Ladies and gentlemen, thank you for standing by. Welcome to Longboard Pharmaceuticals corporate call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Megan Knight, Head of Investor Relations. Please go ahead. Thank you, operator, and good morning, everyone. Welcome to Longboard's conference call and webcast, where we will be discussing top-line data from our phase I-B/II-A clinical trial, the PACIFIC Study, evaluating bexicaserin, or LP352, for seizures associated with a broad range of developmental and epileptic encephalopathies, or DEEs. Joining me on today's call is Kevin Lind, President and Chief Executive Officer, Dr. Randall Kaye, Chief Medical Officer, and Brandi Roberts, Chief Financial Officer. Before we begin today, I would like to remind everyone that this conference call and webcast will contain forward-looking statements about the company, including, without limitation, statements about the potential of bexicaserin, the PACIFIC Study, and plans for a phase III program. These statements are subject to risks and uncertainties that could cause actual results to differ. Factors that could cause actual results or outcomes to differ materially from those expressed in or implied by such forward-looking statements are discussed in greater detail in our most recent reports filed with the SEC. Please note that these forward-looking statements reflect our opinions only as of the date of this call, and we undertake no obligation to revise or publicly release the results of any revisions to these forward-looking statements in light of new information or future events. With that, I will hand the call over to Kevin Lind, Longboard's President and CEO. Kevin? Thanks, Megan. Happy New Year, and thank you very much to everyone joining us. We are tremendously excited to provide you with the top-line data from the PACIFIC Study today. I could not be more proud of the team and the data that we are going to share with you today. We believe that LP352, or bexicaserin, is a potentially best-in-class treatment option for the DEE population and a cornerstone for us to build a world-class epilepsy franchise. For those who have been following our journey, we always start by reminding folks that we have a strong belief that differentiated pharmacology matters, that molecules with greater selectivity and specificity and target engagement should translate into both clinically and commercially differentiated best-in-class products by overcoming or avoiding known challenges for less selective molecules in order to deliver improved safety and/or efficacy. In the case of bexicaserin, the belief was that a highly selective 5-HT2C receptor superagonist could avoid the known liabilities associated with activity on 5-HT2B and 5-HT2A receptor sub-subtypes, while delivering a very compelling efficacy profile. Rather than belabor the point, I will turn it over to Randall to go deeper into top-line data. Randall? Good morning, everyone. Thank you for the opportunity to present our bexicaserin Phase I-B/II-A PACIFIC Study in participants with developmental and epileptic encephalopathies. This is one of the luxuries of the job for us in clinical development because we have the opportunity to talk to you about the results as it relates to a potential treatment for patients and their families that are living with developmental and epileptic encephalopathies. I think as you hear the data that I'm about to take you through, it should reinforce that this is the kind of data that will help families and patients have a desperately needed hope for treatment solutions that will help them in the future. So let's talk a little bit about some of the specifics about the study design. A key inclusion criteria, the patients with DEEs, it was important that they had four countable seizures at a minimum number, on by history in the last three months, and then also to have four or more countable motor seizures in the baseline period. Some participants were also required to be on a stable medication, so they were allowed a number of different anti-seizure medications during the study, actually up to four. However, it was important that they were on a stable dose. I'll point out too an important aspect in the middle of the slide, which is the different periods. So there's the screening period. Participants then move into the once meeting criteria, a randomization and uptitration period. They start off at 6 mg, or placebo, administered three times daily, for up to three to five days. If tolerated, they increase up to 9 mg. If tolerated, they can go up to 12 mg. This up and down titration can occur over the course of the first 15 days. At the end of those 15 days, they move into the maintenance period. This is a 60-day period where they stay on that exact dose. So I've described the up titration and the maintenance period. That equals the treatment period that I'll be talking about later about efficacy. They then do a down titration, or they move potentially into our open label extension. The primary focus of this study is safety and tolerability, but of course, because we are having patients complete diary data, we also have the opportunity to study efficacy in terms of seizure reduction. On the next slide, just a quick backdrop, I've talked about developmental and epileptic encephalopathies. The approach we took is we had three cohorts, patients with Dravet syndrome, a very homogeneous population of patients that have a single genetic abnormality. LGS or Lennox-Gastaut syndrome, this is a fairly heterogeneous disease in patients with these DEEs, but we also wanted to use that as an anchor to compare that to patients that have a variety of other developmental and epileptic encephalopathies, to serve as an ability to make some comparisons, both on the safety as well as efficacy side. We'll now have the opportunity of moving into top line data. On the next slide, I'd like to describe to you the demographics and baseline characteristics. Overall, when we look in terms of age, gender, weight, height, a well-balanced, a slight increase in the number of male patients over female in the placebo group, but with small sum, small numbers, would not anticipate this to be clinically meaningful. You'll note in terms of gender, we had a wider range of patients down to the age of 12 and up to the age of 15. Very pleased to see that we were able to include the pediatric or adolescent population. Let's look down at the lower portion of the screen. Concomitant medications. I've only listed the top four, but there were a variety of medications that are consistent with contemporary, typical state-of-the-art, standard of care medications that are