Good afternoon, everybody, and welcome back to our sixth annual conference. This is Thelma Kayati from the Guggenheim team, and it's my pleasure to introduce our next company, Longboard Pharmaceuticals. And here with me is Brandi Roberts, the CFO of Longboard. Welcome, Brandi. So, to start off, Brandi, can you give us an overview of the company, and what are the key milestones you are most excited about for the year? Sure. Thank you so much, and thanks for having us today. Before I do get started, I want to note that I will be making some forward-looking statements. Actual events or results may differ materially from our expectations. For more information on these forward-looking statements, including factors that could cause the actual events or results to differ, please see our filings with the SEC. So Longboard was spun out from Arena in 2020 to focus on the development of the neurological assets in its pipeline. We are concentrated on the development of two product candidates: bexicaserin, or LP352, a 5-HT2C superagonist 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 a premier neurology-based team. In January of this year, we announced positive top-line Phase 1b/2a data for bexicaserin from the PACIFIC Study, and we're in the process of preparing for our global Phase III program. We think bexicaserin has the potential to improve treatment for patients taking the current drugs being used in the DEE space today, and potentially expand into additional patients that have had very novel treatments to date. As many of you are aware, there is 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 polytherapy. Bexicaserin was designed to be very selective to 5-HT2C, and we believe that the selectivity provides bexicaserin with characteristics that may result in having the 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 LP659 in the first half of 2024. Thank you for that introduction, Brandi. Really great. And so recently, as you were mentioning, you have shown really impressive data from the PACIFIC Study. And what was really remarkable there is that you saw efficacy not only in Dravet and LGS, that somehow was predictable, but also in other DEEs. But let's go by order. So let's look first at Dravet and LGS. If we can dig a little bit into the data, and if you can help us contextualize the results in comparison to what we know from historical studies of Fintepla and Epidiolex, that would be great. Sure. You know, we believe that the data from our successful PACIFIC Study were really profound. As a reminder, what we've said all along is that physicians, patients, and caregivers are looking for safe, easy-to-add-on therapies that provide additional efficacy. Efficacy is interesting because even in indications like Dravet and LGS, where there are multiple approved therapies for those individual diagnoses, there is 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 a broad DEE population, as you noted, and we saw a 53% seizure reduction from baseline in patients that were on current standard of care, meaning on average, 3-4 concomitant anti-seizure medications, and which included certain medications that were previously unavailable when previous studies were conducted. We saw seizure reduction of 72% in Dravet, 48% in LGS, and 61% in other DEEs. The study seemed to simulate what a real-world experience would look like, and bexicaserin appeared to show evidence of a potential safety and efficacy profile that could offer patients benefit in Dravet and LGS, as well as the DEE patients without approved novel therapies. In reviewing these results with experts that are out in the field, they were pleased to see evidence of clinically meaningful changes in seizure reduction across the DEE landscape with a potential safety benefit. Thank you for that. And, as you were highlighting, bexicaserin has a pretty unique pharmacological profile, which can be key for, the commercial application of the drug. So can you actually remind investor about the key features of the drug, and, how important is that from the patient and provider's perspective? Sure. As I mentioned above, bexicaserin was designed to be selective for 5-HT2C, which we believe contributes to efficacy attributes such as seizure reduction. Bexicaserin has no detectable activity on 5-HT2B or 5-HT2A, and we believe that that selectivity against 5-HT2B is very important and will enable us to avoid the potential cardiovascular risks that are associated with some other drugs that do have activity on the 5-HT2B receptor. We believe that the lack of the need for REMS and cardiac monitoring would be meaningful to both patients and caregivers. Thank you. So, as we were discussing, you saw a pretty remarkable efficacy also in other DEEs, and that is a large opportunity for Longboard, as you, you have been highlighting in, many different, occasions. So if you can give us your perspective of the data in the DEEs? Like, it looks like, the efficacy could be even higher than what has been historically shown. So is that the case, and how, promising is that for a possible pivotal program in which you would include other DEEs? Sure. I think that's a really interesting question, and I'm gonna frame it just a little bit differently. Sure. So our PACIFIC study was designed to test bexicaserin versus placebo. It was not a head-to-head study against any other drugs or drug