I think we'll get started here. Hello, everyone. Happy Friday to you. Thank you for joining us. I am Charles Duncan. I'm a Managing Director and Senior Biotechnology Analyst for Cantor, and wanted to welcome everyone to the extension of our Brain Week one. As most folks know, we conducted several fireside chats last week, and unfortunately, we couldn't fit this one in, and it's one that we really wanted to fit in. I appreciate everyone's interest in joining us today, and I especially appreciate the interest of the management team of Longboard Pharmaceuticals. Longboard, ticker LBPH, is a company we cover with an overweight rating and a $16 price target, and it's my pleasure today to introduce Mr. Kevin Lind, the company's President and CEO. Hi, Kevin. Dr. Randall Kaye, the company's Chief Medical Officer, as well as Ms. Brandi Roberts, the company's Chief Financial Officer. Kevin, Brandi, Randall, good to see you. How are you today? Good to see you. Good to see you. It's good to be back. Yeah. Thanks for spending time with us today. I wanted to ask you a question before we get started, and that is, you know, frankly, I'd like to hear all of your opinion on this. What do you think is least well understood about Longboard Pharmaceuticals? What do you think investors should know about the history or about the future of Longboard before we get into some specific details? Yeah, that's a really great question. Give me a second to think about it, while I think about it, just a reminder, we'll be making forward-looking statements, results may differ materially, please see our SEC filings for risk factors. I think what is unique and differentiated about Longboard is the medicinal chemistry history and the scientists that were behind the discovery of all these novel molecules. Those folks were able to go head-to-head with some of the best developers in the world, going after known targets, come up with differentiated molecules from a PK/PD target engagement perspective. You know, what we've seen to date is differentiated clinical outcomes as a result. Our hope is that that is the case for Longboard. It's a great question. Maybe, Randall, do you want to talk about it for a second? Oh, I'd love to. Yeah ... one of the sort of secret aspects about being a chief medical officer is you actually get to go out there and interact with clinical trial sites, and physicians, and coordinators. Sometimes, you know, when we're working with patient advocacy groups, we have an opportunity to talk with those that are representing and living with these really challenging conditions, like Dravet and Lennox-Gastaut. What I'm seeing out there is hope. Yeah ... when a company like ours is out there, we start to talk to people about what we're trying to do, we have, you know, sometimes novel ways of approaching very complicated problems. As a pediatrician, I remember seeing these kids early in my career, I won't say how many years ago that was, there wasn't a lot of hope then. Now you can feel it, and you can see it's really nice, you know, as a member of Longboard, to really be part of that journey. It's great to hear, Randall. Doing well by doing good. Brandi, your perspective? Yeah, I just really wanted to talk about the culture that we're building here at Longboard. I think sometimes for people forget that we are a spin-out of Arena Pharmaceuticals. When we first started back in 2020 and early 2021, we were using a lot of shared services from Arena. As Kevin Lind mentioned, they had a lot of really great scientific background, which we really appreciated. One of our biggest focuses was really building our own neuro-focused team and bringing people on board who are passionate about moving these programs forward. It's been fantastic to be part of that journey and really, you know, building this team and bringing on people who are really excited about what we're doing and understand how we're trying to position our programs and really get these to the people who need it. It's been a really fun two and a half years putting this together. Yeah, it sounds like it should have been. Of course, it was a tough market, you kind of walked into a buzz saw there. I believe that Longboard, you know, there is distinctly a fair amount of underappreciated value in Longboard now, why don't we start with kind of an overview? Longboard as, you know, most of the people on the in the audience know, is a clinical stage neuroinnovator company that's developing novel transformative medicines for neurological diseases, it currently is investigating two products for development of neurological disorders. These are LP352 and LP659. You know, frankly, I think we're gonna mostly talk about LP352 today, which is a serotonin 5-HT2C superagonist, which is being developed for the treatment of seizures, which are associated with Developmental and Epileptic Encephalopathies. It's currently in a study that we look forward to seeing some data from later on this year. I guess to Kevin Lind, you know, before we dive deeper into either of these programs, but again, I'll probably focus on LP352, what do you think, you know, is... Well, I guess I asked the question, what is least well understood, but maybe more to LP352. Why don't you provide us a quick overview of the progress that you've made as Longboard Pharmaceuticals? Yeah. How about I give you an update on kind of both of these programs? Okay. LP352, as you said, it's a next generation 5-HT2C superagonist being developed for DEEs. You know, it's really exciting what we've been able to accomplish to date. We've seen kind of best-in-class selectivity and specificity for 5-HT2C versus other molecules that have been approved to treat patients. We've seen preclinical validation in a number of animal models where other drugs with similar mechanisms of action have shown effect, so shows that we're kind of moving in the right direction