First of all, thank you for everyone here in person and those on the webcast for joining us today for our LUMRYZ Commercial Day. We really appreciate you taking a few hours out of your Thursday morning to come and listen to a lot of the insights that we've gathered and garnered over the last couple of years as we frame out the early launch period and how we think about this unique opportunity. Before we get started, I'll remind all of you and point your attention toward all of our risk factors. We certainly may make some forward-looking statements here today and point you to our SEC filing of our 10-K for December 31, 2022, which was filed earlier this year, and can be found on the investor section of our website at www.avadel.com. Although this is really the LUMRYZ Commercial Day, it really is, in our view, an ushering of a new oxybate therapy. It's an opportunity to not only transform Avadel into a high-growth commercial stage company, but also to transform the narcolepsy market. Today, we're going to spend quite a bit of time talking about our insights and how we view and value this opportunity, and to hear from really important special guests as well. From an agenda perspective, you will see that after my opening remarks, from Avadel's perspective, you'll hear from Richard Kim, our Chief Commercial Officer, on a few different occasions. Start first with LUMRYZ and our view of the market. We'll then are very fortunate to have two important distinguished practitioners in sleep medicine and clinical researchers, and Dr. Anne Marie Morse. Tom Stern, who will respectfully talk about the disease state, the current treatment options, and of course, some of their patients who have gone on to LUMRYZ. To really bring that to life, we're very blessed and fortunate to have a person with narcolepsy with us. Her name is Katie, and we'll have an opportunity to hear her journey in this condition, but also how LUMRYZ has helped transform her life. To our guests, we thank you for being with us today. At that point, we're going to take a little break and go to a Q&A for the KOLs, right? An opportunity to ask Dr. Morse and Dr. Stern questions based upon their presentations or other things that are on your mind. For the second half of the morning, we'll really dig deep into our launch plan, how we think about this opportunity, and then give you some early metrics in terms of how the launch has gone now, just a little bit less than three weeks into it. Closing remarks, and then we'll have a Q&A with management. In summary, what you're going to really hear today is our view of the opportunity. Our view of the opportunity to transform the market and to transform Avadel. We are going to spend some time and introduce you to the capabilities of our team and the organization that we have built, and then provide some early indicators of how the launch has gone, right? Again, we're only a few weeks in, but we feel really good about how we started and why these metrics that we're going to disclose, we believe, are the most important ones in the early part of the launch. Then we'll do a brief review of our financial balance sheet, in particular, our cash position, then again, wrap up with some Q&A. We really believe we're at an inflection point. We're entering into another growth area from where the company is today, and which has been transformational in the last 12 months. If you go back to where we were 1 year ago to where we are today, it's been a major transformation in all aspects, right. Whether it's valuation or where we are from a launch standpoint. That opportunity of where we go from here is really built on a strong foundation, and that foundation begins with a very, very clear unmet need in the narcolepsy marketplace, and in particular, in the oxybate-treated patient population, right? A need that was identified greater than 40 years ago. What is that need? 40 years ago, when sodium oxybate was first being studied in narcolepsy, it was identified that as effective as it was, it needed to be delivered over a 7-8 hour period. It's taken 40 years, and Avadel is unbelievably proud to be the first company to be able to deliver an extended-release sodium oxybate. It's just not us saying that that's important or what was said 40 years ago in the initial research around sodium oxybate. We've heard it from physicians and patients in our discrete choice experiment, who, when they look at different product attributes to oxybates, have said once-at-bedtime dosing is the most important attribute. Patients in our open-label extension study who have switched from the first-generation oxybates have voted with their hands and their actions by saying 94% prefer the once-at-bedtime dosing of LUMRYZ versus the first-generation oxybates. Most recently, FDA confirmed that with our approval and our orphan drug exclusivity, granting us orphan drug exclusivity on the major contribution to patient care over all first-generation oxybates. Again, this foundation is critical to create the opportunity that we're going to talk to you about today. Equally important is to ensure we have the capabilities and the resources to execute and deliver on the full promise that LUMRYZ can offer. It starts with our commercial leadership team, right? Led by Richard, who's got over 25 years in the industry, tremendous track record of leading and building and executing commercial launches, but a team in total that has had over 50 rare in orphan disease launches. A team that's been in place for a couple of years now, who have really built our plan and have generated all of the insights we're going to share with you today that has led to where we are at this point. The same team that has now deployed an experienced sales and customer-facing organization with deep sleep and rare disease experience. The same team that has built an industry-leading and category-leading reimbursement and product fulfillment strategy, which is already bearing fruit for us, which we'll talk about in a little bit. All of you are aware of the cleanup and the actions we've taken on the balance sheet in the last few months. Today, on a pro forma basis, as of three thirty-one, between cash on hand and committed capital with $275 million, we feel we have all the components to really execute and deliver on the promise of LUMRYZ. It's already happening, right? As a company, the one thing we take a lot of pride in is delivering and doing what we say we're gonna do. Whether it's navigating legal matters, filing an NDA, getting an approval with orphan drug exclusivity, launching within a month after a product becomes gets approved, and then generating, starting that promotion and demand shortly thereafter, all of those are things we said we were gonna do and we have done, right? The early indicators, which we'll share with you a little later this morning, have all, we think, are promising, although we recognize it's early, only about 3 weeks in. We certainly are pleased with the progress that has been made early on, and we'll look forward to talking and sharing that with you. That foundation needs to have a clear roadmap of where we're focused, where are we deploying our resources, the capital you've entrusted with us to deploy, to build, you know, LUMRYZ going forward, and those priorities are very, very clear. First and foremost, you're gonna hear about all of these today: driving demand with high-volume oxybate prescribers, activating, educating patients to activate and initiate therapy. Securing reimbursement. We talk a lot about payers, right? Broad commercial coverage within 6-9 months post-approval. Delivering product fulfillment, being able to ensure that patients can get access to the drug by building this best-in-class patient support and reimbursement programs. Now with the approval in hand, we'll talk about lifecycle management. What's next? How are we going to expand the patient population who could potentially benefit from LUMRYZ? We'll cover all of these today, the company is unbelievably focused on executing against these priorities and, most importantly, initiating a successful launch of LUMRYZ. Why? Because we're proud of what we've developed and what we've innovated. We're proud of the seven years of market exclusivity with orphan drug and the long runway we have from an intellectual property perspective, with now 13 Orange Book listed patents in the Orange Book and many more to come, that gives us the runway and the longevity to build a franchise that can create value for the community, for patients, and for Avadel at large. What's critical is that we build this plan on the foundation of insights that really matter. Not on small subsets, not on small sample sizes, but on robust, in-depth, continuous research that'll. As the market has continued to evolve over the last couple of years, to ensure that we have our fingers on the pulse of what is going on and where there are opportunities for us to bring LUMRYZ to places where patients are today, or even places where patients aren't being treated with an oxybate in the future. At the foundation of that is over 25 research projects, over 2,500 physicians and patients who have been interviewed or surveyed, and at the core of how we value this opportunity financially, has been six different demand-based forecast projects over the last two and a half to three years, interviewing in-depthly over 700, about 700 physicians, that have framed out how we think about this opportunity, right? Overlaying that with our analysis of what's actually occurred in the marketplace, looking at the largest claims database that has great visibility to the narcolepsy market itself, we've been able to build all components of our plan around these insights and have thought about the value of this opportunity, which is something we're gonna talk about today. We're gonna talk about how we value this opportunity for Avadel and the significant peak revenue potential. We're not providing guidance, let's be clear, I'll say that at least twice today, that we're not providing guidance at this stage, but we are trying to articulate our interpretation of what has been extensive research and insights into how we are building our go-to-market plan to create a potential blockbuster product that we think offers over $1 billion in potential peak sales opportunity in the future. Starting with an adjustable market based on some very recent insights that we think is probably over 50,000 patients over time. When we do all this research with physicians, and Richard Kim will take this in more detail and build this up for you, so you get a good perspective of how these insights have informed us, but we certainly hear from physicians in these large research projects continuously, that they expect to treat more patients with an oxybate than they are today, purely on the back of the introduction of LUMRYZ. We see that 16,000 number growing to 20,000-25,000 plus. Those same physicians are telling us continuously, time after time after time in our research, that we would expect to command 50%-60% of what the oxybate market looks like in the future, all resulting in 10,000 or greater potential oxybate LUMRYZ patients, and at today's pricing, certainly offers a greater than $1 billion opportunity. We're really excited to be able to share some of these insights with you and our view of the opportunity at large. As I wrap up, I think most importantly is that we've spent a lot of time, and a lot of you have been very patient, and we're very blessed and appreciate that you've gone on this journey with us. We have put the ingredients together to really drive a successful launch and truly create the next round of value creation for our investors and all of our partners, and most importantly, our patients who we're serving every single day. Whether it's the innovation of LUMRYZ, the unmet need, a valuable growing market, a team that is, although we may be new as Avadel, a team that's unbelievably experienced and a plan that is focused on all the right things. Again, thank you for being with us today. We really appreciate it, and to get into some of the details, I'm gonna turn it over to our Chief Commercial Officer, Richard Kim. Richard? Thanks, man. All right. Good morning, everyone, and thank you so much, Greg. It's awesome to be here, just sort of 3 weeks into our launch. You're gonna see me a couple times here. We really wanna start with the unmet need and obviously focusing on LUMRYZ and the high unmet need that LUMRYZ will address. Here's what I'm gonna cover over the next few minutes We're gonna jump right into it. As Greg had mentioned, we have done extensive market research and insights with sleep specialists and people with narcolepsy. We've taken the time to really understand what the treatment gaps are or goals are for people who treat the narcolepsy. From this survey, from 134 sleep specialists, there were several areas, but you can really group them into 4 key topics. Clearly, addressing excessive daytime sleepiness and cataplexy is always one of the goals for people with narcolepsy. Other key components of treatment goals include improving compliance, on the bottom, reducing adverse events, but very importantly, also avoiding nighttime symptoms. When we look deeper into this, addressing and controlling nighttime symptoms was rated as the second or third most important attribute by high and medium volume oxybate users as well. The great news is clinicians clearly identify some of the gaps for treatment goals today. Narcolepsy, the disease itself, disrupts nocturnal sleep. This is from the European guidelines, estimating 65% of patients with narcolepsy experience disturbances in nocturnal sleep. The disease itself has that impact. Unfortunately, today's therapies that are approved can disrupt the night even further. Let me orientate you to this slide. This is adapted from the AASM Narcolepsy Practice Guidelines. On the y-axis, you see currently approved classes and products for narcolepsy, all approved for either EDS or EDS and cataplexy. Across the x-axis, in the light blue, you see some of the most common side effects. What you see, and it's not a surprise when you think about the classes here, we're generally talking about stimulants and wake promoting agents to keep people up and awake. Unfortunately, they can all disrupt the night through either creating insomnia or forcing people to wake up during the middle of the night to take a second dose. As Greg had mentioned, to start off, the oxybate therapy was really thought of as an optimal therapy for narcolepsy over 40 years ago. The thing we have to remind about ourselves about GHB, the active ingredient, is it only has a short life, half-life of about 30 minutes. From a study from 1979, Broughton and Mamelak identified great opportunity for sodium oxybate, but unfortunately, it has a very short duration of action. The hope was, in the future, there could be something with a much more extended or prolonged effect as well. Well, over the last 20 years, there was really no innovation as far as technology is concerned for delivering oxybates. On the left side, we know some of the challenges today already with first generations. There's a very narrow 90-minute window of opportunity for dosing a second middle of the nighttime dose, 2.5 to 4 hours after you take that initial dose. We know consistently from the research that we've done, and actually reported from the trend community earlier this year, that 65% of patients report they've missed a second dose within just the last month as well. If you look at the right-hand side of this slide, this is really the advancement in technology. In 2002, Xyrem was first approved, and it wasn't until 2023, when LUMRYZ was approved on May 1st, where there was really an advancement in the delivery. Even when the mixed salts version came out, clearly, it was using the same technology that came out in the market in 2002. We're here to talk about LUMRYZ. Here is LUMRYZ' fundamental positioning for the marketplace, and we believe it's very clear and intuitive if you think about the narcolepsy condition itself. LUMRYZ' positioning is better sleep, better days. Full stop. That's aspirational, and we'll show how we're gonna be messaging through that to the community as well, but it fundamentally addresses the unmet need in the marketplace overall. It's backed by a plethora of amazing clinical data as well. From our pivotal study, REST-ON, we achieved all three co-primary endpoints with a stat sig of less than 0.001. I love saying that, like 0.001, three co-primary endpoints. We also know one of the key secondary endpoints is the Epworth Sleepiness Scale score, because this is something that people do use clinically in today's world. Patients there started with a baseline of around 16, and at the end of the 13-week period, on the 9-gram dose, the median Epworth score was 9.5. That means over half the patients were in the normal range on the sleepiness scale as well. Greg had mentioned 94% of patients voted with their actions and told us they prefer being on LUMRYZ dosing after switching, after three months on first generations. Also from the free choice experiments, consistently, dosing is the preferred attribute around oxybate therapy. May 1st was really important for us, not only to get our final approval, but obviously, we also got our orphan drug exclusivity. I've actually this is gonna be my 12th product launch. They get more interesting and more exciting. I am so excited about what we have to offer and also what we're gonna be able to communicate about LUMRYZ as well. The fact that the FDA has determined that LUMRYZ is clinically superior to all twice-nightly oxybates, very powerful. It's something I wish I would've been able to say in some of my previous launches. It's a very powerful message for physicians and patients, but sometimes, for us, we have to break down our belief of why we got this superiority claim. I'm gonna walk through a few key components of this because we believe that