typically used in this population. But the challenge is, they're on three or four medications in our study, on average, but they're still having a significant number of seizures. So the question is, can you take a medication like LP352 and layer it on top? Can you add it as an adjunctive, as a potential adjunctive therapy? Let's look on the next, on the next slide, where we're going to review our participants' disposition. So 52 subjects were enrolled in the study, 43 in bexicaserin, nine in placebo. So we're just going to look down the overall, overall numbers. The safety set represents patients participants who were informed, consented, and received one dose of medication or placebo. The full analysis set reflects patients that entered into the titration phase, but also had one piece of diary entry into the maintenance phase. That's what, as I was alluding to earlier, that's what's deemed the treatment period. They need to have data in both the titration period as well as the maintenance period. Overall, there were 35 participants in the full analysis set. 32 participants completed entirely. They made it all the way through the maintenance period. Reasons for... Overall, there were 11 participants that discontinued. The predominant reason was adverse events. These are numbers that are consistent with other studies that have been conducted in this therapeutic area, and I'll go into more detail on the adverse events later in the safety portion of the discussion. When we look at the Dravet population, overall, four randomized to bexicaserin, no patients were randomized to placebo. And while participants were stratified by different cohorts, it's likely that the block design of the cohorts prevented having a patient on placebo in that particular group. However, when you look at both the LGS and DEE populations, you see a nice balance among those groups. Just one other thing I'll call out your attention to is when looking at participants discontinuing due to adverse events, you'll note that in the DEE Other group, a very low number of patients; it's actually only one participant discontinued in that period. On the next slide, we're going to go through dosing that was achieved. Recall, patients did a dose titration. They were dose titrated purely by their tolerability. It wasn't we weren't pushing, strongly encouraging up. It's just wherever they landed. What was important to us is to get them on a dose that they tolerated during the titration period, so they can remain in the maintenance period, so we could get as robust a database in terms of assessment of both safety and efficacy as possible. We were, however, pleased that the vast majority of patients, 86%, actually achieved the 12 mg dose when we're looking at participants overall. And then when you look at the individual cohorts of Dravet and LGS and DEE Other, you'll see a similarity in terms of a general movement towards the higher dose group. Of note, the placebo group, where you're seeing a lot of zeros, that's implicating that all patients who were treated with placebo. They dose titrated all the way up to the highest potential dose. Now, you'd think that's pretty logical. You'd sort of expect that for patients who are treated with placebo. I, in my experience, can't say I always see it that way. Sometimes you see oddly that participants might stop in those earlier stages because they have an underlying severe condition that has associated morbidity. So sometimes you don't always see that. What that tells us, this is a very pristine database in terms of patients or participants are behaving as you would expect. That's consistent with their underlying condition and the medication that they are treated with. So on the next slide, we'll talk about the overall safety results. So looking on the left-hand side of the screen, I'm going to focus more on the bexicaserin treated group. 35, or 81% relative to 88% in the placebo group reported any treatment-emergent adverse event. When you ask clinicians to put a sort of an assessment of the possibility of relatedness, you'll note 65% in bexicaserin versus 33%. This is an expected number and not surprising. Let's go down to treatment-emergent events that actually led to a discontinuation. Nine participants discontinued. But I think what was really striking is, as we analyzed this data a little bit more closely, we noted that the vast majority of participants that discontinued were in that early stage, where they were getting used to the treatment with LP352. Because you'll note only 2 participants in the study, when they were entered into the maintenance period, discontinued due to an adverse event. I'll talk more about that for key learnings. There were three participants with a serious adverse event and no deaths in the study. Let's talk about the most common adverse events. In this slide, we're going to focus on adverse events that occur with bexicaserin with a frequency of greater than 5% and higher than placebo. The most common with that definition is somnolence, decreased appetite, constipation, diarrhea, lethargy, tremor, urinary tract infection, fatigue, pyrexia or fever, and agitation. Interestingly, if you were to look at other medications that are utilized in other anti-seizure medications, both the names that I'm putting out here and the relative frequencies are very, very consistent in terms of typically seeing GI and CNS effects. I made note of serious adverse events in the study. One was ankle fracture, the other one was constipation, and the third participant had increased seizures during the course of a hospitalization. Of note, as I mentioned before, the vast majority of participants stayed on bexicaserin once they achieved that maintenance dose. So when we sort of summarize what we're seeing from a safety and tolerability, this is a very favorable safety and tolerability profile results overall. So on the next slide, we're going to lead into what I know makes a lot of us excited after we clear the safety and tolerability aspect, which is our top-line efficacy. So let's get right into it. Bexicaserin overall achieved a median seizure reduction of 53.3% in countable motor seizures. Typical primary endpoint that is used in many studies in the DE therapeutic area. And this compares remarkably favorably to 20.8% for placebo across the DEE population. We focused on median. We had pre-specified both median and mean as options to look at in our statistical analysis plan. Generally, median is preferred because it takes into account the potential for outliers. And in a small dataset like this, one outlier can have a significant impact overall in the study results. So this result