H. Lundbeck A/S (HLUNB) Earnings Call Transcript & Summary

[Presentation] Good afternoon, everyone. Very nice to see you here. It's actually fantastic to have quite a full audience here in the auditorium. We, of course, also like to welcome those online. We have a number of people who have joined us online today, so it's fantastic to have this audience here. And of course, we are broadcasting today here from our headquarters in Copenhagen. And this is a fully integrated headquarters. We have research, development, we have manufacturing, we have supply chain, we have commercial. So this is a group of people working together here on the site that are simply driving focused innovation. And today is very much about that. It's very much about the simple words that you see on these slides. It's about focused innovation that will drive sustainable growth. And that is everything that we do in terms of our strategy and how we want to build the future together. Now what you will see today, just to orientate you a little bit to the context of today, is very much a dialogue with you to go deeper into our focused innovator strategy. And you will see this through the lens and through the voices of the leadership team here, the executive leadership team who will be on the stage to present also their view of how focused innovation works for us. And the intent of having a Capital Markets Event like this is really to allow us to go deeper into what's the substance of our strategy. And we expect the outcome from today for you to have a better clarity on how we see the midterm growth, better understanding of the pipeline, really what are the milestones and the triggers that will evolve over the next 12 to 18 months, and really what is behind our strategy, the people, the leaders that will help us transform and, of course, perform in terms of building our focused innovator strategy. Before we continue, there is, of course, important safe harbor statements. The discussion today is -- of course, it will include forward-looking statements that are, of course, subject to change. And also importantly, we have made, of course, an announcement last week on the agreement that we've reached with Longboard. We know that this discussion today is only for informational purposes because the tender offer has not commenced yet. And so today's discussion, of course, is not there to solicit any trading of the common stock of Longboard. So it was essentially at quarter 4 last year, about 12 months ago, that we introduced at our Research and Development Day in London the focused innovator strategy. And there were 3 important questions that we addressed and questions that we reflected on ourselves, but also that we heard from many of you. The first was the question on how does Lundbeck grow through the midterm when we are facing some loss of exclusivity. The second question was really, can we see the long-term growth perspective of Lundbeck? So what's in the pipeline essentially to build that long-term growth? And the third one was clarity around our capital allocation strategy. How will you fund that journey going forward? Now I can say today, this is 12 months down the line, that we haven't got all the answers. But we have many more answers than 12 months ago. And I want to share with you a few of those answers to all the proof points of our strategy as we go forward. And this is really what you see here. We are growing our strategic brands by 19%. This is through the half year mark of 2024. We are seeing significant growth on Rexulti, Vyepti and Brintellix as key drivers of that growth. More growth than what we have seen 12 months ago, and that's also why we believe our midterm guidance is being extended and that we can see also different peak sales potential of these assets. We also see fundamentally a very different pipeline that focus on innovation, and what is coming out of this pipeline is a complete different profile than we had 12 months ago. And I will share more about that, of course, in a second. And thirdly, we have also clear swim lanes in terms of profitability and how we think about capital allocation, how we fund that going forward. And of course, today also, we will be clear on that, that our guidance around our adjusted EBITDA will remain within a corridor, even though we will absorb some additional costs due to the acquisition in our development area. And so when I talk about the different profile of the company, this is one important message for you. If you think about Lundbeck, say 12 months ago and where we are now, there's been huge advances in the pipeline and in where we stand today. And if there's one message for you today, then it's one which is in 2026, we will have 4 Phase III programs. That is really the answer -- or one of the answers towards the long-term growth for Lundbeck, the growth that will be delivered in the next decade through many of these assets that we will develop and bring to the market towards the end of this decade. Now we often get the question. Neuroscience, what is that? Is that a risky area? Is this an attractive area? And the answer is, emphatically, yes, it is a very attractive area. We are in this space for nearly 70 years, 100 years in existence, but 70 years in neuroscience. There's a huge unmet need. Societal burden is significant. But we also see a segment of our industry growing at high single digits in the next years. And what we also see, of course, is an increase in regulatory approvals, and we see capital inflow into this neuroscience space. And it's driven by a better understanding of the science, a deeper understanding of what we also call the Decade of the Brain, in a sense, what we are in right now. And Lundbeck is really poised to capitalize on that opportunity. And the way we do this is very much in this illustration here that you see. We start with the patient in mind at the center of everything we do, trying to understand, first of all, the pathobiology, but also understanding the unmet need. What we are working on needs to be differentiated versus what is today available to these patients. And we do that in this clockwise fashion through deeply understanding the biology, the pathobiology. What is really the disease? How can we ensure that we understand the causes of the disease? And therefore, how can we address them? Then as we develop the molecule, we put it through a very rigorous approach to make sure that the preclinical tests are rigorous to ensure that the molecule speaks and it's clearly defined that this is a molecule we want to take forward into the clinical stage, which is where the patient speaks. And that's where we really understand the full value of the opportunity. And of course, in that full circle, we bring these treatments, these transformative treatments to patients through our commercial organization, through our operating model that we have on a global level, and ensuring that we have the best way to serve these patients and have access to these medicines that we bring to them. It really starts there at the center of understanding the patients. And I can tell you through the video that you've seen, this is what drives the company. This is the secret sauce. This is the purpose of why we're here, to really bring differentiated medicines through this rigorous scientific process to bring them to patients. Now as we go into a perspective a little bit on the longer term, I want to again share with you something that I've spoken to you before about. This is our road map, our leadership road map. How do we see ourselves transform the company into the future? We are very much in this phase of focusing on ensuring the allocation of capital to the investment of the organic brands to grow them faster than what we've grown them before. But also to be very clear, that we allocate capital in a way that it's going to drive and fund the innovation pipeline that we need for the long-term growth. And we are doing that through a very purposeful approach around capital reallocation, looking at all areas across the company to ensure that we can allocate either towards growth of our organic or innovation in terms of pipeline. But we see a journey that we are on and journey where we are growing into areas where we can scale, where we can have significant scale. In a way, that allows us to play to win, which is really in the severe migraine space, neuro-specialty, which is one of our pillars of our strategy, but also advancing with the pipeline that you will hear a bit later into the neuro-rare space and also the acquisition that we are -- that we have announced recently with bexicaserin, building that strong neuro-rare franchise that allows us to scale in areas that we haven't been before and allows us to really build a position of diversification of growth into the long term for the company. But we also see ourselves, as we advance the pipeline, we will be open to partnering, partnering on the pipeline, commercial partnering. We are a company with strong recognition, and we attract that commercial partner opportunity as well to us. So continuing to think about how we will bring our medicines to patients might not always be ourselves, but through partnerships as well. And in this phase of scaling, we are also, of course, as of today, building aggressively into this area of how we transform our fundamental engine into AI and ensuring that we are well prepared to leverage this benefit that we would see, both from a research, from development, from commercialization across the company. And as we enter into the end of the decade, we see the pipeline. These 4 -- just at least today, 4 Phase IIIs advancing into launches into acceleration of our growth into the next decade. And of course, through this, we are building an industry-leading neuroscience company and platform that we will have for the future. Behind every transformation, and we are performing and transforming Lundbeck, is a great leadership team that you will see today. This is a leadership team that's highly experienced, bringing significant international expertise. And of course, a lot of this team has assembled over the last 12 months. But I'm very confident with the team we have that we are able to now lead and drive a great future for Lundbeck and really set ourselves up for our ability to play to win. So now I'd like to just conclude a little bit my opening part by just orientate you to what you will now see going forward for the rest of the discussion. We really want to go deeper into how are we focusing to play to win. And you've seen 3 pillars of our company in a sense, our history and our current legacy, of course, in neuropsychiatry. But we also have a strong position with Vyepti in severe migraine in neuro-specialty, and we're building a strong pillar in neuro-rare. So we're seeing through that lens how do we see that evolve over time through the pipeline, through the commercial efforts to bring that forward into a strong engine that will continue to drive sustainable growth and allow us to play to win. So this is the emphasis of where we are and what we would like to discuss with you now going forward deeper into that area, and you will see this through the lens of the leadership team and management team. And therefore, it's my pleasure to welcome on stage first a new member to the team that you might not have met before, Maria Alfaiate, who is our Head of Commercial and Corporate Strategy, and Maria will host the next session. So thank you, Maria. Welcome. Over to you. Thank you.

