Okay, we're gonna get started this morning. All right. Good morning, everyone. Thank you for joining today. We're very excited to have our first in-person and virtual AES Investor Breakfast. I would like to take a moment just to go over our safe harbor statement before proceeding to today's agenda. Okay, onto the agenda. We have quite a few folks here, a lot of new faces. If we just start at the top, we have our Senior Vice President, Scientific Affairs, Alex Aimetti, who will provide a two-year analysis of safety and effectiveness of ganaxolone in patients with CDKL5 Deficiency Disorder. We'll turn to Dr. Eder, Vice President of Clinical Affairs, who will discuss data that we presented at AES on our results of our TSC drug-drug interaction study with cannabinoids. Joe Hulihan, our Chief Medical Off- this morning on our pro-drug efforts and next steps. We'll turn over to our commercial group, where our Chief Commercial Officer, Christy Shafer, will discuss our early launch and continued momentum with ZTALMY. Lisa Lejuwaan, our Vice President of Sales, will discuss early success metrics and key field insights. Paul Voss, Vice President, Access and Policy, will discuss ZTALMY market access and patient services update, and our first quarter 2023 focus. We will then move to Katherine Galica, our Senior Director, Marketing Genetics Epilepsy, to discuss ZTALMY customer engagement, digital and AES footprint with efforts such as our product theater, commercial booth highlights, and speaker programs. Finally, we will turn to Kristin Rudisill, Vice President, Acute Care, to discuss our preparations for commercial readiness for our IV ganaxolone commercial strategy. Thank you again, everyone, for attending today. I will now turn to Alex Aimetti. Great. Thank you, Sasha. Good morning, everyone. Appreciate you all being here in person and those that are joining us virtually. As we near the end of AES 2022, I just wanted to provide a few brief reflections on my experience. This is certainly one of, if not the most important medical meeting for us. We've had a lot of really fantastic discussions and interactions with providers on ganaxolone and our clinical data, and the responses have just been extremely encouraging. I do really believe that there's a lot of strong momentum that we are building within the community, and really starting to realize the potential of ganaxolone, not just in CDKL5, but for a lot of the other patient populations in which we're studying. What I wanted to do first before I dove into the updated open label extension data is just to summarize briefly the three new abstracts that we presented here at AES. The first one is where we looked at some phase I data of IV ganaxolone in healthy volunteers, where we showed dose-dependent pharmacokinetic and pharmacodynamic response following an IV bolus of ganaxolone in healthy volunteers. We presented some quantitative measures such as the Bispectral Index and quantitative EEG to demonstrate the rapid onset and offset of an IV bolus, which we think is a desirable attribute for a potential treatment in status epilepticus. I know many of you are very excited about our trial in refractory status. We had a lot of conversations over the past few days with investigators from our RAISE study. They remain very energized and excited about the program, are really excited about some of the changes that we've made to the protocol that they think will really help increase recruitment and enrollment in that study. In addition, we had a scientific exhibit yesterday where we had half the room between posters related to our oral franchise and those related to our IV franchise. All the providers that came in the room were very excited about the work and the clinical data on the oral side, they tended to also gravitate towards the IV side of the room and asked a lot of really exciting questions and are really interested in those programs that we have ongoing. Second, we presented some more phase I data looking at potential drug-drug interactions of ganaxolone with cannabidiol in healthy volunteers. Again, this was a study that was initiated or conducted from some preliminary clinical work that we presented last year. What we reported on is that there were no clinically meaningful interactions between ganaxolone and cannabidiol, and the combination of the medications was generally well-tolerated. We'll continue to learn more information about this in our phase III TSC study, where we do expect a proportion of those patients to be on concomitant cannabidiol. Lastly, we presented an update to our open label extension phase of the Marigold data, which was our phase III study in CDKL5, where we showed continued that the drug was well-tolerated for an extended amount of time and a maintenance of efficacy in the open label extension. These were all patients with a minimum of one year of data. What I'm excited to share with you right now is an update to the open-label extension. These are data that we have not previously publicly presented. It includes a minimum of two years of data. What I'm sharing with you here, again, out of the 101 patients that were randomized in Marigold, 88 patients entered the open-label extension. At two years, we had data on 50 of those patients. 37 discontinued for the reasons listed below. The baseline demographics of those 88 patients that entered the open-label extension is as was previously presented in other open-label extension presentations. What I'm sharing with you here is the median reduction in major motor seizures in discrete three-month intervals out to two years in the open-label extension. What you can see is at the 22-24 month, three-month interval, we see a median 48% reduction in major motor seizure frequency in 50 patients that made it to that point in the open-label extension. One of the limitations of an analysis like this, where you use all available data, is it does not take into consideration patients that dropped out or discontinued. We did use one of the many methods to impute missing data. Here, Last Observation Carried Forward and looked at the effects of the reductions in major motor seizure frequency in all 87 patients over time. What you see is, again, a continued maintenance of effect out to two years. What I'm showing you here with the dashed line is a reminder of the ganaxolone arm from the double-blind Marigold study, where we showed a 30.7% reduction. That's what that dashed line is intended to signify. What I'm showing you there just is that again, using the Last Observation Carried Forward method, we see a very similar response out to two years. On this graph, what I'm sharing with you is the proportion of patients that achieved notable reductions in major motor seizure frequency. Those that experience greater than 25%, 50%, 75% reductions in major motor seizure frequency, or 100%, which is seizure-free during those three-month intervals. Again, at 22-24 month time point, about half of the patients are experiencing a greater than or equal to 50% reduction in major motor seizure frequency. What we're also starting to see is that there are reporting seizure freedom during some of these discrete three-month intervals, which we, in discussions with caregivers, we believe could potentially have a profound impact on quality of life. The seizure data that I just presented, we think is really exciting and at how we've discussed it with investigators, they're equally as excited. The literature would suggest that there is a waning of efficacy beyond three or six months with existing standard of care. We think these data are really differentiating compared to what's currently being used in this patient population. Providing an update to the safety summary, I'm showing you two tables here. These take into consideration all available data even beyond two years. Table on the left reports treatment emergent AEs, again, very similar to what we reported in the Marigold double-blind. No new safety findings in the open-label extension to date. Table on the right reports on serious treatment emergent adverse events. We believe that ganaxolone continues to be generally well-tolerated in this patient population. Just some quick summary takeaways. As I mentioned previously, ganaxolone was generally well-tolerated in the OLE with safety findings consistent to that of the double-blind. We're really excited to see that maintenance of effects in the reduction in major motor seizure frequency out to two years. There are patients that are in the open-label extension still beyond two years, three years and four years and still continuing to see that type of effect, although I only presented data out to two years here today. Really interesting to see that some patients are reporting seizure freedom and really look forward to looking at those patients on an individual level to understand that those data a little bit better. These are the data that we are actively looking to write up and publish for peer-reviewed in a peer-reviewed manuscript. With that, I'm gonna turn the podium over to Dr. Ian Miller, who's going to talk a little bit about our phase II TSC study and the new data on the drug-drug interaction study. Thanks, Alex. As Alex said, my name is Ian Miller. My experience as a pediatric epileptologist for 15 years in Miami prior to joining Marinus about 18 months ago, and as a result, I have perspective from recent development