For Indivior. We appreciate you all taking the time to learn about our company in anticipation of our US primary listing. I also want to thank our host, Hogan Lovells, for having us and putting on a nice spread. Enjoy. Before we begin, I need to remind everyone that during our presentation today, we may make forward-looking statements that are subject to risks and uncertainties, and that actual results may differ materially. We list those factors that may cause our results to be materially different here on slide two. We may also refer to non-GAAP measures, the reconciliations for which may also be found in the appendix of the presentation that is in front of you and now posted on our website at indivior.com. Let me now introduce today's speakers. From left to right, our Chief Executive Officer, Mark Crossley; our Chief Commercial Officer, Richard Simkin; our Chief Scientific Officer, Christian Heidbreder; Jeff Burris, our Chief Legal Officer; and Ryan Preblick, our Chief Financial Officer. Thank you for coming today. I'll now turn the presentation over to Mark, our Chief Executive Officer. Thanks, Jason, and really excited to have you all here today. Jason talked about the anticipation of the U.S. listing. Just this morning, we held our general meeting and had nearly 97% support, so we're moving ahead. And I think with that behind us on the vote, it's so great to be here today with the U.S. Analyst Committee. It's a big part of why we're coming to the U.S. to increase exposure of both Indivior in the therapy area. So what are we trying to do? In anticipation of that listing, we want to introduce ourselves, outline the clear strategic sort of priorities that we've created and been executing against over the last four years to get durable shareholder value moving forward. And, and as I think you'll hear across the entire team, we have immense confidence in what we're doing in this disease space, where there's a huge unmet need, and we're bringing breakthrough science to help patients. So what's our agenda for today? I'm gonna do a quick overview of the company, the strategy, and then we're gonna get into a lot more detail to help you really get to know the company. Richard Simkin is gonna take you through our products that are in market, give you an explanation of each of them, what does the therapy area look like, what do the products and, and what is their kind of TPP, and why we have such confidence in them. Christian's gonna take you through the pipeline that we've put together to really help people suffering from substance use disorder, an area where we are the leaders in developing the technology that's gonna help these patients moving forward. We'll follow up with Jeff Burris. We have a few legacy legal items that are in our footnotes, and we thought appropriate to talk those through with you so that you have an awareness of them. Then Ryan will take you through what we call operational excellence. It's kind of a herald of how we work, you know, get our strategy, but the excellence in which we execute, deploy capital, you know, and optimize our operating model. So Ryan will take you through that, and then I'll talk a little bit about the listing and move on to Q&A. So why Indivior? We are the global leader in the treatment of addiction, with such a huge unmet need. Less than two in ten people suffering from substance use disorder actually get treatment. Primarily, opioid use disorder is about the only one that has a meaningful treatment out there. So there's a huge, huge opportunity in this space and to lead on the technology as well as the commercial platform. We have a strong track record of execution, and de-risking the business. We've been at this for over twenty years, specializing in the intimacy and the knowledge of these patients who suffer from substance use disorder. We're a management team with very clear priorities of what we're doing and how we're creating value, value for shareholders, and that clarity is both externally for the shareholders, but internally for us, as we try and prioritize what we're doing and ensure we can execute with excellence. And then, of course, the scalable model that we have as we continue to grow, you know, at a strong clip and deliver more cash flow. I think we've all seen in the paper the statistics of addiction, you know, and 85,000 people a year dying, less than 2 in treatment, and the statistics are horrible for a developed country such as the U.S. But when you take the statistics and you put a face behind them, they become even worse. I mean, the people that are falling victim to this disease, you know, they're our friends, they're our family, they're our community members, and I think our--the covers of our annual reports bring that to light. Kyle, who's up in the upper left, he was a financial analyst at a bank, got in a car accident and ended up addicted to opioids. Ashlynn, who's right next door, she was a high school honor student getting ready to go to college, fighting a bit of depression, got exposed to opioids recreationally and entered a horrible cycle of abuse. Down in the lower right-hand corner is Rich. He's a firefighter. He was saving lives, and he got injured on the job and ended up addicted to opioids. So it's you, it's me, it's our family members that suffer from this. The intimacy we have and the understanding of these patients is how we bring disproportionate technology to the market and how we're able to, to deliver operationally with such excellence. It is a huge, huge crisis globally. That's with an unmet need, over 60 million people abusing opioids. You know, the two therapy areas in the middle, which I kind of think of as normalized addiction or certainly becoming normalized with the legalization of cannabis, globally, 219 million users. The US is accelerating in the growth of users, up 50% just over the last two years. And Christian will take you through a lot of those stats. Alcohol, greater than 100 million people globally, actually diagnosed with alcohol use disorder, and then amphetamines and cocaine, with nearly as many people abusing those as you have for opioids. So there's a huge, huge crisis and an unmet need with so few people in treatment. And you see it across the press, the awareness, whether it's the overdose deaths, you know, whether it's fentanyl or the other nearly 1,500 derivatives of synthetic opioids that become more and more powerful. It's in the news every day, and you're starting to see more and more press with regards to cannabis, the legalization of it, and some of the unintended consequences for people that build it into their lifestyle at too high of a pace and become addicted and have cannabis use disorder. And we'll give you exposure to that, all of these, throughout the day. So most of you are new to Indivior and haven't covered the company, so maybe a little get to know you. We have over 1,100 people around the globe in 37 countries that are dedicated to helping these patients. It's a real passion, you know, because when you bring people back to regaining the life they've lost, to have an amazingly normal life, something we all take for granted, it's an incredibly purpose-driven company. We're at about $1.1 billion of revenue over the last 12 months, and you can see it's heavily concentrated in the US. Just one of the reasons for the US listing, because the opioid epidemic has disproportionately impacted us here. When you look to the future, legalization of cannabis, which is our latest stage asset in the R&D pipeline, is also disproportionately impacting the US. On to the right, you can see the mix. Our commercial assets are primarily in opioid use disorder, and we've got three products there that provide a bit of diversification, and we have an asset in schizophrenia that's about 4%. So the big asset there is SUBLOCADE, which is our paradigm-shifting treatment. It's a once-monthly for moderate to severe opioid use disorder, and you'll get a lot of exposure to that through Richard and Christian's sections. For us, the clarity of our priorities, as I said earlier, is key to our success. The number one priority we have as a company is to grow SUBLOCADE greater than $1.5 billion. We truly think of it as a waypoint, and we've altered our strategy back in 2000 to focus on organized health systems and prison systems, and it's led to very, very strong growth in market penetration. Over 54% growth, 2023 over 2022. And we've continued to targetedly add additional commercial investments to fuel that growth moving forward at a lesser rate, of course, than the top-line growth. We're focused on diversification of revenue. You know, that diversification can be organic, where we're taking new products globally into new markets, but it's also inorganic growth. We bought Opiant last year to get OPVEE. That takes our company from just moderate to severe substance use disorder and starts to expand across the continuum of care for patients, meeting them where they are. And in this case, it's a relapse medication. We're building, you know, the world's best pipeline for addiction, and Christian will take you through those. But across cannabis, opioid use disorder, alcohol use disorder, and then, as I said, you know, optimizing, optimizing our operating model from the expense management capital allocation, you know, where we've done business development and we've done a share buyback, and then, of course, getting our listing lined up with where the value is moving forward for shareholders. In December of 2022, we provided medium-term guidance to the market, you know, basically double-digit top-line growth in the medium term, which we said was five years. Margin expansion during that time point for disproportionate cash flow generation. We still stand behind this operating model, and Ryan will provide a lot more color on, on that and why we're very excited about the future as we continue to grow and having so much of that revenue fall to the bottom line to profit. This is just that pictorially, which again, you'll see, you'll see later with the rest of the team. As I get ready to hand over to the, to the detail of the day, starting with Richard on the products, just again, why Indivior? We are the global leader in addiction. Huge unmet need, growing markets, and a need for breakthrough science, which we're providing. SUBLOCADE is in the market and is a transformational asset that's growing disproportionately, helping patients. It's greater than a $1 billion revenue opportunity. We're pursuing additional diversification in areas where there is, you know, a chance to be a leader. Cannabis use disorder, alcohol use disorder, and new assets in opioid use disorder. And our operational excellence, we think, differentiates us from our peers. With that, I'm going to hand over to Richard Simkin to take you through, you know, our products. Thank you. Thank you, Mark. So, good morning, everybody. First of all, I am genuinely pleased to be here today to be able to talk about our products, what we've been doing, and, and what we see for the future. Just before I do that, just a little bit about me. So I joined 12 years ago. I came from Reckitt Benckiser, so I joined pre, the demerger. I then stayed, obviously, and became the Chief Commercial Officer at the demerger. So been with the company 12 years now, based in Richmond, in the U.S. So let's take a look. So first of all, just a reminder of what products we're gonna talk about today. So predominant presentation is really about SUBLOCADE. That's our long-acting injectable for the treatment from moderate to severe opioid use disorder. Mark mentioned that, you know, our view is this is greater than $1.5 billion opportunity. Next, I'll talk about OPVEE. So OPVEE is our product for nasal spray for the emergency treatment of known or suspected opioid overdose. So we purchased OPVEE when we bought the Opiant acquisition last year, and we launched it late last year. Very excited to talk about that when you look at what's really happening in the US at the moment. And we've put a peak net revenue goal anywhere between $150-$250 million. Then we have PERSERIS. This is a long-acting injectable, similar technology to Sublocade, and this is for schizophrenia, with a target of $200-$300 million. Let's start with Sublocade. So first of all, if we take a little look geographically where we are, and I've put all the other products, so you can get a sense, really. So you see where we are with SUBLOCADE. The blue is where we're available, the orange is where we're approved, but not yet marketing. So really, you know, six key countries in Europe, U.S., Canada, and Australia. Then if you look at SUBOXONE Film, while we're not going to talk about that today, I think it's important to recognize while SUBOXONE Film is an older technology in the U.S., actually in Europe and Canada, it's newer technology. So we're rolling that out there, and that's newer technology versus the tablets. So the first point really is the U.S. is our highest value stake in terms of the markets, and if you think about it, there are a few reasons for that. So number one, the opioid misuse, when you look at that on a global scale, and the opioid misuse is really what started a lot of the opioid crisis in the U.S., so the heavy prescribing of opioids. And if you look at the misuse per capita, you see there, the U.S. is significantly higher than anywhere else. So number one, an underlying issue within the U.S. with regard to opioid misuse. Then, if you look at some of the other market dynamics, we already touched on the sort of liberal prescribing of pain pills, and I think, again, like I said, that really started a lot of the challenges that we're seeing. Unfortunately, you've only got 1 in 5 actually getting treatment, so I think you've got a significant opportunity to close and address the treatment gap, and we'll get into some of those challenges and what we've been doing to drive growth, really, to close those gaps. And then the other area is we still have very limited patient access to treatment. And if you think about it, if you try to get treatment for opioid use addiction compared to any other disease, you'll find it's a lot more challenging to find someone that's able or willing to prescribe. And I think that's another reason that you'll find that we've got great growth potential in this market. If we also take a look and say, "So what, what are the dynamics underlying?" We've seen sustained mid- to high-single-digit growth of the market, again, being unlocked by some of the activities that we've been doing. You're also going to find that there are increased access to treatment, and I'll touch on some of those things in a minute. So there are things that are being unlocked. It's becoming more of a normalized, medicalized treatment area. And then finally, if you look at the the political landscape, it is a bipartisan issue. So we found that no matter what or who is there, the actual actions they're taking are really driving towards deregulation of some of the challenges we've got, and also really helping to sort of, like, drive awareness and remove some of the challenges