there. We saw a clinical validation in our SAD and our MAD studies, showing that the drug is getting into the brain in a dose-dependent manner, and the AEs are consistent with what we expected. We've seen some really interesting potential biomarkers, like prolactin and EEG activity. As we said, we did a clinical validation study in CSF and EEG, and we saw that target engagement, that receptor engagement. As you said, we're making great progress with LP352, and we expect to have data from our PACIFIC study around year-end. We'll talk about 352 a lot more over the course of the rest of the call. Sure. The other molecule that we have is LP659, and that's a third-generation, centrally acting S1P receptor modulator, highly selective for S1P1, some activity on S1P5. We submitted an IND to the FDA earlier this year. We plan to initiate a Phase 1 clinical trial in healthy volunteers later this year, and we're in discussions with the FDA on details regarding a partial clinical hold on higher proposed doses, and we'll provide more detail as we initiate the Phase 1. Okay, that's helpful. We'll come back to 659 towards the end of the call. Great. I have to tell you, we've done a lot of diligence in DEEs, and we cover a couple of other companies. I have to tell you, last time I was at the American Epilepsy Society meeting, when it was held in December, there was palpable interest in the work that you were doing, even though it was fairly early at that point. Investigators that I spoke to understood, you know, the scientific underpinnings of what you were trying to do with LP352. Why don't we focus on that? What do you think, Kevin, or anyone on your team, perhaps, really differentiates LP352 from the other 5-HT2C agonists that have come along? You know, help us understand a little bit about it, the underpinnings, but also, what is a superagonist? Sure, maybe I can start by taking a giant step back, and maybe everybody on the phone already knows this, but... Sorry. DEEs are developmental and epileptic encephalopathies, and they're characterized by a triad of features: seizures, epileptiform activity on EEG, and adverse events on development, cognition, and behavior. Yeah. They're further complicated because these patients typically are treatment resistant to standard therapies. If you think about it, there is this umbrella of DEE, and then certain companies have gone down the path of getting individual indications, individual syndromes approved underneath that broader umbrella. There are over 25 described DEE syndromes, and some of them have very strong genetic components, and then other ones, like LGS, don't have a genetic component at all. They do all have these certain characteristics that are consistent across these patients. Starting with that, we think there is tremendous unmet need for these kids again, and some of them grow into adults. We're really excited about the opportunity to treat all of these DEEs broadly. It sounds like these are all characterized by having both as a syndrome, really, both seizure-genic activity, but also developmental, neurodevelopmental deficits that occur for these unfortunate patients over time. As you mentioned, the seizure reduction component of modulating 5-HT2C has been addressed to some extent with earlier-stage drugs, but you're looking not for first-in-class activity, you're looking for best-in-class activity. Do you believe that that can help these unfortunate patients beyond the seizures, but for some of the other challenges that they face? Yeah, I think, let's start with what differentiates us versus some of the other molecules. Yeah. 5-HT2C has been implicated in preclinical models, and then obviously clinically. lorcaserin and fenfluramine are being used to treat these patients. fenfluramine's approved for Dravet and Lennox-Gastaut. lorcaserin's approved for compassionate use in Dravet. You know, the challenge with both these molecules is they have some safety histories. fenfluramine hits the 5-HT2B receptor, and was the bad actor in fen-phen. It has boxed warning, it's got a significant REMS program. There's a risk of causing pulmonary arterial hypertension and valvulopathy, and the patients have to go through an echocardiogram before they take the drug, and then every six months they're on the drug. Yeah. That's a real challenge for these developmentally disabled children, and their families, really. The other interesting thing about both of these is they were really not developed for DEEs from a traditional drug development perspective. They were really repurposed. Yeah. We're excited because we think we have the opportunity to be the first dose-optimized 5-HT2C to go after DEEs, versus just taking the weight loss dose and cutting it, in the case of fenfluramine, and taking the weight loss dose in the case of lorcaserin. What do we hope to see? We hope to see a safer molecule that has dose-optimized efficacy along the way. We do not hit 5-HT2B, and as a result, we're already not planning on, and we're not running echocardiograms, because 5-HT2B is well understood to be the bad actor for the pulmonary arterial hypertension, the valvulopathy. Yeah. 5-HT2C isn't really seen on the heart. We think there's a tremendous opportunity to not only be safer, but also potentially more efficacious. Obviously, what we want to do is go broadly beyond just Dravet and Lennox-Gastaut, and get to a lot of these other DEEs. You fast-forwarded through Sorry No worries. We're gonna dive in deep, and I like that about you. We're going to talk a lot more about some of the specifics. You mentioned safety efficacy, but certainly, some of these things are a big challenge in terms of access and being able to execute on a therapeutic paradigm over time, but also a big challenge in terms of worry for these unfortunate patients and caregivers. Something you didn't mention, so you mentioned 5-HT2B, but how about 