trials that were brought to market and trying to help make the TSC studies smooth using that experience. I wanna start with a brief review of some information that I think has already been shared with investors regarding the phase II TSC trial. There were several lessons in this small sample size trial that help us guide the phase III trial to make sure that it's effective and successful. I want to draw your attention to the right side of this diagram, which is the first opportunity that we've had to look at how ganaxolone works with cannabidiol, which was not in widespread use at the time the MIRACLE trial started, but also Everolimus, which is obviously disease-specific for tuberous sclerosis and therefore we didn't have prior experience with. We were simply gratified to see that there was no apparent difference in terms of the response rates with individuals on these medications versus patients that were not. The efficacy seemed similar. The other lesson that we took away from the phase II, which isn't shown here on this slide, but we'll see data for on the next slide, was an apparent association between the blood levels of ganaxolone and the dose of EPIDIOLEX. It seemed like patients that were on high-dose EPIDIOLEX had, you know, higher ganaxolone levels. Therefore, we were concerned that there might be a drug-drug interaction. That was addressed with the direct phase I study to assess whether a drug-drug interaction was seen. I'm really relieved that we had very consistent and robust data that showed that there was no clinically meaningful interaction between those two medications. This was the poster that was presented yesterday in the poster hall. The association that was seen here was significant enough in the phase II that we were worried about whether a dose adjustment or anything would be necessary. Thankfully it was not. You know, the results of this phase I read out in a way that made us happy with the decisions that we made regarding the phase III execution. The last piece that I want to talk about are the refinements to the phase III that were guided by the phase II regarding the titration. During the phase II study, there was an association between somnolence and a reduction in efficacy. You can see that in the middle of the diagram or the middle of the slide, patients that had somnolence present, which is the right, more pale purple bar, had a lower efficacy rate than patients that did not. We also saw a slightly higher rate of somnolence complaints in TSC than we did in CDKL5 deficiency, probably because TSC is associated with a more moderate cognitive impairment, and therefore these individuals could articulate the fact that, "Hey, I'm feeling sleepy." An AE gets filed, and therefore it looks like it's higher, although the biology of ganaxolone, you know, isn't expected to be different beyond that communication piece. That led to some really, I think, productive discussions of how the metabolism and the, you know, the absorption was occurring. We realized that the peak absorption occurs essentially right here at this line, at about the 50% point of the titration schedule. If you look at the old titration schedule, which is here in the darker purple, we were reaching that really at day seven. When we went back and looked at the AEs in the phase II, that's when the somnolence was presenting itself. We thought we were being very cautious and going slow doing 25% of the dose each week. In actual fact, if you look at the absorption, they were getting to their goal dose at, you know, day seven, and then we were simply super saturating the absorption and they weren't getting any more. We were not using the titration timeframe that we had given ourselves effectively. I think this is the single change to the phase III that is gonna be most productive in terms of addressing those issues and really hopefully lowering our AE rates. We are starting really low and starting out kind of with slow increments. It's kind of subtle, but the increments get bigger and bigger as the weeks go on, it takes until day 21 to even reach that 50% mark, and then we simply super saturate and make sure that we're not fluctuating around the limit of absorption for those individuals. The last piece of data that I'll share with you that kind of provides some corroboration for that idea and hypothesis is simply this noisy plot on the left. This looks noisy, but that's kind of the point. This is a look at dose adjustments in non-responders. If you look at the individuals who really didn't respond well in the phase II, they had a ton of adjustments. These lines are going up, they're going down, they're going up, they're going down, and these are clinicians trying to find the sweet spot of maximum tolerated doses. Not surprisingly, those individuals who had the most adjustments did not respond as well. The informed decisions that this is helping us with are helping myself and my counterpart, Dr. Murray Madum, be not only very, very rapid in our response to simulant's complaints because we now recognize that this is going to be a major driver in our success. Also being very consistent in how we adjust doses in response to those complaints. We're really homogenizing the way in which these investigators will guide their patients to lower the dose and then either re-challenge or not based on their response. With that, I will turn it over to Joe Hulihan regarding second generation product development. Thanks, Ian. One of the things we've been spending a lot of time on over the past several months is development of a new formulation, a second generation formulation of ganaxolone. The current oral suspension has relatively low bioavailability and as Ian mentioned, saturable absorption. We have two approaches that we're taking toward developing a second generation ganaxolone. One is a reformulation, using a different excipient, a different method of formulating ganaxolone. We wanna get a consistent dose exposure relationship. We want to be able to individualize dosing, particularly at the higher end of the dose range, for patients who are particularly refractory. That's very valuable for epileptologists to be able to do that. Right now we have TID dosing. We'd like to get to once or twice daily dosing, and we wanna reduce the variability from peak to trough during the day. We selected two candidates for clinical assessment, and I'll update you on where they are. For the prodrug, we wanna develop both oral and IV prodrugs. The goals of those are obviously different. The oral prodrug, we wanna improve bioavailability and provide sustained delivery of ganaxolone and potentially once or twice a day dosing. The IV prodrug, the goals are different. We want to improve the solubility of the compound, and that would be a prodrug that converts rapidly from the parent to ganaxolone once it's in circulation and would allow us to deliver higher doses. Right now, ganaxolone is highly lipophilic and insoluble, requiring us to use Captisol as an excipient. There is a concern with renal toxicity at the higher end of Captisol dosing from animal data. We haven't seen that in our patients, but we're limited to 50 g of Captisol a day in the IV formulation, and that caps us at about 830 mg of ganaxolone. The higher end of the dose range is limited by the Captisol, not the ganaxolone. We've identified lead candidates for both the oral and the IV prodrug. Let me update you on those. The reformulation candidate one, we have phase I data from two cohorts of healthy volunteers. A third cohort is being assessed. In the first two cohorts, and these are single ascending dose studies, doses of 100-900 mg and given with or without food. The table on the bottom, the first three rows are the first cohort that evaluated doses of 100 - 400 compared to the reference, which is the current oral suspension, and then progressed to doses of 400 - 900 with the second cohort. Again, fed and fasted states and compared to the reference oral suspension. This is the data for the reformulation in the fed state. We did see a food effect, as we do with the current oral suspension, but this is just the data in the fed state from 100 - 900 mg. We see a nice dose exposure relationship, with increasing Cmax and AUC up to 900 mg. One thing that's notable is that there is a reduction in elevation in the Cmax at the higher doses. You have a fairly linear proportional increase in Cmax up to 600 mg, but then only a slight elevation in Cmax from 600 - 900. To illustrate that, this is comparing the historical data with the current oral formulation. As we've mentioned, at a certain dose, absorption is saturable. On the left is the AUC of the current oral suspension and the reformulation. On the right is Cmax. The AUC in the blue of the new formulation increases fairly linearly all the way up to 900 mg. The historical data with the oral suspension above 600 mg, you know, at 800 or 1,000 mg, you don't get any increase in Cmax above what you get with 600 mg. I'm sorry, AUC. AUC on the left. Actually for the oral suspension, it's the same story with Cmax. Above 600 mg, you get a leveling without significant further increases in Cmax. The oral reformulation, while it is linear in terms of AUC, there's a flattening in the increase in the Cmax. What that in theory would mean that you increase overall exposure with a lesser increase in Cmax. For increase in efficacy without compromising