in the marketplace. We expect our patient numbers around 2.8 million by 2030. If I drill down and take a little look, and you can see here we have a chart that shows different ranges depending on the source, so we typically use the middle, and we think that's the most accurate in our opinion. So there's about 9 million people currently misusing opioids, so they may not have a diagnosis, but they're misusing opioids. If you then look and drop down, there are about 3.1 million people who have been diagnosed with opioid use disorder. So they're currently people that have recognized that they have an issue that they need to hopefully do something about. And then the 1.8 million, that represents people within a year that have sought out treatment. I want to talk about BMAT. That's buprenorphine medically assisted treatment, which is the active ingredient that sits in SUBLOCADE. So 9 million misusing opioids, 3.1 million that have got a diagnosis for opioid disorder, and about 1.8 million in the year getting some form of treatment. So what's been going on, and why are we seeing the market starting to grow at mid- to high-single digits? And I think there's a number of reasons, and I've pulled out some key, key points here. First of all, DATA 2000. So DATA 2000 was the legislation that originally allowed the prescribing of these medications within doctors' offices, but it came with a number of restrictions. So first of all, the physician had to be waivered. They had to take some level of education, be waivered to be able to be allowed to prescribe. There also became with data... With the patient limits. So when they first became waivered, they could only prescribe to 30 patients. That could extend to 100, and then more recently, that changed to 275. But what actually happened at the end of December 2022 was this was all removed. So if you look and think about the marketplace, it's starting to operate and look more like a normal condition. If you went to get treated for hypertension, cholesterol, you'd walk to a physician, and they would be able to prescribe it. So these areas are removing some of the barriers that we saw. If you look at the prison system, and I'll talk a little bit more later about that in more detail, but if you look at the prison system, there are a significant number of people that are in prison that are suffering from opioid disorder. If you go back 2 or 3 years, there was hardly any access to any drugs for people incarcerated, and just today, we've now got at least 15 states that are offering comprehensive treatment behind the prison walls. I think that will continue to grow quite fast. Telehealth expansion. Again, if you think about stigma, apathy, patients trying to find somewhere to go prescribe. During the pandemic, they allowed the prescribing of these products via telehealth. This, again, is another opportunity that's continued to be extended, and I think, again, another example of how we're seeing access being opened up so patients can get the treatment that they need. Then finally, if you look at the sort of areas of spending, we've seen significant increased spending being put into this area. Today, the government's over $45 billion.... Actually, the other area is if you look at the global opioid settlement funds, so these are the funds that you're all aware of, and they're going to be spent over the next 19 years. So today, they're being passed from state to county, and their expected endpoint is meant to be used for the help of treating opioid use disorder. So we expect that the $50 billion over the next 19 years will start to trickle down and will start to really help drive this market in terms of access and penetration. Let me just dive a little bit on what Mark spoke about with regard to the overdose crisis that's really, really impacting in America. So what I've done here is I've taken a chart, and I've tried to show what's really happened over the years. So on the left-hand side, you've got the deaths per thousand, and today, at the moment, you've got about 75,000 people dying every year due to synthetics, and that's just in the U.S., synthetic opioids. So what you see there, wave one really started with, as I mentioned, the prescription opioids, and you see there the green line, and you see what started to happen there. So this is where addiction started to happen. You start to see people overdosing there. Then you started to move into heroin. So again, as the pain pills became harder to get, people were accessing heroin, and you see there the blue line. But what's terrifying is wave three, which is the synthetic opioids. So these are easily manufactured, not difficult ingredients, cheap, and unfortunately, you can see, you know, in terms of power, they're significantly more powerful than heroin. And what's going on is they're actually within, you know, the illicit drug supply, so a lot of people aren't even aware that they're taking pills that contain fentanyl, and you're having... Well, you can see there for what's happening. So you've had this huge explosion in people, unfortunately, you know, dying due to overdose, taking with synthetics and fentanyls. And I'll talk about wave four when I talk about OPVEE. I think there's more relevance there. So actually, you've got a situation in the U.S. at the moment that opioid overdose is a leading cause of death for people aged between 18-45, and 92% of the deaths are due to synthetics. So, stark facts when you consider opioid use disorder. So how has that changed, and what's the relevance for our organization? Well, what I tried to show here really is what were the goals before for a treating physician? So the goals before were about abstinence, really. So how do you stop someone from taking illicit drugs and get them into treatment? Now, what typically would happen is to take them, you'd have course of relapse, and it would be a cyclical process of acute episodes, but the risk of anything was quite low. You'd be treating with Medicaid, with medication for opioid use disorder, typically buprenorphine, and you're looking at therapeutic levels. Now, we talk about here 2 nanograms per ml, so this is blood plasma levels, and Christian will go into a lot of detail about why that's key. But simplistically speaking, what ASAM, the American Society of Addiction Medicine, how they were talking about the treatment goals is you want to be managing the withdrawal and suppressing the craving. So withdrawal is the pain a patient's feeling when they're not taking an illicit drug, and the craving is the desire. So they were looking to treat to a certain level when the withdrawal and craving subsided. You're looking at blocking the high, so if a patient tried to take a drug, they wouldn't get a reinforced benefit from the high of taking an illicit drug. And really, it was about getting patients into recovery activities, back with the families, back into a job. So those were typically what you were seeing, and they were happening cyclically as people fell out. They disappeared for a few months, then they came back. When you think about now the greater risk due to the synthetic opioids, you know, what's happening now is really, it's an obsession about reducing the relapse rate. Relapse rates now have a significant higher risk than what they did before with regard to overdose. So it's about reducing the relapse risk, reducing the risk of overdose, reducing mortality, and really trying to, you know, extend the time that patients remain in treatment, not relapsing and putting themselves at risk from overdosing. Now, if you think about what that sorts out the need, you're looking for something that's going to last longer, because prior to a long-acting injectable, it was a daily tablet. So the patient had a choice whether to take it every single day. So you're wanting something to last longer. The challenge with dailies is that the blood plasma will go up and will go down, obviously, over the 24 hours. So you're looking for something that's going to be more even over the full month. And then now with the sort of situation with synthetics, you're looking to have higher blood plasma levels, not just to maintain the withdrawal and craving, but to actually start to look at how can you reduce mortality rates if a patient does slips and takes an illicit drug. And again, Christian will really explain the science behind why that's relevant. So if you look at the SUBLOCADE, first of all, I'd say, you know, we really think this is a product that's really meeting today's challenge of synthetics and what a doctor is looking to achieve in treatment. So first of all, we have two strengths. We have the 100 milligram and the 300 milligrams. So the 300 milligram, you typically will inject for 2 months, and then the physician has a choice whether they want to continue on the 100 milligram, which typically delivers 2 nanograms per ml over the, over the month, or whether they would like the patient to retain on the 300 milligram, that typically delivers more like the 6 nanograms per ml that we spoke about. Today, we have over 40% of the patients in growing that are staying on the 300 milligram. So if you think about what SUBLOCADE is doing, it's suppressing the high. You don't get the daily fluctuations. You get the continued sort of like clean level of plasma. We know we reduce the illicit opioid use. We know this from our pivotal trial. We know this from six years of real-world evidence... and we extend the efficacy and the higher potency of opioids. So we, in most cases, block after one injection, nearly all, and then after, continued effect for eight weeks after the second dose. So again, we're putting patients in a, in a good place. So what have we really been doing since launch? So on the left-hand side, we're showing you the number of patients that we've been treating on an annual basis. If I look at quarter one for 2024, that's continued to grow in the same vein. You know, so the greater than $1.5 billion we're targeting, about 270,000 patients, we're already halfway there, so we're confident of delivering on the +$1.5 billion target that we, we've set ourselves. How we've gone about it? Really, I'll talk a little bit more. So one is about accelerating adoption in the organized health systems. I'll, I'll talk about patient sites and what these things are. Secondly, it's about continuing to expand access to the criminal justice system. Today, that represents about 25% of our net revenue if I look at Q1 2024. And we've really refined and got a proven go-to-market success model, I would say. So it's about how we continue to refine and how we continue to support in key areas where we think we can drive further improvements. I'll, I'll touch on that also. So if we drop down a little bit, trying to show here, where do those 3 million patients, where are they flowing through? So if you think about an OUD patient, they typically are flowing through different areas. It's not that they're static sitting in one. So, for example, while I know there's about 1.2 million potential patients behind the walls in criminal justice system, clearly, if they're in a state prison, they may be there for 3 or 4 months. They're gonna come out, they may end up in a key account. So you've got to see this as fluid. So what's critical for us is to gain access in all the key channels so that wherever a patient presents, there's an opportunity for treatment. So if you look at integrated delivery networks, these are really hospitals, federal healthcare systems will be like the VA, and then key accounts will be things like in-treatment patient facilities. If you look at why we've been successful there, we quickly identified that they're very organized, and they have the resources required to manage a product like SUBLOCADE, which is an injectable product. So the delivery of the product, the storage, the security requirements, the coordination of the patient. So again, a great fit, and they were really looking for, you know, a product that could help them in terms of managed costs. So a good fit there. Criminal justice system, again, an LAI is a really great fit. If you think about an oral product, if you're trying to treat a patient with an oral product, you would have to have 2 officers take a patient down every day. They would have to wait with them for 5-7 minutes while the product dissolves buccally under the tongue. Then you would have to make sure they've not cheeked it. You would then have to walk them back to their cell. So if you think about the time, the cost, and the coordination, versus a LAI, where basically you'll take a patient down, you can give the 1-month injection, and you can take them back. So again, from a prison system, the LAI is really the thing that's helping to unlock this opportunity, and it's why we've seen quite a bit of success in this area. And then finally, we have the independent practices where we had, you know, great business previously with SUBOXONE Film. But what was obvious from the launch was that, you know, they don't really have the resource to manage something like a long-acting injectable in any scalable way. Now, what's happened with DATA 2000 is one of the really good things is that with, with those changes, it allowed us to launch an alternative site of care. So that really is now an area where an independent physician can send a patient to go get an injection somewhere else. So they will manage the logistics, the coordination, the storage, the security. So really relieving the burden and the thing that was really challenging for them. So that's something that we'll start to look at also. Now, this is a busy slide, but this is intended to really show you at the heart of our model, what we're tracking, how we track, and how we're doing. So on the top, with the three circles there, we track how many facilities exist within the organized healthcare systems. Then we're looking at how many HCPs sit within those facilities, and then how many patients we think are flowing through those facilities. And we really drive our organization to unlock, one, the facility, then get the doctor to start prescribing, and then get the doctor to start adopting in terms of changing the number of patients they're treating. And if you look on the right-hand side, we've shared with you a little more detail there to show what growth rates we've been really achieving versus 2022. So these were the in 2023 numbers. If you look at CGS, where we started later in our journey, you can see again how we're looking at facilities. So how many facilities do we think would be able to treat in this area? Do they have the ability to? And then, how many patients are really sitting there? So you can look at how many facilities we've activated and how many ordering facilities we've got. And if you consider now that that's, you know, 25% of the net revenue, you can see again, you know, great potential in this area. So we spoke about, you know, our proven go-to-market model. So one of the things we did this year is that we increased our field capabilities. So we increased it by 50% for the field force, so now we've got a team of about 180 people