5-HT2A, which is, you know, potentially a target that lorcaserin hits. So, you know, to add to the challenge, these people may have to endure some psychological impact of taking these drugs, correct? Yeah. Randall, do you want to take that one? It's not just me monologuing the rest of the call. One of the interesting things about the compound that we developed, LP352, is that fenfluramine, the tablet, is simply an opportunistic drug, as Kevin was describing. Yeah. Not dose-optimized, not targeted at all. If you can dose-optimize, and if you can develop the perfect molecule, why have a compound interact with anything but what you know for a fact is contributing to efficacy? Yeah. Off-target activity like B, let's get rid of, and we did. Off-target activity A, actually, in its purest form, if you really interact with A very, very strongly, you could have hallucinations. Yeah. In a milder form, it could be as simple as silence or difficulty sleeping. Yeah. Not an advantageous adverse event in this, in this population. I'll make one comment, 'cause you asked before, Kevin, something about superagonist. Yeah. That also is a potential differentiator. What do we mean by that? The natural agonist of 5-HT2 is serotonin. Yeah. It appears that LP352 binds more strongly on the receptor than the native endogenous, serotonin, which is really interesting. We'll see in the clinic whether this is. Yeah gonna translate into efficacy, but a very, very interesting feature of our compound. Very good. That's helpful, Randall. You know, I'm excited to see the data. We'll get into, you know, the trial that you're running, et cetera, and what would be good. It sounds like, just to unpack a little bit what Kevin was saying, ultimately, what you'd like to see is enhanced efficacy. Just before we get into what good could be, when you think about the current treatment paradigm for any one of, you know, these DEEs that is currently being treated, so with fenfluramine or other agents, you know, how long do they work? What is the therapeutic paradigm? What does that look like? You know, then do they treat some of the overarching syndromic problems with DEEs? Yeah, you know, Chas, I was going back to your original question, what do people potentially get wrong about the Longboard story? Yeah. The challenge you were having in articulating it is, this is a really unique opportunity, and a lot of biotech companies have to have just a safer drug. Just a more efficacious drug. If they don't win on either of those, the drug is dead. Yeah. The interesting thing here is, we have tremendous optionality, but it's really hard to articulate that to investors. As you think about it, there are four ways plus for 352 to win. Getting people to model it the right way is tough. Yeah ... getting, investors to think about all those options is really a challenge because so often everyone wants to fixate on just one outcome, one node. What I love, coming from the investing side, what I love coming from somebody who's been in the industry for this many years and seen it from so many different ways is, there are so many ways for us to win. Let me kind of walk you through it. Okay because it's different and unique for each one of these DEEs. Easiest, earliest, we show safety benefit that is consistent with what we've seen to date. No activity on the heart, no challenges there. We remove potentially the black box warnings that's seen with fenfluramine, we show some level of efficacy in the indications where they are approved, Dravet and Lennox-Gastaut. There's a tremendous opportunity for us to be a step-through molecule on the way to fenfluramine if our efficacy is lower. Yeah. Now, having said that, we're dose-optimizing. We are a superagonist. We have an opportunity to have better efficacy in both those indications. That's another way to win. Mm-hmm. That has a different outcome for what the prospects are for LP352. The first one could be tremendously exciting. The second one is obviously a blockbuster. Mm-hmm. The third one is, we go after broader indications. Mm-hmm. Remember, there are only four of these 25 DEEs where there's an approved molecule. Mm-hmm. It's terrible. It's really tragic that the other DEEs have no access to these newer medications, that includes cannabidiol, that includes EPIDIOLEX, that includes these other, you know, drugs that are on the market. There's a tremendous opportunity just to go broader than Dravet, LGS, TSC, and CDKL5. Finally, the last way to win is something that's really something that I care truly about because I think from a society perspective, we need to move in this direction. We actually need to come back and get drugs approved for DEEs. Mm-hmm. We truly believe that these molecules are generally consistent across these multiple DEEs. Remember, ganaxolone or EPIDIOLEX is not a CDKL5 drug. It's a- Right ... it's a focal-onset seizure drug that didn't work in its phase III, but as a result, they're running it in, you know, refractory status epilepticus. Fenfluramine's worked in Dravet, LGS, and there's some early data on it working in CDKL5. Take cannabidiol. Cannabidiol is approved in Dravet, LGS, TSC, but it's also being used off-label in a bunch of these other DEEs. We think there's a tremendous opportunity for us to win on any one of those 4 nodes, and I'm sure there are 5 others, but it's really hard for me to articulate that in a 20-minute, 30-minute conversation with investors. We understand, it's even harder for investors to model out all of those nodes. For us, that's what gets me excited. That's... It's really, that's the area where I think it's a little bit hard to articulate to investors the multiple ways to win. Well, you laid out four scenarios, and we're gonna unpack those and talk about your existing, clinical programs. Before we do, let me ask you about the fourth scenario. Mm-hmm ... with regard to regulatory