candidates. Additionally, it's important to remember that patients are going to be treated with three to four anti-seizure meds on average at a time, and more importantly, they're likely to cycle through many anti-seizure meds during their journey. So we believe the real question is: could bexicaserin be easy to add on to current medications like cannabidiol or Ztalmy to potentially provide additional benefit? In PACIFIC, bexicaserin appeared to show evidence of the potential to have an exciting safety and efficacy profile in a broad number of DEEs. We think this data will be helpful in talking to the FDA about our intended broad development in our phase III program. We're encouraged that we did see comparable placebo-adjusted seizure reductions in the range of 27%-28% in both LGS and DEE other, both of which are very heterogeneous populations. Indeed, and that's actually a very interesting point you brought in about the complexity of these disorders, where patients have not only the epileptic load, but also the cognitive deficit. And I'm kind of curious to know if you think there is any possibility that the drug may also work on the cognitive domain. And I wanted to ask you if there was any cognitive endpoint during the small study. I know it was a very small one, but just curious about that. Sure. So, you know, in thinking about the unmet need, it's really a complicated question to say, is epilepsy or seizures really the main problem for these patients? Patients with DEEs have multiple medical and developmental issues, and seizures and SUDEP are certainly of concern. For investors, reducing seizures matters because it's probably the most objective measure that we have in our studies and what will likely to be the endpoints for our pivotal studies. But when you think about our mechanism of action, if you talk to caregivers, which we've done plenty of, there are other issues like cognition and sleep that register as high needs, too. You know, if their child could be more aware of things, smile more often, be engaged, sleep better, those are all really big deals for these caregivers. We believe that if you're able to reduce the seizures, then you may have an impact on some of these non-seizure outcomes like cognition and sleep. But we believe it's important to start early. We think effectively dealing with seizures early in life would be helpful in a number of ways, and that's why we plan to study patients with DEEs down to the age of two in our phase III program. As you mentioned, you know, our PACIFIC study was a pretty small study, and we did not assess cognitive function in that study. And we had a relatively short intervention period as well in that. And when you look at the adolescent and the adult population, impact on cognition would not really have been anticipated when we looked at those age groups. But it's a good question as we plan for our phase III, and we think about going down to ages that are two and up. And we'll think about that as we plan that study and what other non-seizure outcomes might make sense. That makes a lot of sense. And looking at the safety profile of the drug, so that's a key differentiating features- Mm-hmm. And it was confirmed, its excellent profile was confirmed indeed by the phase I. But there was a one point, the discontinuation rate, that raised a little bit of comments from investors. So it was a little bit on the high end. What was the main factors for those discontinuation, and is there anything you can do for the during the pivotal program to improve on that? Sure, happy to go through that. So the main reasons for discontinuation were really due to CNS and GI-related adverse events. And of note, the majority of those discontinuations occurred in the titration period. The discontinuation rate that we saw in the maintenance dose was just under 5%, which we thought was very good. The discontinuation rate was a bit higher from a percentage perspective, but not really from an end perspective in the titration phase of the study. But we recognized this early on in the study, and we were able to take a lot of key learnings away as we think about the Phase III program. As physicians got more experience with bexicaserin, they were able to better understand the adverse events that were seen and how to handle those before moving to the next dose. That was really important with our hands-on approach, that we talk about that with the PIs as they went through this with their patients. As the study continued, we saw the discontinuation rate stabilize, and importantly, 86% of the bexi-treated participants were able to achieve and maintain that top 12-milligram dose. Additionally, we were able to move all 9 placebo patients through a titration period and onto a maintenance dose of bexicaserin in the OLE study. We think we've got it dialed in for the phase III program, but definitely understand why it was a question. Got it. That's helpful. And now, a key question for investors is mainly what's next? Like, what's gonna happen in the pivotal program? And first of all, I want to ask you if you already have the end of phase II meeting with the FDA, and how are you thinking about the pivotal program? Sure. It's really... This is a question we get all the time. It's anyway- It's really hard to believe, but we only had top-line data about a month ago. So we're still compiling the rest of the