the FDA took the time to really understand this and break down the fundamentals of not only the condition, narcolepsy, but what LUMRYZ can offer to people with narcolepsy. The first thing is the unmet need. Xyrem and Xywav necessitate a nocturnal awakening to take a second dose, which disrupts sleep architecture, the fundamentals of the condition again. Now, what does LUMRYZ do? LUMRYZ, once a bedtime dosing, does not involve disrupting or fragmenting sleep. Very simple, very clear. Additionally, the FDA recognized this is a chronic condition. You have to take these meds to have your functionality. The fact that you don't have to wake up is easier and less burdensome, especially considering that narcolepsy is a chronic neurologic condition. Now, when I joined the company, someone said to me, "Richard, geez, is that a convenience thing, once a night versus twice?" I'd say, "Hell, no!" The FDA has clearly put that to bed. What LUMRYZ does is it addresses the fundamental issues and the gaps of current treatments in the marketplace today. All right. Let's build off of some of the constant validation work that Greg had teed up before here as well. This is a slide that Greg showed earlier with a few more caveats to this. Super proud. When I joined the company, one of the things we determined that we had to do as a small company, was we wanted to have the best knowledge of the narcolepsy marketplace to help make the best decisions that we can make as well. Greg talked about all the extensive research that we've done. We are working with one of the largest claims databases in the country that has access to 330 million American lives. They churn about 15 million in healthcare encounters every single day, and it covers the vast majority of the current narcolepsy market and oxybates as well. We don't just look at numbers, we actually talk to people as well. Thank goodness, Dr. Morse and Dr. Stern are here because we listen to our experts, we listen to people with narcolepsy, and we take all of their insights as well. Overall, if we sort of package all the insights that we've received together, here's what we consistently hear about why LUMRYZ is positioned to be the market leader. Clearly, oxybates are viewed as the standard of care for narcolepsy. As we saw from the FDA, the ability to minimize sleep disturbances and decrease sleep fragmentation is essential in this field. You do that by avoiding twice-nightly dosing. People also recognize, as the FDA did, treatment is chronic, so compliance is important for people to have more consistency in their day-to-day activities as well. Maybe something we don't talk about a lot is our pre-measured packets. Actually, you know what? I got one right here. This is what it looks like now. You no longer have to carry a 180 ml bottle around with you. These are pre-measured packets that have your entire dose in one packet. What's nice is you get that consistency and that reassurance that the patients are going to get the full prescribed dose that the physician intended for them as well. Greg mentioned that we have done deep research into demand around what we think physicians are telling of us about where LUMRYZ will fit in this marketplace. Six studies done over the last three years, as recently as the last one, finishing just a couple of weeks ago, from almost 700 sleep providers as well. Here's what we have learned. Across these six studies, the share given to market to LUMRYZ within the oxybate marketplace is between 48%-61%, with an average of 54%. Lots of orange is good for us, and the pie in the middle is the variance here, of course. What's really also interesting with this is, this is done with zero promotional effort from us and without us messaging around our clinical superiority messaging. We really consider this the foundation of where we're starting our journey, and now we're clearly in the process of communicating the value proposition, the full and balanced proposition to sleep providers across the country as well. 48%-61%, with an average of 54%. Additionally, the market research shows that LUMRYZ will drive market expansion. We'll get into that a little bit more around the reasons why, what the research has showed, physicians have told us they would prescribe LUMRYZ to more oxybate patients, growing the marketplace for new patients between 35%-113%, or an average of 58%. Consider today there's about 3,000 new starts every year for oxybates for first generations. Physicians tell us that that number should grow going forward as well. Once again, no promotion, no security claim that's been tested with this as well. LUMRYZ, there's a huge unmet need. We believe that there's the ability to not only address daytime symptoms, but also to potentially give patients the chance in an uninterrupted night's sleep. We're super proud of the clinical body of evidence that supports LUMRYZ and clearly, having the orphan drug exclusivity and the FDA declaring that LUMRYZ is clinically superior to all first-generation oxybates doesn't hurt at all either. As much as we believe in LUMRYZ and what it can do for people with narcolepsy, it's great to see the consistent validation that we've seen time after time when we ask physicians, "Where will LUMRYZ fit into your current practice today, and where will it fit in the future as well?" You'll see me again later on, but with that, I'm going to introduce Dr. Jennifer Gudeman, our Senior Vice President of Medical and Clinical Affairs. Thank you, Richard, and good morning, everyone. I have the distinct pleasure of introducing our three distinguished guests, beginning with our first key opinion leader, Dr. Anne Marie Morse. Dr. Morse is the Director of Child Neurology and Pediatric Sleep Medicine at the Geisinger Health System in Pennsylvania. She consults to a number of companies in the narcolepsy space, including Avadel, Harmony, and Jazz. Dr. Morse has significant clinical experience and interest in pediatric and adult patients with sleep-wake disorders, particularly central disorders of hypersomnolence, which, of course, includes narcolepsy. Because of this expertise, Dr. Morse is also the medical advisor to a number of different patient advocacy groups. Dr. Morse is extensively involved in clinical research as a principal investigator in many studies, and she is passionate about ensuring the patient voice is heard and understood, which has led to her having quite a large social media following. With that, Dr. Morse, welcome. Thank you. Thank you so much. You're right about this. Thank you, guys, so much. I appreciate the opportunity to be able to speak with you in regards to what my clinical experience is, as well as the participation in this study. I always like to start off just giving some background as to how did I get here? Not really like by car, how did I get here, but how did I get to the point of standing here as an expert in front of all of you? The background that I have is as a neurologist. Why did I become a neurologist? My mom has multiple sclerosis. She was diagnosed over 30 years ago. If you reflect on that disease state, it's one that you probably are all very familiar with. However, at that time, there were 0 treatments available. We now look at that field, and there's an explosion of treatments. Why? Because when you heard the word multiple sclerosis, an image came into your mind. It was an individual who was disabled, obviously disabled. When you think of an individual who has narcolepsy, there probably is not that same image that comes to your mind. However, the same detriment that occurs for a person who has multiple sclerosis, which is marked by socioeconomic disability and physical disability, is also present. It's an isolating, marginalizing disease that requires very specific attention and resource. Currently, what has been highlighted is that the current treatment landscape, although it's beneficial, still has tremendous inadequacies. Therefore, I am privileged to be standing up in front of you today to talk about how the market is shifting, and we are now actually addressing the needs that patients are stating is necessary. We're going to discuss that narcolepsy is a 24/7 disease. Very frequently, when people think about it, they reflect on the movie Deuce Bigalow, where these are individuals who just kind of are falling asleep in front of you and not necessarily having any type of normal interactions. This is a very inappropriate representation of what this condition looks like. As had been mentioned, sleep state instability is an innate component of this disease. There's sleep intruding during the day and wakefulness intruding during the night, therefore, there's a representation across the full 24/7, which we'll talk about in the next slide. I've already alluded to the fact that the current treatments are unsatisfactory. They all have very specific limitations, which I'm going to describe for you, many times when I'm speaking to my patients, we're discussing what are the trade-offs? What is the acceptable unsatisfactory component of the treatment options that I'm offering you? Finally, really digging into how LUMRYZ addresses these needs. As I mentioned, narcolepsy is a 24/7 disorder, when we're talking about this disorder, the most sensitive symptom, which is present in 100% of patients who have narcolepsy, is excessive daytime sleepiness. You'll find that every single drug that we currently utilize, that's the main thing they focus on. However, it fails to recognize that there are four other major pentad symptoms, including cataplexy, which is a transient episode of loss of tone. Many people think about this as them collapsing to the ground. Unfortunately, that only is present in 10%-15% of people, generalized cataplexy. The majority have partial cataplexies, which we don't think about as being so burdensome, but this is where people have difficulty holding things in their hands, their knees buckle, they trip over their own feet. These are individuals who are fearful of holding their own children after birth. They're fearful of giving birth because they're afraid of the compromise or the detriment that their child might experience. When we look at the nocturnal symptoms, more than half of this pentad is represented by night. Disrupted nocturnal sleep paralysis, this is temporary episodes where you feel frozen or stuck, and sleep-related hallucinations. These are auditory, visual, and tactile hallucinations that people will experience, and many times, those two come together. One of the challenges when you have disrupted nocturnal sleep is it introduces more opportunity for sleep-related hallucinations and sleep paralysis. You may hear that and go, "Well, that doesn't sound so horrible." I have a patient where her sleep paralysis and sleep-related hallucinations was quite impressive. She used to sleep with a sleep mask up until the night where her sleep-related hallucination was that a man had broken into her house and was coming to rape her, and she was frozen and stuck in sleep paralysis and therefore could not respond to it. You can see how that would propagate further disrupted nocturnal sleep. She no longer sleeps with a sleep mask. These are things that become addressed, in my opinion as a clinician, when I'm able to introduce an oxybate, and especially one that does not require a forced awakening. I'm removing the opportunity of these things. Other features that are not included on here, but are extraordinarily impactful in individuals who have narcolepsy, is that because this is a condition marked by REM dissociation, meaning that they're having very frequent REM sleep phenomena, is that they have recurrent, horrible nightmares, again, spilling into the sleep paralysis and sleep-related hallucinations. They also can have dream enactment behavior, REM behavior disorder, kicking, punching, fighting. The same patient I had just described to you had tremendous dream enactment behavior. So much so that she broke a window with her elbow, trying to escape, because many times these are very frightening experiences. It is really important that when we look again at the current treatment landscape, the majority are focusing on excessive daytime sleeping. That's completely neglecting the components of this disorder that are extraordinarily detrimental and burdensome. In addition, it is important to recognize when we look at the treatment landscape, there are innate limitations to some of these treatments. Whether you're looking at the traditional stimulants, the alerting agents, or the first-generation oxybates, these are conversations of trade-offs. As you can see, across all the current treatment landscape, I am trying to achieve better days while compromising their nights. For me, as a sleep doctor, that makes no sense. It's not that when we're looking at the traditional oxybates, that I'm saying that this is a bad thing. We have a lot of experience since 2002. It has been transformative therapy for patients. It was first studied in the 1970s, and so we have over 20 years clinically since 2002, but since the 70s it's been studied, of the positive impact that it has in the marketplace for these individuals. However, there are innate disadvantages. There is a forced awakening in the middle of the night, and many patients, I can say clinically, don't even want to hear about it because they say, "Doc, I don't think you understand. I have a sleep problem. I'm waking up frequently at night, and you want to give me something that puts me asleep. I'm already sleepy, and then you also want to wake me up in the middle of the night?" They don't want to hear it. I can also share with you it's not patients alone. As an educator, I speak internationally on this disorder. Very frequently, I have physicians come to me and say, "I don't even offer this in my clinic because I have to think too much around the timing and the safety, and how do they wake up? How do I figure out this dosing strategy?" You're being met with an innate limitation, where patients don't want to hear about it because of having to wake up, and physicians don't want to offer it because it's too complicated to do. Because of this, it does create some anxiety in the household. When you're looking at what is the current strategy, typically we're having our first dose, 2.5-4 hours later, it's a second dose. Then you also have to be mindful that a person shouldn't engage in anything until at least 6 hours. You can see where the math is happening for a physician. "Okay, you're going to wake up at this time, and then I'm going to do this." There also is this innate challenge of either too early or too late, both which it's not a matter of that's inconvenient or that's a challenge. It's a matter that there are innate safety concerns there. This is a CNS depressant. If I take it too early, I run the risk of overburdening that person's central nervous system with too much of a depressant. That carries a risk of respiratory compromise, coma, death. Now that's a person where I still have active drug in my system, and I have to get to work. Better yet, I have to drive my kids to school. You don't want to be on the road with those people. There was a very well-designed study called a discrete choice experiment, asking physicians, "What are the top attributes based on the three different formulations of oxybate?" If you're not familiar with this kind of study, it really is evaluating if you have to make these trade-offs, which ones are the highest priority? The highest priority for physicians is that it's a once-nightly regimen. Why? Not for convenience, and not even because I don't want to do math, but because we know it's going to improve adherence. When I have a greater consistency of night-to-night management, I have a better consistency of what the daytime experience looks like. It is very important to understand the complexities of this condition. I've already gone over with you the innate components and symptomatology associated with what narcolepsy is. However, what has been wonderful in the last few years is a tremendous amount of research that is really trying to understand what does this journey look like? What does the patient medical burden look like? In 2017, there was a study done looking at retrospective claims data that gave us our initial insights in recognizing that there's a suggestion of things like maybe there's increased risk for cardiovascular disease, maybe there's an increased risk for obesity, maybe there's an increased risk for other sleep disorders. However, claims data are limited because you don't know the full details of those individuals. It's based on what the codings were put in. Just recently, there was this presentation of data, which is actually looking at the Mayo Clinic's electronic health records. The Mayo Clinic has one of the largest databases and one of the largest followings of people with narcolepsy. They were able to look from 2000 to 2020 to understand what are the other medical complexities that are there? The first callout is that the cardiovascular conditions were not replicated in this evaluation. It's an important thing for us to think about, it's correlative, we don't really have a clear causation or replication of it in clinical data. Other things that we do see is comorbid sleep disorders are there. It's important to recognize insomnia is present there. Medications that we're using currently are propagating that. restless legs syndrome, medications we're using are propagating that, obstructive sleep apnea as well. When we look at these other conditions, it's important to understand this because when we're talking about trade-offs and what is it that I wanna treat and what I don't wanna provoke, I have to think through all of these different capacities. Is there an elephant in the room? Sodium is a hot topic. It's a hot topic from the American Heart Association. It's a hot topic in many family practice and primary care, and now it's a hot topic in sleep. contain identical amounts of sodium. It's