strategy. I understand you can't really speak to your regulatory strategy, and you would be speculating on how the agency approaches this, but I'm gonna ask it anyway. That is. Sure ... do you think that the agency doesn't agree with broad seizure reduction as being clinically meaningful or even achievable across these DEEs? Do you believe that perhaps some of the agents that came before had some safety issues, and so the agency wanted to, you know, walk first, walk before running? Do you think some of these other agents may have activity, or do you think that their safety and other issues really stand in the way of them moving forward as well? You know, it's a great question. I'm gonna try and stay away from the U.S. regulators because... Okay look, I can't articulate, I don't know. I wasn't involved in any of the conversations that maybe GW had, maybe Marinus had. Mm-hmm. You know, I will... Randall, I don't know if you want to jump in instead of me, but, you know, we've been, I'll just say ILAE, right? The International League Against Epilepsy. Yeah. Randall, do you want to talk about that, or do you want me to kind of cover that one? Yeah, happy to go through it. Chas, at the end of the day, it comes down to evidence. Yeah That's what we're working towards. The approach that we've taken with the PACIFIC study is to get evidence of what happens when you observe treatment effect, seizure reduction, comparing a maintenance period to the screening period. If you look at the current novel agents, the ones developed over the last five years or so, the primary endpoint is consistently, seizure reduction, over a 20-day, 28-day period. Mm-hmm. There's remarkable consistency with different sponsors, with different compounds across the well-known DEEs, LGS, Lennox, Dravet, TSC, CDKL5. In fact, if you look at the placebo responses, they're almost identical. Mm. I think with evidence, and a plan, and a discussion with regulatory authorities, whether it be European or US, I think one can make a very strong case, for a broad way of studying these conditions. There's great precedence out there. You know, you and I have a back history on Avanir that had. Yeah ... very sort of interesting approach, where they approached a relatively uncommon neurologic condition, and they came at it with a broad-based approach in the way they studied it, and ended up having a very useful broad label. It was observed that there was consistency across, in that instance, across the spectrum of pseudobulbar affect. Yeah. I think we can make a good case, for it, and I think we'll start to have some very interesting, preliminary data around the end of this year, that'll probably support a bit of a more, you know, richer discussion. It does sound like you need to start with a good drug, and so we'll start to get into that. A good drug being one that can be dose-optimized, a good drug that could be taken over time, and perhaps not have, you know, call it accruing, potential safety issues. Yeah, can I just add one more thing to what Randall said? Sure. Yeah. Remember, we have composition of matter patent protection out to 2041 with PTEs. Yeah ... versus a number of these other molecules don't have patent protection, they really needed to go after an orphan indication. Yeah that, you know, I think there's just as much of a. Yeah ... decision made by the drug developers, due to some of the situations that they had in hand, that might have had an impact on those conversations beyond just, where we are. The other point is, I think the KOLs really understand the problem they've created today, right? Mm. They finally figured out, like, initially, it's, "Oh, my gosh, it's amazing. We'll have a drug approved for Dravet. We have nothing for Dravet. Mm. Now we've seen multiple drugs over the last, as Randall said, the last five-ish years, where they've now realized, look, the drug gets approved for a narrow indication, it gets priced at a high price point, and then the payers don't allow it to be used off-label, and drugs that could be used broader than just Dravet, just LGS, just CDKL5, are limited. Yeah. Remember, Lennox-Gastaut is a basket in and of itself. There is no underlying genetic cause for LGS. LGS is a basket. It truly is. Talking about LGS as a basket versus DEE as a basket, in our mind, doesn't really differentiate. Yeah, you make a very good point, Kevin. It may have been some of this, call it, developmental or regulatory strategy could have been driven by intellectual property considerations, which is very different from the approach that you have. You have a drug that was designed to be the best-in-class drug, and as you mentioned, a very long IP. You can take, you know, a broader, maybe more strategic approach to developing these drugs and providing for patients in need. Yeah, I mean, look, the congrats to the GW folks with EPIDIOLEX… Yeah ... but there was no patent protection for that molecule. Right. Right. From the very beginning. Well, beyond EPIDIOLEX, let's talk a little bit about fenfluramine. Sure. The data that I have in my hand suggests that at least, you know, given the kind of limitations of cross-trial comparison, if you look at fenfluramine in terms of its effect sizes, you know, its impact on patients in terms of median, you know, seizure reduction over the course of a month, it seems to have, you know, arguably the biggest effect size. Because of that, it gives me confidence in the drug that you, in 3.2, that you're developing. I guess, you know, what have you seen just with normal human volunteers, the Phase 1 PK/PD data, that gives you confidence in the activity in the target product profile for 3.2? Yeah, Randall, you want this one? Yeah. We ran this study, Chaz. This is our 102 study. Seems routine, it's not. We asked the question, we already know drug gets into plasma, but let's run a study that looks at, does drug get into