data, working on things like the clinical study report to get ready. We have a lot of documents to prepare for an end-of-phase II meeting, and we're gonna get that on the books as soon as we can. But it's important for us to take the time to really prepare for a program that makes the most sense. The PACIFIC Study provided us with great data that we think will be helpful in discussing a path for Dravet, a path for LGS, and a path for broad DEEs, so we're taking the time to do that. That makes sense. And traditionally, these studies have been studied, like, these disorders have been studied individually. But you had this particular type of design where with a basket approach. So how feasible would be that in the pivotal program? What do you need for such a design by a regulatory perspective, and what did you hear from the FDA in such regard? ... Sure. So we don't really think about this in terms of a basket study. I think when you think about a basket study, we usually kind of think about that in terms of like early stage oncology studies with varying multiple types. We think that the data from PACIFIC will help us continue to follow science and potentially advance the treatment paradigm for a large number of patients without access to novel meds. In this case, we believe that LGS is a comparable indication to a DEE indication. LGS is a very heterogeneous syndrome with no underlying genetic cause. If you look at the ILAE definition of DEE, it's not particularly different than the definition of LGS. So really, when we think about it, if LGS is an improved indication, why shouldn't we work to make DEE an improved indication? That's the conversation that we wanted to have the PACIFIC data to be able to go to the FDA and further discuss. So you think, like, it's feasible from the FDA perspective to run a study, let's say, for three indication or something like that? I don't know if you have narrowed down the number of indication- Yeah! you would go for. Yeah, we haven't narrowed that down, but that's definitely what we want to talk about with them, is: How can we consider a path for Dravet, a path for LGS, and a broad approach where we might be able to get a, a broader label over that DEE indication? That's helpful. Okay, and in terms of a dosage, will you use the same dose you used during the phase 2, and the titration scheme will be the same? Yeah. So we anticipate using a similar titration scheme in the adults and the adolescent population in our phase III, and we're gonna incorporate weight-based dosing for those lower weight pediatric patients. We learned a lot about dosing from PACIFIC. We're gonna spend some time evaluating those learnings while we prepare our protocols and finalize the titration schedules. But in general, we were happy to see that a majority of the patients in PACIFIC were able to reach the 12 milligram dose, and we think that the ability to dose optimize is a great differentiator for bexy. Got it. You can tell, I call it bexy sometimes, short for bexicaserin. That's better. It's easier. Yes, it's a little easier. Indeed. Okay. So, and about the BID formulation, that's another question we get pretty often. What's the status of the formulation, and will you be able to use it in phase 3? Sure. We intend to use a BID formulation for the Phase 3 program. We wanna evaluate all of the data from PACIFIC before we officially sign off on moving to a specific BID formulation, and we don't really believe that a TID formulation is a challenge commercially. A lot of these patients are on feeding tubes, but we do believe that a BID formulation is relatively more convenient, and we intend to progress our plans for PK modeling to support dose selection. Got it. About the pediatric population, so you were mentioning at the beginning, if I got it right, that you are planning to include the pediatric population in phase 3. What do you need to show to be allowed to do that? Sure ... first of all, and yeah, will you need the OLE data? Sure. So, as I said, we do plan to go down to age 2 in our phase 3 program. We had patients that were aged 12 to 17 in the PACIFIC Study, and we can use PK modeling from those patients to determine dosing in the lower age and weight group for the phase 3 program. So we feel comfortable with that PK modeling that will help us get down to age 2. Got it. When do you expect the results from the OLE? Yeah. So, you know, OLEs are very helpful for these studies. I think it's really important for caregivers that an OLE is an option, and we were happy to see great participation in the OLE- Yeah ... with 100% of those completing the PACIFIC Study moving over to the OLE. Since it's an open label study, we can pull data periodically, but we're really interested in how bexicaserin is doing long term. So since it's a 12-month OLE, year-end 2024 is probably a good estimate at this time, but we'll continue to update you. Thank you for that. Okay, so looking a little bit at the commercial perspective, how do you envision positioning, Bexicaserin in the context of the different DEEs? Sure. So we don't think that the polytherapy approach is gonna change in DEEs. Unfortunately, these kids are pretty refractory, and multiple mechanisms of action are needed to reduce seizures. We believe bexicaserin has the potential to be a 5-HT2C of choice, and we could see a world where a DEE patient's on two generic anti-seizure