an essential nutrient. Very frequently, we talk about it in regards to a mitigator for cardiovascular disease. There's very important components that you need to understand when you're talking about the oxybate market and when you're talking about individuals with narcolepsy. Number 1, oxybate, gamma-hydroxybutyrate, in order for it to be transported from your gut and into your brain, it is dependent on an SMCT1 transporter. It is a sodium-dependent transporter. Sodium is not all that bad. The second thing is that when we're talking about all the medical complexity that comes along with narcolepsy, the reality is we don't fully understand it because of the fact that we're still understanding the pathophysiology of where does orexin play a role. What I can tell you is the innate deficiency of orexin, which is a neurotransmitter that is lost in individuals with narcolepsy type 1 and likely dysfunctional narcolepsy type 2. That itself has underpinnings for a whole myriad of different disease states. Although we like to consider the idea of that, if I apply general recommendations, lower sodium, the American Heart Association says everyone in the United States should have at least 1,000 milligrams less sodium. That may not be relevant or appropriate for patients with narcolepsy. I'll further that example by stating, because this is a neurologic disorder, these individuals are also very likely to have dysautonomia. My autonomic nervous system doesn't work. A primary symptom of that tends to be POTS, postural orthostatic tachycardia syndrome. The keystone treatment for POTS is 3-4 grams of sodium. You tell me in what world it makes sense for me to remove sodium, to give it to them in a different capacity. Now, with that stated, I'm a big believer of the fact that we need to think through everything that passes our patients' lips. These are patients who have high risk for obesity. They have high risk for a variety of other things. If we're gonna talk about sodium, we should also talk about artificial sweeteners, because that's our trade-off. Our current mixed salts, the replacement in it is sucralose. When we're thinking, if we wanna have a conversation about cardiovascular, I'll engage in a cardiovascular conversation. The reality is, we need to be mindful of what are the risk factors for cardiovascular disease. The World Health Organization, as of May 2023, has stated artificial sweeteners are an independent risk factor for cardiovascular disease. How much is too much? I don't know. I know I've stopped drinking diet soda, and I'm watching how much gum I chew. The reality is that we recognize this, and artificial sweeteners have been linked to a variety of different things. Paradoxical, it's associated with increased fasting blood sugars, insulin resistance. I try not to have sugar, but it's making it more likely for me to have diabetes. It also is associated with increased likelihood for having worsened inflammation, again, independent for cardiovascular disease. Finally, it also can influence your gut microbiome. I'll tell you, as a neurologist, when this concept of the brain-gut axis was first introduced to me, I said, "There's no way in hell that my stomach is telling my brain what to do." I'll tell you, I went through a complete 180 recently, and it's quite impressive of the data that does support this. In addition to that, there's very unique data that comes from my colleague in France, Yves Dauvilliers, that demonstrates that patients with narcolepsy actually have unique changes in the microbiome. Now we're risking the potential of aggravating that, and that could have its own consequences. As mentioned, obesity is much more common. So when you're talking about which risk factor do I want to treat, I'll tell you which one I do want to treat. I do want to treat obesity. I can tell you when I see both kids and adults, I can tell the patient when their onset of disease is just by looking at their growth chart. Most typically, I can say, "You're a 25th percentile, you're a 50th percentile, and this year you went to 90th percentile. That's when you developed your symptoms of narcolepsy." We don't fully understand it. A lot of people think it's just the sleepiness. One of the things that I see as a value proposition in treatment of my patients with narcolepsy is that although weight loss is considered an adverse event, for many of them, this is a welcomed adverse event to experience. It is important to realize that in the studies, we see that 1 in 5 patients experience a greater than 5% weight loss from baseline. That's huge. That is a risk-mitigating factor for cardiovascular disease, diabetes, and all-cause mortality. In summary, we're evolving the status quo in the management of narcolepsy. We no longer are requiring a forced awakening in the night. There is that obviously is a benefit. There's no long-term tolerance that is associated with it. There is now no longer the need for this 90-minute window of when you are gonna take it. There's not also the super low intake that you have to be concerned about. I think the main take-home point that you can hear from me is that this is a medication that I am offering to my patients. It's a medication that even for my patients who I haven't seen in clinic recently, are reaching out to me to ask if they're candidates for. These are both patients who are our current oxybate users and those who I have offered oxybate in the past, and they have told me, "I'm not waking up for a second dose." I do truly believe that there is a broadening of the market, not only in my clinic, but I can also share that when I was at the National Sleep Conference, speaking with a lot of different people, 'cause I do a lot of education, people have said, "I feel more comfortable thinking about offering this to my patients now because I don't have to do all those calculations." Thank you so much, Dr. Morse. I learn something new every time you present, and I'm sure the audience very much appreciates your perspective. I'm delighted to introduce our second key opinion, excuse me, second key opinion leader for today, Dr. Thomas Stern. Dr. Stern is a pulmonologist in private practice in Charlotte, North Carolina. Dr. Stern completed his fellowship in pulmonary and critical care medicine at Case Western Reserve University. He is board certified in five different areas of medicine. Like Dr. Morse, Dr. Stern is extensively involved in clinical research, including studies in narcolepsy for NLS, Takeda, Jazz, and most relevant for today's discussion, as a principal investigator in our open-label study, RESTORE. With that, I'm delighted to welcome Dr. Stern to the stage. Before I get started, I just want to manage expectations. Dr. Morse is a tough act to follow. I'm not a academic neurologist. I'm a simple country doctor from North Carolina who happens to treat some pulmonary and sleep disorders. I've also had the good fortune of working with Avadel since 2019. While the general market is just getting to learn LUMRYZ, we've had the good fortune of having lots of patients on it for 4 years. I'm going to share some of those insights that we've had. First thing we're going to cover is the optimization of the pharmacokinetic profile. The reason LUMRYZ exists, which is optimization of the drug. We'll talk about the phase 3 data, which was positive all around, then finally, talk about my experience in clinic with LUMRYZ over 4 years. These curves are classic curves that you'll see whenever you're comparing an extended-release version of a drug to an immediate release version of the drug. In my time in medicine, I've seen these curves, and it applies to blood pressure medicines, it applies to COPD medicines, and now, thankfully, applies to oxybates. In the blue is the pharmacokinetic profile of LUMRYZ. In the orange is the old-fashioned oxybates. What you see when you have an instant release medicines is lots of peaks and troughs, right? When you have peaks, you get side effects from the medication. When you have troughs, you get symptoms of the disease. Again, it doesn't matter what extended release versus instant release, type of drug you're talking about, this is a very classic curve. The other thing that I want you to note about this curve, or the LUMRYZ curve, is that it very much reflects the typical curve of a human sleep drive. Everyone in here has sleep drive. It's likely that you're going to fall asleep and stay asleep, and your sleep drive builds as the longer you're awake. The longer you're awake, the more likely you are to fall asleep and stay asleep. The most sleepy time of the day is when you first fall asleep, and as you stay asleep, your sleep drive decreases. That's exactly what you see in people that take LUMRYZ. They're most likely to be asleep early in the night, and the longer they're asleep, the less they're likely to stay asleep. This mimics a normal human sleep curve. Oops, did I do something wrong? Okay. Not as much of a peak, less troughs, is a benefit that you get to see in LUMRYZ. Another big step that a lot of you probably won't appreciate, but I certainly do, and patients do as well, is the packaging. Old-fashioned oxybates, they give you 90 grams in a bottle. You got to measure it out, mix it, and because humans are doing this, it causes error. Every month, I get a call from the REMS pharmacy, and they're like, "Oh, you know, Mr. and Mrs. So-and-so, they're going to run out of their oxybates a day or 2 early. Is it okay if we refill early?" Because of the, you know, the controlled substance, they have to get permission from me. Literally happens every month. So, you know, a few more calls that I won't have to deal with it will be great because now it's just a very consistent dosing. They have a package, they pour it in a cup. It's much harder to miss a dose. There's also, you know, some people that you can unintentionally overdose with Xyrem if you're not paying attention. Anytime you do something routinely, you don't pay as much of attention. That risk is definitely decreased when you use LUMRYZ. This highlights the results from the phase 3 study, and it's broken down into 3, it's really the top is the main result. That's the total population of people enrolled in the study. There's what we call subgroup analysis. They break it down to narcolepsy type 1 and narcolepsy type 2. This trial is unique in that a lot of times the NT1 versus NT2 is not differentiated, or they just include NT1. LUMRYZ works in any type of narcolepsy, NT1, NT2, and, you know, they have different measures. The NWT as a pulmonologist, I like physiologic measures. I like to see physiologic data. If you look at MWT, sleep stage shifts, and nocturnal arousals, those are all seen on the EEG. It's right there in front of you. It's very objective. We also have subjective data from clinicians, the CGI, that's how we feel like it's working, and also patients in sleep quality, refreshing nature of sleep, and Epworth Sleepiness Score. You know you have a good drug when you see improvement in physiologic measures and also subjective measures. In the total population, there was significant improvement on all measures. When you break it down into NT1, NT2, you know, NT1, the more severely symptomatic patients, again, had clinical significance in all measures. NT2, there were, you know, again, consistently positive. There were a few that weren't statistically significant, even though they showed improvement. That's because the study wasn't powered to exclusively look at symptoms in NT2. When you have fewer symptoms, you need more people, right? We didn't have enough people, and I think, you know, we would if we had the right power to the study. The one thing that I want everyone in this room to understand is narcolepsy is not a disease just of daytime sleepiness. Narcolepsy is complete dysregulation of your sleep-wake cycle. What we notice about people that have narcolepsy, 'cause we see them during the day, is they're excessively sleepy. What we don't appreciate is because we're not with them at night, is they don't sleep at night either. It's very rare that we optimally manage someone with just one drug. The current conditions of the healthcare system, you know, make it difficult to get the newer medication. In my clinic, the first time someone's diagnosed, and I see them, everyone gets started on a stimulant. Not everyone can stay on a stimulant because the side effects, but they all get started. Because they're cheap, I can get them immediately, they can go pick it up at the pharmacy. It's going to make them feel better. I gain credibility when I make someone feel better. You know, then for most insurers, you have to show they're not optimally controlled on stimulants to even qualify them for an oxybate. That will take weeks of fighting and then they have to get it mailed because of the controlled or the REMS program. Most people with narcolepsy end up on multiple medications because one doesn't do the job. The interesting thing about the LUMRYZ study is that it showed improvement even in people when they were taking stimulants. It's not an issue. Stimulants, you know, are not going to prevent the use of LUMRYZ. People on stimulants are going to benefit from the addition of LUMRYZ. It's something that is not always appreciated. The open-label study started back in March of 2020. Current condition or conditions of the world at that time required an extension. Good news is no safety signals. you know, there's not any concern about that. We've got lots of safety data now over 20 years of using oxybates, and often the fear is not validated by the reality. In the open label study, there were three types of participants. There were people that rolled over from the phase 3 study. There were people that were switching from that had been on the old-fashioned oxybates and were going to switch to LUMRYZ, and then people that had never been on oxybates before. After they took the once a night dosing for a while, the switch patients filled out a questionnaire. What we learned is that prior to switching to the once a night, two-thirds of them had missed a dose in the previous couple of months. When those people miss a dose, they're symptomatic. 80% of those people complain of symptoms. Twice a night dosing causes problems. You know, what is either as bad or maybe worse is that some of them take it late, so again, it's still in their system when they wake up, not optimal either. You know, you don't want a medication to cause anxiety, but when people worry about waking up to take their second dose, they can feel good the next day. It does. 30% of people reported anxiety, and a quarter of the people needed someone else in the house to help them get up and take the second dose. It's not just disruptive to the patient, it's disruptive to the family. You know, after they had experience with both, they said, "Which would you prefer?" 94% said once a night dosing. I don't think this is an overestimation, and if you look historically at the other, you know, indications for long versus instant release medications, everybody prefers the less dosing in not just narcolepsy, but lots of disease states. As of earlier this month, I still had 9 patients in the extension study. Anywhere from 16-31 months. We have young, we have senior citizens, men, women, and Type 1 and Type 2 narcolepsy. A good variation of backgrounds. I'm gonna tell you about one of my patients. I've known this kid since, well, he's a kid. He was a kid when I met him. He was 13 years old. We diagnosed him with narcolepsy. Started him on some stimulants, also was using some an antidepressant for cataplexy. Not optimally controlled. We started him on Xyrem. He is in a family with a single mom. Mom had to get up to help him take the second dose. You know, when people wake up for the second dose, they do things like go to the bathroom and eat, and especially when you're a teenage kid, even though they know they're supposed to stay in bed, they don't always listen to their doctor. His mom would find him in compromising situations. She's found him on the toilet. She found him in the bathtub, those are not places, as a teenage boy, you want your mom to find you. Switched to LUMRYZ in 2020. He's still on it and has done so well. His job is actually he gets up to make the donuts at Dunkin' Donuts. We love this kid because every time he comes in, we get a dozen. It would be impossible for him to do that, if he wasn't able to use an oxybate successfully. Switching to the other spectrum, our senior citizen that's on the trial. Again, narcolepsy for a long time, always on stimulants, on antidepressant, not optimally controlled. Started her on, the old-fashioned oxybates. You know, again, when you wake up to take the second dose, you don't stay in bed. You know, she would always go to the bathroom. She'd wake up to go to the bathroom. People don't wake up to pee. They pee because they're awake. She would get up, she'd go to the bathroom and would not uncommonly fall. One time she fell, she hit her head, ended up in the emergency room. But switched her to LUMRYZ a couple of years ago, and is much happier with her current treatment. You know, in summary, like I said, the PK profile, this is not another oxybate. This is a different oxybate. This is a improved oxybate that certainly has a better profile than what's available. The dosing, the ability to dose with fixed doses obviously is improvement. You know, 9 out of 10 over 9 out of 10 are gonna improve or choose once a night if they can. Like I said, we've had a lot of experience that confirms this. Thank you very much. Thank you so much. Thank you, much. Thank you, Dr. Stern. That was absolutely wonderful. As Greg mentioned in the beginning, we have a third special guest, and Katie, who is a person with narcolepsy, really represents the center of all of our efforts at Avadel, where we're constantly thinking about the person who is living with this chronic and debilitating disorder, and how we can help them along that