reflects a delta of 32.5%. I made the comment about mean. We did analyze mean and just to share that information, bexicaserin did achieve a placebo-adjusted mean seizure reduction, actually, with an even higher delta of 66.8%. The P value was 0.051, so close, but not quite. That puts it into the framework of trending very favorably. When we transition into the next slide, I think this is the information that we really want to understand, because does it help us reinforce this concept is: Can you study and can you potentially treat patients across the DEE spectrum? Do we see similarities in both the safety and efficacy side? Here, we're going to focus on efficacy. So all the way to the left, Dravet, as I described before, a very homogeneous disease, a treatment effect overall of 72.1%. As I mentioned earlier, no comparative group in terms of placebos because no patients were randomized to placebo. We then move into LGS, 48.1% versus 20.8% with a delta of 27.3. Makes it very readily predictable when we start to think about our future development programs, our phase III program. Then we look to the right, looking at DE Other, 61.2% versus 32.6%, a delta of 28.6. So just to take a pause, if you focus your eyes just on LGS and DE Other, two very heterogeneous populations, this remarkably supports the hypothesis that we went into with our study design, that we felt that safety and potential and efficacy would be similar across the groups, and you can really get a feel for the patient population, these patient populations having remarkable similarity. It really helps us think a lot strategically of the future development of bexicaserin. My last slide is just going to be a quick summary. It says, well, what's the implication when we think of this overall? The PACIFIC results, they paved the way for a global phase III program. When you look at these results, the PACIFIC study demonstrated meaningful efficacy with results across a broad spectrum of DEE population, as well as the individual DEEs of LGS and Dravet. Just to reiterate, bexicaserin achieved a median percentage reduction from baseline in seizure frequency during the treatment period, 53% in broad DEE, 72% in Dravet, 48% in LGS, and a remarkable 61% in the DEE Other population. This is important. These results were demonstrated on top of contemporary polytherapy background. So this is essentially a real-world experiment. It helps us understand that you can take patients that are on a variety of additional ASMs, provide another medication, and have incremental, clinically meaningful, important incremental benefit above and beyond. This data provides a favorable safety and tolerability result. Just by reminder, no echocardiograms were required in the PACIFIC Study, predominantly because the mechanism of action of bexicaserin would not warrant that. Secondarily, just by way of reminder, bexicaserin is metabolized by an alternative pathway, the UGT pathway, not the typical CYP system. That sets up the potential for reduction of drug-drug interactions. You can imagine these patients with DEE are on polypharmacy, and drug-drug interactions is an important aspect of how our participants are managed. 100% of participants who completed the study, they entered into the open-label extension. Why is that important? Because that will give us an opportunity, we'll talk about this at a later time, to look at durability, and the safety as participants will be on drug in the open-label study, for an additional year. We are awaiting additional analyses of the full, of the full data set. Our intent would be put that in the public domain, find an important conference, where the scientists and clinicians in the community can really talk through the data and understand the full data set. But obviously, we're utilizing the key learnings for incorporation into our global phase III development program. Just to give you an example, it was striking. If you get patients into the titration period, move them through this titration period at a dose that they can tolerate. When they get into the maintenance period, they maintain in it. So an important concept that is intrinsically part of the current study design is to start low and go slow. Wait for participants to tolerate the medication, and when they tolerate it, then they can go up to the next step. It's a key important learning, and that will ensure our ability of getting into a high percentage of getting into maintenance. Because we saw once they got into maintenance, they were able to stay on the medication. Just one quick side note. It's what we observed in the transition from the PACIFIC Study into the open label. All nine participants were able, who were on placebo, were able to transition into the open label extension successfully. But again, more information on that in terms of the open label at another time. So thank you for the opportunity to to talk about this medication. I can't wait to start to talk with our investigators, our patient advocacy groups, and, and families, because I, we, we really feel strongly that this is the kind of data that will give patients and their families the hope that they need. And at this point, I'll transition back to our CEO, Kevin Lind. Thanks, Dr. Kaye. Currently, there are over 25 DEE syndromes. Recent drug development has focused on a handful of DEE syndromes. As a result, there are multiple approved therapies for four of the DEEs: Dravet, Lennox-Gastaut syndrome, CDD, and TSC. We designed the groundbreaking PACIFIC Study with the belief that there is a better approach that is far more fair to the DEE community, and that would result in an adequate safety and efficacy data set across the DEE spectrum. To understand the potential commercial opportunity for bexicaserin, I'd like to refresh you on the efficacy demonstrated by the newer DEE agents. As a reminder, these data do not reflect head-to-head trials, and I'm comparing our Phase I-B/II-A data with the Phase III results.... I think it's helpful to contextualize our results in the market. You can see on the left that in Dravet Syndrome, bexicaserin compares favorably to the profound seizure reduction seen in the Fintepla Dravet pivotal studies. And on the right, you can see that it could potentially have the most robust efficacy amongst the newer agents in LGS. As Dr. Kaye said previously, the bexicaserin results are on top of the contemporary, best-available anti-seizure medications and are in predominantly adult patient population as well. Additionally, echocardiograms were not required, which are a challenge to patients and caregivers. Moving on beyond Dravet and LGS, there are two additional DEEs with recent