Thank you very much. Good afternoon. As Charl just alluded to, next week, I will be completing my first 3 months with Lundbeck. So I decided, since I'm new to most of you, just to give you a bit of a background on myself. I've spent the last 20 years working for big pharma for Bayer, for AstraZeneca and also for MSD or Merck & Co. in the U.S. over a variety of different roles. So some roles, more operational at a country level. Others, more strategic at a global level, across sales, marketing, early commercialization, portfolio strategy and also market access. And I'm delighted to have joined Lundbeck. We are at a game-changing period in the life of Lundbeck. And I'm also delighted to have joined the executive management team. For the next section, where we will be showing you what focus means for us at Lundbeck and how we win, I will be accompanying my colleagues from the executive management team and I would like to welcome them on stage now. Tom Gibbs, who's our Head of the U.S.; Michala Fischer-Hansen, our Head of Europe and International Operations; and also, Johan Luthman, our Head of R&D. So as Charl mentioned, our focused innovator mindset permeates everything that we do across the value chain. And through this next section together, we will be providing you an overview of how indeed we are focusing and how we're planning on building a pipeline for future success. So we will start by looking at our operating model. We will start by looking at the performance of our end market brands and how we're really driving them for growth and also how we are partnering with R&D to deliver life-changing medicines for patients. So I would like to introduce the next section, where we will be understanding a bit more about how innovation in patient care and in customer centricity is indeed driving growth for our brands in the U.S. with Tom.

Thank you, Maria, and hello, everyone. During Charl's presentation, he outlined the key principles of our focused innovator strategy. And when I think about how we translate this strategy for the U.S., it's very clear that the greatest contribution that the U.S. can make in support of our focused innovator strategy is to help deliver our midterm growth and to do this by accelerating Vyepti and Rexulti performance as efficiently and effectively as possible. Now delivering on this imperative requires that we build a commercial engine that operates at a higher level, functions at a higher level, as we think about it through how we're engaging our customers but also how we're functionally internally. So let's first think about this through our customer-facing model. One of the things that we had to do first was really increase our patient focus. Now put yourself in the shoes of patients in the U.S. They have to overcome significant complexities to get the diagnosis and treatment they need and the outcome that they seek. And this is especially true when you think about diseases that are treated by specialists or in rare disease. So we've created an integrated patient-centric model that fully supports patients across their journey to help them overcome barriers. And then if we think about our model through an HCP lens, health care practitioners are incredibly busy. And we have to develop and we are developing new, innovative and more impactful ways to engage HCPs the way that they want to engage with us to deliver relevant information in a timely manner to influence behavior. And then when we think about our internal operations, I want to start with our culture. We needed to change the way that we come to work every day. We need to change the way that we approach our business. As Charl said, we needed to play to win. And we needed to be guided by the leadership behaviors associated with our focused innovator strategy. So curiosity, making sure that we create a psychologically safe environment, where people feel compelled to speak out, to share their thoughts and perspectives and know their voice will be valued and heard, and have the courage to bring forward bold solutions for significant challenges and significant opportunities. Adaptability, driving innovation in everything we do, whether it be improving the known or creating the new, and then combining our purpose-driven organization with a performance-driven organization. And that performance-driven organization links to the fourth pillar of our commercial engine, which is comprehensive capital allocation. We need to make sure that we maintain a high level of financial discipline, where we're dynamically and disproportionately allocating resources to our greatest opportunities informed by advanced analytics, facts and data. Now over the past 12 months, we've made a set of strategic choices to support the 4 pillars of our commercial engine. And we've translated these strategies into an operational plan to drive precision execution in support of our focused innovator strategy and accelerate performance. And to date, the results are encouraging. Let's look at Rexulti first. When we compare MAT July 2024 to MAT July 2023, Rexulti has grown 18%, and that's driven by the successful launch of our AADAD indication. Vyepti. When we look at the time frame from July 2023 to July 2024, Vyepti market share has increased 33%, going from 6.6 to 8.8. And then if we look at the Abilify Asimtufii launch, I would suggest the Abilify Asimtufii launch is ahead of schedule, and it's enabled the Abilify LAI franchise to sustain double-digit growth in a relatively flat market in 2024. So when I think about it, I'm incredibly proud of what the team has delivered to date. Yet we're also humble enough to know that we have significant work in front of us. We now have a differentiated product portfolio, an incredibly innovative pipeline where we have the opportunity in the U.S. to build multiple billion-dollar franchises. And that begins with delivering $1.3 billion for Rexulti by LOE. Now this assumes a positive outcome for our PTSD indication. We have the ability to build a $1 billion-plus severe migraine franchise, driven by the results that you're seeing with Vyepti. And we have an opportunity to establish a rare disease franchise model that supports a multibillion-dollar neuro-rare disease portfolio, anchored by amlenetug and bexicaserin. So I talked about how we're looking at optimizing our commercial model within a single market. Now what I'd like to do and what we would like to do is be able to talk about how we're optimizing the commercial model across markets. Michala?

Thank you, Tom. Good afternoon, everyone. It is truly a pleasure to be in front of you at such an exciting time in Lundbeck's history. I want to give you a bit of insight into how I plan to drive this transformation within the region of Europe and international operations. If we start by giving you a snapshot of what this region looks like, this is truly a diverse region. We are represented by roughly 2,500 employees across the globe. We have offices in more than 50 affiliates and partnerships in many more, and we represent DKK 10 billion revenue, about half of Lundbeck's business. We have all the brands. Roughly 60% of our business is coming from the strategic brands, and they're growing at roughly 20% compared to last year. And then we actually have a sizable business in the mature brands, roughly 40%, which is holding steady and actually remaining stable despite significant competition. What is critical for us is we're building on a very strong foundation. And we have to, of course, maintain this solid performance through the midterm, while we prepare ourselves for the future and transforming towards a focused innovator. So let's take a look at what that looks like. Essentially, this is really about evolving our commercial model across the geography and ensuring that our go-to-market approach fits the needs of the business and the patients. When we look at the region -- or we look at Lundbeck, we have about 80% of our revenue coming from 12 markets. Those 12 markets, we need to make sure that we capture all the potential that is there. These are markets that have 80% strategic brand share, and there is significant more potential just from the sheer size of these markets. Key is really that we transform to become a focused innovator due to the good environments in these markets and allocate the right investment level, so that we can play to win in these 12 markets. We have a handful of basically Northern Europe and Central Europe markets as well that are smaller markets, still hold potential. But of course, due to the sheer size of these countries, the potential is not unlimited. Here, it's really about making sure we capture the synergies across the markets and that we leverage the best practices and learnings from other markets so that we don't overinvest in these smaller markets, but that we still capture the potential that is there for us. And that leaves roughly 25 markets affiliates, where we need to evaluate the best commercial model for Lundbeck in the future. This really means that we need to look at our current model. We need to look at what is the right model for the future when we transform into a neuro-rare, neuro-specialty business. And this can involve both changing our current commercial model in the market, but of course, also evaluating partnership opportunities. So really, in essence, it is about for us to target our capital spending to support long-term growth for the key products and the key markets that we have in the region. So Tom and I have now given you a sense of what we are planning to do commercially to transform to become a focused innovator. But of course, we can't do that without a sustainable and innovative pipeline. So I invite Johan to give you some insight into that.