just visiting the healthcare professionals. And partly the reason for that is that the change in the law allowed us to now target the independents. It means we can go from a call platform of about 8,000 doctors to 12,000 doctors at the right frequency that you would need to be seeing these doctors. We also took the time to increase our criminal justice team. That's really gone very fast, so now we have a team of 40 dedicated people that are targeting only the criminal justice system. And on top of those numbers, what you don't see, we also have a key account team of about 25 people that are working to unlock the organized health systems.... Now, while I don't have the medical affairs team reporting to me, they report to Christian, we thought it relevant just to share on this slide. So clearly, with the increased coverage that my team has, we'll be getting more medical questions. So Christian took the opportunity also to extend his medical science liaison team to help with some of the more challenging questions that get put through his team. On the right-hand side, this is a pin graph just to show you where we are with these alternative sites of care. So as I've mentioned, the law recently changed. This allowed us to start thinking about this. So we've done a partnership with Albertsons, and that's why you're seeing a very heavy west geographic sort of like program. But our intent over the next 1-2 years is that you'll see this fill out in the center and to the East Coast. Our vision is that any physician, wherever they are, has an opportunity to send a patient to an alternative site of care. And if you also think about telehealth, the telehealth people, we're wanting to send patients also. So by doing this, we really start to unlock independence, we really start to unlock telehealth in terms of making these, these areas really potentially scalable. So just to close out on SUBLOCADE, we think this remains a compelling opportunity. We remain confident about the $1.5 billion. And I think if you look at some of the statistics and things that I've put on there, just to remind you, you know, you've got a 1 in 5 treatment, a big gap there. You've got things like a growing, increasing awareness and funding. You've got a product that we believe is well suited for today's crisis, and Christian, again, will really double down and go into the science to explain why we're confident about that. And then we've got a model that's working. You know, we've got compelling growth rates, and we think that will continue for the foreseeable future. Okay, so now I'm going to move, and I'm going to talk about OPVEE. So just a reminder, OPVEE, we launched late last year. It came with the Opiant acquisition, and this is really a reversal medication, a simple nasal reversal medication. Very excited on this. So I promise I'd come back to this chart. It's slightly different than what I showed you. So what I wanted to touch on here was really wave four. So you're aware of the deaths that are happening due to opioid overdose. You're aware that it's fentanyl and the other synthetics that are driving this due to their, you know, powerful nature. But what I want to show in wave four was what we're seeing, and what's being reported is, there's a growing level of deaths that are happening, not just now with someone thinking they're taking an opioid, but you may take cocaine, and the cocaine is laced with fentanyl. So now what's happening, unfortunately, things like, methamphetamines, cocaine, have been laced with fentanyl. So suddenly, you're having deaths on cocaine that you weren't seeing before. So this whole area is taking on an even scarier sort of like, position, I would say. So what's going on there, and I tried to show in the chart, so this is fentanyl with no stimulants involved, but fentanyl with stimulants. So look at the death rates there. So again, this isn't a situation of someone wanting to take an opioid, they're taking fentanyl and overdosing. Now, you're seeing this is someone that's thinking they're taking cocaine, and they're overdosing on cocaine. They don't even have an issue with opioids. So you can argue it's poisoning rather than someone with opioid use disorder looking to find illicit medication. And on the right, there was just a couple of stats. So this one came out last week. 115 million illicit pills were sort of like seized by the U.S. authorities. If you look at what that was in 2017, again, that goes along with what you're seeing with the deaths and the spike. I think what's going on there is, you know, the concerning fact for me is it isn't the ones that seize it, the ones have not seized, bearing in mind the simple, easy nature to produce and manufacture. At the bottom, I put a penny so that you can see, you know, how much fentanyl is required to be potentially lethal. Again, Christian will actually touch on that a little bit, but we're talking hardly anything. So, you know, quite terrifying statistics. It's the reason why we really bought Opiant, because we saw great value in OPVEE. Now, if you look at what's going on here, you've got the National Institute on Drug Abuse leadership. They're calling out for stronger, longer, better products. In fact, you know, they actually were responsible partly for the development of OPVEE via a grant. So they've supported the development of this product. If you look now to save a life, first of all, you have to assume a synthetic is involved, so you need a product that's going to deal with a synthetic. And the standard of care today is naloxone, or you might know it as maybe Narcan, which is the brand name for naloxone. Unfortunately, now you're needing, you know, numerous sequential Narcans to potentially save that life, because, again, when that was launched, that was a heroin or a pain pill issue. Now, it's a synthetic issue, so multiple doses required. And again, if you look at people that are, that are using it, unfortunately, they're recognizing that you need multiple doses. So, you know, if you've got multiple doses, great. If you haven't, then, you know, you've potentially got an issue. So if you look at OPVEE, again, we've got something that works fast, lasts long, and is really uniquely suited for the synthetics. So, you know, on the label, we've got that it's for synthetics. We're the only one that have that. And I think going back to the development, and this was done by NIDA, and also the Biomedical Advanced Research and Development Authority, which is the, the authority really looking after the US. So they were concerned that fentanyl could be weaponized, so they're concerned, so they also, you know, helped in the development of this. Now, I'm not going to touch on the science. Again, I'm going to leave that to the clever person, and he'll explain really how this is working. But what we have here is a product that really will deliver on, you know, the synthetic risk that we've got. My team's job really is twofold. One, we've just launched, so we need to open access fast. So how we open access fast, there's two things we're doing. One, we need to make sure every state a standing order is in place. And our standing order allows is a prescribable product like OPVEE. It allows the free movement within that state without an individual prescription. So it allows this to be used, it allows this to be sort of like moved along within the state. So we're targeting states, and we're really changing the laws if required, or we're changing the language patterns if required. So we've made great progress since launch there. And on funding, again, we wanted to make sure that if-... Anything that was funded for naloxone was also funded for OPVEE. Again, I think with the SAMHSA grant updated, we've pretty much achieved that. Again, if you're wanting to use OPVEE, the same funding vehicle should be allowed as they would be today with naloxone. Where are the areas that we're targeting? I've put up there on the right. I'm not going to read through them, but I'm going to give an example with the law enforcement. One of the key things that we identified very early on was experience programs are going to be critical to show what we can do and leading to adoption. You know, Narcan and naloxone has been the standard of care for a lot of years, have saved a lot of lives. But what we need to show is, what's the difference? So how can I get what I see from the clinical trials, and how can I show what that does in real life? We undertook a pilot in Oakland County, Michigan, and I have a few points here. What we did here—well, we didn't do it actually, but what the people did, they basically created the funding. They made sure there was a standing order in place, and then they took the key people within that police department that saved multiple lives, about 20 officers, and they trained them on OPVEE. They weren't going to use Narcan. You're going to use OPVEE. We trained them. They were trained to make sure that they only use one OPVEE, and they wait 2.5 minutes. So this is not a product where you're needing to do multiple shots straight away. You do one, you wait the 2.5 minutes, and then, if required, you would do another one. What we saw there on the bottom, you can see we had, as of tenth, we had 63 reversals and only 74 units reversed. So I think you can do the math with regard to how many units are being required to save a life. They've already ordered again, and the other area what they've done, they've now expanded that to the rest of the force, to more of the, more of the team there, they've been trained. And at the bottom, we just got a quote. You know, "We are seeing amazing recovery responses for respiratory response, conscious and cognitive restoration." So we know that they saw what we believe the product could do. So experience programs really is what we need to be driving that will lead to adoption. And as I wrote this, I think we had about 180 lined up. I already know that's above 220 as I checked in yesterday. So we're getting a great response from that, and we expect, you know, with the access opening and with the experience programs, that we should, we should see good results. So BARDA, I touched on, you know, they've, they've, they've really supported it. So we executed a contract in 2023. It's potentially worth up to about $110 million. It's a 10-year contract with options in, and we really expect the first delivery of this in Q3 2024, for a value of about $8 million. So, you know, we're pleased to get that and move that along. So again, just in summing up, $150 million-$250 million is what we believe. We have a differentiated product that's really right for today's crisis. We've got an experienced commercial team, so what I didn't touch on is that when we bought Opiant, we brought the commercial team with them, and they were the team that launched Narcan back in the Adapt Pharma days. So again, you know, for us, we didn't want to have to relearn this market. We wanted a team that could cut through it very quickly, so we brought them with us, and I think their insights and knowledge and people have been excellent, and I do think that'll help speed up, you know, success commercially for us. And then, as mentioned, we've got an experience program that we've put in place. Okay, PERSERIS. So this is our product for schizophrenia, long-acting, injectable. Just very briefly, just touch on what happens with schizophrenia. So I've tried to capture here a typical patient and maybe what happens. Unfortunately, their life is going to be always with schizophrenia. This is not curable, and it's going to be a life where you will have cognitive decline, relapse, cognitive decline. One of the critical areas of treatment really is about helping patients stay in treatment and on medication to avoid the relapse, which causes the cognitive decline. So a long-acting injectable that lasts a month really is going to be, you know, a great product in this market. Very relevant. If you look at the patient funnel, similar to what we showed on SUBLOCADE, you've about 2.8 million patients with schizophrenia, a lot more of those patients in treatment, but yet still only 500,000 on an LAI, even though they were launched back in 2003. I'll show some of the market now, and in fact, if you show there, quite a slow climb for a while. Competition started to come in. That really started to legitimize LAIs, more salespeople selling it, and you can see there, and then a rapid growth, and in fact, it continues to grow rapidly, yet it still sits at about 17% of the total market. Where are we? So the market splits based on patients. So on the left, you've got patients that present with positive symptoms, so this will be things like hallucinations, paranoia, and we sit in there in the largest part of the market, which is about 67% with risperidone. And then on the right-hand side, it's negative symptoms, so mood, depression would sit on the right-hand side. So again, we're in the largest part of the market, and interestingly, the one monthly format represents about 80% of the market. So we sit in the largest market, in the largest format in terms of the, the treatment paradigm. Why are we confident on PERSERIS? So I think, again, if you think about these patients, the key thing is to get them into treatment and stabilize them as fast as you can. So we have a product that gets to peak plasma in about 4-6 hours, so very fast. Doesn't require loading dose, oral supplementation. So the good news is it's one injection, 4-6 hours, and then we have optimal dopamine receptor occupancy for the entire month. So again, it's one injection, 4-6 hours, no on-top dosing, and it lasts a month. So again, very good product in terms of the needs of a schizophrenic patient. And then we have the, the known safety profile of risperidone, which is a, an old molecule. So again, from that point of view, that's good for us.... One little insight. So if you look on the left-hand side, this is the market, and you can see there the number of prescriptions, but then you can see how many new to brands within the last 12 months, or how many people are moving within there. So it's about 7% are swapping a new brand in the last 12 months. If you look at PERSERIS, that sits at 16%, which tells me that as we go forward, our share will continue to grow as we attract new patients at a faster rate, yet we retain the old patients at the same level as the, the rest of the market. So in summary, remains an attractive dynamic drawing market, still representing only 17% of the market, and I think there's a long way to go for LEIs in this market. We've got a differentiated treatment profile, and we have, you know, great executional excellence, where we've been delivering for a number of years. With that, I will now pass to Christian, who will take you through the R&D section. Thank you. Thank you, Richard. Good morning, everyone. My name is Christian Heidbreder. I'm the Chief Scientific Officer at Indivior. I joined the company back in 2009, so 2024 is my 15th year with the company. Today's agenda from an R&D perspective is actually sixfold. First, I will give you a general introduction to the