journey. I've had the pleasure of knowing Katie for several years now, and she is kindly gonna share some of her experience, both on the path to a diagnosis of narcolepsy, as well as her treatment experience, and probably what you all want to hear most about, her experience with LUMRYZ specifically. With that, Katie, welcome. Could we put the slide back up? Oh, okay. Never mind. Sorry, sorry. Hi, Katie. I'll say what the slide says, which is, "How LUMRYZ transformed my life," because I think that sets the stage for what Katie and I are gonna discuss. We talk about PWN, people with narcolepsy, because we want to think of this community as people first, patients second. With that, I'd love to hear a little bit about your life, Katie, before you started experiencing any symptoms of narcolepsy. Yeah. I was in my senior year of high school, and I was pretty unstoppable at that point. I, at that time, played three different instruments. I was an interpreter for our chorale, our traveling chorale. I was competitive robotics, and I also had a job on top of all of that, so... Oh, my gosh. Academically, you were doing really well and all of these activities, just balancing a ton of stuff. Yep. What started to change when you were in high school? It started pretty subtly. I needed naps, and it would happen maybe 30 minutes in between. It started... Thank you. I can open it for you. It started to bleed more and more into those activities that I cared so much about. If I just skip a class, then I can go to robotics later. Well, if I skip robotics, maybe they won't notice. It started becoming more and more mandatory. I started missing more and more of the things that I was loving about life. That must have been so devastating to have all of these hobbies and interests, and to find yourself so sleepy and so tired that you weren't able to fully participate.... We hear so often that it's 8 to 15 years on average when people start to experience their symptoms before they receive that accurate diagnosis. What was the pathway for you to a diagnosis? Yeah. I'm actually extremely lucky in the sense that during one of those naps one day, I looked up on the TV, and there was an ad that said, "Excessive daytime sleepiness." It was a light bulb moment, and I was like: "I have excessive daytime sleepiness." I run downstairs. I'm like, "Mom, Dad, you will not believe what I just saw." That's when my dad revealed that he also has narcolepsy and just hadn't shared it before. Oh, my gosh! yeah. Wow! It was a light bulb moment because you finally had a name to what you were experiencing, and you found out that your dad had been diagnosed but had not shared this with you previously. Wow. At least you were able to put a name to your symptoms. What happened next? Yeah. We, both me and my dad, ended up getting into a sleep specialist pretty quickly, and as I was explaining to my sleep specialist at that time what was happening, he's like: "Yeah, that does sound like narcolepsy, and the sleep study not long after proved it. Wow. You were one of the fortunate ones, as you said, because you were able to receive that diagnosis fairly early. We heard a lot about treatments from our two physicians who spoke earlier. What was your experience with treatment? Yeah, Dr. Stern explained my experience pretty spot on. Started with stimulants and went through multiple different treatments that would do nothing or would make me sick beyond belief or would keep me up at night, until eventually I was asked to consider going on oxybate therapy. Wow! What did that conversation look like when they explained that you would need to take 1 dose at bedtime and then wake up 2.5-4 hours later? It didn't make a whole lot of sense to me. I was willing to try after being through so many different treatments. I had heard that it could be life-changing at that point. I was like, "Okay, I don't think it makes sense to wake up, but I'll do it. Sure. That makes sense. You were probably desperate to find something that would work for you. Absolutely. How were those first few nights, weeks on, Xyrem? Incredible. I'll never forget waking up and just feeling alert. It's bright outside, and I wanna go straight downstairs. I didn't need 30 minutes, 45 minutes to convince myself to get up. I was ready to go. Wow, that sounds incredible. You were then taking Xyrem for a longer period of time, and I think you were still living at home at that time. Tell me some more about your treatment experience. Yeah. As I was getting closer to my therapeutic dose, it was becoming more and more difficult to wake up. The alarm that just comes on my phone wasn't loud enough, so I tried a different app with louder alarms, and that did nothing. For me, at least. I learned a little bit later on that it was actually waking up my sister, who I shared a wall with. It wasn't the alarm waking me up, it was my sister hearing the alarm and then coming into my room to wake me up. Wow, that's a good sister to do that for you. Yeah. You moved out. You were getting older, and it was time to be in your own place. Without having your sister to wake you up to take that second dose, what happened then? It would lead to me just waking up randomly, very unpredictable, but almost always past that window of when I should have taken it. At that point, it's the math Dr. Morse was talking about, except it's 4 or 5 A.M. Mm-hmm. I'm half asleep doing that math. Mm-hmm. -of if I take my second dose, will I be able to safely drive to school or get to school? Should I just skip it and risk feeling awful for the rest of the day? That's not a good choice for anyone to make, no matter what your age is, but especially when you're taking a medication chronically. What led you to being able to try LUMRYZ in our clinical study? Yeah. I was in a psychology class not long after being diagnosed, and there's, like, a whole section about how clinical trials are extremely important in the medical field, and I was like: "Well, I have narcolepsy now. Maybe there's something I can participate in. Yeah. I actually came across a different trial that I wasn't eligible for, but it meant that I was put on the list to be, like, 1 of the first to try LUMRYZ in the trial. I was ecstatic, waiting for that to start. That's fantastic. For the audience, Katie has been taking LUMRYZ since September of 2020. She was enrolled as the first patient at the particular site that you were at. I would love... I never get tired of hearing your experience with LUMRYZ. Tell us a little bit about how that has been going since that time. Yeah. I wholeheartedly believe that LUMRYZ has changed, in some way, every aspect of my life. On the day-to-day basis, I have a much more consistent schedule. I don't have to play with my wake-up time anymore. I can guarantee every morning that I'm gonna wake up at the same time, because I'm not playing a game of chance with my second dose. Which, you know, leads to small things like being able to have breakfast. That's sometimes the only time in the day I get to hang out with my family, or just to see the sunrise. It's pretty remarkable. For example, now that I'm here in New York, as a person who loves theater more than anything, it's pretty remarkable that I got to see 2 shows. Mm-hmm. In the past, I remember falling asleep during the one chance I got to see my favorite show ever, and it was devastating. Now I'm at a point where I can watch these shows, and not just watch these shows, I can go to them after a full day. Mm-hmm. I don't have to pick and choose what to do when I have those good times. Mm-hmm. Now it's all kind of good times. I can go to dinner and a show. I can see my family and go hang out with friends after. I can do it all. That's incredible. You're not making sacrifices. You're not having to make those trade-offs because you're not able to fully participate. Mm-hmm. This has been a liberating experience for you. I'm so glad to hear that. We had two of the country's top physicians who spoke a little bit about how they approach the care of narcolepsy. If you had the opportunity to speak with other physicians who are treating people with narcolepsy, now that there are three different oxybates that they could choose from and discuss with their patients, what would you want them to consider or maybe ask the patients that they're seeing? I would ask that they start asking more questions. As I said, I struggled greatly taking that second dose. I never thought to bring it up to my physician because I felt like it was a personal fault. I felt like it was something I was doing wrong. I knew, wow, there's so many people on this life-changing medication that I'm on. Mm-hmm. Well, it felt obvious to me that they could all wake up for their second dose, so I never brought it up, and I just kinda struggled with it until I got on LUMRYZ. You know, now that there's options, I would encourage physicians to ask those questions that people like me might be too afraid to ask. That is such good advice. I have to say, Katie, I've known you for a couple of years. I've heard your story many times. I never, ever get tired of it because it's so inspiring to us. It was not until the last couple of days that I knew that you never brought up to your physician the fact that you were missing the second dose because you felt it was a failure on your part. Obviously, it was not, but it underscores that culture of silence, where because the medication, the moiety, can be so transformational, people in the past have been willing to have not always optimal therapy, and your experience with LUMRYZ represents what's possible for the future. Thank you so much, Katie, for sharing your experience. Okay, we'll take a little break from the presentation, maybe open it up to Q&A with Dr. Stern and Dr. Morse and Jen. Hi, can you hear me? It's Frank Brisebois with Oppenheimer. Thanks for the presentation. A lot of interesting things here that were said. Thank you, Katie, for sharing. Maybe a first question here. Just wondering to the clinicians, the size of your narcolepsy practice and maybe the% of patients that you have that are hypertensive. With some of the very interesting comments today, I was wondering, if you do have a hypertensive patient, would you ever still consider LUMRYZ as an option? That's the first question. Dr. Morse, go. Sure. I would say that I have one of the largest practices of patients with central disorders of hypersomnolence in Pennsylvania. I do have patients who fly from all over the country to see me. Not a small practice. In regards to hypertension, my practice does span all ages, so my youngest patient is 5, my oldest is 75. In a pediatric population, it's less common. We can see incident development of hypertension with some of the stimulant therapy. A close colleague of mine, Kiran Maski, at Harvard, actually has some of that data that has demonstrated also, she's gonna be working on publishing this soon, of the transition from stimulants to sodium oxybate and demonstrating a decrease in blood pressure. In terms of the patients who have preexisting hypertension, I am not going to withhold a treatment that's gonna be transformational to their day because of the concern for sodium. I'd much rather see them being like Katie, being able to go and exercise, being able to be mindful. I think it also is very important to recognize that there is a change in behavior. If I give you something with a high sodium, you're unlikely to choose other foods that are also high sodium. Your body has a normal homeostasis that is going to help you self-regulate that. Dr. Stern? If you include all disorders of hypersomnolence, including, you know, idiopathic hypersomnia, we have several hundred patients in my clinic. It's because those patients are sticky. You know, this is a lifelong disorder. They don't leave. They come back every three months, six months, whatever. You know, I've been doing it for 20 years, and I've been using oxybates for a long time, and I can tell you, I've literally never encountered hypertension from an oxybate, ever. The stimulants, you know, way more cardiovascular effect and certain stimulants like Adderall, are, you know, we've had to adjust because of usually more tachycardia than high blood pressure, although they go hand in hand. That's been an issue, you know, using the stimulants and the cardiovascular toxicity literally never been a problem with oxybates. Okay. Thank you. I think it's working. As the, you know, launch just started, I was just wondering, you know, Xyrem, Xywav have been around for so long here. Well, Xywav, not as long, but oxybates have been around for a very long time at the SLEEP Annual Meeting. Can you just talk about, I know oftentimes it's more KOLs, but this is a concentrated prescriber base, so can you just talk about the awareness amongst physicians? Clearly, what's extremely important here is the awareness with the patients, and is there a tight network of patients? Just trying to get a feel. Thank you. Yeah. Sure. As Jen has shared, I'm a medical advisor for pretty much all of the organizations. The main ones being Wake Up Narcolepsy, Project Sleep, Hypersomnia Foundation. If you wanna talk about a tight network, they are the prototype, they're the epitome of a tight network. They are probably also, which is common in rare disease, incredibly well informed. You'll find most physicians will say, tell their patients, "Don't use Google as your doctor," right? I encourage that from my patients. Why? Because they actually teach me more than I can teach them, when there are new drugs available, they know it many times before even their doctors. Now, when you're asking about how informed is the physician community or the medical community, everyone's waiting for the next new treatment. What else is there available? As I had alluded to earlier, with the twice-nightly, there is a smaller market of prescribers in comparison to the number of possible prescribers. There does very much appear, based on the research that has been done, but also I can say again, I'm an educator, I speak internationally, that this is a question I get very commonly about the once nightly and how they plan to utilize it and enroll in the REMS program. I do think that you're going to see not just a marginal increase, I think it's going to be a very sizable increase. You know, I'd echo, the narcolepsy patients are very well informed and often come with the questions of, you know, clinical trials, and is it available yet? I haven't, you know, got this data specifically from my clinic, but there's a large population that's waiting for the once night to come out. I use this analogy and, you know, 'cause, you know, most of us cannot relate to being so tired, you literally fall asleep in very awkward situations. You know, I've stayed up a few times, 36 hours when I was a resident. I don't think even that is what these people deal with on a daily basis. All of us can relate to being nauseous, right? We've all been nauseous, we've all had GI illnesses. You know, if I came to you and said, "Hey, I've got a great treatment for nausea. All you have to do is eat this greasy pork sandwich." You know, you'd look at me and be like: You're crazy, you know? You know, if it made you feel better, you'd force yourself to do it, right? The same thing is true with narcolepsy patients. You know, when I tell them, you know, it's like Emery said, "Oh, you know, you just have to wake up in the middle of the night and take a dose." They will honestly act like, "Are you serious? Yeah. There is a big portion of patients that are very aware of what's going on with this drug and are just waiting. Yeah. You know, the other thing that most people don't appreciate is how difficult it is to get oxybates and has been for 20 years. You know, you don't just write a prescription, they go down to their corner store. You know, it's, you know, you have to get them enrolled in the REMS program. You have to fight with insurance, and so these have all been barriers. And it's gonna be no different from LUMRYZ, but, you know, it's going to be easier. You know, Greg and his team are setting up multiple pharmacies that, you know, you can interact with. So, that's gonna make things easier than having to deal with one, you know, pharmacy. Yeah. If I can just add to that, I already have six patients in the process. Four of them are already approved by insurance. In regards to the challenge, it is a matter of also, how you're able to kind of navigate that process. One other piece that I, that I think is really important, is that you don't have to take our word for what the buzz is. Go to social media, you'll see it. You'll also see comments like what Katie had described. They're not describing these issues to their physicians, but they're posting it all over social media, of the missed doses and the consequences associated with it and the constant choices. I do think that those are really important points to consider. Hi, this is Ami Fadia from Needham. Thanks for taking my questions. I've got two. Firstly. I believe Greg mentioned earlier in the presentation that market research has indicated that the total number of patients taking an oxybate would expand with the availability of LUMRYZ. I wanted feedback from both the physicians. You know, where do you see that growth coming from? Is it predominantly patients who had tried an oxybate in the past, and now will come back and try this? Also, if you could talk about what are the common reasons for which they would have discontinued an oxybate in the past. I've got a second one later. Sure. I think that it's important to recognize several things about the disease state, right? It's estimated that about 200,000 people in the United States have narcolepsy, and that's with the accompanying estimation that 50% of people with narcolepsy are walking around undiagnosed. Okay? The number is likely underestimated. I think that with more drugs coming to market, it's going to increase awareness of the disease state. It's going to