Thanks, Michala. It's truly an exciting time to be in neuroscience. I have, through my many years in academic and industry research, never felt that we have a better time than now. If you look at what's happening across the neuroscience field, if you look at molecular neuroscience to system neuroscience, network analysis, we have great tools today. Every week, there is some new tool coming through that we can apply in our research. We can also bring more in different drug modalities into play here. Basically, every drug modality that is used in the pharma industry is actually today being applied in neuroscience drug development. You will later, those of you that participate in a breakout session, visit our bio-therapeutics labs. We have the last 4, 5 years really built an excellent capability in bio-therapeutics, which is one of those drug modalities that play a very fundamental role in neuroscience. What has also been quite remarkable is the development of various biomarkers. And those are not just biomarkers for early readouts for looking at drug effects on target. They are actually now also becoming biomarkers for drug registration. And we have a number of biomarkers now that are validated for accelerated approvals or are co-primary endpoints for full registration. The regulatory pathway has really been changed a lot. And if you look at the field of what I mentioned, accelerated approvals, neuroscience is #2 in terms of accelerated approvals after oncology. And if you look overall, neuroscience is the top 3 of drug approvals with FDA and with EMA. The last 8 years, neuroscience has been among the top 3. So what is coming through the pipeline? Well, it's really been a remarkable journey in migraine. We have now prevention treatments where there were none. We have now a CGRP class of drugs that came 6 years ago into the market, and Lundbeck is part of that journey. We have also now, since many, many years of nothing, a breakthrough in Alzheimer's disease. Last year, we saw 2 full drug approvals in Alzheimer's disease after 20 years of nothing. One of those drugs were Rexulti. For a complete new indication, behavior and psychological problems in Alzheimer treated particularly towards agitation. This is a complete new breakthrough together with the disease-modifying drugs we saw last year and this year. Neuroimmunology. You may say that's been around for quite some time. Yes, MS has been extremely successful, but we still see very successful drugs coming into the MS space. But now, neuroimmunology goes beyond MS. Myasthenia gravis, neuromyelitis optica syndrome and other indications are now coming through with strong and very powerful mechanism, where we have very, very strong underpinning biology. Rare neurology. It's an amazing space. We are entering into this field more and more. We've been there before. Here, you see very innovative drug modalities coming through, anti-sense, gene therapy, et cetera, for diseases with very, very high unmet medical need. Many of them inborn. And finally, we also see some breakthroughs in psychiatry. A very different thing here. You see well-established mechanisms that finally break through and start to deliver to the marketplace. So there are many, many drugs coming through that explains that neuroscience is among top 3 in drug approvals. So how do we operate in this space? We have a long, long legacy. Over 70 years ago, we launched the antipsychotic drug. And since then, we've been in neuroscience and fully dedicated to neuroscience. We have a strong legacy to build on. Now we're embarking on a focused innovator strategy, building further on our psychiatry core, reinforcing what we do in neuro-specialty and now bringing forward a number of products for rare neuroscience diseases. How do we play in this space? We are listening. We're listening to the biology. We're listening to the molecules and to the patients. We have systematically built our R&D to start with strong biology. Why? Because that's where we find the best readouts, and that's where we're finding those biomarkers I talked about. This is fundamental to be successful but also, quite frankly, to kill your darlings in Phase I. We really need systematically to weed out and bring forward the best opportunities. The best opportunity should be underpinned by really strong molecules. That's why we're listening to the molecules in early development. And finally, we like to take the molecules that we tested out into the right patient populations. Stratification of patients, better innovative trials, all these are things you will see from us in the future and already seeing in some programs. We have, as I said, a very strong legacy in psychiatry. We had delivered a number of very, very strong impactful drugs. Most recently, Rexulti for agitation in Alzheimer's disease. And we also have brought forward Abilify Maintena 2 months recently. We're still building on that, but now we start to focus more into the neuro-specialty field. And here, we have a strong position with Vyepti in migraine, and we're building further on that with our PACAP and the PACAP molecule as well as other things we can play with now. We are also building up a neuro-rare presence. Amlenetug, multiple system atrophy antibody, is moving ahead towards Phase III now. But we also have other very interesting ingredients in our port. One is the anti-ACTH molecule that I will come back to. So Maria, how do we meet the patient needs?

Thank you very much, Johan. We've been giving you a lot of information, so I will try to summarize the key points here. By optimizing our operating model, in reality, what we're doing is still meeting the needs of patients in different markets. And you've heard from Tom, on the one hand, how we are creating a true patient-centric model in the U.S. but also how we are creating a unique customer experience that will be very relevant as we move into newer disease areas in the future. You also heard from Michala how the focus in Europe and international operations is allowing us to really unlock the potential of key markets, leaving no patient behind ideally. And you also heard from Johan how our choiceful R&D allocation of capital allows us to leverage our resources for brand support on the one hand, but also how it will help us continue to build our pipeline into the future. So moving from focus into how we win. We've previously shared with you that, again, focus will be a part of how we win in the future. We've already shared with you some of our key or these 3 key areas, where we believe we will be able to win. But I would like to take you back to our mission video. There, I believe it's very clear that Lundbeck has the history in neuroscience. We have the legacy. We have the skill. But I would like you to also understand, we have the will to stay true to our legacy, to our history, but to unlock the potential of the future. That's exactly what we will be doing over the next few presentations. We will take you through how we build on our psychiatry core and use it as a springboard into the future, but also how we are reinforcing our neuro-specialty position and also how we establish a neuro-rare franchise. So to tell us about how we've made advancements with Rexulti in the field of AADAD, back to Johan.