research and development and medical affairs and safety organization. Second, I will give you an overview of the pipeline in opioid use disorder, and I will focus on three main products, SUBLOCADE, that Richard introduced to you. And then two products currently in development, INDV-6001, which is a three-month long-acting injectable formulation of buprenorphine and INDV-2000, which is a selective orexin-1 receptor antagonist. I will then talk a little bit more about OPVEE and the current situation we are facing from an opioid overdose rescue perspective. And then we will shift the gears towards cannabis use disorder, where we'll talk more about our partnership with Aelis Farma and the pharmacotherapy that we are currently developing. And then finally, alcohol use disorder. General introduction with respect to the fairly dreadful epidemiology data, as well as the product that we are currently developing in collaboration with Addex Therapeutics, which will lead me to draw some general conclusions. So let me start with the R&D and Medical Affairs and Safety organization. As you can see, we have a dedicated and experienced team globally. I'm very proud of leading this team with all the key functions in research and development, as well as medical safety and field medical affairs. We do have main laboratories and offices in Richmond, Virginia, Fort Collins in Colorado, as well as Hull, Slough, and London in the United Kingdom. You can see we're about 235 full-time employees, 137 in R&D, and almost 100 in medical affairs and safety. We do have long-standing innovation leadership in the treatment of opioid use disorder. Actually, it goes back to 1966, when we discovered and synthesized buprenorphine in the Reckitt and Colman labs in Kingston upon Hull in the United Kingdom, where we are still manufacturing the buprenorphine drug substance, and where we do have R&D facilities. Actually, that discovery led to several buprenorphine-based products for the treatment of opioid use disorder. We have sublingual buprenorphine tablets, sublingual SUBOXONE Film, and then more recently, the first monthly long-acting injectable formulation of buprenorphine that is SUBLOCADE. Mark talked a little bit about the numbers that you see there in terms of addiction medicine. Clearly, because of the changes from an epidemiology perspective, our main strategic focus is on opioid use disorder, cannabis use disorder, and alcohol use disorder. But also, we always look for the right opportunities in other forms of substance use disorder as well as associated comorbidities. At the end of the day, our vision is to really pioneer drug discovery and development in addiction medicine, and we are doing that by generating, world-class, science, new real-world, evidence, and also by articulating the clinical and economic value of our medications. This is our pipeline. Richard talked about SUBLOCADE, OPVEE, PERSERIS. Then, I will give you a little bit more information about all the new real-world evidence that we are generating right now to support, particularly SUBLOCADE and some of the new science to support OPVEE. Then I will take you through all the programs that we currently have in our pipeline. Let me start with opioid use disorder, and, let's, go for SUBLOCADE first. I think it's very, very important to go back to the scientific foundations of SUBLOCADE, and that lies actually in a very in-depth understanding of the relationship between plasma concentrations of buprenorphine, mu opioid receptor occupancy in the brain, and then clinical efficacy and safety. So I want you to pay attention to this graph. You can see that, actually, and I see if I can use this. Yes, it seems to work. So if you increase buprenorphine plasma concentrations here, you can see that there is a threshold at which you start seeing clinical efficacy and keeping safety. That said, if you manage to further increase buprenorphine plasma concentrations, you continue to see some clinical benefits. And incidentally, the first concentration you see there, 3 ng/mL, leads to this additional increase. Now, if you manage to go a little bit farther up, up to 6 ng/mL, and this is actually what is delivered by SUBLOCADE, the 300 mg, you continue to see improvements in terms of abstinence, management of withdrawal symptoms, and management of cravings. And at the end of the day, if you think about this, all this makes perfect sense. And the reason for that is that if you are really there at the low levels of buprenorphine, unfortunately, few brain mu-opioid receptors are occupied by buprenorphine, which means that more mu-opioid receptors are actually available to illicit opioids. Now, look at what happens if you are there in this sweet spot between 3-6 ng/mL. Now you're in a completely different situation. More than 70% mu-opioid receptors are occupied, which means that few mu-opioid receptors are actually available for illicit opioids. So this is really where we started. And then the goal, pardon me, was to generate a new real-world evidence to really translate all that scientific understanding into real-world evidence. So I will now spend a few minutes to share with you some most recent data. The first part is to stay along this mode of thinking of relationship between plasma concentrations of buprenorphine, and in this particular case, the probability of respiratory depression and actually probability of apnea, that is cessation of breathing, if you are exposed to fentanyl. So let me try to take you through this particular graph. Here again, you have buprenorphine, plasma concentrations, probability of cessation of breathing, and then here you can see increasing doses of, fentanyl. Now, I will take you through two examples. If you are here, that is very low levels of buprenorphine on board, but you have been exposed to a high concentration of fentanyl, you basically have an 85% probability of apnea that will lead to respiratory depression and lead to cardiac arrest. So 85% probability of death. If now we go along this continuum, and you reach 2 nanogram per ml and 5 nanogram per ml, and I remind you that these are actually the concentrations that are delivered by SUBLOCADE, that probability of apnea decreases down to 12% with 2 nanogram per ml and 5% with 5 nanogram per ml. That is to show you the power of that relationship between plasma concentrations of buprenorphine and clinical endpoints. Again, we can link all that to calculations we made in terms of mu-opioid receptor occupancy in the brain at different plasma concentrations of buprenorphine. Let me now talk a little bit about rapid induction with buprenorphine. Currently, according to label, patients need to be exposed to sublingual buprenorphine for at least seven days before they can receive their first injection of SUBLOCADE. Now, in this study, we are trying to see if it is actually feasible to induct treatment with SUBLOCADE significantly faster. So what we are currently doing in this particular study is to expose patients to a single sublingual administration of buprenorphine of 4 milligrams, and then we give the first injection of SUBLOCADE immediately afterwards. The big question today is: How do you do that, particularly in patients who have been exposed to fentanyl? And in this study, we actually compare two groups that you can see here, fentanyl-positive patients and fentanyl-negative patients. And we measured what we call the Clinical Opioid Withdrawal Scale or COWS scores. You can see that baseline, most of these patients are in a moderate withdrawal. They receive then their first administration of SUBLOCADE, and you can see that in both groups, within 24 hours, they go below a value of 5 on the COWS score, which basically means no active withdrawal at all. In this study, we looked at retrospective chart reviews of patients with opioid use disorder who had initiated opioid agonist treatment, that is either sublingual Buprenorphine, methadone, or SUBLOCADE, and we looked at the total non-fatal opioid overdose events. Look at the data, they speak on their own. We could see that SUBLOCADE treatment was associated with the lowest rate of non-fatal overdose events. Only one event there, 10 events for sublingual Buprenorphine, and about 18 events for methadone. We are currently confirming these retrospective data with prospective clinical trials that we actually are currently publishing. Now, here we are sharing with you the first pilot experiment of using SUBLOCADE in the jail system. Actually, in this particular study, Dr. Josh Lee was very much interested in what would happen if you administer SUBLOCADE prior to release, and then see what happens several weeks after release from jail. The first observation is that patients in the SUBLOCADE arm had significantly fewer jail-in-jail medical visits per day, compared with sublingual buprenorphine. Second observation is that the percentage of patients retained on any form of community buprenorphine treatment, 8-week post-release, was about 70% for SUBLOCADE, 35% for sublingual buprenorphine. If we look at the retention on the originally assigned treatment, again, 8-week post-release, 57% for SUBLOCADE, 35% for sublingual buprenorphine. Negative urine drug screen was, again, 55% for SUBLOCADE, 38% for sublingual buprenorphine. And then they looked at reincarceration, it was about 8% for SUBLOCADE and the double for sublingual buprenorphine. So these data, again, clearly indicate that, first of all, treatment with a long-acting, injectable formulation of buprenorphine is feasible in the jail system, but very, very importantly, it would basically help the patients to remain in treatment post release. And you may have seen this data. This is what we call our RECOVER study. So the RECOVER study was really fascinating in the sense that we were trying to understand what is actually happening to patients who have been exposed to SUBLOCADE but stopped the treatment. And so we followed these patients up to 12 months after their last administration of SUBLOCADE. And the beauty of this study is that, actually, you can see that we had different groups of duration of SUBLOCADE treatment. So some patients had between 0 or 2 injections, 3-5, 6-11, or 12, months, so 12 injections. And we basically looked at what happened to them in terms of abstinence 12 months after their last SUBLOCADE injection. And you can see the results here. So for example, if you had received a SUBLOCADE for less than 2 injections, 12 years later, you had a probability of 24% to be still abstinent. However, if you had the chance to be in treatment with SUBLOCADE for 12 months, 12 months after your last injection of SUBLOCADE, you still had a 75% chance of being abstinent. This clearly indicates the very important message here, that the longer the SUBLOCADE treatment duration, the higher the likelihood you will remain abstinent, and the higher the likelihood that you may recover from this dreadful disease. This is the last slide for SUBLOCADE. Basically, in 2024, we have four main pillars in our strategy. First, a couple of label updates. The rapid induction data, you saw some pilot data today, but also what we call the alternate injection body site. Currently, according to label, SUBLOCADE is being administered in different parts of the abdomen, and we wanted to demonstrate that actually, the pharmacokinetics of the product is similar, irrespective of the injection site, so the abdomen being equivalent to the back of the arm, the thigh or the buttock. And so this is what we are going to share with the FDA in the third quarter this year. Then there are two scenarios: either we have priority review, in that case, the label would be approved in the first quarter next year, or under a regular review, then would be approved in the third quarter next year. Second pillar, as you have seen a little flavor today, but to continue to generate new real-world evidence data, externally sponsored studies with external collaborators, and independent medical education grants, as well as, of course, peer-reviewed publications and conference presentations. Third pillar is the product optimization. We basically used an oxygen absorber desiccant to extend room temperature of the product and shelf life extension. Then the fourth pillar is to continue to extend access to treatment. The second program that we have for opioid use disorder is INDV-6001. That's a three-month long-acting injectable buprenorphine. It is actually the result of a business development acquisition of the exclusive global rights to develop, manufacture, and commercialize Alar Pharmaceuticals' portfolio of long-acting injectable formulations of buprenorphine. And so we are focusing, for the time being, on a proposal for a three-month long-acting injectable formulation of buprenorphine. We are preparing currently a multi-dose phase 2 clinical trial, so that we understand better the pharmacokinetics properties of this product, either in isolation or in combination with SUBLOCADE to initiate treatment. And then in parallel, we continue to optimize the drug substance and the drug product manufacturing, as well as the required toxicology studies. And then the second program that we currently have under development is a selective orexin-1 receptor antagonist, which is actually being developed as being a non-opioid mechanism for the maintenance treatment of opioid use disorder. And this is very important because some patients may not be willing to stay on an opioid-based medication for extensive periods of time. So for those, we are developing this completely new approach, but there is a little bit more to this, and I will share that with you in a few seconds. But first, we published this article very recently. That is the full pharmacological characterization in vitro and in vivo of this molecule. So if you are interested, I recommend you to read the paper. You will have a lot of information there. It produces very high levels of receptor occupancy in the rat brain up to eight hours. And then in non-human models, so in animal models of addiction, we demonstrated that this compound decreases self-administration as well as cue and stress-induced reinstatement of drug seeking. So we have been doing a lot of things. It started really in 2019 with an NIH, National Institutes of Health, grant of $10.6 million. It really allowed us to move this compound from non-clinical stages of development to clinical phase one. So you can see a lot of activities there in terms of characterization of the safety and the tolerability of this drug in human beings. But we did a lot of work also from a formulation development perspective and preliminary talks, studies. All that culminated in November last year in what we call an end of phase one meeting with the FDA upon which we agreed on all critical aspects of non-clinical and clinical development enabling us to start what we call a clinical phase two proof of concept. And I'm glad to share with you that the first subject first visit was achieved on the first of May. We are also initiating now drug substance manufacturing making sure that the drug will be available for future clinical phase