increase the number of people being diagnosed, and if you look at studies that have assessed claims data, it is showing that same trajectory. There's increasing numbers of individuals being diagnosed. It's not that the diagnosis is happening more. It's just that it's increasing. The second piece is the market's going to come from two places. You're going to have people who have tried and discontinued, and then you're going to have people who are completely naive. The naive patients are going to be those who refused in the past and then those who are new diagnoses, right? You have a growing population, you have a growing number of people who are going to consider it, and then you're going to have people who failed in the past. Reasons people failed in the past, I would say that my experience in my clinic, and then getting people as second opinions, is that when I get them as second opinions, the titration was not appropriate. The physician was not familiar with the drug enough, where they either titrated them too quickly or didn't, or didn't utilize things like asymmetric dosing, et cetera, to allow the patient to actually tolerate the drug. Okay? There also were many patients who failed it because they couldn't get up for the second dose, therefore, they're only taking one dose. They're not getting really any benefit, and they're only experiencing side effects, kind of the greasy pork sandwich example. In my practice, I would say that it most commonly is that people will discontinue because of the missing of the doses. They just can't, they can't make it fit their life. The conversation I have with all my patients is I want to create a regimen that fits your life, not a life that fits your regimen. You need me up top? You know, I think there's three groups. The ones that have never tried oxybates are going to try them. The ones that have tried and failed will probably try again, the ones that are using them successfully are going to switch to once a night. I mean, there's going to be three places that patients come from. Thanks. My second question is about patients who would switch, and sounds like there's a lot of pent-up demand and, you know, broad-based awareness amongst physicians and patients about the availability of LUMRYZ. What is going to trigger that switch? Is it that patients are calling your offices? They are already doing that. for that? They are already doing that. They were doing that even before the drug was actually clinically available. I think our experience might be a little bit more unique because we're research sites for it, and so patients who weren't eligible for the trial definitely are reaching out. Yeah, they're already doing that. I think it's coming from a combination of things. The other thing is, you know, the, again, these are sticky patients. If they're on stimulants, they have to see them every 3 or 6 months, all of them. You know, you get multiple touches a year, and one of the things I always ask is, "Hey, is there anything new? Mm-hmm. I would say, "Yes, you know, there's something new." Literally, I'll have this conversation with all my, unfortunately, narcolepsy now, hopefully, idiopathic hypersomnia in the near future, you know, at least once this year. They're just a very... Like I said, we see them multiple times a year. Go ahead. Hi, thanks. This is Oren Livnat from H.C. Wainwright. Could you tell us where sodium oxybate is in your armamentarium, which line of therapy now, and why? Is it, if it's not early line, is it primarily just for access issues, insurance headaches? If there were no insurance barriers, would oxybate be theoretically a first-line therapy that you would offer to any new patient that comes in, and does that change meaningfully with twice versus once nightly? There's so many ways I want to answer that question. Number one, not just for me, the 2021 guidelines for central disorders of hypersomnia was clearly positioned as a strong recommendation for use of sodium oxybates. When you look at the approach to treatment, first-line therapy is alerting agents or sodium oxybate, and second or third line is your traditional stimulants, methylphenidate and amphetamines being third line. If you look at the European guidelines, you'll see the same positioning. Especially if an individual has disturbed nocturnal sleep, it's really your only option, right? That's first and foremost. In terms of when you look at all the other options that are available, most of them have tolerance associated with it. Although there has not been any systematic evaluation of tolerance in prescribed oxybates, what I can tell you is based on my international collaboration with other providers who have many, many, many more years of experience than I do, we don't see tolerance clinically. The third piece is that there was just a publication published earlier this year, which I think is building on historical evidence in the literature that oxybate has more than just the clinical value. What I mean by that is, if you look back several years, like back actually in the early 2000s, there were initially data looking at animal models who suffered hypoxic ischemic encephalopathy and applied oxybate, sodium oxybate to those. And what they had identified was that not only that there were obviously changes clinically, but that there actually was a neuroregenerative opportunity there. The reason I bring that up is because most recently, there was a publication that was done. In 2018, a research group had looked at the use of opiates in animals models, and had demonstrated an increase in the number of orexin hypocretin neurons, okay? They were smaller in size. The same group looked at sodium oxybate in animals models, and what they had identified was it actually increased the size of orexin hypocretin neurons. When I see that as a researcher, one of the things that I wonder about is: Is there a salvaging of the phenotype by utilization of sodium oxybate, and do you actually do a lifelong change in the trajectory of these patients? What I mean is that if I find someone like Katie, who we get her at early onset, and I expose her to oxybate, do I change her life? Not only did I transform her life, do I change her life? Because these patients develop this accumulating disease over time. The bigger question to ask is, do you actually mitigate some of those other development of other disease? That's I think that's the big wild card that we have right now. I think that there's a lot of good science that demonstrates that this drug has benefit beyond even what Avadel is able to advertise on. You know, in an ideal world, I would introduce oxybates early, and stimulants would be last. You know, I prefer to use drugs that have been developed specifically for the disease, and so, you know, the histamine antagonist, you know, hopefully one day we'll have orexin agonist. You know, that are really addressing the pathophysiology of narcolepsy. I would have almost everybody on oxybate if, if I could give them a prescription, they go to the store and pick it up. That's not reality. You know, like I said, in order to get the oxybate, they have to fail stimulants first. Mm-hmm. It's not ideal, but it's the reality of the healthcare system we're in. Hopefully, you know, adding LUMRYZ to the armamentarium will make it easier to get oxybates. Maybe one more question, if we can. Quick. Courtney. That gentleman has been having his hand up for a long time. Which one? Him right there. Matt? Go ahead, Matt. Yeah. Oh, sorry. We'll get to you. There's one at the table. Yes. Sorry. Hi, good morning. Thanks for taking the question. Just I want to see the... You know, obviously, it's early on in the launch of the product, but your experience with, patient access, and specifically, how you help the patients, and how much time it takes you to navigate, whether it's insurance reimbursement, them, you know, getting access, using, I guess, the programs that Avadel has put in place? It's so early. I mean, it's been less than 3 weeks or about 3 weeks that we've been able to try. It's hard to speak specifically about this experience. You know, so far so good. You know, but it's learning to play the game, whether it's this or, you know, there's, you're going through the prior authorization and fighting with insurance. It's a game you learn to play. You get your canned letters, you get your canned responses, you fill out how to correctly fill out the form, which is different for each insurance company. You know, that's across the board for a lot of commercial medications. We'll figure it out. Like I said, it's really too early 'cause we literally are just enrolling our first patients. As I mentioned, I have 6 patients who we already have enrolled in the REMS program, and 4 of them who already have insurance approval, and that is including one patient who's 16 years old. Just like any program, REMS programs are not unique to oxybate as a neurologist. There are other drugs that I use that have REMS program. It is a matter of just having a process in place in your office to be able. Irrespective of what the drug company has, there has to be a process in the office. What I would say that Avadel has done, and I think is intelligent, is that they talk to me and my office staff to understand how to duplicate our success, and they listen. Even when I may give hard feedback, they respond, and they make changes that are meaningful and make it easier for the patient and for the provider. I also think it's important for all of you to hear that although we, as physicians, may sound like we're being cynical about, like, the process, the reality also is a very important process for the safety of our patients and the safety of my practice. REMS programs, historically, in the oxybate world and specifically in the past when... and currently, I still use medications from Jazz. Those programs are quite useful for our patients. There's a lot of resources built in there. Although we kind of will joke about, like, oh, it's this big burden, it actually, once the process is in place, it's not overly burdensome. I think that that's going to just continue to get more streamlined. Yeah, Matt, I think we'll cover a little bit about that in the second half and have a chance to, you know, chat a little bit about our views of what it's gonna look like early and what it has looked like early at this point. I know we're a little bit over on the Q&A. I think we're gonna pause now. We'll have a chance to come back to you, John, don't worry. We'll pause now so we can keep going and try to keep reasonably on schedule. Dr. Stern, Dr. Morse, Katie, thank you so much. Appreciate it. Okay, we're gonna spend the next part of the session really digging deeper into our plan, how we view the opportunity, the buildup that we referenced earlier, and then introduce some early launch metrics from that standpoint. I'm gonna turn it over to Richard. Richard? All right. Thanks, Greg. I'm back. All right, here we go. I mean, that's a hard act to follow up after Dr. Morse, Dr. Stern, and Katie, but we're gonna get into a little more detail about what we're doing, and I think maybe in the next section, some of the early indicators to support the first few weeks of LUMRYZ's launch. Let's talk about a little bit about the current marketplace. We're gonna talk about the core elements, the decisions that we made going into this launch. We've talked about three patient segments previously, those who are on currently on oxybates, discontinued patients, and naive patients, as you heard from Dr. Morse and Dr. Stern, and talk to you about some of the deeper insights that we have in each of those segments. All right, let's start with where the marketplace is today. first-generation oxybates for narcolepsy, the market has, in essence, plateaued at about $1.8 billion in sales, and at any given time, around 16,000 patients on therapy. This is over the last five years of data that we have. You know, very notably, even with the introduction of the mixed salt version, it didn't grow the overall oxybate marketplace. In fact, probably decreased the growth if you look at the curve here as well. You know, unfortunately, as you've heard from Dr. Stern and Dr. Morse, it's, you know, there's a lot of patients, and unfortunately, maybe even some patients who have still haven't considered using an oxybate. When we actually look at oxybate prescribers right now as well, the left side of the graph is actually there are about 39,000 physicians who prescribe therapies for narcolepsy. Now, some of them are doing refills and primary care and other things like that, but there's currently about 4,500 active oxybate prescribers. We have actually done a new claims analysis and slightly adjusted some of our numbers. If you look on the right side of the page as well, once again there, the number of oxybate prescribers year-over-year has been flat. Some of the things that go on within the marketplace for first-generation oxybates, about half the patients who are eligible are not on them. As some of the story, the comments that we heard from Dr. Morse and Dr. Stern, unfortunately, a lot of eligible patients for oxybates, first-generation oxybates, just refuse to take it for the reasons that we've heard. That's sort of where the marketplace is. We took a lot of the insights from our market research, data analytics, and the ongoing conversations that we've had to really think about the pillars of how we build our launch plan. We really think about three key areas when you think about a launch. Demand generation, how do we get people interested in prescribing and taking LUMRYZ? Reimbursement is absolutely critical, especially in this country. Then, as some of the questions that have already come up, how do we help people actually get on once that prescription has been written? I'm going to start with demand generation. Some of the things that we have done, super glad that our organization is built. Our sales representatives are now fully trained and out in territory. As of this week, they're, we have the coverage for our sales force as well. I'll share in a moment, in a little bit, our campaign, Once at Bedtime, For the Daytime. That is our messaging that supports our positioning that we spoke about earlier. You will see that and hear that throughout our promotional campaigns, both in front of physicians and online as well, and through our social media. Then, the APSS meeting was the ideal time for us to announce that LUMRYZ was commercially available and have launched. That occurred, June 3rd to 7th, and in fact, I got a few pictures here as well. On... Keep in mind, on June 5th is when we announced that LUMRYZ is commercially available. Here are a few pictures. You can see our booth. We were actually pretty popular. It was great to hang out and meet old friends and new friends at Sleep as well. Remember, this is the largest congress for sleep medicine in the United States, and the majority of clinicians who attend are from the U.S. We had hundreds of scanned interactions, way more than we could probably actually scan. Jen and her team, with the, obviously with the great input from thought leaders from across the country and around the world, had 12 posters and six oral presentations of data supporting LUMRYZ. We hosted a project, a product theater. You can see Dr. Morse speaking on the picture on the bottom there. She has lots of nice outfits if you haven't noticed Dr. Morse's attire in the past, but eloquently speaking about the need, and Katie was actually there as well. On the bottom left, on my head, I guess bottom right on your side, this was what was dubbed the Great Wall of Avadel. All the posters sort of encompassing, engulfing the poster sessions from all the data generated. Actually, that term came from someone in our industry, not at Avadel as well. We really appreciated their acknowledgment of the great clinical data that's been generated to support LUMRYZ as well. Our sales force is real now. Like, we have people, they're out there seeing customers. I also remind myself, a lot of our customers are getting to know Avadel for the first time, so we don't win everyone on the first visit. Jen and I sort of joke, you don't ask someone to marry you on your first date. We're building our credibility out there over calls, over time here as well. It was really important what we built and the characteristics that we needed for our team. First and foremost, these are the skills that we looked for, rare and orphan disease, sleep experience. If they didn't have sleep, the vast majority of our team had experience with the types of clinicians, either neurologists or pulmonologists from the past, over 400 product launches. The other very critical, tangible things that we've offered, or we look for, is people who want to win for patients first. That's always number one at our company. The second thing, they have to live up to our core values because it's the foundation around where our company, Greg, has built our company. The third thing is, we want really competitive people who know how to win in complex, competitive marketplaces, right? We're super proud that our team is out there now, sort of fully as of this week, our sales force has our full coverage. The next component, of course, was our strategy around payers. We believe that the coverage, and the channel for LUMRYZ is going to be predominantly commercial, about 80%-90% of our future business. We've made great progress, and I'll give you a few of those insights in the next section here with the PBMs and the GPOs that are over top of them as well. The three major GPOs will account for about 85% of the commercially covered lives for LUMRYZ. That's with Ascent, that's with Zinc, and that's with Emisar. One of the fundamental decisions that we made, and I'm glad that Dr. Stern sort of said this is a good thing around the specialty pharmacies, is we have each of the specialty pharmacies with those GPOs in our network. Sometimes people say, "Why did you guys do