Yes. Thank you, Maria. I talked about it already. I think it's a remarkable thing that we brought this very well-established product for other indications into agitation associated with Alzheimer's disease dementia, AADAD. That's the indication we have in the U.S., and we are expanding this drug into several other markets, but the U.S. is the main market. We have generated more data on this molecule. And I think this is extremely important, what you hear, because many of you know what I'm talking about. You're caregivers. You're taking care of Alzheimer's dementia patients. And we went out and talked to caregivers and asked them what is the most bothersome thing with your loved one. If you think about cognition, you think often about dementia. And that is a problem truly in Alzheimer's, but agitation is the true problem that drives people to the nursing homes. Agitation symptoms that caregivers bother most about are in the aggression realm, cursing, verbal aggression is part of that, spitting is actually very high on the list. We have also physical nonaggression like trying to be in other place, wandering about, leaving home, being found out on the streets, big problem. And verbal agitated, repetitive sentences or requests for help. That is what bothered patients and caregivers the most. Rexulti has the strongest effect on those behaviors. We also took a look from our pivotal trial, the last one we did, the [ NACETA 3 ] pivotal trials, the 213 trial, and continued that into an OLE, trial 182. And what you see in this graph, I think, is important data as well because it shows that when you continue treatment with people that have responded well to the treatment, here defined as a clinical meaningful effect, which are 20 points on the Cohen-Mansfield Agitation Inventory Scale. You see that already at the end of 12 weeks, which was the registration endpoint, we had over 50% of the patients showing a clinical meaningful effect. But when we continue out, that goes up even to 75%. What we also see in this OLE study is that when we switch patients from placebo over to active treatment, they are also quickly reaching that 50% and they also go up towards 75%. So that means that we're showing sustainability of the effect for the treatment. It's an intermittent treatment in the label, but now we show beyond the 12 weeks in the trial. As you may remember, we took this drug also into another indication, PTSD. We had a readout last year, and it was somewhat mixed. First of all, I'd like to emphasize this trial was run at the height of the epidemic -- COVID epidemic. And that's not a good indication to study during the epidemic. PTSD, people don't want to leave home. So that's a hard trial to execute, but we managed to finish it up eventually, 2 trials in that program. One trial was positive, clearly positive. The other one didn't beat placebo. However, overall in this program, we also had a Phase II program. And when we pool these data set together, you see what you see on the left side here. So overall, we see clearly a benefit of the treatment. This, we generated in discussions with FDA. We had a pre-IND -- a NDA meeting with them and discussed what they wanted to have. And we've been working on the data set they wanted to see. And now we submitted for an sNDA approval last year, and we're looking forward to PDUFA date, February 8. So how are we doing in the marketplace? Well, Tom?

Thank you, Johan. So to me, commercial performance begins with meaningful clinical differentiation. And the data that Johan just presented further enhances the overall clinical value proposition of Rexulti to drive further growth. And this is particularly true when we look at AADAD. The strong growth that we're seeing in AADAD is now propelling the overall demand growth for Rexulti. So if we look back to March -- or May of 2023, when Rexulti received the approval for the AADAD indication, monthly TRx volume has grown 361% based upon the latest data that we have, which is July 2024. And during that same time period, the non-AADAD business has grown 15%. AADAD now contributes 17.5% of the overall TRx demand for Rexulti and 22% of NBRxs. We expect by the end of the year that the AADAD indication will contribute over 20% of the total TRx demand for Rexulti and play a more meaningful role in terms of driving growth of the overall brand. So when I think about how we're performing in AADAD, I would say we're pleased but not satisfied. From a performance standpoint, the results are in line with our expectations. But when we look at AADAD, we see so much significant opportunity in front of us, as the diagnosis and treatment rates are still very low and the unmet need is significant. If we look at Alzheimer's disease, it is a public health issue in the United States. 6.7 million Americans age 65 and above are diagnosed with Alzheimer's. 50%, one out of every 2 patients, will develop agitation at some point during their disease course. And only 34%, 1/3 of these patients, are being treated. So as we look at it through an alliance lens, Lundbeck and Otsuka are committed to investing the necessary resources to maximize the opportunity for AADAD, both from a business standpoint as well as from a patient standpoint as well. And we think these investments will continue to help drive growth for Rexulti, both from a brand market penetration standpoint but also from a market growth standpoint as the diagnosis and treatment rates go up. So now what I'd like to do is for us to look at how we view the overall potential for Rexulti. It's important to remember that Rexulti was launched with 2 indications, schizophrenia and MDD. And at the asset level, we have been able to build a blockbuster in a very competitive MDD market. And we continue to believe that we will drive incremental growth in this base business. But where we see the accelerated growth, it's in AADAD as we just talked about. So if we take our current indications, our base business with MDD and schizophrenia, and combine it with AADAD, we believe that Rexulti will achieve blockbuster status from a Lundbeck point of view. Now when we think about how we fully maximize the opportunity with Rexulti, it does include that PTSD indication, which we believe is an exciting and significant opportunity. But as Johan said, we're also cautious because we know that there's risk involved with the sNDA filing, which we'll find out in February. So if we do get that indication, we do see further upside, and it will be further upside based upon the midterm guidance we have given because the PTSD indication is not included in our midterm guidance. So we've talked about Rexulti becoming a blockbuster product, exceeding that $1 billion threshold for Lundbeck in the U.S. And now what we're going to talk about are Brintellix and Abilify LAI franchise, which collectively have the opportunity to deliver over $1 billion or DKK 7 billion. Michala?

Thank you, Tom. So let's start with Brintellix, the little engine that could. Here, you see a brand that has several years in the market. And you see here 6 years of continuous growth, delivering almost 15% compound annual growth rate over the period. This growth is largely driven through Europe and international operations, and we really see that it is the big European markets, Japan and China, that have driven the growth. The focus here is to continue to maximize the potential, and we expect to see mid-single-digit growth in Europe. We, of course, have patent expiries coming. And in the U.S., as you know, we have given the rights to commercialize or we will seize the commercial activities for Rexulti -- for Brintellix, sorry, as of January '25, giving it back to Takeda, so that we can continue investing in other opportunities here in Rexulti. The Abilify franchise holds a similar story, also a product that has been on the market for an extensive period of time, but continues to deliver strong growth. Again, you see almost 15% compound annual growth rate over a long period of time. And you see here that the growth is coming from many places. We actually hold over 30% market share in several of our key markets, and we continue to outgrow the market. The focus here in the midterm is really to roll out and launch the 2-month option, Abilify 2-month option, and ensuring that we drive the conversion from the 1 month to the 2 months. We believe the 2 months provides patients with a very relevant alternative, both in terms of sustained efficacy but also in terms of convenience of a 2 monthly injection versus a 1 monthly injection. As you know, we got the approval in Europe this year and have begun to roll out in Europe. We launched in U.S. last year and very encouraging results so far. I think Tom touched upon it earlier, but we're seeing now 15% NBRx, and we're seeing almost 11% of total Abilify LAI franchise share in TRx. So a very strong start for U.S. in converting. And the encouraging news is that we see that the conversions are not just coming from the 1 month but also from the oral version, the aripiprazole version in the market. Analogs suggest that we can expect conversion of around 20% to 25%. We are cautiously optimistic that we can probably exceed that ambition. This brings our psychiatry core part of the presentation towards the end. But again, you're getting a lot of information. So to ensure that we are hammering the points home for you, I invite Maria to close.