three trials. I forgot to mention that, that clearly, on the one hand, we are excited about developing a non-opioid mechanism for opioid use disorder, but we also believe that, this, mechanism of action may be relevant to other forms of, substance, use disorder. There has been, really nice, literature on, stimulant use disorder and even alcohol use disorder. So for all those patients who may suffer from polysubstance drug, disorder, that might be an additional opportunity that we will certainly explore during the, clinical development. So that's for opioid use disorder. Let me now move to opioid overdose, rescue, and, perhaps again, mentioning, some dreadful, situation, here. Richard already mentioned these absolutely horrific numbers that were released a couple of weeks ago with the 115 million pills containing illicit fentanyl seized last year by law enforcement. And again, to give you an idea of the magnitude of the situation, this number was 2,300 times greater last year compared to 2017. Now, there are a few additional very, very challenging numbers that I would like to share with you. So in the U.S., we now have more than 20%, and actually, in some regions, it's more than 35% of fatalities that actually had evidence of naloxone administration. So we found naloxone post-mortem, but that clearly did not prevent a fatal overdose. The other thing that Richard actually mentioned already is the unintentional fentanyl use among people without opioid tolerance. So in other words, these are people who have never abused opioids. They are not chronic opioid users, and yet they suffered from an opioid overdose. And that is because what you see now is stimulants or even cannabis being laced with synthetic opioids... And then some numbers again, and please note that all these data are very recent. They were published in 2024. Adolescents and even children younger than six years of age and are exposed to potentially lethal doses of synthetic opioids. So I hope that this is giving you a flavor of the dramatic change that we are facing, and that comes with major challenges in order to reverse these overdoses. So what are we doing then, from an R&D and medical affairs perspective? There are many things that we started. First of all, in collaboration with the Biomedical Advanced Research and Development Authority, BARDA. This is an organization that is also helping us to initiate post-marketing requirement studies that we received from the FDA at the time of the NDA approval last year. So we are performing pediatric studies and some additional toxicology studies to characterize the nasal absorption enhancer that is in the formulation of OPVEE. Product optimization to extend the shelf life from 28 to 36 months. And then from a medical affairs perspective, we started generating real world evidence to really understand how OPVEE is actually behaving in real world. Pharmacovigilance support, making sure that we monitor constantly the safety of OPVEE, but also comparing to intranasal naloxone, and then peer-reviewed publications and conference presentations. Now, talking about peer-reviewed publications, I would like to take two examples of those that are very recent. And let me start with this first study, where we basically compared intranasal naloxone to intranasal nalmefene in response to remifentanil, which is another synthetic opioid, remifentanil induced respiratory depression. Now, let me try to explain this graph here, and how we typically model basically a respiratory depression. So what you have here is a relationship between time and what we call minute ventilation. That is basically the respiration. So because we are dealing with healthy volunteers, the first thing you have to do is to try to create hyperventilation. So you increase respiration, you increase minute ventilation, and you do that by exposing the subject to carbon dioxide. Once you reach a certain level, this is the point at which you administer the synthetic opioid, and as you can see, very, very quickly, these synthetic opioids decrease respiration, so we have a massive decrease in minute ventilation. It is then at this point that you administer your antidote, that is either intranasal naloxone or intranasal nalmefene, and then you observe, basically over time, the difference between the two products. I want you to pay attention to the little inset here. So you can see that with intranasal nalmefene, OPVEE, you could go back to the pre-remifentanil baseline within the first 5 minutes, whereas it took approximately 20 minutes to achieve the same effect with intranasal naloxone. So that was a very, very important piece of data. Very fast onset of action, and this is exactly what you need for synthetic opioids, because they themselves are so fast. Now, the next one is a little bit more challenging, and I swear I will not take you through the left-hand side of this slide. But this is a model that was actually created by the Food and Drug Administration to really model a synthetic opioid overdose and how you can potentially reverse it with an agent such as either intramuscular naloxone, intranasal naloxone, and then we did the work for intranasal nalmefene. So at a very high level, basically what this model integrates are pharmacokinetics, data of the synthetic opioids, in this case, fentanyl, carfentanil, and then of the so-called antidote. The FDA started with intramuscular naloxone, then they did intranasal naloxone, and then I will show you what we have done with the model. There is then a receptor binding component on the mu-opioid receptor in the brain, and a pharmacodynamic component that is basically all the factors supporting ventilation and respiration. So what we have done is as follows: first, we wanted to reproduce the data that the FDA had published, and we did that with intramuscular naloxone. Then we reproduced the second paper that was published by the FDA with intranasal naloxone. Then basically, we expanded the model with intranasal nalmefene data, and we also included in the model the data I shared with you on the previous slide with remifentanil. Then what we did was to predict cardiac arrest events caused by a synthetic opioid dose, either fentanyl or carfentanil, following rescue with either intranasal naloxone or intranasal nalmefene. So let me show you some of the data, and let's focus on fentanyl first. You may actually wonder why 1.63 milligram or 2.97 milligram. Actually, these numbers were calculated based on approximately 500 fatalities and the discovery of synthetic opioid levels, in this case, fentanyl, in these fatalities. For your information and benchmark, the Drug Enforcement Administration today is also considering that a 2-milligram dose is a lethal dose of fentanyl. And we also know, now unfortunately, you remember the statistics with the 115 million counterfeit pills, 70% of these pills had more than 2 mg of fentanyl in them. So you can see that with 1.63 and 2.97, we are in a pretty good shape and very close to the real situation that is currently happening. So let me focus first on the left-hand side, the 1.63 fentanyl. So first of all, let's pay attention to this. If there is no intervention, so no antidote on board, you basically have a 52% chance of cardiac arrest and death. Now, let's see what happens with a single administration of intranasal naloxone. It decreases that probability of cardiac arrest down to 19%. But now pay attention to what happens with a single intranasal Nalmefene. It decreases the probability down to 2%. But now let's have a look on the right-hand side. If unfortunately, you were exposed to a higher dose of Fentanyl, if there is no intervention, you have a 78% probability of death by cardiac arrest. 1 intranasal Naloxone brings that down to 47%. 1 single administration of intranasal Nalmefene brings it down to 12%. Another very interesting part of the data indicates that simultaneous administration of 4 doses of Naloxone barely reaches the levels of success that you obtain with a single administration of intranasal Nalmefene. And then last but not least, and this is a very, very important point, these data are from chronic opioid users. Unfortunately, if you're an opioid-naive subject, you are at significantly higher risk. In other words, plotting the same graphs in opioid-naive individuals, you see what we call a shift to the right. That is that, for example, without any intervention, you would have a more than 90% chance of dying from cardiac arrest. And so you see the challenges that we currently have in reversing these overdoses triggered by synthetic opioids, which means that we need new tools. We need to adapt to that situation as well. And we believe that intranasal Nalmefene, obviously, is one part of the solution. Let me move to cannabis use disorder, and first, a few epidemiology data. In the US, let me first say that as of January this year, about 38 states plus Washington, D.C., legalized cannabis for either medical or recreational purpose. You may have seen, also actually, this happened on the 21st of May, so a couple of days ago, a proposed rule by the Drug Enforcement Administration to actually transfer cannabis from Schedule I of the Controlled Substances Act to Schedule III, which means that the prevalence of use, if anything, will continue to grow and probably grow fast. We currently have about 62 million users in the U.S., but the scary part there, as you can see, about 19 million people have now been officially diagnosed with a cannabis use disorder. In Europe, the situation is problematic as well. About 23 million users and about 1.6 million officially diagnosed with a cannabis use disorder. What is becoming very, very clear, over the last few years, and there is a growing, growing literature in the field, is a much better understanding of the negative health effects of chronic cannabis, use. I will not take you through all the details here, but they can now be split into short-term effects and long-term effects. But what we really now understand is that it is probably a quadruple confluence of factors that is actually leading to an increase in cannabis use disorder diagnosis. The first one is clearly a growing prevalence of use, and you have seen the epidemiology. This is not going in the right direction. Second, an increasing intensity of use, in terms of frequency and quantities. Third, very importantly, rising in the THC content of cannabis products. So THC is one of the primary active of the cannabis plant that is responsible for the rewarding effect of cannabis and, and other effects as well. If I look at the data, 20 years ago, on average, cannabis had a 2%-6% THC content. Today, on average, we are above 20%, but some products now have more than 70%, 70% THC content, and that is becoming very, very problematic in terms of health consequences. And then the fourth factor is the age of cannabis use initiation. So what are we going to do with this? Well, this is where we started working with Aelis Farma, which is a small French biotech company. Because scientists at Bordeaux at the Inserm, which is a little bit the equivalent of the French NIH, discovered that actually THC increases brain pregnenolone. And they discovered something really fascinating. They discovered that actually there is a little allosteric modulation site on the cannabinoid-1 receptor, which is really the key receptor that is translating a lot of effects of cannabis. Now, why is this important? If you block the cannabinoid-1 receptor right here with a CB1 receptor antagonist, what is going to happen is you block all the signaling pathways, certainly the ones that are responsible for the intoxicating effect of cannabis, but also a series of others that actually you don't want to touch because you will have a lot of side effects, and you will have safety issues. So by selectively modulating, I would say, negatively, this pregnenolone site here, you actually only block the extracellular pathways that are responsible for the intoxicating effects of cannabis. So that was a major discovery. Now, you will tell me, "Well, yeah, that's very clever, but why don't we just use pregnenolone then? That should do the trick." Good point, but there is an issue, and the issue is threefold. 1, pregnenolone has a very short half-life. 2, it's metabolized in a bunch of active steroids, and so that would be a liability from a safety perspective, and it has very poor oral bioavailability. What's the solution? Aelis discovered basically a synthetic inhibitor at the pregnenolone site on the CB1 receptor, and this is what AEF0117 actually is. So the first step was to characterize this product. Actually, this is a nice publication from Aelis Farma last year in Nature Medicine that basically represents the entire characterization of this compound non-clinically and in phase 1 trials, and basically demonstrating that the compound has good safety profile and tolerability as well. Then they performed a phase 2A study looking at preliminary signs of efficacy, and the first thing they did was to demonstrate that actually the compound reduces the positive subjective effect of cannabis. So a few examples here, intoxication subscale, good cannabis effects, cannabis cigarette liking, and so on. And then they demonstrated that the compound significantly decreases cannabis self-administration. So very encouraging data, and it's actually on that basis that we decided to build an agreement with Aelis Farma. So where are we? So we started with the agreement with an upfront payment to actually have an option on this compound. We are currently in the option period, and there are two main events that will happen later this year. The first is the outcome of a phase 2b trial. The phase 2b trial was really looking as a primary endpoint at the effect of the compound in reducing cannabis use from five or more days per week to one or less day per week. We are going to have top line results of this phase 2b in the third quarter of this year. And then in the fourth quarter, what we are trying to organize with the FDA is what we call an end of phase two meeting, where we will not only review this data, but we will also start discussing the future of the clinical development in terms of phase three, and very importantly, the FDA views on clinical endpoints. And then once we gather all this data, then we will make a decision as to whether or not we want to exercise the option and then take full responsibility for the remaining part of the clinical development plan. And then the last section is on alcohol use disorder. We always talk about the gravity of the situation with the opioid crisis, but look at the numbers for alcohol use disorder. So worldwide, 108 million people actually diagnosed with an alcohol use disorder. In the US only, you have a pool of 137.4 million alcohol users, but almost 30 million diagnosed with alcohol use disorder. A really sad part of the statistics, as you can see there, is that only 2% of these patients receive any form of treatment. 