Hello, everyone, and welcome back to H.C. Wainwright's 26th Annual Global Investment Conference. My name is Patrick Trucchio. I'm a senior healthcare analyst at H.C. Wainwright. It's my pleasure to introduce our next speaker, Brandi Roberts, EVP and CFO of Longboard Pharmaceuticals, a clinical-stage biopharmaceutical company focused on development of centrally acting compounds designed to be highly selective for specific G protein-coupled receptors, or GPCRs, for neurological diseases. So first, you know, this has been such a, I think, a pivotal year for Longboard, some really important readouts, and more to come. So I guess first, maybe you can talk about the formation of the company, the relationship with Arena Pharmaceuticals and Pfizer, the science that underpins the pipeline, and then we'll go into each program. Yeah, sounds great. So thanks for having us here today. Really appreciate it. Before I do get started, I wanna remind people that I will be making some forward-looking statements, and these statements are subject to risks and uncertainties that could cause actual results to differ. So please see our financial statements that are filed with the SEC. That makes the lawyers happy. Thanks for starting with that. But in general, Longboard spun out of Arena in 2020, and they had these great neuro assets, but they were already in three other indications, and so they didn't really have the expertise in-house to work on these neuro assets. And so the idea was spin it out as a separate company, really build the expertise, and that's what we've been doing over the last three to four years, is really putting together this world-class neuro team. As everybody knows, Arena was purchased by Pfizer in 2022. They've continued to be a great partner for us. They do get low- to mid-single-digit royalties on both of our programs, but they currently don't have an equity stake in Longboard, and so, it's been great to work with them as we've continued development of the assets. And as you said, both of our assets were really designed to have greater selectivity than predecessor drugs, and we really hope that that can translate into better efficacy and improved safety profiles. So starting with bexicaserin, formerly LP352, maybe we'll start there with the mechanism, potential differentiation, and why do you believe it could be compelling treatment for multiple epileptic indications? Sure, so bexicaserin's a 5-HT2C super agonist, and it was designed to be very selective to 5-HT2C only. It doesn't hit 2B or 2A, and 2B is well known to be associated with pulmonary arterial hypertension and other potential cardiac issues, and 2A can be associated with psychiatric symptoms, and so it was our belief that a highly potent 5-HT2C could be helpful in reducing seizures, specifically in the DEE space. Got it. And can you tell us a little bit more why Longboard chose to go with an oral delivery approach for bexicaserin? Yeah, absolutely. So in this case, this patient population, an oral drug is really the most suitable option. A lot of these patients are on feeding tubes. Got it. And then, just when we think about epilepsy, this is kind of a pretty. It's a broad therapeutic area. We're looking specifically here at developmental and epileptic encephalopathies, or DEEs. So how do you. First of all, tell us a little bit more about the DEEs, and how do you characterize the unmet need, and for DEEs and seizure disorders? Sure. So DEEs represent a group of devastating epileptic disorders that appear early in life, and they're really defined by three things. The first is developmental delays, the second is refractory seizures, and the third is abnormal EEG activity. And there are over twenty-five individual types of DEEs, but only about four have been studied in the clinic and have approved therapies in the U.S. It's actually assumed that there could be over nine hundred genes that are contributing to DEEs. There's a significant unmet medical need for the 20+ DEEs that only have traditional kinda anti-seizure meds available for them. And for the four that do have specific approved treatments, we're still seeing a large number of patients that don't have adequate seizure control. And so, you know, in total, this represents a really significant commercial opportunity for bexicaserin. So just a follow-up there on the prevalence of Dravet, Lennox-Gastaut, and CDKL5 deficiency disorder. Maybe talk about the prevalence of these and, as well, the treatment paradigm in each of these indications. Sure. So, there's varying numbers on the individual DEEs, but according to our sources, we think there are about 21,000 Dravet patients, 48,000 LGS patients, and about 1,800 CDKL5 patients in the U.S. All of these patients have refractory seizures, so the current treatment paradigm is to have them on three to four anti-seizure meds to try to keep their seizures at bay. And usually, the older generic ASMs are used first, and then some of the newer treatment options are added on. But when you think about these numbers, we really just see this as the starting point. When you add up all the patients that have Dravet, LGS, CDKL5, and the other DEEs in the U.S., we think that that number could be between 150,000- 250,000. Now that we have breakthrough therapy designation for DEE, that's really the opportunity that we see ahead of us. Again, that's just in the U.S., and we'll talk more about that. I was mentioning that we have our R&D day coming up on Monday. We'll talk more about that then. Right. Awesome. Well, so earlier this year, we had really exciting phase II data that came from the PACIFIC program. Maybe you can provide some more background on PACIFIC, as well as phase I data, learnings from that data, and then the phase II portion of the program, also the open label extension data, and if you want to, since you mentioned it, maybe a preview for Monday. Sure. Yeah, so the PACIFIC study was a phase Ib/IIa study. It was designed to assess safety and efficacy across a broad range of DEE patients. Based