tolerability, presumably side effects like somnolence are Cmax related. If we can continue to see that in our third cohort, where we're gonna go up to 1,200 mg, maybe even further blunting of the Cmax and increase in AUC. Again, the third cohort will be single dose, single ascending dose PK, comparing oral suspension and the reformulation, again, fed and fasted. One additional thing we're gonna do, this reformulation is presumably gonna be a sprinkle formulation. In the first two cohorts, we dissolved it in water. In some of the groups in this study, we'll do some preliminary food effect assessment and have them give the sprinkle with yogurt rather than dissolving it in water. That third cohort is in progress. We'll have results of that third cohort early next year. There'll be a go, no-go decision point, if the results are favorable at the higher dose, we'll then proceed to multiple ascending dose and some additional modeling, PK modeling, and then full clinical development, currently planning to do that in Lennox-Gastaut syndrome. The MAD studies would start mid-year next year. Turning to the prodrug. On the left, this pyramid is, you know, typical prodrug development. Of course, develop the structure, synthesize the analog, and then look at stability in simulated intestinal and gastro-gastric fluid, and then look at the compound in liver microsomes, human liver microsomes, do some additional preclinical in vitro work in dog microsomes, and then in vivo work in the appropriate clinical species, make sure that it's druggable and nominate appropriate compounds for development. We do have, as I mentioned, candidates for the oral and IV prodrug. They look like they have good properties. The properties we're looking for, the oral prodrug, compound one, slow conversion, giving greater than 24 hours of exposure. It's at the stage of in vitro conversion in human and dog microsomes. There is conversion from the parent to ganaxolone. Compound two, as desired for the IV, exhibits rapid conversion, also, in vitro. That's gonna proceed to in vivo studies. The solubility is much more favorable than the current ganaxolone itself. We're still identifying additional prodrug candidates, potentially to achieve even greater solubility for the IV. We're continuing that work and, look forward to getting some initial results of that, in the coming months and years. That's the end of the clinical piece of the program. I'll turn it over to our Chief Commercial Officer, Christy Shafer. Thanks, Joe. It is my privilege to be here this morning. Good morning. I'm thrilled to be able to give you an update to the launch of ZTALMY. Not only that, it's my privilege to be able to introduce my commercial leadership team to you today as well. To give a quick summary of what we were able to communicate during our Q3 earnings call. We've had incredible early demand of over 50 prescription enrollment forms received for CDKL5 deficiency disorder patients. Of those, 30 of them were new, naive patients to ZTALMY. What's interesting to note is we have had an incredible amount of breadth of accounts that have also been interested in ZTALMY. Of those 50 enrollment forms, they are coming from 40 distinct and deliberate accounts across the United States. What's been really great is that with that momentum and demand from the physician community, we've been able to support that with payer access momentum that has been able to support these patients. We've had positive payer criteria published in over 57% of the U.S. commercial payer plans, they've extended that coverage as of November 1st. This early published criteria has been to label at its most restrictive, in some cases, less restrictive than our label. Of those 50 patient enrollment forms that we received, over 40% of them have received reimbursement as of November 1st, which is also very, very encouraging. What's also been great to see is that in the past two years, the ICD-10 code, to go back just quickly, the ICD-10 code is only two years old. Over that timeframe, we've seen increased usage of the code that's also been supportive of this reimbursement. We have 16 sales reps that are across the United States, and we've underscored the fact that early days of our launch, we knew that education was going to be imperative not only in the HCP community, but also to patients and caregivers. We've used not only our new published Marigold data in The Lancet Neurology, but we're also very encouraged to see that the first international CDKL5 guidelines have been published in Frontiers in Neurology. Those 16 sales reps have been focused on about 265 accounts across the United States. That's inclusive of 8 CDD centers of excellence and 40 large national epilepsy centers. In addition to the HCP outreach that we've also underscored, we know that it's very critically important that we continue the feedback loop with all of our advocacy partners. It's been wonderful here at AES to interact with many of them here today. What we're understanding is those patients that are going on therapy, those patients that could be appropriate for therapy and understanding what's important to them. What's been great is that not only is this the data that we're seeing in the first 9 weeks of launch, but now we're about double that into 16 weeks of launch, and I think that the trends are continuing in a very, very positive direction, and we're really encouraged about the future. I'm excited to now introduce you to my commercial team. I'll start with Lisa Lejuwaan, our VP of Sales, and they'll each take a deeper dive into this data. Thanks, Christy, it's a pleasure to be here today to talk a little bit about the sales team. I've been in this industry for about 30 years. Lucky to spend most of it in rare disease, starting at Genzyme, where I cut my teeth on rare disease and learned that if you put the patient first, the rest will follow, and that really is true. We hired a team of 16 sales reps, a small but mighty sales force, if you will, that has learned that this is very important, to put the patient first in everything that they do. They cover 16 geographies across the United States. You can see from the map here the areas that we cover. I'm pleased to say that through October 1st, this field sales team, designed of reps that have a background in both epilepsy and rare disease, has been able to execute on the sales goals thus far. They're doing very well out there. They've learned to navigate and triangulate the different healthcare professionals that treat these patients. We've learned a few things as we've been out there, talking to these doctors over the past nine weeks. You might ask how do 16 reps reach all the far corners of the United States of America and these patients where they are. One thing that came from the pandemic was the ability to engage virtually, and our sales reps are able to engage both live and virtually with our stakeholders to make sure that they meet the patients where they are. We've also learned that caregivers play a really valuable role in this. They are the ones that are seeing their kids day to day, experiencing the changes in seizures. These kids have a very heavy seizure burden, as we know, and they're the ones that are involved heavily with their healthcare professionals in making the decisions around what's gonna come next for their child or their adult patient. We've seen both. What we know is our sales team has been integral in educating the HCPs on how do you talk to your patients and families about ZTALMY and about what the benefit is that it can provide to your child or adult patient. We've also engaged, as Christy mentioned, with all of the advocacy groups, helping to further communicate this to the families out there. One thing we've seen here at AES, and we've also seen in the field, is that HCPs are accustomed to treating syndromes in epilepsy. Epilepsy's evolved over the years. It's evolved in a genetic testing perspective. We know that in the past, I heard a physician say this week, the tools that they have with these kids are EEG, MRI, EEG, MRI, just trying to manage the seizures that they see. Now they have the added tool of EEG, MRI, genetic testing. Boom, is what the doctor said that I heard talk about this. Being able to identify the underlying etiology of disease is really helping to treat these patients. ZTALMY is an example of this. It is a drug that was studied specifically in CDKL5 Deficiency Disorder, that can now be an option for these patients that have had no other options in the past and are still dealing with the seizures. Where are we finding these patients early on? My experience in rare disease has shown 1 thing. I mean, when I was at Alexion for many years, we, when we launched into two rare neuromuscular diseases, the patients didn't show up immediately at the KOLs. They didn't show up immediately at the academic centers. They showed up in the community because that's where they live, and that's where they're getting some of their day-to-day changes in therapy. The same has been true here. Some of our early prescriptions were certainly in the community. Over time, over the past few weeks, we've seen that move into the centers as well as the COEs. Their needs are being met where they are right now, and our sales reps are able to reach to these doctors that need the education, which has been a fantastic thing to see early on. These HCPs, now that they have