approvals: Ztalmy for CDKL5 disorder or CDD, and the third indication for Epidiolex in tuberous sclerosis complex, TSC. As you can see from the data in DEE-other, the magnitude of response demonstrated by bexicaserin is in line with the responses seen to those two new drugs specifically developed for targeted DEEs. It's important to recognize that this bexicaserin response was achieved in a group that was broadly inclusive of DEEs, where not only patients with CDD or TSC, but with any of the other 20+ DEEs with no specifically approved therapies, were potentially eligible. Bexicaserin shows the possibility to provide a significant new treatment for these individuals with DEEs who have no approved therapies, where the epidemiology makes clinical trials difficult, if not unfeasible, and for whom insurance on-label requirements can be a significant access barrier. We are very excited that bexicaserin demonstrated safety and efficacy in a wide range of DEEs, irrespective of the underlying etiology. So in summary, these unprecedented PACIFIC data give us the confidence that bexicaserin has the potential to fundamentally change the landscape for the treatment of DEEs broadly. I want to reiterate that with IP protection out through 2041, we have the runway to maximize the full value of this asset, and we are rapidly moving forward with our phase III activities. I'll conclude by saying that the entire team is truly excited about the potential for bexicaserin to make a real difference for the incredible DEE population. We'll now open the lines for your questions. Operator? Thank you. As a reminder, to ask a question, please press star one, one on your telephone and wait for your name to be announced. To withdraw your question, please press star one, one again. Please stand by while we compile the Q&A roster. The first question comes from Josh Schimmer with Cantor. Your line is open. Great. Thanks so much for taking the question, and congrats on these stellar results. I have three questions. Number one, for the LGS patients, you gave us the median, a reduction in, I guess, all seizures, but not drop attacks specifically. I assume that we'll get that data at a medical conference. But what was the rationale for not reporting the drop attacks as we've seen with some of the other approved therapies? Number two is, when can we expect additional details on the phase III trial and design? And what are the gating steps prior to initiating that trial? And then number three would be, do you see a potential accelerated approval path for the other DEEs, considering this very strong efficacy signal and lack of approved treatment options for those patients? Thank you. Josh, hi, it's Randall. Let me take you the first question around drop seizures. We're presenting top-line data, and top-line data that entails the primary endpoint, which was defined as countable motor seizures. It's generally felt to be by far the most objective and the most consistent assessment in terms of looking at the impact of a pharmaceutical intervention over a placebo. Drop seizures, while have been an important component of assessments, I think we've seen that a while ago with fenfluramine in the LGS population. They're becoming more and more of a challenge to use that as a primary endpoint. The reason for that is many of these participants are wheelchair-ridden, so drop seizures are becoming increasingly redefined. So if you have a patient that's sitting in a wheelchair and their head drops, and they would have fallen, there needs to be a, frankly, a very subjective, "Would have fallen." They become... I don't want to say totally out of favor, but it's just, they're becoming a little bit less objective. Did we assess that? Yes, we did. That'll be data that I think would be important to include as we look through the remainder of our data set, and that will be other seizure phenotypes that go beyond just drop seizures. And we'll look forward to, as I noted earlier, probably likely we would present that data at an upcoming medical conference. Yeah, and one other point on the countable motor seizures. We really were happy with the fact that countable motor seizures can be consistently counted across the entire DEE population. And so as we think about what should be the next steps for this entire space, it shouldn't be seizures associated with TSC, it shouldn't be dropped for this patient population than something else. It really should be consistent across the board. It's in line with our thinking about how this molecule can be developed long term. So, I think your second question was timing for next steps and really, is there a path towards accelerated approval? I think those were your next two and three questions. Let me kind of bundle them together. As we have been planning for our phase III program, we want to remind everyone it's a phase III program, not just individual clinical studies. So while I'm not going to give specifics on timeline today, we're still really processing this data and really moving along. We have been planning along the way as well. Our current thinking is a phase III program designed to achieve multiple goals. In particular, we're focusing on time to market, broad DEE usage, and commercially and clinically relevant differentiation. That's going to come out across multiple studies that are going to have different starting points and potentially different ending points. But we really want to optimize that phase III program design before we roll it back out to investors. But as you can imagine, we are incredibly focused on time to market and moving quickly and rapidly. These patients need help, and it's our goal to get it to them as quickly and safely as possible. Got it. Thanks so much for the answers, and congrats again. Thanks, Josh. Please stand by for the next question. The next question comes from David Hoang with Citigroup. Your line is open. Hi, good morning. Thanks for taking the questions, and congrats on this robust data set to start us off in the new year. I had just two. So first, could you just comment on baseline seizure rates between the bexicaserin treated patients and the placebo patients? Anything that stands out to you there? And then secondly, this is more of a commercial, I guess, potential type question. I believe at the recent R&D day, you talked about doing market research with docs and presenting a TPP for bexicaserin. And I think it was something around 74% or 75% or so of docs would, I think, utilize bexicaserin over Fintepla, given the profile you presented at that time. With what you're seeing today in terms of the efficacy being north of 50% seizure reduction in the overall