plasma? Does it then get into CSF, into the central nervous system, in a dose-dependent, predictable manner?... We asked this extra little question in healthy volunteers. We looked to see whether or not there was receptor engagement. We did qEEGs. Yeah -to assess this. No one's done this before. What we found was, drug gets into plasma, but it gets into CSF in a dose-dependent, absolutely predictable fact, manner, with correlation coefficients of 0.9, 90%. It's, like, gives you. Yeah great confidence. What we saw is, we started to see receptor engagement just right after the first few doses. The real question was: What happens when you do continuous doses? Does it go away? It doesn't. It actually becomes a little bit more pronounced, looking at alpha waves and beta waves, and delta waves. That'd be hard to predict what seizure disorder, what phenotype is this drug going to work in based on that, the key was receptor engagement in a dose-dependent manner. That is really novel, exciting data. That gives me the confidence as a drug developer that my drug is going to get where it needs to be. It's acting centrally, it's going to give the best shot at really having the potential for an efficacy signal. You have the activity, the drug gets in, have activity. Was there any, you know, I guess, food effect or anything else that may limit its potential over time? I think that was with a 3 times per day dosing. Do you think, 2 or even 1 day, per day, or once-a-day dosing is potentially in the future? Maybe I'll take- Yeah the first question, Kevin. Go for it. In the initial standard SATMAD study. Yeah ... singly ascending and multiple-ascending dose, we did do an assessment of food effect, and what we learned is, no impact on food as it relates to the dosing of LP352. Nice. Why is that important? It's important because of this patient population. They're on polypharmacy, multiple drugs. Having to another thing worry about is taking it on an empty stomach is a real challenge. Yeah no food effect. Yeah. Kevin, you want to, talk about, our dosing plans? Yeah, as of right now, we're TID, but we have plans to get to BID for the phase III study. Okay ... we've got, multiple, paths we're looking at for that, but we expect to have it for the Phase 3. Okay, that's cool. We'll come back to that. Once a day, you know what was interesting? Consistently from the KOLs, twice a day was preferred to once a day. It's just kind of generally in line... Nice with how EPIDIOLEX is dosed, and a lot of these others are dosed. We think twice a day probably is the better way to go than even once a day. Well, that makes sense to me, especially some of the feedback I've gotten from prescribers that deal with these types of seizure disorders. There's an intensity of dosing that is desired because you really want to keep track of it, right? Going beyond the Phase 1 with normal human volunteers, let's talk about the ongoing PACIFIC study, because that's particularly interesting to me. It is a basket study across a range of DEEs. I guess, first of all, why don't we talk a little bit about your kind of approach to designing that PACIFIC study? I think you've alluded to this, but I'm not certain if we really understand the strategy behind that being a basket study. Yeah, look, I think, again, just as a... I'll start, and then, Randall, you can jump in as well. As we think about this, first of all, it's a phase 1b/2a, right? Yeah ... designed to help us figure out where we want to go in our pivotal studies after this. From our perspective, we want to actually elucidate whether or not this basket approach, this broad DEE label, is potential, is real, is viable. That's really how we decided to design this study. Randall, do you want to add anything? I know I'm kind of kicking it over to you. I'm just going to give a quick overview. I'm just going to go back up a little bit. Patient population, 12-65, that was a modification. As we had more non-clinical data available, we went down into the adolescent population. That's really important. The treatment paradigm in the DE spaces, earlier treatment. Yeah have the potential for an impact on non-seizure outcomes. Yeah. Kevin was talking about the developmental aspects. If you really want to help these patients, get them on the right drug as early as you possibly can. This is an all-comer study. What I mean by that, they can have any of the developmental epileptic encephalopathies. In our initial thinking, we were thinking approximately 10 patients with Dravet, 10 with LGS, and about 30 other, not really knowing what we would hear and see when we got out there. It felt like sort of a good, solid number to at least go in with and guide our investigator sites. Kevin, okay if I? Yeah kind of keep going? Yeah, you want to do the next part? Yeah. 30 sites across the U.S. and Australia. We brought Australia in in the early part of this year to give us confidence to be able to deliver this study within reasonable timelines. I'm sure you've noticed that other companies that are working in this space are having challenges. These are not- Yeah easy studies to do. Yeah Not every family member wants to get their, you know, their kids involved in these studies. That said, good progress. Kevin mentioned earlier, we're expecting top-line data around the end of this year. We plan to complete enrollment this summer. You know, could holidays drift things a little bit into early 2024? I guess it's, I guess it's possible. You know, it's hard to predict when do they we're rolling into open-label, and so forth. We feel pretty confident around the end of this year. Relative to other companies, we feel actually pretty good that we're this close to what our plans are. Maybe I can talk a little bit about, you know, just early, a little bit what we're sort of seeing. Yeah, for sure. Number one, and two, and three, excitement. You saw it. You