that?" Well, here's why. First and foremost, the payers like to dispense within their own specialty pharmacy network, so it's good for payers. What's also important, as you heard from Dr. Stern and Dr. Morse, a lot of people with narcolepsy are on multiple therapies. If you have an in-network pharmacy, they are able to look for concomitant medications as well. Good for the payer, good for the patient. We're hopefully going to make it good for the providers as well with all the services that we offer. Of course, our fundamental strategy has been, from an oxybate coverage perspective, parity with the best of the oxybates, to not be stepped through any other oxybate. We're not going to disrupt the apple cart now, but we do not want to be disadvantaged compared to any oxybate right now. That has been the cornerstone pillar of what we've been doing. Recall, anyone who's already been exposed to an oxybate on or previously discontinued, has, in essence, already stepped through a first-generation oxybate. Typically, what I would say, as I mentioned, I've had the pleasure of doing 11 previous launches. If you can get pretty broad coverage within the 6-9 months, you have done an excellent job, and that has absolutely been our goal as well. The other component is, can we help to fulfill the product? As Dr. Stern said, it ain't easy in the United States. The system makes it very difficult for you for no matter what product or what category you're in. A few things that we have done. The first thing we did was listen to our customers, which are providers, medical assistants in those offices and patients, all right? Some of the essential services that we're offering through RYZUP, our patient support services, is on the left side, a $0 commercial copay for eligible patients. We don't want affordability to get in the way of patients being able to access LUMRYZ. We have a patient assistance program for those people who cannot afford, through their insurance, to be on LUMRYZ. We also, very importantly, have a temporary assistance program. One of the things we hear a lot is people who are anxious and eager to get onto their therapy. We have programs that can help to bridge patients before their benefits investigation are completed, and that's something that we will work on an individual basis with the provider and their patients as well. All right. The services are really important, but the people who man it or woman it are very important as well. We have, in the middle column here, we've provided very personalized services. Maybe the most important feedback that we received in building our services is: do not treat me like a number or a transaction. Treat me like a person. Can you help develop a relationship with me, so I don't speak to four different people over a three-month period of time? One of the things we wanted to do in our patient centricity is have our staff at RYZUP be nurses, people who actually understand clinical practice and patient care. That's our front line that we have through RYZUP. They actually have all gone through a program called PACS, which is to be Prior Authorization Certified. Very importantly, our nurse care navigators, through RYZUP, are geographically aligned across the country. If you're in Texas and Houston, that clinician in that office will speak to the same nurse care navigator as well, their patients. It will be an ongoing discussion and dialogue. Maybe when a nurse care navigators goes on vacation, we will have that case history and have one continuous conversation, not having to start this conversation at step 1 every single time. Maybe the most essential thing that we heard in the feedback in building RYZUP. On the far right, very importantly, we also have to help because a lot of times offices will have multiple cases. We actually have, as you heard from Dr. Morse... We actually have built our field reimbursement team as well. There's 12 of those folks who are currently in the field right now, going into offices, helping, listening, taking feedback, adjusting where needed here as well, to make sure that we can support those people in the offices. The MA job in today's world is very difficult. My son is a freshman in college. He's doing it. He's like, "Dad, they don't pay these people enough money to do what we do," right? Having folks who can work with clinician staff hand in hand and look at the overall composite of what goes on, because we also have built a real-time data platform. When FRM goes into the office, they'll know who's queued up, who hasn't been certified, where they are in the system, whether or not the drug has been dispensed, so they can have a holistic conversation within an office as well. Really essential components of what we've done for our patient fulfillment as well. They've got a lot of experience. We have talked about three patient segments throughout many months and maybe probably the last year and a half here as well. We've had a chance to sort of refresh our look at some of these patient segments as well, with both research and some claims data. We're going to get into that right now. We're going to start with the current marketplace, 16,000 patients, approximately, who are on first-generation oxybates. We know that there are 3,000 patients who are new to starts to oxybate annually every year. It's been pretty consistent. When we go back to claims, we can see that in the last 5 years, there have been 32,000 unique patients who have been on first-generation oxybate. The math would tell you about half of those 16,000 are on today, and about half of them are no longer on a first-generation oxybate. There's a lot of patients who have been exposed to an oxybate, first-generation oxybate, just in the last several years. That's our foundation. Now let's switch to what could LUMRYZ offer to these segments as well and people with narcolepsy. Let's start with that currently on treatment segment again as well. We have done extensive market research in these segments, and what we see is patient willingness to switch to LUMRYZ being greater than 60%. Physician intention to prescribe being greater than 60%, once again, prior to any promotional effort or our claim around clinical superiority as well. As you heard Dr. Stern eloquently say, patients have voted with their feet from RESTORE. We're not communicating that directly, but we know that we have that real-world evidence as well. It's just been great to sort of see. By the way, this is the patient feedback that we get is for patients both currently on the first-generation sodium oxybate and mixed salt oxybate as well. Let's talk about those discontinued patients. What we can say through claims is the vast, vast majority of these patients are still under the care of their healthcare provider or sleep specialist. they generally do not disappear if they've failed on oxybate because they still have the symptoms of narcolepsy. it's a big segment, 16,000. We're not saying every one of them reengages, but our market research and patient willingness to try LUMRYZ from a few different vantage points has been 33%-65%. physicians in interest and intent to prescribe greater than 60% for this segment as well. All right? I think we heard very eloquently from Dr. Stern and Dr. Morse some of the reasons why patients have discontinued in the past as well. Maybe one of the more interesting things that we've learned in the last little while is when we went to claims is naive patients. We've actually gone back into claims, and what we can now see is there are clearly a lot of patients. We talked about 25,000 patients. This segment that we describe as oxybate naive, have all been treated already with at least two stimulants, and many of them, three, and also a wake-promoting agent. Two-thirds have already been on an antidepressant. As you know, as you know, with this condition, sometimes they will start before the narcolepsy diagnosis for an antidepressant. Sometimes it'll be added on to address some of their cataplexy as well. This is a real population under the care of physicians right now, and our estimate is about half of these patients are currently under the care of physicians who treat, currently use oxybates as well. Physician intention to prescribe in this segment, greater than 50%, and patient willingness to try LUMRYZ is 35%-40%. Some people might say, "Hey, that's kind of low." Considering they've not been on an oxybate, we think that's a great place to start because they would be switching or adding, to Dr. Stern's point, from taking stimulants, wake-promoting agents, and other therapies other than an oxybate as well. This is sort of how we look at the overall opportunity. When you think about where first-generation oxybates are today, that means today they're about 12% penetrated into this naive segment as well. As much as we think about the opportunity to grow double, whatever, we also sort of say we don't need to penetrate this market that much more to actually have more patients potentially be able to benefit from LUMRYZ as well. When you stack all these three opportunities together, greater than 50,000 patients, Greg had alluded to this in the beginning. On the bottom, we know that we have a clear and relative benefit, and there is high interest from both physicians and from people with narcolepsy. When we get to the orange segment of patients who have discontinued first-generation oxybates, they are highly unlikely to try another first-generation oxybate. This is almost exclusively an option, opportunity for LUMRYZ. We look at naive, the naive segment. There are clearly patients within current oxybate prescribers today that can be considered, but we also see future opportunities to potentially expand the treater base as we go forward on our launch journey as well. Hopefully, I've sort of covered in this section the fact that there is opportunity beyond the first-generation oxybate marketplace. We've built a very clear plan based off of market research, data analytics, and speaking and listening to our customers. We clearly see from the market research and the work that we've done, that we can win in all three patient segments. The good news is there's no transition. I'm going to introduce myself. Hi, I'm Richard. Good to see you guys again. I'm going to go into my last section, which is maybe where some of you are very interested, is some of the early signals that we're seeing for the launch. Right now, our launch execution is well underway. It is on point, and we believe we have seen some very early strong signals for the launch. As I was able to show you before, there's the 4 packets of LUMRYZ. I showed you the 7.5. They are available in 4.5, 6, 7.5, 9 gram packets. We have 8 SKUs because they're available in 7 and 30-day counts. And they're pre-measured. You don't have to measure how much you're pouring out of the packet. You dump it into water, you swirl it up for 60 seconds, you ingest it, swirl it again, and you're good to go once and only at bedtime. LUMRYZ has been now available for the last few weeks at all of our specialty pharmacy networks, Accredo, CVS Specialty, and Optum Frontier Therapies. Optum opened up a new arm of their specialty pharmacy, specifically for rare disease, we're really proud to partner with all three of these groups to help us distribute LUMRYZ. Here's our campaign, The Doorway to a Better Day. Once at Bedtime, For the Daytime. It's the first and only single-dose sodium oxybate. When we've done the research, what patients want, as you heard from Katie, is the chance to live the life that they either had or hope they could experience as well. From transitioning from that bedroom into what looks like sort of their what their day could look like here as well. What was really great for us when we tested our campaign, is it tested equally well with providers and with people with narcolepsy. Dr. Morse says this a lot, hopefully, I'm quoting this the right way. If you think about the treatment paradigm for most providers or sleep experts, the patient is actually the captain, and the provider is the first mate, and together, they're formulating that plan. The fact that this resonates with both providers and people with narcolepsy, we were really thrilled about as well. Our materials are starting to get there everywhere now. First on the left-hand side, these are things that we're doing for our HCPs. And also for patients. Our LUMRYZ website has been updated. We're gonna have another update coming soon here as well. In the first few weeks, we've had 7,000 visitors to our patient site and 5,000 unique visitors to our HCP site as well. On the right side, these are just thumbnails of all many of the materials that our sales force and our field teams have to actually communicate and go over the value proposition with LUMRYZ in healthcare providers' offices as well. Patients, that's very important for us here as well. Early last year, towards the end of 2021, we rolled out a campaign called Narcolepsy Disrupts. We had several thousand people who opted in to learn about narcolepsy and really talk about not only the daytime challenges, but the nighttime as well. When they registered, on the bottom left, you could actually get a sleep diary. One of the things we often hear from people with narcolepsy is, "I need a place to capture all my thoughts," because oftentimes that's the point of the conversation that a patient will have with their provider when they have a follow-up visit as well. We have now begun to transition patients from an unbranded conversation around Narcolepsy Disrupts to now hear directly about LUMRYZ. We've begun that transition around hundreds of people who are now opting into our branded campaigns. What we can sort of see from our survey data, 'cause we're actually learning a lot more of these folks, is, the people clearly who are transitioning into the LUMRYZ communications are predominantly oxybate experienced patients who are now signing up for those activities as well. We have a really cool how-to video as well. I think it's, we have a cat in there. There's a big debate around using a cat or a dog. The cat people in our company won, it's a great opportunity to really actually understand it's a relatively straightforward process for how to actually administer and take LUMRYZ as well. I'm guessing this is the section you probably are the most curious about, how we're doing for the first few weeks. It is early. There's a lot of room, a lot of room to, a lot of things to still do for our launch, but we do have some early indicators for what's going on with the launch. I'm gonna caveat this: we may not show the same information every single time we speak to you, but at this point in time, we thought it was relevant to frame out what's been going on for the first few weeks. The first question is, can we see people? The answer is yes. As you know, from those 4,500 active oxybate prescribers, about 1,600 make up 80% of the total prescription volume in the United States. Keep in mind, about a quarter of our sales force has just been making calls starting this week, but through the first few weeks, we've already been able to see about two-thirds of these top-tier offices, sleep offices. All right? For us, that's great. Once again, we're introducing ourselves, we're introducing Avadel, but we're very quickly getting into the conversation to LUMRYZ because that's where a lot of sleep providers want to go as well. Once again, our sales force is now fully trained and in territory as of this week. Okay, lots of caveats here. We're 3 weeks in, very early, but we're gonna share with you some of the behavioral activity metrics that are probably important early signs that we believe really start to encompass the interest level that we've seen from the narcolepsy community around LUMRYZ. The first thing you have to do as a provider in this country to be able to prescribe an oxybate, and specifically LUMRYZ, is get certified in our REMS program. All right? It's relatively straightforward. You have to attest that you've read the PI. There's a brochure that signifies that, and then you attest online that you have read those documents as well. In our first few weeks, there are over 625 physicians who have REMS certified for LUMRYZ. They've taken that first step on their journey to be able to actually prescribe LUMRYZ to their patients who have narcolepsy as well. Pretty exciting, right? That's a good start, right? We got more room to go. Maybe the next part, as you start to go through the funnel, is then who's being enrolled into our RYZUP Patient Support Center? Very early, literally, once again, we've started our promotion just for the last few weeks, but we have already 140 patients who are now enrolled in our RYZUP Patient Support Center as well. I'm gonna caveat, not every one of these will absolutely go on to product. That's sort of the way it works in the United States, but some early insights that we have, the majority of these patients are previously on oxybates. They are on, or they're switching from oxybates, and about half of them are coming from mixed salts, and about half of them are coming from sodium oxybate, first-generation oxybates. We have seen people and patients sort of voting with their feet here early on here as well. This is just in the first few weeks. You got to go through that process, and then we're also super thrilled to announce that our first patients have now received LUMRYZ. Very interesting as well, Anne Marie said she's actually had some success with the payers as well. Our first patients have all been reimbursed for commercially paid for patients as well. We're not guaranteeing that's the way it's gonna work all the time, but I was asked before, "Are you just gonna be giving away free product to everyone who starts LUMRYZ?" The answer is No. There's a few insights here. As Anne Marie and Tom have said, or Dr. Morse has said, and Dr. Stern has said, the practices are unfortunately used to dealing with getting medicines that are difficult to acquire