on the selectivity of bexicaserin and the phase I studies that we had run to date, we had a belief that a more selective 5-HT2C could be helpful in this patient population, and so really looking across the broad group of DEEs. It didn't really matter which underlying DEE they had. That was the hypothesis we wanted to test. In terms of the results from PACIFIC, I wanna start with safety, 'cause that's what we always start with, with a Ib/IIa. Especially since this is our first study in patients with DEEs, it was really important to us. And what we saw was, a favorable safety and tolerability profile in this specific study. The AEs were consistent with what we would normally see in other serotonin receptor agonists. And in terms of efficacy, we were very excited to see how well bexicaserin performed in the PACIFIC study. The full analysis set included 35 patients that were on bexicaserin, nine patients that received placebo, and what we saw was, a countable motor seizure reduction of almost 60% in the bexicaserin group versus 17% for the placebo group. And the placebo-adjusted seizure reduction was 42%. And as a reminder, that was on top of current standard of care, so t hree to four other meds as well. You mentioned that we just had OLE data as well. We just put out our nine-month cut of the OLE data, and we were pleased to see continued durability of the drug. We saw a seizure reduction of about 58% across the patient group, and, you know, we were happy to see that all of the completers from the PACIFIC study went on into the OLE study, and we still have over 92% participation at the nine-month mark. Right. Great. And then, maybe you can summarize your end-of-phase II discussions with the FDA? Sure. At the beginning of July, we announced that we had received breakthrough therapy designation from the FDA, and that was for seizures associated with DEEs down to the age of two. We are the first and only company to receive this designation for DEEs, and our end-of-phase II meeting with the FDA was the first official meeting under breakthrough. Really, though they were kind of a combined process there, having our end-of-phase II meeting and then getting the BTD as well. What BTD provides us with is a pathway for our phase III program to encompass the broad DEE population. Our plan is to have two studies: one that has patients with Dravet syndrome, one that has a mix of LGS and other DEE patients, and again, we're gonna plan to share a lot of those details at R&D Day on Monday. We can't wait. We're excited. So, maybe, you know, I know we're looking a little further ahead here, but maybe you could talk about the emerging product profile that's coming for bexicaserin. Sure. So again, we'll cover this in R&D Day, too. But in general, we're hoping that bexicaserin can be the 5-HT2C of choice when physicians are really considering multiple treatment options for this patient group. We wanna be able to show a safety profile that's acceptable to caregivers, patients, and physicians, and efficacy that can be very impactful to these patients' lives. You know, the idea is that if we could possibly control seizures earlier in life, then maybe we could provide a greater quality of life for these patients, and that's really important when you talk to these caregivers. It's really a devastating condition here. So when we think about some of the other compounds, you know, Fintepla and Epidiolex, maybe you talk about differentiation compared to Fintepla, and then whether you see bexicaserin as maybe being complementary to some of these other, drugs, like Epidiolex. Sure. So, first of all, bexicaserin was designed to really only hit the 5- HT2 C receptor. It doesn't hit 2 B at all, which we know is the receptor that is known to be involved with PAH and potential cardiovascular issues. Fintepla has a black box warning because of that 2 B interaction, and accordingly, patients are required to get echocardiograms every six months. Echoes were not required for our PACIFIC study. We do not hit the 2 B receptor at all, and we don't plan to run them in the phase III program as well. So that's probably our biggest differentiator. You know, in terms of efficacy, I'll caveat my response in terms of. You know, it's very hard to compare clinical trials because there's, you know, different time points as to when they were done and differences in terms of how we develop those clinical trials. But in general, I think bexicaserin performed very well. You know, we were very happy with the results that we saw from the PACIFIC study, and then you mentioned Epidiolex as well, so that's a question that we get often, is, in terms of, how could we work with Epidiolex? This is a polytherapy approach. These kids are on multiple drugs. In the PACIFIC study, we had about a third of our patients on Epidiolex, and so we think we could be used in combination with Epi or, or perhaps even ahead of it, so we see, you know, their use as headwind for us. One of the things that we highlight as well with bexicaserin is that we are metabolized through the UGT pathway, which potentially reduces the risk of drug-drug interactions, which is also very important since these kids are taking multiple treatments at one time. We know that due to DDIs, there are some other drugs that have to be modified in terms of what their dosage looks like, and we're hoping to avoid those types of issues with bexicaserin. Right. Great. And so as we look ahead to the phase III program, you know, is it just a matter of showing certain level of seizure reduction in these phase III trials? What do you need to demonstrate, both from an efficacy and safety perspective? Yeah. You know, so as I said, we were the first company to really generate the clinical data to support a broad DEE approach. Getting that was very significant for us because that means we'll be able to work with the FDA as we progress with the development of bexicaserin. We're gonna work with them to ensure that our phase III program is designed and implemented