were at the AES meeting. Yeah. I felt like we were the sort of the new kids on the block, where everyone wanted to kind of hang out with us, 'cause we're super cool and well, kidding aside, a lot of interest in this study. Yeah. It is a novel way of approaching things to development. It's also more fair. Yeah. It's not fair to run a study to do it a developmental approach, where you start with one condition, you get your data, then you move on to the next one, then you move on to the next one. It leaves a very large percentage of patients that probably never will have access to these novel therapies. I mean, yeah, there's a chance of off-label, that's becoming impossible anyway. Yeah ... just from the, on the insurance company side. Plus, most are looking for some degree of safety and efficacy information. This is what we're seeing, and they're interesting surprises, or they're interesting upsides. In LGS, huge amount of interest. Easily exceeded what we were kind of hoping for to get that sort of, you know, around 10. Lot of interest. The day I started and started interacting with our sites and key opinion leaders, they all pointed to one thing: "I'm really excited that you're trying this novel approach of looking at DEE others." What we've seen is a large amount of demand for this other group. You know, that supports our kind of overall thought that LGS is fairly heterogeneous, and also same thing in the, in the DEE population. I'll just make one sort of final comment. Dravet, it's interesting, because when we first started, we had an adult study. We knew going in, our expectations were a little low in terms of Dravet, the ideal approach. Yeah. The reason why some other medications are being successful is, you're identifying these patients early, family members and these patients to get involved in the study. Generally, it should be earlier. Yes, we're going into the adolescent population, and that would potentially open up for more patients with Dravet. I don't know if we'll end up hitting the 10 number. I do know is we're doing great on LGS, we're doing great on DEE other, and we'll have a study that will be very interpretable around the end of this year. That's a great conclusion in terms of interpretability, we look forward to that data. Let me pick apart a few of the assumptions that I need to make in terms of the interpretability. You mentioned Dravet versus LGS, that makes a lot of sense to me, and then the interest from the broader DEEs, I'm excited to hear that. You also have a big range in terms of the enrollment criteria with regard to age and perhaps frequency of seizures. Let me ask you, and then I will ask you about prior therapy. Just your perspective, Randall, do you anticipate enrolling patients who are harder to treat? Are these patients going to be exposed to a lot of time with the seizure disorder or other drugs? Are they going to be harder to treat? And in terms of how will that be seen, with regard to efficacy, if at all? That is such a cool question, Chas. Thank you. all of these patients, Dravet, LGS, TSC, refractory epilepsy, been managing these patients throughout for long periods of time. They are all difficult to treat. Mm. To put a paradigm of like, I'm worried about DEE other, because they're gonna be hard to treat, I, frankly, as a developer, I put them all in my category because they all have refractory epilepsy. It's like trying to figure out in treatment-resistant depression, right? Yeah. If they failed 3 therapies or 4, are they hard to treat? Yeah, they are. The ones that have failed 5 times and 6 times, these are really difficult to treat. Kind of kidding aside, there's a commonality, and that's why we've partnered with the Epilepsy Study Consortium to make sure there's consistency of the patients that are coming in. Mm-hmm meet the criteria for Dravet, or LGS, or DEE. It's consistent with what Kevin described earlier, the International League Against Epilepsy's guidelines in terms of what is and what isn't. We set a minimum criteria for the numbers of countable motor seizures. Mm-hmm that they have coming in. I, as I said earlier, believe we're gonna have a very interpretable study that's gonna reflect the patient population out there. Okay, let me ask you a question about the use of other drugs prior to enrolling in this study. I know that fenfluramine and lacosamide are explicitly, I believe, prevented, or is there a washout? That's kind of the question. Are you allowing prior exposure to 5-HT2C agonist? The second question is along the lines of, you know, call it recreational use for not so recreational use of cannabidiols, either those approved or those not. Prior use of fenfluramine is allowed, with some important exceptions. They could have been a failure, meaning it didn't work. Yeah or they could not tolerate the adverse events. A way someone could potentially enroll in the study is, maybe they got the first echo, and after a few echoes, they became of a pain, and they decided to bring them in. This is not gonna be a common route to be entering into our study of previously on fenfluramine. The cannabidiol is a rather more interesting one. Yeah in the U.S. and Australia, Epidiolex is available. There are, in Australia, early on, there was some pharmaceutical-grade approaches, which was not just the compound that came out of Greenwich, now Jazz. Yeah. Depending on the formulation that's being used, we do allow it. It touches upon something that's really important. I know you're gonna get into this, but I'm gonna seed you with it a little bit. Co-prescribing our compound, LP352, with cannabidiol, we're comfortable with. Yeah. It's a multiple mode of approach, using a 5-HT2C receptor agonist as our mode of action. Polypharmacy is a or polytherapy is a typical approach that's taken. If clinicians are, "I wanna pull the best 5-HT2C receptor agonist off the shelf, and I wanna