Thank you very much. So Michala already started summarizing for us. The key thing that you need to retain is that by building on our psychiatry core, we're still able to accelerate growth with a focus on our key markets. You've heard from Tom that the performance of Rexulti is indeed accelerating. I mean you heard it has even surpassed some of our initial estimations. The growth on Trintellix and Brintellix in Europe and international operations is significant and again reinforces our position in psychiatry, but also how we are fully leveraging the performance of our strategic brands with this focus on the key markets. So moving on to the next area of focus for us. You've heard us also mention that we want to reinforce our position in neuro-specialty. And as you know, Vyepti was this first step into this space. It was, so to say, our beachhead into creating a migraine franchise. And given the performance of Vyepti that you're familiar with, I would say that not only Vyepti gave us the right to play in the migraine space, but it is becoming a clear signal that we should have the right to lead in migraine. So to tell us everything about how Vyepti continues to exceed our expectations in the market, Tom.

Thank you, again, Maria. So Vyepti is the foundation of our neuro-specialty franchise and will continue to be the foundation moving forward, and we're going to continue to invest in Vyepti to make sure that we can drive and maximize growth of this asset. So although we do look at all of your estimates for Vyepti, the way that I measure performance is really focused on how we're doing within our competitive market space and then our performance versus other industry analogs. And when we use these benchmarks, Vyepti is setting new industry growth records when we compare Vyepti to other medical benefit products at the same time point in its life cycle. So back in -- at the end of 2022, we were analyzing Vyepti performance versus other medical benefit analogs, and we are performing basically in the middle of the pack. In 2023, year 4 on the market, we set an ambitious target to drive 50% growth in demand, which would match the highest growth rate of medical benefit products within year 4. And as you can see, in 2023, our demand grew 63%. We exceeded that forecast and set a new benchmark in terms of performance for medical benefit products. And if we look at 2024, year 5 in the marketplace, we expect, based upon current performance, to at least double the rate of growth of our nearest analog competitor. And we do expect this dynamic to continue, and the reason for that is based upon favorable market dynamics as well as strong brand fundamentals. So if we look at it from a brand market dynamics standpoint, what we're seeing is that the number of subcus that are being used are getting fewer and fewer until HCPs are transitioning to Vyepti. And then from a brand fundamental standpoint, we are seeing 66% of our growth coming from existing prescribers, so increased depth, and 33% of our growth coming from new prescribers, increased breadth. And what's helping deliver that growth for Vyepti is really this patient-centric model that I referred to in my previous presentation. Through our patient model, we're making it easier for physicians to prescribe Vyepti and making it easier for patients to get infused with Vyepti. I think it's really important to understand that we manage our Vyepti business at the patient level, not at the population level like other migraine companies. So we have built a fully integrated patient ecosystem that supports the patient across the patient journey from activation, origination, diagnosis, treatment, reimbursement, fulfillment and persistency. And what that allows us to do is to activate levers within that patient journey to help patients overcome barriers, but also to influence brand choice. And over the last 12 months, within this differentiated patient experience, within our Vyepti infusion network, we've been able to increase the written-to-infusion ratio from 50% to 65%. The 12-month persistency for Vyepti has increased from 45% to 55%. And just for reference, the 12-month persistency for Botox is 37%, the 12-month persistency for subcus are 31%, and it's 27% for QULIPTA. So as we look ahead, we see the opportunity to even further elevate and enhance the efficacy of our patient model, taking conversion rates from 65% up to 75%, which will be best-in-class, elevating our persistency rates to that 60%, which will further define what best-in-class persistency looks like. And importantly, this model also gives us the ability to scale to develop a rare disease model that will be able to support our emerging rare disease franchise for amlenetug and bexicaserin when launched. So as we think about Vyepti, we do see a $1 billion opportunity for Vyepti in the U.S., but we also see significant opportunity for Vyepti in Europe and international markets. So Michala?

Thank you, Tom. To me, Vyepti is really an amazing story. We launched it 4 years ago in the U.S., and we began the rollout outside the U.S. in 2022. Today, 30 countries have access to Vyepti, and patients are benefiting from Vyepti on a daily basis. It is truly becoming a global brand, and Lundbeck is well positioned to take a significant position in this marketplace. There's still a high unmet need in migraine treatment, and that's why I think we have so many opportunities here. We've seen phenomenal growth in the U.S., and we've seen Tom's plans to continue this. In Europe and international operations, we're gaining significant momentum, growing triple digit, and we're benefiting from the great learnings and practices that the U.S. have shared with us so that we can expand our position with Vyepti in these markets as well. And key for us is really to ensure that we allocate the right investment to the right growth markets. As Maria said, growth of Vyepti is really exceeding our expectations, and we're confident that we will reach blockbuster status earlier than originally indicated. And on top of that, Asia represents a significant opportunity, of course, depending on the SUNRISE readout that Johan will come back to in a minute. To me, the launch of Vyepti really demonstrates that Lundbeck has the ability to successfully build a market and launch a global brand and drive a very strong launch performance across the globe, and we can do that on our own when we need to. To give you a little more on what lies ahead from a clinical point of view, I invite Johan back to the stage.

Yes. Thank you. First time I met the CGRP biology was over 40 years ago, and I did studies on the human distribution of CGRP. In 2009, I got really involved in the CGRP class for drug development. At that time point, I had no idea that the best drug that will emerge out of this would be an antibody, and an antibody for IV administration. Vyepti has really converted into a remarkable drug, I have to say. This is a very impactful class, but Vyepti is really the most powerful agent in that class. And we continue to build on this with more data. Here, you see a few examples of that. One to the left here is when we look at sustainability of the effect. Here you have a combined index of headaches and the severity of the headaches, which, of course, are clinically very relevant. And we see data after 2 years. This is extremely important that we see the sustained effect over such a long time, because one of the problems in migraine is that people cycle through different treatments. But here, we see a very sustained effect, with reduction throughout 2 years. Migraine, for those that don't have it, you think it's headache. It's much, much more. One of the most troublesome symptoms is actually not the headache and pain attacks, it's something called brain fog. Brain fog is really what it sounds. It's being foggy in the brain, cognitive deficits. You basically are not performing where you like to perform. That can occur during attacks, but also in the interictal periods. Here, you see some data on Vyepti that I think are quite remarkable. If you see the effect on brain fog through a different rating scale here, 86% of patients see some benefit in the brain fog. What we also see, that almost 1/3 have very much improved in the brain fog. So this drug really goes beyond the migraine attacks themselves. I said we're letting the patients speak. We're also letting the patients speak when it comes to the treatment effect of Vyepti. We did a pioneering adaptive trial in the Asia markets for Vyepti. We started with the SUNLIGHT trial, which was really trying to understand how the Chinese population and also Japanese population responded to the drug, which was very important because there were, at that time point, very few studies done in the Asian markets. Through the SUNLIGHT pioneering study, we got important information so we could build the SUNRISE study, the follow-up study, the pivotal study in a much more solid way. We're looking forward to have a readout of that trial within shortly. That will, if it's positive, build the foundation for us to enter into Japanese and Chinese markets. So I just been talking about how great CGRPs are, but unfortunately, that is far from enough. 40% to 70% of patients are still not responding well in spite of the set of drugs we have now, including the powerful CGRP class, well to treatment. There are lots of remaining medical needs in migraine, and that's why we like to stay in this field, to try to serve the patients with all those symptoms. Treatment response, of course, very important, but also symptoms beyond the migraine attacks. I talked about brain fog, but there are many other cognitive and other behavioral problems you have with migraine. Quality of life is very, very important to restore in people, particularly when you have chronic migraines. Convenient treatments are important. So we see a great potential as a company to stay in this field, not only because we like to serve the patients with a still remaining unmet need, but also because the market potential. Maria?