2%. So if we believe that the situation is already very sad for opioid use disorder, with less than 20% of patients in treatment, look at this number, only 2%. How is that possible? Well, there are multiple factors, of course, but one key factor is really linked to the limitations of the current pharmacotherapies. So first of all, they have marginal efficacy, and there is a very high percentage of relapse within a year of treatment. There are safety concerns, particularly in some patients of populations. Compliance is very poor, and then most of these medications lead to unpredictable treatment outcomes. In other words, it may work for some patients, but certainly not the great majority. If we don't really understand why that is, there might be some pharmacogenetics component. We simply do not know. Unfortunately, from a clinical perspective, this is not a good situation. It means, however, that there is a huge unmet medical need, and this is where we are trying to make a difference with a GABA B positive allosteric modulator. So this is based on a pretty extensive research with GABA B agonists, such as baclofen, that have been demonstrating to actually reduce alcohol use and prevent relapse to alcohol seeking and alcohol taking behaviors. But these compounds have a lot of limitations. Very challenging pharmacokinetics, high elimination rate, which means that you need to administer the compound three, four, five times a day, which, in the case of alcohol use disorder, is definitely a no-go. And there are additional safety concerns. So we believe that with a GABA B positive allosteric modulator, and it has been described in the literature, we have a chance to develop better compounds with better compliance, better pharmacokinetics profile as well. So this is what we have done to create INDV-1000, through what we call a lead identification and lead optimization program. In other words, we had to recreate completely new molecules in order to try to make a difference. So where are we? We selected originally two lead molecules. We are selecting one of these two leads as we speak, and by the end of June, we are going to make a decision as to whether or not that molecule has a chance to go to man in 2025. So we currently are doing everything we can in order to make sure that one lead molecule will go to man next year. In conclusion, I hope that you have seen that our vision is to really pioneer addiction medicine and build competitive advantages with a unique portfolio of assets to address unmet medical needs, but also a compelling body of scientific evidence through real-world evidence generation, new clinical trials, as well as key collaborations, peer-reviewed publications, and conference presentations. Then you have seen that over the last 12 months, we actually achieved several business development milestones. OPVEE was approved in the U.S. last year. AEF0117 is completing phase 2B, and we will be in a position to make a key decision as to the future of this compound. We now have 2 additional compounds in the clinical phase 2, and we continue, of course, to constantly looking for the right opportunities in order to boost and grow our pipeline. On that note, I'm very, very pleased to introduce you to my colleague, Jeff Burris, our Chief Legal Officer, who will update you on certain legal matters. Thank you, Christian, and good morning. I really look forward to the opportunity to talk to you all today. My name is Jeff Burris. I'm the Chief Legal Officer at Indivior. I joined a little over 2.5 years ago, but I've... If you include the time I've been at Indivior, I've spent over 16 years as a chief legal officer or general counsel of biotech companies. Before I discuss the four matters that we have here, I just want to discuss the company's philosophy pursuant to which we look at these litigation matters. We've actively managed our litigation risk. We've settled litigation legacy cases where it makes sense for the right value, for certainty. As you know, over the last few years, we've had a number of cases that we've settled. Given what I know about the settlements, I'm very pleased with what we have done. We're going to continue to evaluate our ongoing matters with the same philosophy, settling cases where it makes sense for the right value, for certainty. We're not going to settle just to settle, and we will go to trial where we cannot get the right value for the right certainty. So I'm not going to talk about all of our litigation matters. I'm going to talk about these four because these are the ones where we receive most of the questions. I will refer you to the legal proceedings, footnote, and discussions contained in our earnings release, dated April 25, 2024, as you listen to my remarks for both detail and additional context. As we disclosed in our earnings release in April, we don't have any provisions for any of these four matters. We also believe these matters are manageable. So first, let me talk about the antitrust litigation and consumer protection. After we settled the antitrust MDL last year with the 3 plaintiff classes, there were 7 insurance companies that had opted out of that settlement. So we now are in a situation where we're going to trial or having ongoing matters with them. This summer, July fifteenth to August fifteenth, we will have a trial with 5 of those insurance companies in Roanoke, Virginia. The 2 other insurance companies, the timetable for those cases is much later. They're very early on. Excuse me. Turning to the civil opioid litigation, what we usually refer to as the opioid MDL. As we discussed in our earnings release in April, we're a defendant in more than 400 of those civil lawsuits. Most of those cases have been consolidated and are in MDL in the U.S. Nearly two-thirds of the cases are with municipalities, cities, and counties, while nearly one-third of the cases were filed by individual plaintiffs, most of whom assert claims relating to Neonatal Abstinence Syndrome. Litigation against Indivior in the opioid MDL is stayed. There are about 35 cases outside of the opioid MDL. Those are in state and federal courts. They're all in early stages. The U.K. shareholder claims. So Indivior PLC was sued by, in the U.K. by shareholder plaintiffs in what is called a representative action and a multi-party action. The claims made in both generally allege that Indivior PLC violated U.K. law by making false or misleading statements or material omissions in public disclosures, including the 2014 demerger prospectus. Indivior PLC filed an application to strike out the representative action, which was granted in December of last year. The plaintiffs appealed the strikeout, and last week, the court agreed to hear the appeal. They didn't grant the appeal, but they've agreed to hear that appeal. The hearing date for that appeal has not been set. While the representative action is going through this process, the multi-party action remains stayed. Lastly, I'm going to talk about the dental multidistrict litigation, the MDL. This is much more unlike the other three cases, which are more of our legacy litigation cases. This would be construed as more of a normal pharma company product liability lawsuit. We have been sued now in what is over 650 cases that have been consolidated in the MDL in the federal courts in Ohio. The plaintiffs in this MDL generally allege that Indivior failed to properly warn of the risk of dental injury associated with SUBOXONE Film and that SUBOXONE Film was defectively designed. The plaintiffs generally seek compensatory damages as well as punitive damages and attorneys' fees and costs. All of these cases are in the very early stages. The initial status conference of the MDL was in March, and there's been a follow-up status conference and certain procedural matters that have been discussed with the courts. Please note that there are some plaintiffs that could file actions in state court, not in the MDL, because the MDL process may not be available based on federal diversity jurisdiction requirements. In most states, the statute of limitations for these types of allegations is two years. So based on the plaintiffs' representations to us and to the court, we expect a bolus of cases to be filed before June 17, 2024, which is the 2-year anniversary of when we changed the label for SUBOXONE Film. However, there are states where the statute of limitations is longer than 2 years, and the statute of limitations time bar can be technically different, varying by state law, so additional cases could be filed in the MDL after June 17, 2024. We are also aware that a few plaintiffs, represented by a law firm in Canada, have filed a request with courts in Quebec and British Columbia, requesting authorization for class actions in Canada, either at the national or at the provincial level. I've talked about the four cases, but I want to reiterate the philosophy we have as an organization as we deal with these. We will continue to manage these cases. We will settle where it makes sense for the right value for certainty, and if it doesn't make sense, then we will continue to litigate those matters. Thank you, and I'm now going to introduce my colleague, Ryan Preblick. Thanks, Jeff, and good morning to everyone. My name is Ryan Preblick, and I am the CFO. I've been with the company now since 2012. It is certainly a pleasure to be here today to share more details on our medium-term financial outlook, including our growth and our operating margin profiles, as well as our capital allocation priorities. I will also highlight a few key points from our Q1 results. In my session, I want to leave you with four key takeaways. First, we have an attractive growth profile based on our currently marketed portfolio, and we expect to add to this over the longer term with our pipeline and potentially through business development. The key is, of course, SUBLOCADE, on which we expect to deliver a peak net revenue of over $1.5 billion. Second, we have a scalable business model with a unique commercial platform, which we will leverage this model both through traditional field sales and, more importantly, our dedicated efforts across organized health systems, including the criminal justice system. This will be supported by patient-focused systems, including our patient hub, and by a back office platform that provides value-added support services, including our rigorous compliance capabilities. Third, our focus is on the strategic priorities Mark spoke to. Growing SUBLOCADE, diversifying our business, progressing our pipeline, and delivering operational excellence are all well-funded through our growing EBITDA and healthy cash balance. Our balance sheet gives the flexibility to invest in growth, to meet our obligations, and to generate shareholder value. Lastly, we expect to generate strong free cash flow, which we will deploy according to our capital allocation priorities. Consistent with our strategic priorities, this framework is focused on reinvesting in our growth drivers, de-risking the business, including through diversification and potential business development, and returning excess cash to shareholders. Let me start with our growth profile. Since 2020, we have delivered an attractive net revenue CAGR of 19%, powered primarily by SUBLOCADE. Our full year 2024 guidance assumes a similar growth rate of 18% at the midpoint. The growth of SUBLOCADE has resulted in a substantial improvement in our net revenue mix over that period. In 2020, our legacy film and tablet business accounted for over 3/4 of our net revenue. In 2023, our long-acting injectable, SUBLOCADE and PERSERIS, together delivered close to 2/3 of our net revenue. Having touched on net revenue, let me now discuss margins. Between 2020 and 2023, our adjusted operating margin increased from 14% to 25%. This, in turn, resulted in our adjusted operating profit tripling over that period. Looking forward, we are confident that we can generate further margin expansion in the coming years, with the primary driver being the growth of SUBLOCADE. In addition, we will leverage the significant structural growth investments we have made over the past several years to support SUBLOCADE in organized health systems and in alternate sites of care, and to expand national sales coverage for PERSERIS. We expect this will result in sales and marketing spend growing at a more modest pace than our top line. For R&D, we will focus our spend on building a strong and balanced pipeline and on phase 4 SUBLOCADE studies. This is likely to result in R&D increasing as a percentage of net revenue as we move closer to benchmarks in the industry. For G&A, we will maintain a disciplined and efficient approach. And finally, we expect our gross margin to benefit from an approved product mix and from manufacturing savings beginning in 2027, which I will come back to in a minute. When we take the expense vectors I just highlighted, together with the expected improvement in gross margin, we are confident we will deliver sustained margin expansion. In fact, our full year 2024 guidance projects around 300 basis points of adjusted operating margin improvement at the midpoint. Expanding on my earlier point on manufacturing savings, in November of 2023, we took an important strategic step in establishing long-term supply security with the purchase of an approximate 80,000 sq ft multi-use sterile manufacturing site in Raleigh, North Carolina. The total upfront consideration for the site included a cash payment of $5 million, plus assumed contractual obligations, which will result in modest annual losses through 2025. Over the next couple of years, the facility will continue to manufacture a product for existing customers, while tech transfer activities enabling the manufacture of SUBLOCADE and PERSERIS take place. Total capital investment is estimated to be between $45 million-$55 million, with the majority occurring in late 2024. From 2027, we do expect the facility to deliver annual savings of around $20 million, supporting the expansion in our growth margin. I now want to touch on how we will reinvest our profits for growth, meet our obligations, and return value to shareholders. Since 2020, we have nearly tripled our EBITDA, even with the step-up in growth investments we have made over that period. This, in turn, has helped us to maintain a healthy cash position, despite substantial outflows, primarily related to the legacy litigation matters. This balance sheet strength, when set against our relatively constrained capital expenditure requirements, gives us tremendous flexibility. It means we can fund our strategic priorities while at the same time meeting our obligations. It also means we can pursue organic and inorganic growth opportunities to strengthen our leadership position in addiction treatment and science. Lastly, it gives us the opportunity to return excess cash to shareholders. This slide sets out our capital allocation priorities in detail. As I mentioned, we expect to maintain the financial flexibility to prioritize growth and shareholder returns while also meeting our obligations and de-risking the business. We will also place a great emphasis on operating in a responsible and sustainable manner.... Our growth investment will be focused on commercial