through specialty pharmacy. They've got a lot of experience doing this here as well. It's really been great to sort of see, and we can also sort of say that we've actually had all 3 of our commercial pharmacies already ship out product to patients as well. These are very early signs. To be very candid, I wasn't sure if we were gonna have any patients ship product by the time we got to this day, but it's been really cool to sort of see. The top of the funnel is there, and now we're starting to pull those patients through to actually get LUMRYZ shipped to patients as well, 'cause ultimately, that's what it's all about. You might ask, how are we doing with the payers? In my next life, I wanna come back as someone who deals with reimbursement payers because they're like gold. Like, it's so hard to sort of work through the systems here. We have an outstanding team that has been able to engage with payers now for the last couple years. We've probably had a little bit more time to talk to them than we wanted, but we have some early payer achievements and success that we've had here as well. We're very thrilled to announce that we've signed 1 of the 3 GPO contracts. That as of July 1st, LUMRYZ will be on the Express Scripts National Preferred Formulary across the country, right? That is a major achievement for us to have in the first few weeks of our launch. We also now already have 10 Blues plans, Blue Cross Blue Shield plans, who have published PA criteria at parity with other oxybates. To very candid, that happened a little bit faster than I was expecting, right? We have coverage with one of the largest multi-state integrated healthcare systems, which in my past life may have taken a couple of years. We got that in the first 3 weeks post our launch as well. If you collectively look at all this, we've already have coverage in about 40 million covered commercial lives in the United States in our first 3 weeks post-approval. If I'm candid, that has definitely exceeded my expectations. We have more work to do because they don't always come this quickly. And obviously, for some of the plans, like, the GPO contract is through Ascent, now our teams have to pull that through to some of the PBM, other national PBM plans as well. Tremendous progress with offices, tremendous progress with the payers, and going forward, we get asked a lot, "What are you gonna keep reporting on?" Well, we've always been transparent. I've been super proud to take part in the conversations that Greg and Tom have had with many of you over the last few years and many months as well. Here's our commitment to you: We're gonna keep updating you on where we are with the payers, 'cause that's so essential, that's the gateway to getting onto products in the United States. We're gonna give you feedback on how our product fulfillment is going. If I'm candid with you, it's a new process, and new sometimes is viewed as difficult. As you heard from Anne Marie, Dr. Morse, we are listening to our customers, and our goal is to win every person over, one person, one interaction at a time, as well as we all adapt to a new process as well. We'll talk to how many patients are reimbursed on therapy when we get to our quarterly earnings here as well, which will be probably around the second week of August. We'll continue to give market research, and clearly, our fiduciary responsibility is to also report on the revenue that we have as well. Our goal is to try to stay committed and transparent to our launch, and make sure that you are understanding how we're making progress throughout as well. Okay. Greg sort of teed up this greater than $1 billion opportunity. I'm maybe gonna go a little bit, lift the hood, and maybe give you a little bit more of our insights, why we believe that's the opportunity, plus for LUMRYZ. Clearly, right now, we're at the time where we're doing this more focused launch. We made very strategic decisions around where to focus and launch the services to build here. We believe, as you've heard from Dr. Morse and Dr. Stern, the chance, the opportunity to expand the marketplace through new prescribers, new types of patients, and the other thing that we believe we'll see with LUMRYZ is some increased persistency as well, knowing that you only have to take the dose once at bedtime. Greg will talk a little bit about some of our future opportunities and indications as well. One of the questions we get asked a lot about is, how are these generics? Not just the AGs right now, because to be quite candid, we don't think we've seen much impact as far as the branded oxybates are concerned, but besides Xyrem, but how will the future generics impact the marketplace? Our fundamental belief is, even when generics come in, potentially as early as 2026, it really doesn't fundamentally change the growth opportunity for LUMRYZ. Let me sort of start on the left side and maybe walk through the elements here. First, our beliefs and our conversations with payers are anyone who is on LUMRYZ at this point is highly unlikely to be forced to ever switch to a generic first-generation sodium oxybate. It'd almost be unethical. Patients who have already experienced being on a first-generation oxybate can continue to switch, as we believe they will be able to do now, to LUMRYZ as well. None of those fundamentals really change even in the future. The focus could be on the naive segment. There's a large segment, but they're the smallest patients who go on to oxybate therapy on an annual basis as well. We believe that in the next 2 years, it'd be surprising if a lot of people looking for treatment options don't know about LUMRYZ. We believe both provider and patient awareness will be very, very high. Our other belief is that generic companies may be less likely to invest what we and other branded companies are into patient services and support that exist in the marketplace today. We're not gonna predict what's gonna happen in 2026 today, 'cause if I could, I'd buy the Mega Millions ticket from the guys on the corner this morning. We see there's two pathways for continued growth for us, right? The first, on the far right, is number 1, if there's a step through generics for naive patients. Here's what happens from our side. We don't have to rebate more with the payers. Why would we do that if they're forcing a step through another product? We would just wait for them to step through that product. What happens there then is our switch opportunity begins to grow again, right? Sort of, as we sort of see now, and that would sort of, grind, and we sort of see that switch opportunity growing at a much faster rate than clearly even exists in the market today. The second option is we don't have a step, and we probably have to give a bigger rebate. A lot of that we believe will, sort of depend on where we are in the marketplace by we get there. The great thing for us is we're sort of in control of our own destiny, and we don't have to decide today what we're gonna do. In either path, there is a clear opportunity for, LUMRYZ to continue to grow throughout this, in this marketplace as well. Now I'm gonna get back to the slide that Greg teased you with in the beginning of his opening, which is sort of looking at our future peak opportunity. I'm gonna sort of break through each of the elements along the way. We talked about the 50,000 patients. I showed you just previously the 3 segments of switch, discontinued, and naive, and our updated claims data that supports why we believe there are over 50,000 patients who are at least an addressable population for LUMRYZ. We're not saying we get them all today, but they're an addressable population. The next thing is the market research we have seen that talks to this 35% to 100%+ growth. You heard a little bit about that from our experts today as well. We see that opportunity for LUMRYZ to expand the marketplace, and that expansion from our market research is predominantly exclusively for the growth of LUMRYZ. Today, the marketplace, 16,000 patients. If we do the math, maybe you get to 20,000-25,000 patients who are on oxybate therapy. We're not trying to stick our necks out too far here. As Greg stated, and I sort of showed you some of the results, specifically through 6 unique demand research projects, physicians tell us they're gonna give us a 50%-60% market share as well. You put that all together and not taking the aggressive end of the spectrum for all of these assumptions, that gives us a potential for greater than 10,000 patients. What's crazy is you don't have to win massively in any of the segments. You can win a little bit in some, you can win big in one. To get to 10,000 patients, we see 10,000 as just the beginning. Clearly, the opportunity goes well beyond that. We think that's probably a good place for us to start, which once again translates into a greater than $1 billion opportunity for us at today's pricing. The great thing for us, and the reason why I'm super proud to be at Avadel, is we only win if people with narcolepsy win. I always sort of say, "Good business only comes through good science and the focus on doing the best thing for people, patients." That's what we are really focusing on here at Avadel. You know, as I sum up sort of my portion before I hand it back to Greg, our launch execution is absolutely on track right now. It hasn't been easy. There's been a lot of long nights and a lot of people, you know, unfortunately working on their vacations, if they can even take one right now. Things are working, right? We're gonna have some speed bumps. We're gonna have to make some adjustments. That's how you go through any launch. Our foundation is exceptionally strong from the strategic decisions that we have made. We believe we've got some really strong indicators early. People are starting to take actions towards wanting to prescribe LUMRYZ, as we go as well. We're gonna keep providing updates, and, you know, we're really proud that we have this great new therapy that financially can also be rewarding for shareholders as well. Once again, for us, it comes down to our ability to help more people with narcolepsy and provide more options to the sleep experts who see them as well. With that, I'm gonna turn it back to Greg to close us out before we get to our Q&A. All right? Thanks, Richard. Thank you. For those on the webcast, we are going to slide 110. We'll go to slide 111. Again, I just wanna comment on a few of the things, as we've heard a lot of data here today and a lot of information, and I'm sure you have a lot of questions, and I'm the only thing between you and your questions, and then a lunch. We'll certainly try to be efficient, but I wanna be clear, A, we're not guiding right now. I don't think we're uncommon to any other company at this point in time in their launch. We're not giving financial guidance, we do think that these are important leading indicators for us in terms of that will lead to the sort of, you know, ramp and uptake in the, as we go through the next couple of quarters, that are key. We can't get anybody to prescribe LUMRYZ unless we have doctors who can write it, and you've seen a little bit of that early indication, already in the first few weeks. Obviously, patient starts, right? A patient's intent to want to enroll into our system with an intention to go on our therapy, right? You've seen a little bit of that in the first few weeks. Then, of course, these major payer decisions, you know, are obviously important as we expand that base that has already started to grow for us, and I'm sure there'll be more updates that we'll share in the coming weeks and months in that regard. A common question I've received from many of you, even leading up to today, was, "Okay, you're launching LUMRYZ." Like, "What's next?" Right? "Where are you gonna go from here?" Like, "What's your plan to diversify the business," right? We've always talked about kind of the three legs of the stool, right? Most important thing we can do is successfully launch LUMRYZ, which creates as much optionality. It becomes, how do you leverage the innovation that's LUMRYZ? How do you leverage the investment we're making in commercializing LUMRYZ? Can you apply our technology to any other, you know, oxybate-like opportunities, right? We're not gonna talk about all that today, but we are gonna talk about the importance of how can we expand the patient population who could benefit from LUMRYZ. Call that our lifecycle management strategy, right? Investing in the innovation and the differentiation that is LUMRYZ. Three areas we can do that in: age, indication, formulation, right? We've been working on... Let me step back. Richard talked about the sleep meeting a little bit. There was a lot of excitement, a lot of physicians who were congratulating us on our approval, but much like you asking us the questions about what's next, we got similar questions from physicians at the sleep meeting, which were much more specific. "When are you gonna do pediatric?... When are you going to do a study in IH? Like, it came immediately after, "Congratulations to your approval." If we ever had any question of whether or not we should do that, I think it became pretty clear that there's a lot of interest in the clinical community. We've been working on pediatrics for quite some time, right? We've been engaging with the FDA on this matter. It represents about 5% of the current narcolepsy market opportunity, based upon the claims data that Richard and I have described previously. The one thing we can say is, besides the physician interest, like, we hear from patients, we hear as much or from parents, excuse me. We hear as much from parents of patients on oxybates, as we do at times from patients themselves, right? These are patients of children, you know, who are pediatric patients. We hear from adults of parents of adult children as well, who wake up every night to wake their child up so they can get to work the next day or get to school the next day. Clearly, pediatric is something we're going to do. We've worked with FDA to have a pathway. We would expect to file our supplemental NDA, as the slide says, later this year. We'll give you an update on that, but we would expect that supplemental NDA to be filed later this year. Where are we on IH. People ask us a lot, where are you on IH? A lot of interest on LUMRYZ for IH, Dr. Morse and Dr. Stern can certainly talk more eloquently about this. What we hear from clinicians is that the deep sleep inertia that these patients suffer, the challenge of waking up is arguably maybe more so in IH than it even is in narcolepsy. The value proposition of the LUMRYZ innovation may be even more compelling in that patient population as well. From our standpoint, we wanted to understand the market. What is this market, right? We've only seen one approved, formally approved product. We've seen their uptake over the last, you know, 5 quarters or whatever it is. We have seen in this same claims database, over 45,000 uniquely diagnosed patients. About 80% of them are on some sort of therapeutic intervention, and about 5% of them are on the first generation, twice-nightly oxybate that has the approval for IH. We certainly view that as an opportunity to do the clinical work, as the community has, you know, certainly suggested and recommended we do. We are in, I would describe, as pretty advanced R&D planning stages. We'll update more specifically on timing. There's a number of components to that, not only what's your protocol, but, and who's your CRO, but you got to get clinical supply. It, you know, it does require a quota requirement. You got to work with the FDA on our IND. We'll update these things as we go, but it is clearly in our pathway now that we've cleared the approval and have our orphan exclusivity. Lastly is formulation, right? We believe all patients who are interested in, you know, having a once-at-bedtime treatment option should have that. We obviously have the technology to deliver that, right? We're certainly targeting our own no or low sodium formulation for at-risk eligible patients, those who are salt sensitive, that's what our label says, with a target product profile to be bioequivalent to LUMRYZ. That's what we're trying to develop. Why? Because that could potentially enable us a PK-only development pathway, assuming the FDA agrees with that, and that's the approach we're taking. We've been working on this for a little while, as many of you know. We continue to advance this. We're still in our preclinical formulation stage, as that advances as well, we certainly will update the street as appropriate. Again, we believe now, with the priority number 1 being successfully launch LUMRYZ, the opportunity to expand the potential patient population is an important next step for us as we continue to build our company out. Just a quick snapshot on where we are from a cash standpoint. We talked about our balance sheet. Many of you are aware of the things we've done during the course of the last few months to sort that out. Again, $275 million of, let's call it pro forma cash and/or committed capital as of 3/31. We do believe that combined amount, based on our current operating plan, is adequate to fund our operations through cash flow break even. That is our plan today. We believe we're in a very strong spot from a balance sheet and cash availability standpoint, to help support the operations and successfully launch LUMRYZ and do all the things that Richard Kim has described over the course of this morning. Maybe the last slide before we wrap up and move to a Q&A is we covered a lot of things here today. We, you know, many of you have waited a long time for this period of time and this, and in some cases, actually today, to hear our views on the market, right? We're very, very focused as a company to deliver on the right priorities, to create the right sort of value for all stakeholders, from patients to shareholders to the company at large. We've tried to disclose and open the, you know, the curtain up a