the tools to genetic testing, the access to genetic testing and education around this, there were many sessions at AES this week about genetic testing. I think it's evolving, and it's going to be a very beneficial thing for our patients and our kids that are living with CDD. COEs are a wonderful place for these kids to get multi-physician care. They come there because on a given day of the year, they can see a GI doctor, an ophthalmologist. They can see all the different specialties that they need. The challenge of this is they can only get in there to do this specialty clinic, you know, two, three, maybe four times a year at best. In the meantime, the doctors close to home where they're being treated are pulling the trigger on changing the medications for the patient. That's been very, very helpful. With that, I'd be remiss in acting like all the success comes from the sales team that's out there. They are a phenomenal group of people that really care about the patients. What came before that was an incredible marketing brand strategy and also a market access platform that has opened the doors for our patients. Paul's gonna dig a little bit deeper into that, and I'm gonna let him share that with you now. Thanks so much. Good morning. I'm Paul Voss. I lead market access at Marinus Pharmaceuticals. I come to Marinus with a fairly lengthy orphan and rare disease background. I'm thrilled to be a part of this leadership team and to follow Lisa and Christy. There's a couple of things that they touched on earlier that I'm going to expand on relative to our pre-launch and launch efforts around our market access strategy. One of the things that I know to be true are if you build a program that considers the reality of a medical benefit drug, you're likely gonna meet the needs of a pharmacy benefit drug. This is a pharmacy benefit drug, and we've invested in strategies both in how we segmented, how we approached our payers, but also the resources and the tools that we built to be able to support our HCPs and patients. What you see here is a direct reflection of that. I'm gonna touch on our commercial, do just a quick update on our commercial and government payers, and then I'm gonna focus in on our patient services. I'm also gonna give you a little bit of an update on where we're headed for 2023. We've done some amazing work in a really short period of time, and Christy kind of talked a little bit about that. At the end of the day, we've been able, with 57% of our commercial lives, we've already been able to confirm coverage. A lot of that is a reflection of about 20 plans that we went out and targeted. I'm representing here that we have 20 plans and approximately 70 million lives covered. That's going to continue to build. We went out with a strategy that really focused on, again, recognizing that we are a pharm on those large PBMs, and those largest PBMs have a direct impact on performing clinical evaluations on behalf of their payer clients. We knew if we had went after those largest PBMs and we educated them and supported education through our value proposition, that that would be reflected in payer decisions with their downstream payer clients. We're seeing that. In less than four months, we've made tremendous progress already with about 20 plans representing about 73 million lives. On the government side, again, incredible progress. If you recognize and understand the government approach, we can't really engage any of these states until our national drug rebate agreement is established. They won't even meet with us. We weren't able to accomplish that until we commercially launched our drug. They won't accept our NDRA until we launch. In less than four months, we have established a footprint of access on the government side that is really unprecedented in this short period of time. Part of it because epilepsy is considered to be a mandatory covered disease, but a lot because we have a team that comes from the Medicaid space. Our government account director is an ex-pharmacy director, and she's been able to not only be able to support the reality of those initial optional states that extend access immediately after our NDRA is accepted. From there, we've been able to establish a limited access footprint. We've been able to go state by state. As patients have, veiled themselves to us through enrollment, we've been able to go to those individual states and be able to actually speak to opening up access before their decision dates. What you see here is tremendous progress in incredibly short period of time relative to both commercial and government payers. From a patient services perspective, you may have heard of ZTALMY One. ZTALMY One is our all-encompassing patient services program. It does represent both our efforts through enrollment, but most importantly, our designated specialty pharmacy. We knew that if we, invested in a very specific specialty pharmacy strategy, we would be able to meet the needs of these patients, and we've done exactly that. We have a designated specialty pharmacy whose sole purpose and experience is around rare disease. That has been translated by us identifying an enrollment form that in advance of payer decisions, considered what we believe to be the coverage criteria that we would likely see, and we've accomplished that as well. We have a very defined enrollment form that considers all the aspects of what it is we thought and what it is we are seeing in terms of utilization management controls and coverage criteria and published coverage statements. I think you heard Christy say earlier, we're seeing that being reflected as covered by our label. In that, our patient services, we're finding that from an out-of-pocket perspective, we are meeting their needs. We have both an out-of-pocket program, and we have free drug programs that do address patients as we bridge them both from clinical trial, but also as we bring those new individuals on. We're seeing that moving forward really, really nicely. Finally, 70% of our patients dispensed to date have had Medicaid as a secondary. What does that mean? Well, what we're seeing is we have a number of patients who have, yes, commercial primary, and that's a reflection of our targeted approach, but they also have Medicaid as a secondary, which means that their copay will be covered by Medicaid. Again, little to no out-of-pocket for the majority of our patients, which is fantastic news. Our patient services programs are meeting the needs of our patients. They're also supporting the needs of those caregivers who are taking care of these fragile patients. From a Q1 2023 perspective, we're going to evolve our tactics to, again, continue to focus on bringing home those mandatory states that will start extending access come January 1st. We're also gonna continue to focus on those downstream clients that I mentioned earlier of those largest PBMs. Those are the regional payers, right? Your Blues payers who represent the largest majority of lives within a given state. While UnitedHealthcare, Anthem, you know, those largest payers cover the universe of the United States, we know that there are some key payers within a given state that have great impact on individual patients' ability to get access. We're gonna expand our reach now to start targeting those. They've always been a part of the approach, but now we're gonna put very specific focus on it. As those PBMs have now been able to publish their coverage statements, we're starting to see those downstream regional payers start to pick those up. We wanna make sure that they pick it up in a way that continues to reflect our label and this patient population. Thanks for the time, and I'm gonna turn it over to Katherine Galica to tell you a little bit more about our marketing efforts. Great. Thank you so much, Paul, and good morning. It's a pleasure to be with you all this morning. My name is Katherine Galica, and I am the Senior Director of Marketing here at Marinus Pharmaceuticals. I'm excited to share with you an update on our commercial marketing efforts here at AES, and also provide an update on our ZTALMY digital launch performance. To briefly introduce myself, I have worked in this industry for over 12 years, and through this experience, I've really developed a passion for working in the rare disease space. These families, and these patients are really incredible, and the CDKL5 community has been a highlight of my career working with these families. They're pretty incredible and the resilience that they show on a daily basis is remarkable. I've been at Marinus since May of 2021, and prior to joining Marinus, I helped to lead the global marketing efforts for a gene therapy at Bluebird Bio. We worked on a product in the hematology space, prior to that, I also worked at Alexion Pharmaceuticals, where I helped to build out a brand for U.S. HCPs in the neuromuscular space. This is also where I had an opportunity to meet and work with Lisa Lejuwaan and Christy Shafer. As Paul mentioned, it's been an absolute honor to join this commercial leadership team. My job as a marketer is to increase the educational awareness of ZTALMY among our targeted healthcare providers and the CDKL5 caregiver community. This weekend was an extremely exciting one for our team. For the first time, Marinus attended AES as a commercial company. Our commercial presence at AES is an important part of further establishing