execution to drive SUBLOCADE, OPVEE, and PERSERIS, and on progressing our pipeline. We will also proactively seek business development opportunities. Regarding the latter, we had a busy 2023, including the Opiant acquisition to bring on OPVEE. We acquired the Raleigh site to ensure volume and generate savings, and we continue to build out and strengthen our pipeline. Lastly, we will consider the return of excess cash to shareholders when appropriate. We are in the midst of a $100 million share buyback program we kicked off in November. We believe this balanced approach to capital allocation will drive substantial shareholder value in the short, medium, and long term, and help us deliver on our vision and mission. As Mark touched on earlier, here is more detail on our medium-term profitable growth framework. Based on the excellent prospects for our long-acting injectables, we expect to deliver double-digit compounding net revenue growth over the medium term. Let me walk you through some of the considered assumptions. First, we expect underlying BMAT growth to be in the mid to high single digits. Second, we expect SUBLOCADE, OPVEE, and PERSERIS to build towards peak annual net revenue of greater than $1.5 billion, $150-$250 million, and $200-$300 million, respectively. Third, we expect SUBOXONE Film share to trend towards analogs. I remind you that we do not promote this product in the U.S. Lastly, we expect to deliver modest rest-of-world growth. We expect to generate positive operating leverage, as I discussed earlier. We will focus our growth investments on U.S. commercial and R&D as we scale our business model. With the benefit of improving product mix, we expect to lift our gross margin to the mid-eighty range, and from 2027, we will additionally benefit from the manufacturing savings. Lastly, we expect to generate strong free cash flow. Our CapEx needs are relatively modest, despite our ongoing investments in the Raleigh facility and IT. Our strong free cash flow will allow us to take the balanced and disciplined approach to capital allocation I set out earlier, focused on delivering sustainable growth and shareholder returns. In my final comments, I would like to take you briefly through the highlights of our 2024 first quarter results and our full-year 2024 guidance. As a reminder, our first quarter total net revenue grew 12% versus prior-year quarter. SUBLOCADE net revenue increased by 36% year-over-year, but sequential growth was below our expectations, with dispenses and net revenue up 4% and 2%, respectively. The sequential slowdown reflected two transitory external forces, specifically a higher-than-expected rate of Medicaid patient disenrollments and a cyberattack at Change Healthcare. Together, these reduced SUBLOCADE sequential dispense growth in the U.S. by a mid- to high-single-digit percentage rate. In addition, we saw abnormal destocking during the same time frame as the Change cyberattack of $5 million-$7 million. Over the balance of the year, we expect subsiding impacts from these transitory items, which we believe are masking the strong underlying demand for SUBLOCADE. We have already seen an improvement since Q1, with performance trends for the month of April in line to the growth levels we had initially planned for in the first quarter. Furthermore, we expect to reap the benefit from our recent salesforce expansion and from our continuing momentum in the justice system. For these reasons, we are confident that the total net revenue and adjusted operating profit will accelerate through the year, particularly in the second half. As a result, we are reconfirming our full year 2024 guidance, which includes SUBLOCADE net revenue of $820 million-$880 million, and approximately 300 basis points of margin expansion at the midpoints of our guidance range. With that, I would like to thank you for your attention, and I'll hand it back to Mark for an update on our proposed U.S. primary listing and closing comments. So thanks, Ryan and team. Listen, a dense day, but I think one that kicks off, you know, where we are. This U.S. listing is, it's all about, you know, aligning with our current and future growth profile. It's about aligning and with our desire to attract both more U.S. investors as well as a deeper understanding via more U.S. analysts covering the company. Also allowing inclusion on U.S. indices, which provide a more passive sort of trading in the stock versus what we see on the FTSE. And then to better reflect the growing proportion of U.S. investors that we've seen since we took on a secondary listing, where we're now approaching 50%. Today, I think, was a good start to this engagement. We look forward to an ongoing engagement with each of you as you consider covering Indivior moving forward. For me, just before we go to Q&A, you know, just to reemphasize and end where we started, which is, I think Indivior has a really, really great opportunity to transform the lives of patients and also provide durable shareholder value moving forward. We are the global leaders in addiction treatment, where there is a huge unmet need. We have a breakthrough product on the market, as well as a portfolio of products that hopefully you heard from Christian, a strong amount of belief in helping with huge unmet needs that are to come. And we have a track record of operational excellence, which converts to strong cash flow generation. So with that, I'm going to turn the meeting over to you, and I'm going to open up for questions and answers. If I could just ask, as we're going to get some mics around, but just please name and which firm you're with, and then we'll hit the questions. There you go. Okay, thanks. David Amsellem from Piper Sandler. Have a few questions. So number one is on SUBLOCADE. Can you talk to competitive dynamics, given that there's another long-acting injectable form on the market, Brixadi? How you're thinking about competitive dynamics, the extent to which that product is having an impact, if any? So that's number one. The second question is on PERSERIS, also a competitive question. Teva has UZEDI, another subQ form of risperidone, on the market. And I know that you talked to the relatively low penetration of long-acting injectable antipsychotics. Maybe talk to, you know, how you see the competitive dynamics there playing out, and also how they might play out to the extent the long-acting injectable form of olanzapine launches down the road. Then the last question is a general question on business development. You acquired Opiant, and looking at, you know, the growth and profitability, how are you thinking about other tuck-ins down the road? Thank you. Perfect. So maybe I'll handle PERSERIS and the business development discussion, and then I'll—that'll provide a little time for Richard to think about his answer on SUBLOCADE with regards to the competitive environment. So with regards to PERSERIS, yes, you're right. UZEDI came into the market with another risperidone monthly product last year. I would say that that did cause confusion in the markets because we were the only risperidone monthly asset out there, and they have a much larger sales force than us because they're already in the space. That caused our growth to flatten in the third quarter. But as the market has started to sort out and as folks have gotten some experience, you know, with UZEDI as well as our products, we've returned back to that double-digit quarter-over-quarter growth. So we see that sort of settling out. On the long actings on, on the other side, the negative symptoms, I think those markets are spread out. We're still competing in the 66%, so I think they'll be battling for market share on the side with, you know, the long-acting Abilify and the, and the product from Alkermes. With regards to business development, listen, we've been quite active with regards to near to the core. We think about treating the whole patient, in their, in their continuum of care for addiction, and so we look for assets that are differentiated and provide a major help to these patients with huge unmet needs. And Christian and his team track key mechanisms of actions and assets that are going through the pipeline, and at any time, if one of those hits a key milestone where we think it's de-risked, we could take it in. We're not a discovery house, right? We have a connect and develop sort of model, so we tend to do this via partnerships, and we see ourselves as a destination for these bio companies that are developing these drugs to help these people with substance use disorder. So with that, I've given Richard a little bit of time. Richard, would you like to talk about, you know, the competitive environment? I have thought about this a little, Mark. Yeah, thanks. Does this work? I think they can turn it on. Hit the button on the- I'll try. Oh, well, that's good. Yeah, great. So good question. So I'd say there's probably three points. I think point one is if you look at the journey for LEIs within the market, we sit about 6% at the moment. Research would say anything between 25%-30%. I think you could look at the analog of schizophrenia as well, you know, where they're at 17%. So I think, number one, there's a significant way to go for LEIs. Number two, I'd say there is room in the market definitely for two, and I would even say that having two in the market is probably going to drive LEI penetration faster. But I think the important point and how we feel about it is, if you look at our product, if you look at the profile, specifically, you know, we spoke about the 2 and the 6 ng/mL for the reasons that Christian explained. You know, we think ultimately, you know, we'll, we'll win in this market predominantly because I think the market dynamics will continue to change. They'll change in a negative way. Fentanyl will move to carfentanil, will move to something even more powerful. So I think you're going to find that actually, you know, the clinical profile and the needs of the HEPs are going to be better met by SUBLOCADE. So, you know, not being arrogant, we feel confident that we have a good product that meets the needs in a compelling way and, and, and for the future as well. Just a little more context on that, David, to tease in what was shared earlier. There's well over 1,000 variants of synthetic opioids, and you talk—you started with fentanyl, which was 40-100 times more powerful than heroin, and now you've got items like nitazene out there that are 600 times more powerful than heroin. So you're seeing that increase, and then you heard Richard talk, too. We have over 40% of our patients that are staying on that 300 milligram because they need the 6 nanograms per mL that's being delivered there to protect them. So thank you for the question, David. Please. Last. Can you comment a little bit about payer coverage and reimbursement, specifically on SUBLOCADE? And I believe you had some disenrollments from Medicaid. Just speak to that, how that's progressing. And also on the increase in sales force, which verticals are you pursuing most? What's kind of intense in terms of capital spend on that, and has that kind of peaked? And then second, on specifically to PERSERIS, it seems to be outside of your core vertical of abuse. And you know, what are your potential plans for that asset long term? Thank you. Thanks for those. And maybe what I'll do is I'll cover the PERSERIS and the disenrollments, and then I'll let Richard talk to our payer coverage, you know, our co-pay program, and then how that sales force alignment's working in the different verticals. You know, so for PERSERIS, it's interesting because so many people do say this is a little bit out of your wheelhouse. It's not an addiction asset. But when you think about treating the whole patient, 60% of people that suffer from schizophrenia also have a comorbidity and substance use disorder. Often it's the schizophrenia that causes them to reach across the aisle and self-treat, and they become addicted. So when we think about that whole patient, from moderate to severe, rescue, schizophrenia actually falls right within that continuum of care, and we've had this asset, this long-acting with risperidone for some time, and are able to bring it to market with a differentiated profile. So, you know, long term, we still... You know, as we look at the profile today, we still see it differentiated and still see being able to get to $200 million-$300 million of sales. From a disenrollment standpoint, I think, you know, as we talked about the disenrollments at the Q1 results, we had seen a major disconnect from our retention curves and treatment that we've really had validated for the last three years, where we lost about 6,000 units from that curve shifting to the left, which we believe was due to the acceleration of the Medicaid renewals as well as, you know, the Change Healthcare, that's UnitedHealthcare's group, which covers and processes about one in three of the claims in the U.S. healthcare system. We saw that disconnect happen for the first time in over three years. What we saw in the first few weeks of April was that those things returned back, and we were back to the same growth rate we were at the first half of the quarter. So back, back to where we were looking to be. So, Richard, if you wanna talk through coverage. Yeah. So, yeah, so from coverage—from the launch, we worked hard to ensure we had good coverage. I think there's 2 or 3 things I'd say. 1, typically, you know, an injection in an office is a medical benefit. We worked hard to make sure and try and get it into a pharmacy benefit side of the thing. That's more automated, less challenges in terms of access. So 1, we worked hard to do that. 2, I'd say from a payer coverage, we have great payer coverage. We have minimal gaps. The majority of the business, about 65%, flows through Medicaid. And on that, if you look at the out-of-pocket for patients, you know, we have a co-insurance program, so the majority of patients are paying minimal co-insurance, $5, $10, really, in terms of the buy down. You know, we're in a good spot with regard to access to patients with regard to price and also coverage from a payer point of view. So then I think the second was the investment that we've made in the sales force and the verticals, how we're, how we're thinking about growth in those areas. Yeah, great. So I think there's two things I'd say on the sales force. One, the change in legislation really opened up independent HCPs, along with our sort of, like, alternative sites of care. So that was a bit of the catalyst for the investment. And you can't really add 10%, 15%, because the investment requires a disruption in all your sales force. So you do it once, and you hope that's going to be it for a while. The other reason for doing it is, as we've been successful in bringing on new healthcare professionals, as we penetrate organized health systems, we penetrate more physicians, you know, there was a coverage gap that we needed to make sure we didn't have, so we could continue the growth. Now, you know, we take our business from an 8,000 call ratio to about 12,000 without diluting