supplement it with an efficacious cannabidiol," and maybe in the future, the right gene therapy that can go along with it and supplement it, is probably the way that we're gonna go. You know, just as an aside, we're commonly expecting to see cannabidiols that patients are currently on them in our study, and we're perfectly comfortable with that. Excellent. In the pain space, they call that multimodal therapy. I think in this space, you're referring to it as polypharmacy, it sounds like what the data that you're going to get, that you're gonna be able to interpret, is not gonna be an artifact of a very narrow and tightly controlled clinical study, but one that has not only readout for LGS, but also broadly DEEs, but also kind of a real-world study. Well, that's the goal, right? The goal. Okay to really advance the treatment paradigm here, and to really look at it and say, "There's a rationale for all these drugs to be used broadly." Because, look, for some of these molecules, the gene therapy, sure, it doesn't make sense to go beyond a Dravet if you have an SCN1A molecule, right? Yeah. For most of these others, we feel that the data is consistent, that they're broader anti-seizure medications, and we think that that's the 5-HT2C mechanism. Sure. Let me ask you a little bit about the conduct of the PACIFIC Study. I know we're not ready to talk about data, but you have 3 doses on offer: 6, 9, and 12 mgs, and there's an up titration process. Mm-hmm. You're not fully enrolled, but what are you seeing so far? Are patients able to endure that up titration? During the maintenance period, what are you seeing in terms of the use of the drug? Yeah, it's a little premature for that conversation. Okay. I will say that, you know, the way trials are designed, you try and limit the dose titration period at, to as short as possible. If you actually talk to the physicians who are involved, if you talk to the KOLs, if you talk to the community, they actually push back on that. Their traditional view, and their current view, is low and slow. Really try and work your way up. Yeah. Again, we do have 3 doses, but patients, if they tolerate the first dose, can move to the next. If they can tolerate the next dose, they move beyond there. That's how we're designing the study, to really figure out what's the right dose here? How do we dose optimize? Again, from the 5-HT2C perspective, we are the only molecule being dose optimized. Really trying to figure out where's that balance out is going to be important. We don't believe that every patient needs to be on the highest dose, particularly as we get down to 12-year-olds. Along the way, you know, if you were to call a KOL, they would say, "Look, I would go slow and low on titration," pretty consistently. That's just a challenge with clinical trial development. You don't want to have, you know, a 3-month dose titration period. Especially in epilepsy. Let's talk about down titration. You have a maintenance period of about two and a half months or so. It's kind of a three-month study with the primary efficacy endpoint, if you will. This is a safety study. Really, you're just looking for activity. That being the last month of median seizure reduction, you have a down titration period. Help us understand what you would like to learn about that period within the study. Um- Randall? Not a tremendous amount. The down titration period is used to get them off drug because they decided to not continue in the study for whatever reason. Okay. I see. ...... Um, the, the, the, the purpose- Yep of it is to get them to go down to a level, because we don't know if they're on drug or a placebo, so we have to assume everyone's on drugs. We get to titrate them down, and then move them over, if they so choose, into the open-label study. The primary analysis, you're right on target. It's safety. Yeah ... it's tolerability, we are getting, daily diary counts. Okay Seizure reduction is an important aspect of the efficacy assessment. The efficacy assessment will be restricted to the maintenance period and the up titration period to some degree. Okay. Actually, Randall, that's a great segue to the next question I wanted to ask, which is the open-label extension. I assume it's a little premature to talk about this, but have you had patients get through the study and then enter the open-label? Can you give us a sense of the interest in that, in addition to the interest in enrolling in the study in the first place? How long will you run that open-label extension? And- Excuse me, Kevin, do control arm patients have an opportunity to join that as well? Yeah, great question. We're going to be a little bit cautious about sharing what number of patients have rolled into OLE, how many patients have completed the study. Yeah ... that sort of thing. Randall, do you want to cover... Let's see, what was it? Duration of open-label extension and, yes, every patient who is on control or active can get into the OLE. Maybe, Randall, I can't remember off the top of my head, what's the duration of OLE? We're going a pretty, quote-unquote, "standard approach" for a drug that's in Phase 1b/2a. Okay What that means is they complete the LP352-201, the core aspect of the study. A few weeks prior to the end of the study, we offer all patients, we're all blinded, so we offer all patients through the site to assess their interest in going into the open-label extension. The open-label extension is a separate study. They complete the LP352-201. That way- Okay ... you know, towards the end of this, around the end of the year, when we're doing database lock and so forth, it's a separate, discrete study, and they go into this open-label study. The LP352-202 OLE is framed as a one-year study. Okay. What company sponsors typically do. We'll be looking at data around the end of this year. That'll help make an informed decision of the right thing to do, of