe. We might not decide to launch in Japan, we might not decide to launch in Asia, but we think we have the ability to go it alone, and we're excited about that. Okay. All right. That's perfect. Anything else before we wrap up that you'd like to highlight for investors today? No, thanks very much, Jay. We're obviously very excited about the upcoming year, and we believe the data from PACIFIC was very compelling, and we're very committed to moving bexicaserin along as quickly as possible. Excellent. Thank you so much, Kevin. Really appreciate the opportunity to catch up with you on all the impressive progress you're making at Longboard, and we'll look forward to future updates. Thanks, Jay. Thank you.