Thank you very much, Johan. So as Johan mentioned, there's still huge unmet medical need in migraine. So despite the good results that we see with Vyepti, the task is not done, and we step up to the task. So you know that in terms of our pipeline, we've shared already some of the highlights. We have assets that have the potential to be first in class, meaning that they can help us address the needs of migraine patients all over the world. We know that we have with this the potential to build a true migraine franchise of which Vyepti was the first step, as we've mentioned before, but we're talking about addressing the needs of something like 2.5 million to up to 3 million patients worldwide, and you know the market currently is worth $11 billion.

Yes. Thank you, Maria. In R&D, there are many some things you can do, but the most fun thing you can do is to have a positive clinical proof of concept. We had that last year with our anti-PACAP molecule. In April, we had a readout from a proof-of-concept study with IV administration of this antibody that we took from preclinical level up to this stage. So now we're embarking on a more ambitious program, aiming to bring this molecule into a full pivotal program. But before we do that, we'd like to sort out a few things. One is it may be a very mundane thing, but it's fundamental for R&D: finding the right dose. So now we have a dose-ranging study for dose arms, but we also try out an alternative administration route through the subcu administration. So we have the PROCEED trial ongoing right now. It started this summer. It's sort of 1/4 into it. So it's still early days. But we hope to have a readout from this trial so we can guide the pivotal program when they start in 2026, with a potential market entrant, if the trials go well, in 2029.

Thank you very much, Johan. So of course, there is indeed the potential to build a true migraine franchise. It's what patients want. It's also what the market wants. Migraine has been a way for us to reinforce our neuro-specialty position. And we have spoken to you about how we continue to drive growth using Vyepti as a base, but also using Vyepti to prepare us for the future with other assets in this area. We're fueling the growth in the U.S. with a true patient-centric model, with a true unique customer experience as well. But also by focusing on our key markets, we are able to drive an amazing performance in Europe and international markets. By addressing unmet needs with Vyepti, we're also not forgetting that the job is not done, and we're in this for the long run. So we will be bringing to the market drugs like anti-PACAP and developing a franchise with amazing growth opportunities still. So we're approaching the final of our dedicated areas where we said we would be playing, and that is exactly how to establish a neuro-rare franchise. And through this section, Johan and I will do a tag team to take you through the key considerations. We spoke to you before about our appetite or our openness to consider external innovation. It's not a big mystery. Most of the successful pipelines in the industry are made up exactly if this combination of internal and external assets, and we see it at Lundbeck as one of the ways to augment our internal innovation to ensure that there is enough strategic fit between the inside and the outside, and we see it as an opportunity to increase our success. You were probably curious about what this meant for us. We have received questions from you in the past. So I imagine last week, Finally, you're able to see how we were becoming more concrete with our deal with Longboard and how we are now adding bexicaserin, the latest pearl to our collection, to join an already amazing set of assets that hold [ really ] for the future.

Yes. Thank you, Maria. I'd like to take you through a few slides that explains why we're so excited about the potential to acquire this company and this asset. So we'll focus on bexicaserin, which is the lead asset of Longboard. But before we go there, I'd like to explain a little bit what we're dealing with here. Epilepsy is a major clinical problem. Another major problem is that we have very few treatments that are fully effective. Many patients are not responding well to treatment, so there is a big need for additional treatments. You probably also know there is a lot of add-on treatment. You're combining its polypharmacology in this field. About 25% to 40% of epilepsy patients basically are drug-resistant. Epilepsy is today classified from various angles, but one angle is the type of seizures that you have. You can have generalized seizures, and that is actually a seizure that starts throughout the brain. The whole brain starts to backfire or over fire. There is also focal seizures that were called before partial onset seizures, quite often from the temporal lobe, that can spread out to become generalized seizures. You can present with different types of behavioral problems, epilepsy. So seizures can be very discrete events, clinically, to major grand mal attacks. The underlying reason why you get an epilepsy varies. It can be acquired. Brain trauma, infection, tumors, first sign often of an astrocytoma in the brain is seizure. Syndromal. There are many syndromes, metabolic, et cetera. What we start to figure out now is many of them actually have polygenetic common variant reasons. So they have a little bit of underlying genetics also, those syndromal ones. And then we have a big, big group of genetic causes. That's actually the majority. Over 50% of all seizures are due to monogenetic causes. Those could be ion channels, transporters of signaling molecules, et cetera. Sodium channel mutations are the most common. There are more than 900 different monogenetic reasons for getting an epilepsy. Developmental and epileptic encephalopathies, that's a subgroup of the big field of epilepsy, but it's a very, very important subgroup because that's where the really severe diseases are. These are patients with developmental disorders, so they have other problems. They have cognitive problems, behavioral problems, motor problems, they could be autistic and then they have epilepsy. The epilepsy is part of the pathology. It actually drives some of the other symptomatology, including cognitive deficits. And often, they regress in the development. They hit at very early ages in many cases. And of course, in the monogenic cases, you're born with the problem. So if you look at this group, very big group of developmental and epileptic encephalopathies, there are only a few of them that have approved treatments, but there are a lot of different types. So drill down a little bit more on this. So these are U.S. numbers, but if you look in this DEE group, as we call them here, there are about 120,000 patients in the U.S. with approved treatments. That's for Lennox-Gastaut, for Dravet and the other indications that have approved drugs. But when it comes to many of the other DEEs, there are no treatment around that is approved. There's some off-label use, of course. So within this big group of DEEs, we have Lennox-Gastaut, we have Dravet and then we have other DEEs combined into this. Why did we get so interested in bexicaserin? Well, it had an interesting mechanism of action and good data. So let's start with the interesting mechanism of action. This is, if you may, the best-in-class molecule, but it's actually also have elements of being first-in-class. This molecule is selective for its agonistic effects on 5-HT2C receptors, which is a validated target for anti-seizure effect, but it doesn't carry any binding agonistic effect on other 5-HT2 receptors. And that's fundamental, because the 5-HT2B receptor carries a big liability: valvular pathology, heart disease. 5-HT2A receptors carry problems with pro-psychotic effects. So here, you have a validated mechanism and a unique mechanism being selective for the 2C. The selectivity by the way, is carried by this secondary [ amine ] in the 8th position of the molecule, for those that are chemists here. That's really very important to say, because the company that is behind this, Arena and Longboard, they really know what they were doing. They had the structure activity relationship going after that selectivity. So this is very, very nice underpinning for the rest the story. Of course, they did a classical thing of preclinical evidence, anti-seizure models. They went into healthy volunteers and looked at the effect of the drug. What is important here is, of course, drug-drug interactions that is well behaved in terms of other drugs as part of the equation here to be effective. But was -- of course, what was driving our big interest was, of course, the so-called PACIFIC study, a Phase IIa study that looked at various DEE populations. These data were communicated earlier this year, and they also initiated and have communicated an open label extension part. This molecule carries differentiation potential because of that unique profile that I talked about. If you compare to other common treatments, in some of the these cannabidiol and fenfluramine, we have a potential here for Dravet syndrome patients by themselves to be more efficacious and definitely have a better, more compelling safety and tolerability profile. We also have the possibility for Lennox-Gastaut to have a very strong effect, but also across the DEE spectrum into pediatric populations, of course. Eventually, you like to include children down to 2 years into this, because that's really where the big medical need is. There are a lot of other benefits with this asset, and one is that the FDA also liked the data, and they provide a breakthrough destination for the molecule for this new indication of DEE. The selectivity also carries the potential to avoid burdensome safety monitoring REMS programs. So this is a truly exciting molecule that was underpinned of the data that you see here. Here you see the 3 different populations I talked about: Dravet, Lennox-Gastaut and other DEEs. This is the PACIFIC study, the IIa study that made us very interested in this asset. This is on top of standard of care. The patients are on diet treatments, including EPIDIOLEX. So what you see here, combined in the study on the left side, is almost 60% effect in reducing motor seizures, that are seizures that translate into motor symptoms. That's quite remarkable data on top of other treatments. If you look through the different subgroups, which notably some are small, but in the Dravet symptom, the patients that were involved there, they had a very, very strong response rate, but also in Lennox-Gastaut and other DEEs. The other thing that really made us exciting was the open-label extension study. Because we're talking about an agonist therapy, tachyphylaxis tolerability can play a role. But here, we see out to 9 months a sustained effect, with about 50% reduction in the motor seizures. So this is truly a very strong indication of being a strong drug and differentiated drug. I'd like to shift gear now from this very interesting asset to another, I think, very interesting asset that we have in our portfolio, and that is our multiple system atrophy antibody against alpha-synuclein. For those of you that will be part of the breakout sessions later, you will hear more about this program. We will present specifically, on this program, the Phase II data, et cetera. Unfortunately, Dr. Wolfgang Singer came down with some disease, infectious disease, and couldn't travel, so we'll have another presenter for the clinical background of MSA. Just a few words. I talked about the joy of a proof of concept when it's positive. We've been blessed, because early this year, we had a readout in our AMULET trial. This was a highly innovative trial, adaptive design elements, but also most importantly, Bayesian statistics with a progression model which truly showed encouraging data that this drug works in a disease that has no treatment. Patients with this disease die within 6, 7 years. So Maria, how about the market potentially?