the frequency. That allows us to continue the growth that you saw in organized health systems and at the same time, add on so that we can start to cover independents that we weren't doing previously. Thanks for that, Richard. I would just go back to that slide that Richard had up with the universe and then where we are in the journey, and we're still in the early stages of the growth journey on this. You can look at it from a market share standpoint, you know, 6% for long acting, but you can also look at it as how many facilities, physicians are activated and how many have, you know- Yeah ... gone deep in adoption. Thanks for that. Thank you, Wes. Here, please. Thank you. Thank you. Good morning, everyone. My name is Balaji from Barclays. Couple of questions from me. Firstly, I want to understand really how the entire selling mechanism happens, the commercial structure, how it's set up, and what helps you gain traction with with these accounts, and then how do you go about accelerating adoption in OHS or expanding access in CJS? Yeah, that's one. Two, we also want to get to SUBLOCADE and discuss the label expansion you're working on, and how does this pose an upside risk to your revenue targets or goals as it stands currently? And three, maybe just getting into the broader global footprint that you have, help me understand the markets where you have been approved but not launched, why so, and if these figures at some point in time, and maybe give a comparative written metrics on both of these, OUS—US and OUS geographies. Thanks. Yes. Thank you, Balaji. I think what we'll do is, if we could, I'll talk about the global markets, and then we'll have Richard talk about, you know, the selling mechanics of our ecosystem model that we shifted to, in fall of 2020, and then we'll have Christian talk about, you know, the label expansions. So in the global markets, the places that were not approved, this is all about first getting a decentralized procedure, so we had to go market to market to market for approval, and as we've gotten approval, we then shift into a reimbursement stage. So once we get reimbursement locked down, we will look to launch in those markets as we move forward. So that'll come. Revenue on SUBLOCADE in those rest of the world markets is, you know, over $40 million on an annual basis, growing in line with the rest of the business at over 50% in 2023. So good, solid growth. Disproportionately, though, the growth, the growth comes from the US because the epidemic has so disproportionately impacted the US, and fentanyl has been here, you know, for the last seven years, and it's just starting to hit a little bit in Europe. So that's kind of the rest of world landscape a bit there. Richard, do you want to talk about the ecosystem model- Yeah. and that shift a little bit? Yeah, certainly. So when we launched SUBLOCADE, you know, we were a predominant retail organization, so would sell to a doctor, the doctor would prescribe, the patient would go to a pharmacy. With an injectable, you know, what's happening now is the doctor prescribes, the patient has to present at the office, they have to be injected. So there's a lot more steps involved to get on this medication. And what became very obvious very early in the pre-research was we need an ecosystem, as Matt spoke about. So we need a number of different roles to be able to make sure that this product can be bought, acquired, injected, reimbursed. So at a simple level, we have a network of specialty pharmacies, so they're the pharmacies that will ship the product to the physician's offices or wherever it may be going. We have a team of people, the sales force, that typically will go in and educate the offices around what are the requirements to handle and to be able to prescribe and the logistics of a product like this. We also have an account team, and their role is really to go in at a higher level and speak to more like the hospitals and get that on formulary. So if you think about it, you've got a team that are opening up the access in a, I'll take a, a hospital or a in-treatment facility. You've got the sales force that will go in there and talk more about the mechanics. And then we have all the sort of like platforms required to be able to sort of, like, move the product along on each of the steps. So, you know, including help for the patients, so we have, like, hub support. So again, if patients are getting stuck, we can help them. So, it's a lot of apparatus required just to make one sale, but once you put that in place, which we've done and we've refined, then it becomes quite a very good sort of like model, which works very efficiently, we find. And maybe just one extra piece of color on these. As you activate these accounts, it's a longer engagement. Mm-hmm. It's not like the day they want this, that a week later, they're there. They tend to take 12-15 months from the initial engagement because of all the procedures they have to put in place, the REMS and comply with local and state laws. So there's always a portfolio of these. Well, I did what Christian did, bang in the mic. You know, you... Once you open them, then you can start to pull through, and we see it just an accelerated of adoption in these organized health systems and criminal justice systems once they have the start of prescribing them. Christian, can you talk about the label extensions and sort of the timings on when we think those will get there? And then I can address sort of the net revenue opportunity associated with that. Certainly. So we do have two priorities, a rapid induction, and you have seen preliminary data to really try to stabilize patients as quickly as possible. And then the alternate injection sites to provide patients and providers with a greater flexibility rather than simply focusing on one body site. Timing, as I mentioned, we are going to do the filings, the two filings, actually simultaneously in the third quarter this year, and then we will apply for priority review. If this is the case, it's a six-month review, so approval in the first quarter next year. If it's a regular 10-month review, it would be the third quarter of next year. And as you think about, you know, incremental net revenue, you know, we gave our guidance. We upped our guidance to greater than $1.5 billion in December 2022. You know, we gave short-term in-year guidance, which for this year is $820 million-$880 million. We've given interim guidance that we would hit a $1 billion run rate exiting 2025. We've not said when that greater than $1.5 billion will come. Now, is there incremental revenue from those, from those, label extensions, as well as, you know, the alternate sites of care and opening up the independent physicians, which happened after we gave that guidance? There is, but we think it's covered by the greater than $1.5 billion. You know, as we continue to assess the business, if there's a time to increase that, you know, we will, of course, let the market know. Thank you for the questions. Please. Hi, Leland Gershell from Oppenheimer. Just two questions from me. So in terms of SUBLOCADE, it seems like you have a, you know, a controlled environment in the criminal justice system where people start on therapy and, you know, there's sort of a attrition when you go outside. Are, are there sort of any controls or changes in motivation or any, any elements that, you or maybe the environment, you know, may have control over that could improve, the retention, you know, of those patients? Maybe you could speak to those dynamics a bit. Also, a question on OPVEE, as you... I know it's still early days, but as you see accounts starting to adopt this product, do you see kind of a binary shift to, on an account-per-account basis, shifting to Nalmefene, or do you see them sort of trying it, still ordering the nasal Narcan, and then over time, you know? So I guess, you know, are they, are they ordering both products, or are they really shifting either, you know, to Nalmefene or sticking with the, the nasal Narcan? And thirdly, on one seventeen, it seems like, you know, given the history of the CB1 antagonists, you have a risk of safety. It sounds like with your approach, you're targeted into avoiding issues in the CNS with respect to depression and suicidality, but just wanted to make sure that you're, from what we know about the biology, that you're truly avoiding that risk, and if there is any, you know, latent risk that you may be still concerned about there. Thank you. Thanks for the great questions. I'll, I'll handle the SUBLOCADE CJS. Richard, you'll, if you will handle the OPVEE and what we're seeing on the accounts and expect on the accounts, and Christian on AF. I think the great opportunity in CJS and what we're seeing from these accounts is they're really trying to stop the revolving door, right? 65% of patients with OUD come in contact with the justice system by the nature of the disease. They need more and more drug to physically stabilize themselves and to get euphoria and to prevent precipitated withdrawal. So they end up stealing, they end up coming in contact, and they end up behind the walls. The big issue, I think, as you've highlighted, is once they're getting treatment behind the walls, is how do you get continuity of care as they reenter society? Sometimes they're going to a halfway house in between, you know, sometimes, you know, they're—they don't have Medicaid coverage as they go out because that gets suspended while they're behind the walls, and they have to reapply, and that can take up to about 90 days, kind of on the extreme, if they apply with that figure. So what are we doing? First of all, let me say, we're not at anywhere near a utopian spot. There is still a number of people that fall out. We don't like that at all, but we're partnering with the criminal justice teams to try and really target physicians and link the patients with physicians outside who prescribe long-acting injectables rather than a doctor that does addiction treatment, who might only be doing orals at the time. So we want continuity of care on the long-acting so they can get there. In addition, in recognizing this issue with regards to them not having healthcare as they come out, we've set up a bridge program where we're providing two free doses of SUBLOCADE as they come out of the prison system to protect them at the time where they're most vulnerable from relapse. They get out there, they're back with their family and their friends, the friends sometimes who they used to abuse with, you know, they can stay in treatment as they come out for up to two months. And we've seen that program starting to pick up after initiation, you know, at the end of last year on that. So those are efforts we're working with to try and get that activated. It is less than optimal, but that is a huge opportunity to keep these patients in treatment. Richard, do you want to talk through OPVEE in the account? Yeah. Just one other comment, Mark, on SUBLOCADE. So also in the prison system, there are changes in legislation going forward, where they're wanting to allow access to Medicaid when you're behind the walls. And I think, you know, there's a number of states who applied for that. We can expect that to take some time. There's quite a lot of logistics and changes that would be required, but I think going back to Mark's point, that would be great from continuity of care, so they're actually gaining access to Medicaid whilst behind the prison wall before they come out. So I think that's just another point. With regard to OPVEE, I would say it's early days. I really wouldn't be called on that. I think what I would expect is that you have to assume now every overdose is a fentanyl or a synthetic overdose, if you look at the statistics. We personally don't think you're gonna be carrying two different sorts of reversal agents. We expect it'll be one or the other. So, at the moment, clearly, we're just in the phase of opening up access, gaining trial. So I think, you know, in a year, we'll have a lot more insight. Are people switching fully post-trial and adopting OPVEE? But I think our view is it's gonna be one or the other in a lot of places. Christian, could you talk about the AEF, please? Definitely. This is probably one of the most important points that we try to address mechanistically, that is the safety of these products. This is the reason why we did not go down the path of cannabinoid 1 receptor antagonists, because we know the history there, regulatory agencies as well. And so this is a major discrimination between allosteric modulation at that site on the CB1 receptor versus blocking the entire receptor. We will see, of course, the outcome of the phase 2B trial, but so far, in all phase 1 and the phase 2A, we have a very good safety and tolerability profile. Next question. Tim, something online? There is. Two online questions from Max Herrmann at Stifel. Mark, you hit a bit on jail recidivism data, which is very compelling with SUBLOCADE versus without. How are you able to use this data with CJS and more broadly? And the second question, gross margins were closer to 90% previously. Why are you only returning or guiding to mid-80s% when SUBOXONE Film becomes negligible? Thanks. Thanks to Max, and maybe I'll handle the recidivism data, and then, and then we'll hand over to Ryan to talk through the gross margin. Listen, I think the beauty with criminal justice systems is we're pushing on an open door here. They want to treat patients while they're in there. If you go back two to three years, you had less than a 5% treatment rate, very few treatments going on. And with SUBLOCADE out there as an optimal sort of treatment while behind the walls, you know, we're seeing them proactively reaching out to us, working with our CJS sales force to activate. The data is additive to an already motivated criminal justice system to help these patients and stop them from in and out, in and out of their systems to save costs. So I think the data is supplemental to that, and it helps also with policymakers and people that are controlling budgets that go down to the criminal justice. Ryan, could you talk to gross margin dynamics in both the short term, but also, you know, the medium term? So certainly with SUBLOCADE growing, as we discussed today, the margins will benefit. But in addition to that, as we mentioned, our top line is gonna grow not only because of SUBLOCADE, but we're excited about the potential of OPVEE, PERSERIS, and the rest of the world. And those segments are not as profitable in regards to gross margins, so we are gonna see a slight impact to the margins compared to where we used to be. Thanks, Ryan. Any other questions? Okay, well, let me close with just a huge thank you to the existing analysts that cover us, to hopefully the new analysts that will cover us as we shift to a U.S. primary listing. We'll be around after we close up, and then, of course, as you start to contemplate adding Indivior into your coverage, and if there's additional calls or engagements that are needed, we're certainly available to do so. So thank you for attending. Really appreciate it.