continuing allowing patients to continue in the open-label extension. There's options of way of extending it. Right now, just because you have to put a start and a stop on a clinical trial. It's one year right now. Two other quick questions, and then I wanted to ask about financial resources. The first question is probably one you can't answer, but would you anticipate, with the AES study or AES meeting occurring late November, early December, would you anticipate being able to provide an update, at least on the conduct of the study, if not top-line data, by that time? Yeah. The guidance is around year-end. There are too many variables around patients rolling into the OLE-. Yeah ... how long, you know, we just got Australia up and running. We don't really want to shut them down early, you know, all those sorts of things. You know, we're not going to give that level of granularity on when we expect data. Okay, that's fair. Understood, Kevin. Takes two to tango, right? another question, not unlike that, not too different from. Yeah ... that last question, which you weren't able to answer, is, if we're talking in a year, would you anticipate that you would have had a meeting with the agency, talking about top-line data, and that you would have at least designed, if not operationalized, a phase 3? Randall's gonna kill me. Look, my hope is yes, right? My hope is the data are really clear, really straightforward. We can go to the agency and talk about how to advance this entire space. It goes back to there are multiple ways to win, right? Yeah. We don't have to have the DEE-labeled indication to have a blockbuster drug, right? Fenfluramine expects to be an $800 million drug, largely in just a fraction of the Dravet population, with very limited usage in Lennox-Gastaut. We can have a really large drug if we go down the traditional route. I just think the right thing for patients, the right thing for society, the right thing for this space, is to advance it. Again, it gets back to all those multiple ways for us to win. Yeah, it sounds like that fourth scenario is a little bit of an upside, even in your mind. It certainly is to us. Well, I just don't like over-promising and under-delivering. I agree. I don't like talking about something that's not under my control, and obviously, we don't control the agency. Yeah. I think if you talk to the KOLs, if you talk to the Jacqueline French of the world, the Helen Cross of the world... Yeah ... the Ingrid Scheffer of the world, who have really been driving this forward for many, many, many years, they really understand the bind they've created for themselves, and why there needs to be a new way to move all these molecules forward. It's not just us. Randall's probably gonna kill me, too, in terms of that timeline. Yeah. I mean, thank you, Chaz, for just. You're welcome. I'm helping Kevin select my goals for next year. Yeah. I promise to return that favor. You didn't have enough stress. You didn't have enough stress in your life. Okay. Well, someday we can enjoy a cup of coffee around that. Before we do, though, let's talk to Brandi and ask her how she feels about the financial resources of the company in terms of being able to turn over some really interesting value-creating cards here soon, or milestones. Absolutely. Happy to cover that. You know, obviously, our cash management strategy is really important. I think we've been talking about a lot of things that are important to the company. Obviously, we are looking to the specific data to really help us inform us for our Phase 3 approach. I think we're gathering a lot of the data. I am really proud of our medical and our clinical teams. I think they have taken an amazingly hands-on approach with this study. It's not only gonna do good things for this study, but it's really helping us set us up for our Phase 3. We are building some really great relationships with these investigators, and we're looking forward to working with them for the long term. In terms of cash, we wanna run our clinical trials as effectively and efficiently as possible. It's really important for us to make sure that we have the cash to do that. You might remember when we went public back in 2021, we knew that this specific study was gonna be our biggest driver. We wanted to make sure that we had the cash to get through it. We still felt comfortable that we could do that. In February, we decided to do a small raise. We did a $23 million raise. We brought a couple of new, great funds in, who are really interested in what we're doing, and gave the opportunity to some of our existing investors to top up a little bit there. We're really excited. We're really excited about what we've got. We're guiding to mid-2024 for our cash runway right now. We're really appreciative of the shareholders that we've had that have taken us through the Series A, our IPO, our follow-on here. I think that's really a great testimony to what we're trying to build here with 352, and the unmet medical need, and how we think we can impact it. Well, given the historical acquisition, M&A, activity in this space, and given, you know, the very thoughtful medicinal chemistry and long IP, for your assets that you're developing, I can imagine there is growing, or there should be growing institutional interest in Longboard as you turn over some good cards with turn over some good data with a differentiated drug, Brandi. This is very helpful. I really appreciate you folks taking time to help me better understand the fundamental setup going into the next 12 months. Yeah, to Kevin, to Randall, to Brandi, I appreciate your time. I appreciate the time of the or the interest of the audience, and I hope everyone can enjoy the upcoming holiday. Thank you. Yeah. Thanks. Everyone, have a great Fourth of July holiday weekend, and thank you so much for having us. Thanks, Kevin. Be well. Take care. Bye-bye. Bye.