cohort, how might that affect the usage by physicians? Thank you. Thanks. Do you want to take, Randall, do you want to take the first one? So, excuse me, baseline seizure rates. Remember, patients had to have on average four to get into the study four countable motor seizures in each 28-day period. I'm trying to scramble through really quickly to find the exact number, but it was 38 countable motor seizures in the bexicaserin group, and it was 20.8 in the placebo-treated group. For mean numbers, I don't have that in front of me. Those numbers would have been higher. Obviously, that's where you end up with some the potential for significant outliers. I think that 38 versus 20 represents two things. It gives us a good, solid data set to look at the potential for reduction, and it also sets up two good, solid comparative groups to make conclusions about the efficacy results. And hey, thanks to, Randall. So on the second point, thanks, David. Really appreciate the question. For those who aren't as familiar with the R&D Day, we recently conducted some market research, and we performed a quantitative survey, which included 100 neurologists and epileptologists who see these patients, and had familiarity with both Epidiolex and Fintepla. And we followed that up with a quantitative study of 20 or 30 caregivers or parents of children living with DEEs, that are not part of the four that have approved therapies. And so, as we said in the R&D Day, about 74% of the physicians would prefer bexicaserin if it had around 40% seizure reduction, which was around LGS data for Epidiolex. We are bold people. We like to think creatively, we like to think aggressively, and so we did ask the question: What would preference look like if we got to a 50% median seizure reduction in countable motor seizures? And the data were really striking, so really pleased to talk about it. 85% of physicians would prescribe bexicaserin over Fintepla, and interestingly, 85% of physicians would prefer and would prescribe bexicaserin over Epidiolex. So we're really excited about that data set. The caregivers were actually a little bit higher than the 85% as well. And so it just speaks to the tremendous need in this space, but also the tremendous results we saw with bexicaserin in this study. Does that answer your question? Yes. Thank you so much. Thanks, David. Please stand by for the next question. The next question comes from Patrick Trucchio with H.C. Wainwright. Your line is open. Thanks. Good morning, and congrats on the data set this morning. Just a couple of follow-up questions from me. First is, can you talk about the expected dosing for the Phase III program? Is the intention to shift to a twice-daily dosing in the Phase III program? And regarding titration, can you further discuss the learnings from PACIFIC and how titration may be adjusted in Phase III, and how this could be expected to impact that discontinuation rate during the titration? Yeah, hey, I'll why don't I start, and then I'll pass it over to Randall. Just really quickly, our current plan continues to be that we are going to have a BID dose for the phase III. There is some potential IP that could be generated around dosing, and particularly as we think about this data set and the BID dosing. So I think we're going to be a little bit careful on this call around discussing specifics as we continue to learn. But why don't I pass it over to Randall to continue to answer that question? Yeah. I'd talk a little bit more just the general learnings. So the way the protocol was redesigned, patients were initiated on 6 mg. They were supposed to be on it for 3-5 days. If they tolerated it, they were allowed to go up to the next dose, up to 9. Same thing, 3-5 days. If they tolerated, they could go up. They also could go down. It was an up or down titration, so that gives 15 days overall for patients to get to the maintenance dose. It's a little bit different than what happens in the real world. In the real world, clinicians would generally prefer a two-week period between each step, but that's just not feasible in a clinical trial design. It'll massively bias the numbers when you start to think about treatment periods, because titration is a suboptimal dose, and it's just too low. We're thinking towards some strategies where maybe we can do some changes in how long the individual steps are during the titration period. But probably more importantly, to work more closely with the study sites, is that if someone is having some somnolence or some sedation or some GI issues, maybe we could go just a little bit slower, wait till they're able to tolerate it, like you would with any drug that's having an impact on the CNS or GI symptom, wait for that, and then make that next step. But again, we're at a point where we have a top-line data set. I don't have individual line listings yet, so there'll be a lot more learnings that'll come over the next period of time that'll help us better inform what's the best ideal way of doing the titration period. Yeah, that makes sense. And then just when do you expect the next data analysis from the open label extension, and what would you be looking for in the data just in terms of safety, tolerability, seizure reduction? And how could this, you know, further data impact continued discussions or expected discussion with FDA on next steps for the program? Yeah. I have to tell you, I'm like so focused right now on the 201 data. When you ask a question like, "When do you think the data's gonna come out?" I'm gonna push off that one. Excuse me, but I will answer your question directly about what to look at. So we'll have participants that have gone into the open label, both participants that were on drug and those that were on placebo and did a transition. So the two most important things that we can look at is, what is, how are we seeing this from a safety standpoint? What adverse events are or are not emerging over a one-year period? So that's a great database in terms of long-term utilization from a safety standpoint. The second aspect is durability. In open label extension studies, durability is patients, participants, family members, making the decision to continue in the study. Those are probably the two key components: adverse events and durability. I just can't give you a time to stay. My brain's a little bit full right now on the excitement with the 201 data. Yep, that makes sense. Thanks so much, and congrats again. Thank you. Please stand by for the next question. The next question comes from Laura Chico with Wedbush. Your line is open. Hey, good morning, guys. Thanks very much for taking the question. I just have two. So first, following