ourselves as an important industry partner to the epilepsy community, now in this commercial capacity with a marketed product. We've had two days on the exhibitor hall. Today will be day three, and we have an exhibitor booth which prominently features ZTALMY, which is super exciting. As I mentioned, it's a 30 by 30 booth. It's on the front row of the exhibitor hall. If you haven't already been, please come check it out. We worked really hard on it. We'd love to show off what we've accomplished here. It's really been fantastic. It's an incredible accomplishment, and it's a really proud moment for the company to have a commercialized product and be able to showcase that to this community in this way. Over the last two days, we've had several hundred interactions at the booth, which is really exciting. Yesterday, we also sponsored a product theater that was delivered by Dr. Stephen Wolf, who's one of our key opinion leaders. He is the Director of Pediatric Epilepsy at Boston Children's Health Physicians of New York and Connecticut. He gave a fantastic presentation yesterday on our ZTALMY clinical data, and he delivered it to a packed house, which was also really exciting to see. We had tons of interest. The audience was incredibly engaged. We had really dynamic Q&A at the end, so I was really proud of that as well. Finally, the commercial leadership team has had the opportunity to sit down with several key opinion leaders over the past several days. We've had really productive conversations about the CDKL5 Deficiency Disorder market in general, about ZTALMY, and how we can continue to support these families and our physicians in our ZTALMY commercial efforts. Overall, AES has been incredibly rewarding and a productive meeting, and I'm incredibly proud of our commercial presence at AES. We've also recently launched our peer-to-peer speaker programs. We have a bureau of impressive key opinion leaders who will help us to achieve that critically important peer-to-peer educational exchange. Now, in this post-COVID world, it's really important that we have offerings for education that are conducive to all different types of learning environments. So for our peer-to-peer programming, we will include both live and virtual program options. Those have already started, which is great. Okay, switching gears. I wanna provide an update on the performance of our digital promotional tactics that we've had in the market to support our launch. Digital promotion is absolutely critical to any launch, as you may know, and it is an important extension of Lisa's team. She mentioned she has 16 fabulous sales reps on her team. They're doing a phenomenal job. You know, the United States is quite large, and it's really important that we have broad, comprehensive coverage across the country in order to be able to support their promotional efforts. We've launched a comprehensive digital promotional strategy to help educate healthcare providers across the country. Since we launched in August, we have deployed digital promotion specifically targeted to 5,000 healthcare providers across the country. Through those promotional efforts, you can see on the right-hand side of the slide here, I've included some details on the performance of our HCP website to date. I can appreciate that that's probably pretty small for those sitting in the back or even those in the front, so I can kinda walk you through it. We've had our websites on since August. From August, September, and October, we've seen traffic to our website steadily increasing. During the month of October, we had over 5,000 sessions to our healthcare provider site. On the left-hand side, there is some performance details about our caregiver website. The caregiver community for the CDKL5 patients is incredibly important. They are advocates for their loved ones, and they are a huge part and can be a huge part of the decision-making process. Ensuring that we had comprehensive education for the caregiver community was incredibly important. You can see on the left-hand side, similarly to the HCP website, we've seen a steady increase month on month with traffic to our website. In the month of October, we've had over 8,000 visitors to our website. I'm incredibly proud of these metrics. I think they're really, really impressive, and I think most importantly, they really speak to the unmet need that persists for the CDKL5 community. I also think it speaks to the enthusiasm around a treatment that is, for the first time, indicated specifically for these patients and studied specifically in them. So far, we've been really, really happy with what we've seen for our digital performance. With that, I'm happy to turn it over to Kristin Rudisill, who is the newest member of our commercial leadership team to provide you all an update. Good morning. Thank you, Kay. Just a huge congratulations to the entire team on the early launch success with ZTALMY, and an equally impressive commercial presence here in Nashville at AES this week. It's now my privilege to have the chance to present to you today, and frankly, to be joining Marinus at what is a really exciting time as we look to commercial planning and preparedness for the potential to expand ganaxolone's portfolio with our IV franchise and enter into a space that is very near and dear to me and to my career, the hospital or the acute care setting. Having more than 15 years of experience in this space, I have a breadth of experience in selling and leading teams in a variety of deployments to launch, and more often than not, to relaunch and reposition products that had previously entered the market. With this set of experiences, I have the unique insight and in-depth understanding of some of the challenges that are in this space and frankly, some of the commercial pitfalls that hospital launches have undergone in the previous years. With that, I feel really proud and excited that Marinus is willing to make the early commercial investment into this preparedness. My role and focus in this early planning phase will really be dedicated toward leveraging those lessons learned, and translating them to really bolster the commercial opportunity that we have and the unique position that we have with IV ganaxolone. As you know, status epilepticus is the second most critical neurologic emergency in the United States. Around 150,000 of these patients will present each year in the United States in critical and complex emergencies. I'll draw your attention to the patients who have moved throughout the continuum of care and frankly, through the viable treatment options that are currently available to them. These patients who have failed first lines with benzos and second line antiepileptic drugs are in a position, whereby they are now denoted as having a refractory status, or they are treatment refractory. This is a unique opportunity because these patients have very limited and suboptimal options going forward. What happens to these 35,000 or so patients that are in refractory status is a treatment option that's ripe with an increased risk for morbidity, mortality, but is also associated with significant cost increases because of healthcare resource utilization and the care that's required to treat and manage patients that are in this medically induced coma. Part of our unique approach to preparedness will really be using a set of advanced analytics to deepen our understanding specific to the refractory status patients and understanding their longitudinal patient journey as to what had happened in their care before and after, and tracking them over a period of time. These advanced analytics will also allow us to really start to think ahead and to identify the need for real-world evidence and what types of generation we might wanna have following our phase III program to support this opportunity. Should we be successful in our phase III efforts, we will have a unique and robust commercial opportunity. It won't be enough for us to just satisfy the unmet clinical need and to bring a new treatment to the physicians who have frankly long awaited a novel therapy in this space. What we're doing now is also investing in a unique and different approaches that will allow us to educate the market, to really shine a light on the clinical and economic burdens associated with refractory status patients, and for us to begin to engage early and in an ongoing way with both clinical and financial decision-makers. In doing this, we'll be able to understand more about what they are looking to for us by way of economic value, in addition to how we clinically differentiate ourselves versus usual care. We're early in our planning, but as a base case assumption, we are assuming that we'll be deploying a field team of just north of 75 customer-facing representatives who will be targeting around 1,500-2,000 targeted institutions across major tertiary centers and academic medical centers in the U.S. Keep in mind that some of this early work will really inform how we either validate this base assumption or shift it, based on the information that follows. Pending, again, pending phase III success and the subsequent approvals, it's really our intention to provide a total value proposition into the marketplace. Conducting ongoing research in addition to the insights that we're gathering from our phase III clinical sites and stakeholders that are really involved in this space, we're looking to