little bit on our insights on the marketplace. Have a fire alarm at the same time. The things we do to avoid a Q&A, John, right? At the end of the day, this is an exciting, transformative time for Avadel. The police are excited, the fire companies are excited, and we really appreciate all of you being here. Let's hope there's not a fire. Attention, please. Attention, please. This is the Boston Fire- I would be remiss if we didn't say thank you for spending your morning with us, and thank you to our guests, to Dr. Stern, Dr. Morse, and Katie in particular for sharing your story. We really appreciate you being here. For those on the webcast as well, spending your morning and having the opportunity to discuss our thoughts around LUMRYZ and hear from our experts. With that, I'll invite the management team up to maybe open it up to some Q&A. Hi, this is Bhavin Patel with Bank of America. First question on payer coverage. With the Express Scripts' coverage of LUMRYZ effective July first, maybe if you could share what step edits will be required. Maybe if you can also provide some commentary on what you expect gross-to-net to look like with priced at parity to Xywav. Follow-up question on idiopathic hypersomnia. What are you thinking about for the study design? Do you expect it to be a randomized double withdrawal study, or are you thinking about that a little differently? Yeah, let's see if we can remember those. Richard, I'll take the first one. You take the first one, I'll take the next two. As far as what we'll have with the Express Scripts National Preferred Formulary, it will be the same as current oxybate. For the majority of patients, that means you have to try one or two other stimulants. It'll vary a little bit by PBM as they pull it through, but it's the same as what you see for current oxybates as well. Generally stepping through a stimulant beforehand or two. Yeah, I think the gross to net question is one we get regularly. I would say it's probably a bit premature to guide explicitly around gross to net at this stage. We certainly understand where we're sitting from a kind of a contract negotiation standpoint and what that looks like today. I think, you know, with the strategy going into, you know, our launch of parity access and not being disadvantaged to any oxybate, but being at the same place with oxybates is what you've seen at Express Scripts, what you saw at the 10 Blue Cross Blue Shield plans, what you see at the same national... Attention, please. Attention, please. Hotel fire safety director. This was a false alarm. Thank you. I think with, again, what we're seeing emerge with some of these recent wins is, you know, that strategy right now seems to be, you know, playing out early. I would say the best advice and guidance we give around gross-to-net is that, you know, looking at the current kind of net pricing in the marketplace today, we think it is a reasonable proxy right now, and I think it's gonna take us a couple quarters to kind of work through kind of reimbursement and coverage policy decisions and what actual net impact that's gonna have on our gross-to-nets. We'll certainly, you know, obviously share that as we report quarterly going forward. On your question on IH, it's just not something we're gonna share right now. We've obviously evaluated all different sort of trial designs, but, you know, we'll come out with that, you know, in, you know, as we continue to advance our planning. Raise your hand high if you want to ask a question. I know, John. Hi, this is Miriam from LifeSci Capital. Thank you for your presentation. Just a quick question from me. It sounds like you're focusing on the top-tier oxybate prescribers. I was just wondering if you've seen some interest from those who are not currently prescribing sodium oxybate products and who might have been deterred by the twice-nightly dosing and what the clinician described and the complications that come with that. Richard? Yeah, Miriam, great question. The answer is yes. We are seeing enrollments from not actually lower experienced oxybate prescribers, but also people who currently do not prescribe oxybates as well to be REMS certified, and we're seeing some of that early activity coming through the patient enrollments as well. You know, maybe one thing I forgot to comment is these processes all take time. You REMS and enroll, you got to see your patient, you get them enrolled, and then it generally takes several weeks, multiple weeks early on to actually get that enrollment process investigated and product shipped out. The fact that we actually already have patients receiving commercially shipped product is really a testament to how the payers, we believe, are actually viewing the unmet need for LUMRYZ. Yeah, we're also sort of seeing it not only in the highly experienced oxybate prescribers. That's the majority of our activity, but there are signs coming also from people who have little experience or actually have never experienced prescribing an oxybate as well. It's actually one of the benefits of our system, where we get the early indicator, right? If somebody wants to prescribe who's not in that kind of core call plan because they haven't been a historical prescriber, we get the indicator when they sign up for our REMS. It allows us to then dispatch our team. We have a question in from Jefferies, listening in on the webcast, Andrew Tsai, on generic Xyrem. One generic has launched, generic Xyrem at a small WAC discount. Three more could enter in a few days on July 1st. Why should the price of that generic not be at a steep discount that's deteriorating Xyrem as well as LUMRYZ prices? you know, what we've seen so far with the first authorized generic coming to the marketplace, first and foremost, is really a cannibalization of branded Xyrem to the authorized generic. Really, we've seen almost no impact on the mixed health version right now. When the next wave of off-patenters come, they have very severe volume arrangements that are put into place. The ability for them to really impact the marketplace, we believe, is extremely limited. Maybe more important is the feedback that we've received from payers. They've already been working with one, and at this point in time, there's probably little incentive for them to work with others as they do right now, especially when they have volume limits on them as well. You know, as I mentioned, we haven't really seen that much impact, except for the cannibalization of the branded Xyrem to go to the AG. Hi, Frank Brisebois with Oppenheimer. Just a quick one in terms of your billion-dollar peak sales assumption. Are you know, based on the product profile, in those assumptions, are you staying conservative, where you expect a similar discontinuation rate as the discontinuation rate seen with products in the market? If you could just remind everyone what's been seen so far. Sure. Yeah. What we've seen in claims data so far is with the first-generation oxybates, about a quarter of the patients discontinue at about 30 days, and about 50% of new patients discontinue after 12 months. The way I would answer that question, Frank, is if you think about our patient mix first and foremost, we're already seeing activity towards experienced oxybate patients as well. They're on a different slope for that discontinuation rate than de novos. What we've sort of looked at is not being that different, but maybe slightly better than what we've seen historically for new patients than the first-generation oxybates. Hi, this is Ami Fadia from Needham again. Perhaps, if you could talk about what% of your target patient population is covered under ESI, and if you could give us some expectation around when you might be able to complete the negotiations with the other two payers. Separately, slide 94 talks about over 140 patients enrolled in RYZUP. Are these patients that are waiting to get drug? Maybe you can talk about what's the current time frame between when a patient gets prescribed a drug and when they receive drug, perhaps implications around initial sales, given your bridging program. Thank you. Okay. Well, let's start with ESI is one of the major PBMs covered from the Ascent GPO. The Ascent GPO covers about 50 million lives. It's a very significant them, along with Zinc, the CVS family, are the two biggest GPO groups in the United States. It's a very significant win for us to be able to secure that contract. I think one of the questions was then about the duration of time. No, the other two. The other two. Yes, sorry. There are two others. That's right. We are in active discussions and negotiations with them right now. To be very candid, they all work at different paces. Like, sometimes you have to get onto a P&T at a different time. You know, as we sort of said before, what we sort of see as a lot of solid coverage decisions, if we can get them all done within sort of 6-9 months, we think that's a very good outcome. As a reminder, prior to that, as we were already seeing with some of our initial prescriptions, a lot of the reimbursement will come through medical necessity, which offices you heard Dr. Morse say already. I mean, that's what they do right now. They do medical necessity, they do denials. They're highly experienced in this. Even prior to those other coverage decisions coming forward, we absolutely sort of see the reimbursement going through medical necessity, all right? As far as the timeline, as far as filling that, first, the patients going into RYZUP, those are unique patients that are now in there as well. That's the first signal for us, that a patient, along with their REMS certification, is now going through the prescription fill process. As I mentioned, we can't guarantee every single one of those will convert onto a fill product, because that happens in the United States here as well. In general, it oftentimes takes several weeks at a minimum to be able to go through the BI process, benefits investigation. However, we've already seen some of those go through very quickly in our first few weeks here as well. It's a bit of a wide range, and it's hard to be generalizable, but I would say in general, it does take several weeks for those enrollments to convert into product being shipped to a person with narcolepsy. That's especially, Ami, true prior to broad coverage policy decisions being in place, where it's not going through this additive step of medical necessity and the documentation that Dr. Stern and Dr. Morse wrote, which adds to the length of time. It's clear that, you know, the first couple quarters, you know, the time from entering at the top of the funnel and coming out as a reimbursed patient, is gonna take longer than it will when we have broad coverage policy decisions made and things are humming along, right? That's really what's gonna happen in the first couple of quarters for our, based on our expectation. We're pleased that we've knocked a few back early. That certainly is helpful for us. Again, we're in early stages and glad to see that we've seen people and people with narcolepsy who want to go on LUMRYZ come in at the top and actually come out on drug already in the first few weeks, which I would think is something we probably didn't expect to happen at this stage, so. Just a follow-up question. Can you provide an update on the progress of adding another CMO for domestic manufacturing of the drug? Yeah, I think we previously said that we have done a lot of work on redundancy of supply, and that work has been completed, and that supplement was filed immediately after approval. It's pending with the FDA now. Go ahead, John. I actually have a question for the two doctors. I'm curious to know, in the three weeks that LUMRYZ has been commercially available, how many existing oxybate patients have you had, you know, patient visits with? How many did you discuss LUMRYZ with of those? How many of those decided to switch, what percentage once they had that interaction? If you can further that, of the ones that did decide to switch, what was your experience, you know, getting them on? I want to caveat this, that, like, we're three weeks in. A-absolutely. Right. let's, you know, be a little bit mindful, but go ahead. Yeah. As I had alluded to earlier, I already have 6 patients who were in the process. 4 of them are already approved with insurance. Again, I think the unique experience that Tom Stern and I probably both share is that since we're a trial site, it's been an ongoing conversation with our patients irrespective. In terms of the last few weeks with my sleep fellows, we've probably seen 20-30 patients, who are either brand-new patients or returns, who have narcolepsy or idiopathic hypersomnia, and I have that conversation with all of them. Most typically, however, my approach to management of patients is that I don't expect for them to make a decision at the time of visit. I encourage them to discuss with their families, think about it, do their research, right? Because I want them to come back and have a conversation with me. I also want to be mindful of not overwhelming my staff with changing everyone all at once, right? I will say that there will be patients that will stay on twice nightly oxybate. I don't doubt that. The same as in any other disease state that I treat, where there may be the majority who are on a long-acting, but then there are some who won't switch over. I'll have to respond. If I can ask one quick question before. Sure. -get to the other doctor. Out of curiosity, what are some rational or, you know, reasons why they would not switch? This is a disorder where individuals are scarred by the experience that they had prior to treatment, and so they literally have PTSD from the disorder. Even for patients who I've seen as second opinions, where they're inadequately treated, there's such a fear of going backwards, that even when you're offering something that's better, that they don't want to change it, right? I'm not going to fix what's not broken. There is a process of saying, "Let's evaluate what might actually still be broken." The one question I make sure I ask all my patients at every visit is: What can't you do because of your narcolepsy? We use the Epworth, we use MWT, we use all these things, right? The patients don't care about that. I frequently will joke that patients come in, that no one has come in and said, "Hi, I'm a 17," right? They come in and go, "I can't have sex with my husband," right? "Because I'm so tired." We need to be able to address those things. Patients will not switch if they think that there's any risk of me stepping backwards. I would say that that is not the majority, but that is a reason. I just want to make a comment because what we can't capture in research is the notion of when, you know, 140 patients becomes 500 patients, becomes whatever thousand of number, 10,000 patients, whatever it may be, right? What that does in terms of creating, you know, its own energy with across the community, right? Today, we're asking this question in a vacuum of how people think about it today. In three years from now, the view may be very, very different, and that patient who's reticent today may have 100 people around them in their advocacy group who all have switched and are doing great and may have a different view, right? That's where, you know, executing and, you know... That's why our view is that, you know, we got to do it right early and build right experiences such that long term, we can build a highly valuable franchise, and most importantly, help even more patients. Yeah. My practice, I'm the rate-limiting step to getting people converted. I think we have, like, eight people enrolled already. At least two of those were not on the trial. In order to enroll patients, I have to be there. I have to sign electronically, I have to be there while they're filling out the form. We actually have plans this Friday to enroll more. Yeah, unfortunately, my clinic is understaffed. It's just finding hard to find people these days. Like I said, eight so far, two that are not rollover, like I said, I've been the rate-limiting step the last three weeks. Any other questions? Yeah, Matt. Just a question for the doctors in terms of what you think the impact of the entry of generics will be on your management of patients and how that will affect your practice? Again, I'll go back to the ideal world and the real world. If it's up to me, and if it's up to the patients, they'll be on once a night. That's not always the case. Physicians don't run healthcare anymore, so I can see it's possible they'd force people economically to go, you know, but that's beyond my control. Like I said, it certainly wouldn't be my choice or the patient's choice. I personally view it as increased value proposition for LUMRYZ. The reason why I say that is because my personal strategy of how I onboard any person on oxybate is I start them first on a once nightly. I titrate up and then introduce a second dose. What this naturally does, in terms of the positioning right now, is that you get the patient to tolerate the medication. You then get them to experience benefit, and then you're able to identify how frequently are you missing that second dose. You've now created the easiest path forward for a once nightly. I have incomplete benefit, toleration of the medication, and there's an option that will get them more complete benefit. It might delay me to getting there, but it's a great value proposition. Okay. Well, again, maybe we just wrap up with a few final remarks and just say, you know, thank you again for spending your morning with us. Thank you for your questions. I think we've got a number of follow-ups scheduled with many of you over the next few days, and happy to follow up with anybody, either here in person or on the webcast, if you have any follow-up questions, about the content and what we discussed today. Let me again thank Dr. Morse, Dr. Stern, and Katie for being our special guests and spending your time with us as well. Thank you, everybody.