Thank you very much, Johan. So as Johan said and as you know, because we've told you about the assets before, in multiple systems atrophy, we're aiming to have a first-in-class disease-modifying drug. So we're talking about an antibody that has a superior technical profile. Johan already mentioned we have achieved clinical proof of mechanism, but also there is a very clear, well-defined regulatory pathway. So we are talking about potentially addressing something like 26,000 patients worldwide, but with a range of potential from a sales point of view between something like $1.5 billion to $3 billion, and also with the launch around 2029. So 12 to 18 months after the launch of bexi, we could be looking into launching amlenetug.

Yes. Charl talked about potential to have more assets in Phase III by some years, and this is one of them. It's a really, really interesting asset in rare diseases, neurohormonal disease, and it's our anti-ACTH antibody. It's a first-in-class. No one has approached this biology with this kind of mechanist before. We are doing 2 trials now to explore the full potential of this drug. We have already proof of mechanism, I would say, a little bit more than proof of mechanism, in the congenital adrenal hyperplasia study. That's the blue illustrations here. What is that? That's a disease when your adrenals are underfunctioning. You have less cortisol, and with the homeostasis in the body, that means that the pituitary glands says, we need more ACTH. So it starts to fire up. And that leads to stimulation of the adrenal or other things that you don't like to have. If you're a woman with this disease, you get masculinization, which is leading to things like no menstruation, et cetera, hair growth in places you don't want to have it, et cetera. There is really no treatment today that nips it up at the top, at the beginning of this hormonal cascade, the ACTH generation. Looking at an indication like that, it's quite interesting because we have very strong biomarkers. That's why we're so confident even though this is in a very early stage asset. So we have readouts already now that are highly relevant by chemically, but also we see clinical signs of really good effects. The left side here, the red side, is Cushing's disease, where we just started up a study, a few subjects included. Cushing's disease is a very different thing. You have benign tumors in the pituitary gland overproducing ACH. The only treatment that is partially effective is surgery or blocking downstream at the receptors. So again, we go to the core of the problem, keeping the tumor cells that are overproducing ACTH and stopping that from coming out. So we have already now data also from that study, very early, but signals that the molecule is doing its job. And that's why Charl is bullish and pushing me and R&D, that this will be a Phase III program. But we really believe in this one.

And I think Charl is also thinking about the roughly 15,000 patients who are currently being poorly treated. The existing options are not good to address these drugs, that's why we believe in the science, but that's also why we see a market potential. We could be looking at the first-in-human first-in-class antibody with a favorable safety profile that acts, as Johan just mentioned, directly into ACTH. We believe that we will be able to bring clinical differentiation and also interesting characteristics, not only in Cushing's disease, but also in CAH. And there are, of course, clinical diagnostic criteria, which are helping us, are guiding us in the development program. So the potential for these 2 indications combined could be superior to USD 2 billion as well, and here again, we would be bringing the assets to the market roughly around 2031. So you're starting to see a pattern here.

Yes, I talked about that letting the molecule speak, and I will soon talk about one example here, but I said we like to kill our darlings in early development. We just announced that we actually killed the darling. That's the [indiscernible] monoacylglycerol acetate inhibitor molecule, MAGLi, for short, inhibitor 74. It was a briefly restricted molecule that we explored in a nice set of very decisive pain studies and the molecule told us, we don't like this. So we stopped that program that we announced today. That was part of the Abide acquisition, but there are still MAGLi inhibitors in clinical development. That program has not ended overall. But let me talk about something a little bit more exciting: our CD40 blocker. Yes, many of you may know about this biology because other companies work on. It is a pretty exciting area, and exciting areas tend to aggregate R&D people. So this is a mechanist that has been studied for several generations. We are kind of on a third-generation drug here that is substantially derisked from side effects that the previous molecules had. We have a binder. It's not a true antibody, it's blocking CD40 ligand, but not through an antibody type of molecule. It's another type of binder, which binds the albumin. We decided to put this molecule into thyroid eye disease. Why? Because we think the mechanist is well suited for it, and it's also a good indication to test this mechanism of action. We will let the molecule speak here. We're looking at autoantibodies. Thyroid eye disease is a consequence of Graves' disease, where you have extrusion of the eye. So we're also looking at the growth extrusion of the eye, which is very fundamental because we think in the mechanism of action, we may actually affect tissue growth as well. But these are really great mechanisms, broadly active and could potentially work in many other indications. Other companies have shown already this mechanist to work in multiple sclerosis and also some non-neuro autoimmune indications. But this is a big field, Maria.

It is a big field. And although we cannot tell you more about other subsequent indications, with such an interesting target within the neuroimmunology space, which is where we would position ourselves to work, there are multiple opportunities. Johan just mentioned multiple sclerosis, but also neuromyelitis optica, myasthenia gravis and others. So there is tremendous growth potential even by addressing these smaller disease areas, so to say.

Yes.