put forward not just a way to clinically differentiate the product, but also to put that in tandem with a clear economic value proposition that is inclusive of both direct and downstream cost savings for the healthcare system. This information will certainly inform the ongoing pricing research that we're doing. In short, there is a lot of work ahead of us, but we are actively engaging with the right stakeholders, placing investments, and also ensuring that we're putting the resources toward being ready should we have the opportunity to launch in the IV space. We want to do so in a way that really honors the patients who have long awaited new treatment therapies. I look forward to reporting on these early findings sometime in the second half of next year on our investor day. Thank you for your time. With that, I will hand it back over to Sasha Ellis. Okay. Fantastic. Thank you, everyone. I brought my laptop here. This might be a mistake, but I have questions coming in from other analysts. We are now opening up the floor to Q&A. We will also be opening up the Zoom call to Q&A as well. If anyone has any questions, please do keep them brief to about two questions as we are closing the meeting at 10:00 A.M. Central Time. What we'll also do. Let me move this here. Scott will moderate the Q&A. We'll have concluding remarks at the very end. I do have 1 question. I know everyone's very excited here in the room, but I do have one question, and I wanted to get it out there because he did ask it very early. It's from Matt and Jay Olson from Oppenheimer. What would you expect physicians to find as clinically meaningful from the new Marigold OLE data once published? How important is maintenance of effect at around 50% seizure frequency reduction out to two years in CDD patients? How do you believe these data could help drive commercial uptake? Mike, Oh, Joey, you wanna talk a little bit about the clinical and then pass it to the commercial team? It's bottom line is the maintenance of effect in this disease is important. These patients tend to have a honeymoon effect, where they have a response to drugs, and then that drug, that response lessens or goes away. I've asked our experts, you know, is this meaningful? Because it's 50 patients remaining. The patients who do well stick around. You often see good results in open label data. The experts feel this is different, this is important. In, in CDD, this is to them unexpected. I think durability of effect is particularly notable in the open label data for this disease. I know, Christy, do you wanna comment? I'd be happy to hand it to Lisa as well, but to echo, these patients cycle very significantly early in their days, and the cycling of these medications creates a lot of angst with these families. Change is hard. The desire to have something that you can rely on is very significant. We're thrilled. When we heard that this data was coming out, what it looked like when Alex gave it to us, that there was a palpable kind of excitement in the room from the sales team, and they really can't wait to get it in their hands. We've been really waiting for this day to have this data, and it's been very exciting. Okay, great. On to the next, Joe Thome at Cowen. Just in terms of genetic testing. I don't know if there's a mic. Just in terms of genetic testing, kind of where does that sit in the paradigm? How long after sort of initial seizure activity do the patients start getting tested? I know you mentioned there is some sessions here at AES. Is there anything that came out of that to sort of push that decision earlier at all? I have one quick follow-up on RSE, if I can. Christy, Al, you want to talk a little bit about genetic testing, maybe Alex, medical side, and then Christy, your commercial perspective. Yeah. This is definitely a huge trend we're seeing at AES this year. I think there were some rumblings about it last year. Last year was more about let's just educate people around genetic testing. This year it's more about this is how it could really help impact your clinical care. I think for new patients, early onset seizures, present day moving forward, I think a lot of them are gonna ultimately get genetic tested soon after seizure onset with no other known etiology. I think a lot of things that we're learning is that there are a lot of undiagnosed patients still out there. I think there's still a lot of work on educating physicians, providers around the benefits of what genetic testing could provide. There's also been a lot of publications that have come out recently, Invitae and some of the work that they've done, about how patients have received genetic diagnosis and how it's impacted the clinical management of that patient and how it's improved clinical outcomes. I think things like that over time will continue to gain momentum, and hopefully it will spread amongst the provider base. What we've learned in the first 16 weeks of launch is that there's great variability. In large COEs, there is very distinct and deliberate plans to test early and often. You know, Lisa mentioned the EEG, and then immediately, you know, MRI, EEG, and then moving to genetic testing. That it's been great to hear, but we also know that there are either older patients who were not tested early on in life or there's some either financial concerns in older patients that don't have the ability to get genetic testing at this time. It was almost a bit serendipitous to us because we know that this is a strong strategy that we need to be able to tackle from an education standpoint in 2023, and we felt like AES knew this for us. We felt like they were doing everything for us at this meeting, and it has been really the top thing that everyone's been talking about. It directly moves into our strategy for 2023 to educate further. I'm gonna add my two bits here. Okay. What I'd add is, I think we're seeing the industry identifying more and more genetically defined seizure disorder, neurological disorders that have seizure activity, which leads to an update in the genetic panels, which leads to another reason to test more frequently. That's really been, I think, you know, a lot of credit to the genetic testing arena, the interest in doing gene therapy trials. I think that will really create an opportunity for us, I believe, clinically, to study additional genetic subtypes in the future. We've had a lot of interest from investigators on inbound questions around investigator-sponsored trials and subgroups, and we'll support those efforts vigorously over the next few years. I mean, it's probably implied by all these comments, but a lot of these syndromes are clinically indistinguishable, so it requires the genetic testing for diagnosis. Maybe just 1 quick follow-up. Just in terms of your conversations at AES, what's been the response to the updated enrollment criteria for RAISE, those adjustments? I know historically the company mentioned that you're happy with the type of patients that are being enrolled. They're similar to the phase II. Is there any risk that that could change at all, I guess, as you close out the study? No. Actually, so far in terms of seizure frequencies, it's been pretty firm. It's similar to what we saw on stage two, the phase II. These changes to the protocol, and we mentioned this, align it more closely with the phase II population. I think it's almost certainly gonna increase enrollment. In particular, allowing longer duration of IV anesthesia prior to enrollment. I actually think the changes to the trial will increase, and I've said this before, will increase the sensitivity to the trial, detect the treatment difference because now language in the protocol is stronger about IV anesthesia. The next consideration for treatment should study drug fail. Comment. I think last year, we were concerned just in a COVID environment, so many hospitals were constrained, that we tap out around 50 or so sites in the U.S., and it was a big reason why we went to outside the U.S. What we're continuing to see, and we really owe Alex and his team. We have three PharmDs now working across the U.S., and I think with the data that we're presenting, we are getting new U.S. sites every day who are still interested. As long as we can get them up and running in the next quarter, we see every reason to allow them. I'm expecting Q1 to really be a meaningful uptake in the number of sites. I think we are now very careful that it's not only about sites, it's about quality of sites. One of the things we've now focused on is having a champion within those sites. We will not open a new site unless there's a champion. I think the reality of this study is it's an intense 48 hours for a study coordinator, and they have to be paid by challenge. I think, you know, it's interesting, the PharmD team came to me over this weekend and specifically said, "Every investigator we've met with, we're identifying a champion for those sites." I think we as a team have a much brighter outlook about the number of U.S. sites that will participate. I think that's great for the future of the drug. We're still gonna continue to open sites in Australia and Canada. It is really nice over the last three to four months how the younger new fellows coming out of training are really stepping up, showing a lot of interest. I think the neuro-acute care community recognizes that this is the right study to perform, so we're excited about this