up, Kevin, on some of your earlier comments there, are there certain DEE indications that would afford a more rapid time to market than others? I guess I'm trying to juxtapose, you know, Dravet, LGS, versus some of these other categories that haven't had as much focus so far. Just trying to understand how you're thinking about prioritizing some of these individual programs in phase III. And then I have a follow-up for you. Yeah, so let's start with that one. Look, I think it's going to depend on the path forward. What we've told investors to date is, on one hand, we could go with, 3 simultaneous phase III individual DEE, program or studies, so a Dravet, an LGS, and a pick your third favorite indication. And that's very consistent with everyone, what everyone else has done. We know generally the sizes, we know generally the timelines, we know generally the cost. I think as we look at this data set and we look at the broad applicability of this across all DEEs, we have an obligation to continue to think, creatively about how to help those patients out who don't have access to these newer medications. As I said, as we think about the phase III program, one of the things we are going to optimize is time to market. So there is a chance that as part of that phase III program, if we go down that path of going after the broad DEE approach rather than each one sequentially, we could pull out one or two of those and think about a faster time to the market. If we do the broad DEE approach, our thought is, it is not the PACIFIC Study just grossed up and supersized. It will have some creative bells and whistles built in along the way, and hedges that we are not ready to disclose today as we continue to look at the data set. I think it is entirely likely that we could think through some creative ways to get there faster. Randall? Yeah, just to add, you know, early in our discussion, I talked about the hope that this data provides for patients and their families. As a clinical development person, hope a positive data set also will help enrollment. It'll get people excited about this study. You know, if you sort of look at our timelines in terms of completing this study, you know, these are challenging studies to run, but invariably, we're still reasonably on time, and I think a number of our, you know, competitors have really struggled to enroll their studies on time. I think we have an opportunity right now, with the robustness of this data set, that it's really going to get people excited about being involved in studies. You take the example of Dravet, where people wondered, is there any other, you know, new treatment? Can you really get, you know, favorable treatment above and beyond the great medications that are out there? And when you look at a data set with contemporary data or contemporary polypharmacy that's being utilized, and you see an over 70% improvement on top of that, that's going to get family members excited about potentially participating in our studies. Don't want to overpromise timelines, but I think it will help us start to think a little bit about how we're going to get our development program started quicker, enrolled as quickly and, of course, as safely as we can. No, it's super helpful. And then maybe just following up one question on tolerability, and I think you've talked a good deal about the discontinuations already, but just wondering if you can clarify or maybe add some additional context relative to Fintepla on how these early discontinuation rates stack up. And I guess, just to clarify, is the thought process here that a longer titration would have a positive impact on that? Thanks very much, guys. I wish I could do a comparison for fenfluramine in their titration period, and I can't. I tried to find some comparative data. I had data on overall of discontinuation rates, and I think our discontinuation rates compared they were relatively similar. I do think that the key is focusing on the titration period. I don't - I can't tell you right now without line listings whether the focus should be on going a lot slower or a different word, going a little more thoughtful and really thinking about if a patient is having an adverse event, maybe in that particular one, waiting just a little bit longer before you take that next step. But again, really need the individual line listings in order to support that and think through. It's a great question. I just need, you know, I think we need a little bit more time to digest some of the other components of the data set. Understood. Thanks, guys. Congratulations. Thanks, Lauren. Please stand by for the next question. The next question comes from Gavin Clark-Gartner with Evercore. Your line is open. Hey, Happy New Year, and let me add my congratulations on the data also. Two questions. So the first one, I'm just wondering, in this study, kind of on a single patient level and also kind of comparing to other studies, how does the percent seizure reduction relate to the baseline seizure count, if at all? Wow! That is an awesome question that I won't have the answer to because I don't get line listings in top-line data. And I can't say I'm going to get—I can get right back to you in a week or two because I won't. I need the full data set. It's an important thing to look at, and there's two things that we would potentially be looking at in the future. One, that correlation that, that you just, that you just talked through, and the second is to look at a pharmacokinetic analysis of what we're seeing in terms of exposure at different, at different dose levels. It's a great question. I wish I could—I wish I could answer it for you. You know, there's this, there's this interesting view in drug development that patients that have-... A higher number of seizures have more room to go, so they are easier to treat, that's camp one. Then there's another group that says patients at a high number of seizures at baseline are the hardest ones to treat, and they're more severe. I'm in the camp of whatever the data says, so I'll let you know when we look at that data. I would just add, again, reminder, this is in patients who are predominantly adult. We added in the 12- to 17-year-olds later. Again, we're really excited about the fact that we were able to demonstrate this level of magnitude of effect in this patient population, because, again, to Randall's point, there are various camps, but we believe that that adult patient population should be the harder to treat, should be the more refractory. And so one of the concerns we had early on was: Are we going to be able to demonstrate as significant of a, of effect in these older patients, where they've