meds, a cannabidiol, and bexicaserin, if it's approved. The other DEE patients have no specifically approved therapies. They're in desperate need of novel treatment options. LGS patients still struggle with finding efficacious options. So we think there's a clear unmet need for those patients. Regarding Dravet, if we're able to avoid the need for echos, and if we show good efficacy, it seems hard to believe that physicians wouldn't reach for bexicaserin in that case. So we feel really excited about the commercial opportunity in all of these areas. Would you expect a faster uptake in the other DEEs as compared to Dravet and LGS, where you have Fintepla and EPIDIOLEX, or how do you see that? Not necessarily. I think physicians will look at this as a drug on its own, and whether, you know, that really makes sense in the polytherapy approach. Mm-hmm. For us, it was important to consider safety, the ease of use, you know, I think our DDI approach, and the fact that we, we don't use the CYP pathway, we use the UGT pathway, and so hopefully can interact with drugs more favorably. I think all of those are really important components for bexicaserin. Great, that's helpful. And zooming out, at the largest competitive landscape, so what are the major therapies in development for these disorders, and what do you think about, let's say, Stoke, ASO approach? Yeah. So first of all, we're excited to see development occurring across the DEE landscape. There's been a high unmet need in this space for multiple decades. And as the science progresses, such as the selectivity of our compound, bexicaserin, hopefully, we're on kind of the collective journey of developing potentially safer and more effective treatment options across the board. We're happy to see other biotechs working in the space. The needs are enormous, and we think multiple mechanisms of action, as I said, are important. Currently, the ASO studies that we've seen are on top of current standard of care, so we don't view them as competitive with bexicaserin in the foreseeable future, but again, happy to see lots of people working on this. Definitely.... So everybody is obviously focused on bexicaserin, but it turns out that you have another very promising molecule in the pipeline, LP659, about which we talk much less. So can you remind us, the key features of this molecule, and what's the status of the program, and, how is it going for the enrollment of the phase I? Sure. So we're excited about LP659. It's our highly selective S1P receptor modulator. It was designed at the same time as etrasimod, but it's the more brain-penetrant version. And etrasimod was really the cornerstone of the $7 billion Arena acquisition by Pfizer. And it was designed with a lot of the same great characteristics. For example, high selectivity to S1P1 and S1P5, and fast onset and offset of action. We have LP659 currently in a single ascending dose study, and we expect to have top-line data from that in the first half of this year. Okay, that's helpful. Have you narrowed down any indication? We haven't. Okay. We're still working on indication, and we hope to talk more about that, as we progress as well. We do think something in the rare neuroinflammatory, area makes sense, but- Mm-hmm ... but more to come there. Okay, that's exciting. And finally, let's talk about the financial. If you can give us an overview of your cash runway and what's- Sure ... the status. Happy to do so. So at the end of the year for 2023, we had $48 million in cash, and net proceeds from the financing we did in early January after our PACIFIC data were about $226.5 million. We haven't yet provided guidance in terms of runway. Again, we're only a month past top-line data, and we're still working on those phase III plans. And we're gonna need to grow. We're gonna need to support the phase III program, so we expect to see an increase in expenses. But we've been very prudent with our spend since we've really started the company, and we're gonna continue to do that as we grow. You know, we're very focused on advancing our clinical development plans efficiently and effectively. I do also really want to note that we've been fortunate to have great shareholders who have supported us over the last three years. We're very pleased with the interest that we had in our financing, and so it's great to see so many people interested in Longboard and what we're trying to do here in the DEE space and hopefully in the rare neuroinflammatory space as we continue with 659. Definitely. Looking forward for more news. Thank you so much, Brandi, for this great conversation. Yeah, of course. I, I would just say we could not be more excited about this upcoming year. The data from the PACIFIC Study was very compelling. Our team has never been more committed to the clinical development of bexicaserin. We've met so many great people through doing the PACIFIC Study: physicians, coordinators, patient advocates, caregivers, patients. It's great to see so much interest, and it really speaks to the unmet need that's there. We believe that bexicaserin has the potential to be helpful in reducing seizures in a broad range of DEEs, and we're gonna work to get this phase III program going as soon as possible. Thank you so much for taking the time. Really appreciate it. Sure. Looking forward for that. Okay. Thank you so much, Brandi. Sounds good. Thank you.