meeting. I was shocked how many IV investigators we met with. You know, when we have our interactions with physicians, I expected it would be two-thirds TSC, CDD, a third RSE, and it wound up being about 50/50 for us, so I was really enthusiastic about this weekend. Just one more thing about the PharmDs. I mean, these are all ex- ICU pharmacists. I think they provide a great advantage. It's I think a unique capability in the industry, and they get to the hospital pharmacist. It turns out that's a great pathway to get to the study team. I don't know. We went to the Neurocritical Care Society meeting. It seemed like they knew everybody. That's been a great pathway to understand the treatment patterns in the hospital, which can differ. Okay, great. Charles Duncan from Cantor. Good morning. Thanks, Sasha, and thanks to the Marinus team for hosting and the updated information. I had a commercial question for Christy and then a pipeline question. For Christy, I guess I'm wondering, so far the experience in terms of where ZTALMY is being prescribed. Is it being prescribed to younger patients or to older patients? When patients are being identified, but it isn't being prescribed yet, what is the holdback that you hear from docs? Why don't you try this one, Christy? We're having a little mic issue in the room. Thanks for the question. A couple of things. I'll start with who's being prescribed. What's really nice to date is that we've seen an incredible variety of patients show up in the first 16 weeks. I will say that we have had a handful of what you would call young adult to adult patients to start. That was a surprise to us, also very encouraging. I'll remind you that what we've modeled is about 2,000 pediatric patients in the United States. These patients are a little bit outside of that sorry. Again, we're also not updating models. It's very, very early on in this, in this timeframe. I'll update you really quickly on what our models say. Our Marigold trial had an average age of patient between six and seven. We also know that there is great appetite to treat early in these patients. Again, they cycle very, very fast through their medications. Our indication is for two and above. Our models are still staying strong at about a four-and-a-half year old, 16 kilograms for our average size patient right now. Going back to patients that are identified but maybe not going on therapy. Kay built a really beautiful marketing program that dictated that we knew there was going to be a push and pull between the caregiver and the physician. The majority of the time right now, if we are identifying patients and they're not going on therapy, it's typically because the parents just aren't ready yet. They could be in a stage where things are fine, right? Like, they're kind of comfortable in the uncomfortability that they're used to at this time. We know that just that static state just does not happen very often. They will get to a point where something new needs to change. We honor those families. We know that this is tough. They give us really amazing kind of visuals of what their lives are like. We continue to educate through our advocacy partners. We know that they'll hear the success stories that we're having out in the field already. We've heard amazing success stories. It's just a matter of time to get everybody on board. We know that their comfortability is really important. You know, I'll just remind everyone, I think we knew going into this launch we didn't expect bolus of patients. Everything Christy's described, very consistent with what we had been thinking. I would say generally, we're seeing what our expectations were incrementally improve every day, beyond what we initially expected in terms of the launch. Our original guidance around about two years of profit after or two years profitability for this as a standalone business specifically. If anything, you know, we're very enthusiastic and encouraged by our initial thinking to where we are today. If I could ask a follow-up regarding the pipeline. Going back to an earlier question in the data from the open label extension. I guess, the literature would suggest to me that you see waning efficacy over time with regard to other drugs that are used in, you know, DEEs generally. I'm wondering if you have, call it a mechanistic rationale for ganaxolone actually being able to maintain or improve efficacy over time, and what does that mean in terms of this being potentially a disease-modifying agent? Joe, maybe we'll let Sir Alex start on the- Yeah. I mean, as you mentioned, all the literature would suggest that efficacy with existing standard of care would suggest a waning of effects over time out to maybe three or six months, you start to see that drop off. We're particularly excited about the data that we shared with you today. We believe that there's some preclinical evidence that the mechanism of action of ganaxolone being unique to other ASMs out there, particularly GABAergic compounds with its effects at both synaptic and extrasynaptic receptors, is likely potentially what's providing this effect over time. There's some work that's come out of Michael Rogawski's lab a decade or two ago that do show that neurosteroids, the classic compounds, you do not tolerize to efficacy over time. I think it's the plasticity of these receptors, and again, the synaptic downregulation that we see both in continuous seizures or chronic epilepsies, that we think could potentially be playing a role here. To your point, though, too, I think that this is not specific to CDKL5 as well, this potentially could have impacts to other Developmental Epileptic Encephalopathies as well. Thank you. Yeah. I'd add to Alex's comment that in the patients in our phase II PCDH19 studies and TSC studies, a significant number of those patients were still in open label and having good responses. We've seen it on a smaller scale in our phase II studies as well to date. All right. Michael Higgins from Ladenburg Thalmann. Thanks, Sasha. Thanks, everyone for, hosting the conference. Sorry, hosting this event. Your presence is really noticeable at the conference, incidentally. Not totally sure this is on here yet, but, question for you is as I look at slide eight8, I'm wondering what you may find will close the gap over time from LCFF to patients continuing? Is this something that will happen just in time with having additional data or the things that you can do as a team to kinda close that gap? It's Last Observation Carried Forward with your, yeah, thank you. With your open label. Clearly some things you're working on with the titration or different formulation, but other impacts you could make, I'm curious of. Thanks. Well, let me kick off and then I'll pass over to Joe. I think, you know, when we look at all patients on ganaxolone, you know, there's about a 25% of patients who have very robust responses, greater than 50% improvements in efficacy. We've got another third or more who are having mid-30s seizure responses. We've never really done the analysis, Michael, of who starts early and who does better over time, but when you look at the quarter or so of patients who are on therapy for two years from the 100 initially, it's quite impressive, we think that that percentage is having 50% reductions or greater. That being said, we really believe to take a very good drug and make it great, we'd like to see that in 75% of patients. We really believe the key to that is improved blood levels, which is why we're so excited about the two programs we have in early development. I will say, I think with the current formulation of ZTALMY, we see a much more consistent number of patients achieving blood levels. I mean, we've started looking at blood levels over the last few years, and I was talking a little bit about it this morning. I'm more and more convinced that a higher percentage of patients are capable of getting to 100 ng or so in terms of blood levels. We see it routinely now in our healthy volunteer studies. What I think is gonna be critical for our second generation programs is the ability for all patients to get to 100 ng, and really the potential that all patients or some subgroup of patients could get to 150 ng or even potentially 200 ng, and we can really shift this entire curve upward meaningfully. Joe did some tremendous work around Marigold with this. I'm gonna pass the mic to Alex Aimetti. I just have one thing to add to that, though. I think another thing that I'm particularly excited for is the revised titration schedule that we're studying in TSC. I think to the question around closing the gap, you see that we have 50 patients with data at two years, compared to when you impute missing data, 87. There's 37 patients that are not accounted for in the all available data. When you look at the reasons why 13 was lack of efficacy and 10 was due to an adverse event. We're hopeful that the revision to the titration schedule will improve tolerability. Then some of the work that Ian showed, we hope will also correlate to improved efficacy. I think that that's a potential opportunity to continue to increase efficacy, improve tolerability in CDD patients potentially as well, pending the outcome from the phase III TSC study. Yeah, I think you raise a great point, Alex, 'cause when you go back and look at the failed focal epilepsy trial, which dosed ganaxolone twice a day. Not only did you have low