in the most efficient manner possible, and we'll continue to generate data that could support our rationale to go after this broad approach. We do think, again, it's kind of immeasurable to talk about how important that FDA interaction is. By getting breakthrough, we feel very compelled to do everything we can to get this product to market. As we look even further ahead to the commercial opportunity for DEEs, how do you think about that? Yeah, well, I mean, we think it's large. We, you know, based on our estimates today, when we think about the four DEEs that have approved treatment options, we think that that could be about a $6 billion market opportunity. And we know that DEEs encompass a wide range of severe epilepsies, which are driven by mutations in hundreds of genes, and there are at least 20 named other DEEs that are discussed. So we think there's an opportunity for bexicaserin to be a multi-billion dollar drug if approved. We think that's definitely possible. Right. Great. And then, so then just moving over to LP659 here as well, can we start with the mechanism, potential differentiation, and why do you think it could be compelling for neurological diseases? Sure, absolutely. So again, LP659 was created by that amazing team at Arena, who was really focused on designing very selective drugs that could improve on drugs that had come prior. This was the same team that discovered etrasimod. It was designed to be centrally acting, an S1P receptor modulator, but with some of the same differentiating characteristics that were built into etrasimod. It's highly selective to S1P1 and S1P5, which minimizes off-target effects, and it's demonstrated rapid onset and offset of action, which is also important in this area. S1Ps are considered well understood. Early data has been shown to be generally predictive of clinical effectiveness. We've been doing a lot of translational work here, and that, coupled with additional learnings from the I&I space, has opened up several orphan conditions that we think could be very interesting and have attractive commercial opportunities. What indications do you view LP659 as having potential? Sure. So in early August, we finished up our SAD study, and we thought it made sense to have a call and talk about 659 in more detail. And during that call, we discussed eight potential indications that we thought were interesting based on the preclinical work we've done to date, as well as the role of T or B cells in the related disease progression. These included GBS, CIDP, also FTD, and others. We believe that the best path for 659 would be in an indication or indications with high unmet clinical need, where there's strong preclinical data and/or clinical support, and where we can do clinical studies that are feasible and practical. Great. And then maybe you can talk about the phase I SAD data. Sure. So the SAD data was, you know, very helpful in terms of safety. It was generally safe and well-tolerated. The adverse events were mild. We didn't see any abnormal assessments in that study. We evaluated two formulations and multiple doses, and interestingly, we saw a rapid dose and formulation-dependent effect on the reduction of lymphocyte counts, with two of the cohorts showing reductions in the 48%-59% range. And this reduction in lymphocyte count is a crucial parameter for us to evaluate the drug's potential effectiveness and safety profile, so we were excited to see that. And really, the next steps are now to go into the FDA, talk about that SAD data, and then start the MAD portion of the study in the first quarter of 2025. Great. So are there any follow-up questions from the audience? So I think maybe, just with the remaining time, if you could talk through, what you think investors are missing about, the Longboard story and, you know, bexicaserin, 659, the pipeline. Yeah, it's a great question. Appreciate that. We are very happy to see our stock appreciate during the year. We're very excited about the results that we got from bexicaserin. We think that this is a significant unmet medical need, and we are really compassionate about it and passionate about continuing the development of bexicaserin and LP659, because we know that there are patients waiting for this. I would say really talking more about breakthrough and people understanding that we're the only company that has really presented compelling clinical data to the FDA to receive that breakthrough therapy designation for DEEs is really important. It opens up a tremendous commercial opportunity for us, and we think that some people are still modeling kind of bexicaserin with revenues that are well below what we would expect for it based on this broad view of DEEs. If you look at Epidiolex, it's well on its way to being a billion-dollar drug, you know, six years after launch, and if you could imagine that that price has doubled, and we don't think that that would be kind of an issue when you think about prior auth or anything like that. You open up the market to all DEEs, not just the few that are currently approved, you could see how that could be a multi-billion dollar opportunity. There's much more work to be done in terms of pricing as we go through the phase III development, but in general, we think this is a very large opportunity here, which presents a great potential for bexicaserin, and we really want people to understand that we think this is an area that we can commercialize on our own. We've spent the last three to four years building out a great team. We've been very focused on implementing an efficient phase III program. We really believe in a hands-on approach, and we're excited about getting this kicked off here in just a few months, and we look forward to talking more at Investor Day and providing a lot more of the details. That sounds great. Yep, we're looking forward to that on Monday. It's 10:00 A.M. 10:00 A.M. on Monday, yep, here in New York. Awesome. Okay, well. All right. Thanks so much. Thank you so much, Brandi. Appreciate you taking the time.