really been on a lot of medications, and they've been on a very, very long journey, and these parents have really gone through a ton along the way? And so for us to demonstrate this level of effect, not in two-year-olds, not in three-year-olds, where I think consensus would be, that's a lot easier to demonstrate effect. We're really excited about how strong the effect we showed was. Yeah, that's all super helpful. Makes sense. And, Randall, I think you preempted my second question, which was going to be around any exposure response that you can glean thus far. Yeah. Like, maybe, maybe on that concept, understanding you don't have the full PK, exposure response modeling data, are you able to see any early trends on dose response for the patients who are on the lower two groups? And then just thinking about phase III dose, any thoughts on whether you may test higher exposure in some way or still TBD? Thanks so much. Yeah, it's interesting because the way the study designed, by nature, it doesn't really allow you to look at dose response, with one exception that I'll get into in a second. You're having patients dose modify and titrate based on tolerability. So intrinsically, the vast majority you're expecting are potentially getting up to that, getting up to that higher dose. If it turned out, maybe if we were on the higher end of that tolerability spectrum, you know, if we were a lot higher in the dosing, that we would see more equal numbers, like maybe a third in the 6 and a third in the 9 and a third in the 12, I could much more readily give you some kind of gut answers to it. But when you have 86% are all at the higher dose, and I don't have access to line listings, I'd be kind of making stuff up. And then there's this one other aspect. Remember, we included early in the study, adolescent patients, patients ages 12 to 17 or 18. By nature, they're going to be a little bit lower with BMI and weight. So when we start to think later, when we start to go down to the lower age population, for example, down to two, perhaps, when you're thinking about dosing, perhaps weight-based or categorically by age, it messes that thing up a little bit. So a long way of saying, until I can see some line listings, it's hard to answer it. But frankly, even with that, the vast majority are at that high dose. So if I'm going to project a little bit, which I think you're asking, that total dose, which would be 12 mg TID or 36 mg, that we know that the vast majority of subjects or participants are able to tolerate it. Is it? Could we go a little bit higher? Maybe, but with a robust data set that tells you you get 50% efficacy at that dose, 70%+ in Dravet, we're kind of already there. That's super helpful. Thanks so much, and congrats again. Please stand by for the next question. The next question comes from Yatin Suneja with Guggenheim. Your line is now open. Hey, guys. Thank you for taking my question, and congrats on nice results. Just another one on the tolerability side. Could you maybe just talk about and put in context the tolerability as it relates to younger people? As you move to patients that are, let's say, as young as two years old, and how do they tolerate, is the threshold different there? I think Kevin seemed to imply that, at least on the efficacy side, you do get a better response. So I'm just curious, on the tolerability side, the acceptability. That's one. And then, you know, the data that you disclose, obviously, there were 43 patients in the randomized phase, and then you disclose data on the 35 patients. So the 8 patients that you didn't disclose or are not part of that analysis, are they mostly the patients that discontinued before they achieved the full dose or they received the full dose? I'm just curious, like, the disconnect. Thanks. Thanks. Yatin, my thing went in and out, so I'm going to answer your question, and then if I didn't capture it, please ask again. But let's talk about tolerability first, and I think you were looking at how do we translate that into the younger population? The adverse events that you typically see in the DEE populations with anti-seizure medications are predominantly GI and CNS. Now, obviously, a two-year-old is not going to be able to describe somnolence or I'm feeling sleepy, but the GI ones are pretty readily translatable. I don't see any evidence that tolerability will vary as you go to the younger age population. I think it'll be most important to make sure that we're focusing closely on safety and monitoring these patients during that—predominantly during that titration, that titration period. But again, I wouldn't expect to see differences because they happen to be younger age pop, younger age populations, plus that couples with a dose modification for the lower weight patients. My question was on the discontinuations. Yeah. So, you were asking about the discontinuations. Earlier in the discussion, what I described is the analysis sets that we look at. So I'm just going to reiterate that a little because it's confusing by the words. So there's a randomization of titration phase. That's 15 days. There's a maintenance period that's 60 days. Anyone that gets into that titration phase, that's the safety data set. That's the full group of patients, of participants that get exposed that we analyze. The second group that we analyze, it's referred to as the full analysis set. They have to have some data in the maintenance, in the maintenance period. So if they only got into titration and they discontinued during titration, no data is placed into the full analysis set, nor is there any imputation whatsoever. They are removed from the data set. Some companies, including us, will look just at the maintenance period to see what is efficacy during that period of time. That is not part of top-line data. That is part of the full analysis set, and again, we look forward to sharing that data. But I'm not familiar with anyone that really focuses on the titration phase from an efficacy standpoint. They focus more on how do we become more successful in reducing discontinuations during that period. Did that answer both your questions? You're welcome to, Yes. Ask additional questions. Yes, I think that was good. Thank you so much. And then, with regard to the next presentation on the data, are we going to get the 50% responder and the 75% responder, and what would be the timeline around that? Yeah. So I think there's a few pieces of information that would be really interesting in the full data set. 50% responder rates, seizure-free days. It doesn't all... You know, we'll have to see how this looks, and we'll probably put it out anyway, but the use of rescue