blood levels of ganaxolone, but you had a very high discontinuation rate. Those two pieces of the puzzle do matter. And we certainly really have a lot of confidence in the new titration schedule. Folks, we as a team have only had the opportunity to work with this molecule for 3+ years, but really believe that new titration schedule is physiologically the right one. And that improved tolerability, I think is gonna be critical as we expand indications. That makes sense. Very helpful. Just one quick follow-up. It's early, what are your retention rates? Can you share with us how that's going so far? Are patients coming on and off the drug? Are they staying on the drug? Thanks. Early days, Michael, right? Early days. I mean, very, very early days. We've not seen anything that would be able to inform the forecast of anyone coming off at this point. We're pleased with what we have so far. I think just so you know, as we've thought about where we expect to be in two years, we were really modeling the phase III results, and the percent of patients who had a meaningful response above 25% seizure reductions as our core thinking. Early days to really think differently about that, but- One thing I failed to mention, we have informed the forecast with that data as well, that we would expect that in real life. That we would have that attrition rate. Our forecast is supportive of that as well. I'm sure that we'll have some more data by the end of Q1, and of course we'll be sharing that with you. Alex, you wanna- One of the reasons why you would potentially expect discontinuations is possibly due to an adverse event. One of the things that our team on the medical side has been really focused on is going out educating physicians on our Marigold study on the experience in somnolence, when does it occur, what happened? It's been very well-received and epileptologists are very comfortable with how to manage that. I think that that's really helped educate the physicians on what to expect with a new drug. All right, one more question from Charles Duncan. Any more questions from the room? Basma, will you be asking? I have already. Oh, we'll go to Charles first, and then we'll go to you. Okay, great. Charles, go ahead. This is quick. Thanks for taking the follow-up. Scott mentioned the titration schedule, and it made me think of a question, and that is related to the ongoing phase III in TSC. I know you're not going to be able to talk about it all that much, but on a blinded basis, what has been the feedback of investigators thus far in terms of dose adjustments and/or, you know, seeing hypersomnolence? Can you? I mean, I know it would be anecdotal, but what are you seeing? Yeah. Ian is really, our key individual, our key physician on the trial and has had a tremendous amount of interaction, I'll turn it over to him. Thanks. Yeah. I can definitely speak to that quite well just because our strategy has been, you know. the crucial part is that it'd be very, very easy for the patients to report AEs to the investigator and for the investigators to report the AEs to us. Really, the best way to make that second piece happen is to give them my cell phone number and say, "Look, when a patient calls you with anything, please, number one, make sure that they know the right way to get a hold of you. At Baylor, it might be the portal. At, you know, Boston, it might be a call to the clinic, to the study coordinator, whatever. Tell the patients what that low-friction way to get a hold of you is. This is the low-friction way to get a hold of me. Text me, you know, whenever this happens." I can tell you, I've had a couple texts and no more. I do think the titration schedule is working. I'm glad that it is because I'm the one that gets the calls when it doesn't. You know, but it's early days on this side too, but very optimistic so far. Thank you. Look, I'd add, you know, just as we know the, you know, many investigators are skeptical when you put up a 17% median reduction, investigators are too. We really walk them through this titration issue. I think it's been probably the most important tool to drive site engagement, site participation in the study, TSC Alliance has been fantastic working with Ian and holding webinars for patients as well. Look, we do our best to be transparent with you guys. We do the same with the FDA. We do the same with investigators. I think it goes a long way, and I think they believe the scientific story behind it and are certainly willing to participate in the trial. Okay, great. Thank you. Thank you. Basma Radwan with SVB Securities. Hi, good morning. My question is just a very general one. Really about the, in this patient population, CDD, what plays a bigger role for the discontinuation? Is it the incidence of adverse events, or is it the waning of efficacy? In light of these, very promising phase III, early data, would that drive more retention, do you think? Or is it really about the potentially the effect of better titration schedule that where you do this? Or is it a combination of both? What's more important? Specifically in the CDKL5 population? Well, let's start by that. Lisa, you wanna talk a little bit about what you think are the key factors you're seeing out there? Patients are gonna stay on a drug that works. It's simple. That's really the truth. Both are important, as you suggested. I mean, if a kid is sleeping all the time, it's not a matter of discontinuation, in that it's a matter of tweaking the dose, and that's something that our physicians are educated on. Our medical team's done a great job of making sure that they're comfortable with that. I think it is a little bit of both, but if a drug is working and working over a long period of time, kids are gonna stay on it. The parents want this better, you know, life for their children or adults having fewer seizures. You know, I think this community really has a strong advocacy presence. Parents wanna know what other parents have to say. We've had some great interactions over the years with both IFCR, the Global CDKL5 Alliance, the Loulou Foundation. I really feel they're our best advocates. We're eager that as new stories come out, that will help us tremendously. I don't wanna say it'll do Kaye's job, but it'll be a big part of Kaye's job, really relying on the community and their experience. When we meet with our physicians, the ones I met over the weekend, there's no question that patients are looking at what's out there from other family members. That, without a doubt. Joey, you wanna chime in? Yeah. Just, I mean, from the open label data, there's some withdrawals from adverse events, some from lack of efficacy. A lot of patients get tired of being in a clinical trial, and it goes on for years and years. There are as much a withdrawal from that reason, withdrawal by the patient without anything else, by the parent, as there are adverse events or lack of efficacy. Sasha, why don't we take one more? We have one more question here from Andrew Tsai from Jefferies. He says, "You clearly have the first mover advantage in CDD. You're paving the way here." Thanks, Andrew. "Talk in the latest and greatest about the competitive landscape in CDD right now and how you plan to maintain the leadership position in CDD over time. Well, I'll kick it off, I'm gonna put on my old investment hat. We know that, you know, we know that fenfluramine is now in a phase III trial. I find it fascinating that when Zogenix was a standalone company, they put out at least three press releases on the data. I've never seen the data released for our primary endpoint of major motor seizure. Take that as you will, it's always been one of suspicion for me. I would add, we know that trial is continuing. We know some of the key sites in the U.S. It took us about three years to enroll 100 patients. We have some fantastic centers of excellence in the U.S. globally. Many of our centers of excellence are putting patients on ZTALMY today, and certainly have participated in our trial. I'm certainly not losing sleep that there are a lot of new patients who are choosing to go into a clinical trial rather than to a drug that is now approved with a specific phase III study. I think we've tried very hard in Europe to make sure that we have very strong access for patients in Europe. Our expanded access program is growing every day. We've already had multiple requests in Germany, for example, and we as a company are committed to providing drug through the approval process throughout Europe as well. you know, we're happy to see a competitor spend energy in the space. We think it's gonna be a long time for the study. We're still you know, questioning some of the results in the public domain on the phase II. I'd add finally, I mean, Christy told you how this is such an important decision for families. I get that, we talk about that all the time. Adding the request to have echoes every six months, we think is pretty material compared to our safety profile. I'm not losing a lot of sleep. I'm not sure the sales team or the commercial team is losing a lot of sleep on the competitive dynamics, at least for the next four to five years. We look forward to it. Back to you. Thanks, everybody. We really appreciate you coming. I really wanna let the team get back to work and have some interaction before the end of the conference. Thanks again for the live and the webcast participation. Thank you, everyone.