medication is very interesting, generally, or at least to be aware of that data. CGI, Clinical Global Impression, as assessed by the family member as well as the clinician, you know, often is an important component. We do have a quality-of-life instrument that's being utilized, but I can tell you frankly, in a two- or three-month study, that's a lot. That's a lot to expect a small molecule to do in a short period of time, but we'll certainly assess it. And then also, some subanalyses of the individual types of phenotypic seizures. But, you know, I'd caution us because it's a, this is a very small data set. So when you start diving into those, it'll be hard to see additional things. But yeah, those would be some of the cool stuff we'll look at. And plus, you know, you haven't asked, but well, I'm a medical guy, so we also will continue to look very closely at the safety database in terms of, you know, labs and vital signs. I wouldn't anticipate learning anything all that interesting, but it's a good and important box to check. Please stand by for the next question. The next question comes from Kalpit Patel with B. Riley. Your line is open. Yeah. Hey, good morning, and congrats on the data set today, and thanks for taking the questions. First, on the open-label extension, do we have an early sense of the median time of treatment at the tolerated dose, if you have that data available? And second, for the efficacy, not sure if you answered this already, but were there any noticeable differences in median seizure reduction between the fully titrated dose and the partially or non-titrated doses? You asked me the tough ones that I can't answer without the individual listings. I know I keep giving that as an answer, but unfortunately, it is in terms of the question you asked about median seizures in those subgroups. I don't have that available in the initial tables that we received. I don't have an early sense of open label. We really want to make sure that we have a significant number of participants that are well into the open label before I even start to look at that data. I know it's open label, so you know, it's non-comparative, but we haven't even started to look at it. We just want to wait a little bit longer so that we have a substantial number of participants that we can make conclusions or at least assessments of the impact. Okay, got it. And one last one. The SAEs that were reported, did you report any of those as related to the study drug, or were they all unrelated? Excuse me. So there were three serious adverse events. Two were deemed related. They were downgraded by us, the sponsor. One was constipation. This was a preexisting comorbidity, but because the participant ended up being hospitalized and had a G-tube placed, and a procedure, the investigator deemed that that would be appropriate to call it possibly related. I downgraded that, but, by the way, the, by the way it works, it still counts as a related serious adverse event. Our data set is small, with no experience in patients, so it comes off as a serious unexpected adverse event. The second one, increased seizure frequency. It turns out this was a participant that entered in and was hospitalized because of respiratory symptoms, coughing, and some, and some head banging. As they were resolving and working on the respiratory symptoms, the participant had increased seizures, and so the increased seizures caused the participant to have a prolonged hospitalization. By the way, the requirements from a safety standpoint, if the hospitalization was prolonged, that's the primary reason, even though that's not why they entered in. So it really was respiratory. So again, I downgraded that as not related, because it's often that these these patients, when they have respiratory symptoms or if they're menstruating, they have increased seizure seizure frequency. The third one was an ankle fracture. Unfortunately, this was a participant that actually had two independent ankle fractures. We ended up, you know, it counts only as one, as one participant. Obviously, that was deemed as not related. Thanks for that question. Okay, wonderful. Congrats again, and thanks for taking the questions. Please stand by for the next question. The next question comes from Sean Kim with JonesTrading. Your line is open. Hi. Congratulations, and thank, thank you for taking my questions. Just a few questions from me. The first question that I have is about the potential reasons for discontinuation. Just curious whether that was mostly driven by GI side effects or more on the CNS side, like somnolence or sedation. And for the discontinuation rates that were seen in LGS, it looks like the rate was higher for the subgroup versus our DEE subtypes. Just curious whether there is anything to read into it or any underlying reasons for that. And lastly, for the specifics on the next step, would you be requesting an end-of-phase II type meeting with the FDA or some other specific types of interactions? Thank you. Well, thanks. It's Randall. Thanks for those questions, Sean. So reasons for discontinuation, I'm going to focus on the titration period, were both, it was both GI and CNS. I'm just looking at my listing now. Lethargy, somnolence, loss of appetite, dizziness, somnolence, drowsiness. They-- that's predominantly where they... There was probably one or two participants that had both the GI and CNS. I agree with your observation that it was higher in LGS. I don't know what to make of it because when I looked at the other, that would've been the group that I thought, "Oh, my gosh, it's a really heterogeneous population, really, really varied, and it would be a much, much higher number." I was actually pleased as we start to think about the 301 study, and, you know, in our future development programs, that, you know, that's encouraging of the tolerability that we were seeing in the other population. But I would just be making make-believe hypotheses now to figure out why it was a little bit higher in LGS. I think you had asked a question about next steps, about an end-of-phase II meeting. I can't give you timing because I don't know what it is right now. But, yes, there would be an end-of-phase II meeting with FDA that would be part of the planning for entering into a global phase three program. Okay, great. Thank you very much. This will conclude the Q&A at this time. I would now like to turn the call back to Kevin Lind for closing remarks. Thank you all for joining us today. Obviously, we're incredibly excited about the data, and look forward to a exciting 2024. Take care. This concludes today's conference call. Thank you for participating. You may now disconnect.