Thank you very much, Johan. So I'll try to summarize again how we believe that by establishing a neuro-rare franchise, we are indeed creating an R&D innovation engine with a compelling pipeline that will help us build sustainable pipeline and sustainable revenue into the future. We are combining internal and strategically selected external opportunities which include, as you know, bexicaserin as well as amlenetug. There is huge unmet medical need, and we are trying to play exactly in that space by providing scientific breakthroughs. We like to work on what is exciting. And finally, we have the competencies. We have the organization. We are well positioned to exploit the opportunities that come from these science areas. And we believe that we will be able to deliver game-changing products and a game-changing pipeline. So we've taken you through a very big journey, a very long journey, and I will try to summarize how we are. We have a focused innovator mindset. We're driving sustainable growth by creating a pipeline of truly amazing assets with either best-in-class or first-in-class potential. On the one hand, building upon our psychiatry core with continued growth of Rexulti in the U.S. as we've heard from Tom, but also Brintellix in Europe and international with -- and Japan absorbing some of the midterm or upcoming LOEs, enabling also the extension of our midterm guidance. So we're reconfirming that. When we're reinforcing our neuro-specialty position, you've heard from us that as Vyepti achieves things that we believe are wonderful, we're also going to continue to build on this migraine, on this disease area, to establish a neuro-specialty position, and also how we are establishing a neuro-rare franchise with amlenetug and bexicaserin as 2 of the key assets that will drive our future and have the potential to incur a multibillion U.S. dollar franchise. So with that, I would like to welcome Charl back on stage, who will help us through the Q&A.

Thank you, Maria. Thank you so much. So I know we've had -- we've covered quite a number of elements, of course, of today. There is still one part that will follow, which is our capital allocation and financial dimension, but we have addressed essentially 2 of the important questions. One was how do we see the midterm perspective of our organic growth? And of course, how do we look at the long-term pipeline? So we really want to take the moment now to hear your questions, questions you might have. And I would ask you to guide your questions maybe more to the parts that you've heard. And then, of course, the financial part, we will have as a follow-on with additional question-and-answer time as well. And there are also -- of course, those online able to post your questions as needed. Microphones are available for us just to make sure we hear the question very carefully. I see one hand up in the back, please.

Thomas Bowers from Danske Bank. So maybe just kick off a few questions on bexicaserin. So looking at the competitive landscape right now, so of course, fenfluramine with a similar mechanism of action, broadly. So I'm just wondering when you are excluding fenfluramine patients in the Phase III, as I understand it, how should we think of your positioning yourself in the market? And also if there's any plans for any head-to-head comparisons that you need to do in the clinical setting? And then second question, just on the DEEs. So I understand that you are looking at plus 15 or at least 15 different diseases within DEE. So is there anything we should be concerned about in regards to the balance in the Phase III trial? So just maybe to give us any understanding on whether there should be concerns of potential noise in the Phase III? And then just lastly on the formulation. We're looking at 3x daily. So is there anything that you're working on that could make it into a twice or once-daily, also in terms of looking at the competitor space?

Great. Thank you for that question. So maybe we start with the question around how we see this positioning from a clinical perspective against fenfluramine. So Johan, you may want to comment there.

Yes. First of all, the PACIFIC trial did not include fenfluramine or FINTEPLA-treated patients. So they were not included. And there's -- since the drugs have fairly similar mechanism of action, it probably wouldn't make sense. It's more that you can drive the doses up with this one. So you have to think about the ethics for the patients, too, right? The REMS program, the side effects, of course, is where we have the strongest profile, but we expect also through that kind of more unlimited dosing paradigm to be able to drive efficacy more, but we are not including that. And I say we, but it's them still, right? It's Longboard. So we have not concluded this deal yet, right? And there could be things we like to change a little bit in the program if we take over this. But that's how it's planned to go ahead. Maybe I can go on with other 2 also. The DEEs, not 15 others. There are hundreds of others. DEE is a broad, broad family that I tried to explain, right? We're talking about hundreds, maybe thousands of different reasons to have a DEE. So this is the remarkable and also very exciting breakthrough that now the regulators are open to find a treatment that is approved for this big, big basket of different indications. Yes, would that lead to some worries about variability in the study? Yes, it does, because when you have more heterogeneous populations, it could be more variable response. There are various ways to build this together, this puzzle. Longboard has embarked on a separate Dravet study, called the DEEp SEA, and then they have DEEp OCEAN that is just also now starting up. That will be in Lennox-Gastaut and the other DEEs. So there are many possibilities to play here with the different indications, subindications, but the main thrust should and will be overall for DEEs, not slice it up. And as you see, the most sizable populations are still Dravet and Lennox. So that will drive most of the presumed powering of the study that they're having. BID, TID, yes. That's a good question. It's TID right now. It's good half-life, but not perfect, about 6, 7 hours. And you need to have relatively stable exposure. The program has an in-built bridge to look at BID as well.

Good. Thank you, Johan. So I think just to wrap that question. I mean, what we see with bexicaserin is really the best-in-class profile that we see with the selectivity and the design. So as Johan said, I think this is what we see clearly is the opportunity with the ability to differentiate. So we have a question here. We just need a microphone, if possible.

Martin Parkhoi, SEB. Two questions. On the migraine franchise, and we see your peak sales charts on Vyepti, which is also continue to go up after the potential launch of PACAP. So how do you think these 2 products complement each other on a commercial scale? And then just about your new soft guidance on the R&D ratio of towards 20% to 25% by the end of the new strategic period, how much is that driven by Longboard?

Thank you, Martin, for that question. So maybe we first go to how we see the co-positioning Vyepti, anti-PACAP. We spoke about the nonresponders, certainly in CGRPs, but maybe, Maria, you want to comment on that?

Yes, I can start. So as Johan said, we're talking about very different modes of action. So in reality, with anti-PACAP, we could target everyone, including the patients that are currently on anti-CGRP. So it could be used with an anti-CGRP. It could be used with nonresponders to anti-CGRP. We have not yet defined the route. But in essence, one does not exclude the other from a commercial potential point of view.

Maybe I can add a little bit. In the PROCEED trial that we have ongoing now, we allow people that have been on CGRP and have not responded well. So we're going to have a sniff for that differentiation. We're not pushing that hard in that trial, but we're going to get the sniff of that. But as Maria says, it's a broad biology here. This could go into not only the pain signal itself, but also this autonomic system and all the symptoms that are related to autonomic system stimulation and migraine.

Great. Thank you. And Martin, we will certainly come back also when Joerg speaks about the guidance. But what I would say is, of course, as we see the pipeline evolve more to Phase III, there's a natural growth of investment as we enter into those Phase III areas. But strategically, we see, for a focused innovator, being in this 20% to 25% ratio is what we want to go for. Now the way we do that is we have also -- we will discuss a bit more undertaking significant capital reallocation, 10% of our current capital to free that up, to reinvest in innovation. So -- and of course, we're looking, as Michala said, at our commercial operating model. So those effects allow us to have that flexibility to operate within that 20% to 25% range while also maintaining this adjusted EBITDA of 30% to 32%. Today, we're, of course, guiding more to 30% because of the acquisition that comes in there. So -- but happy to discuss that more when Joerg is there. So we have questions, please. Yes. Thank you.

Charles Pitman-King from Barclays. So just maybe first on Rexulti. Thank you for the new kind of peak sales guidance today. You've kind of given 2 targets: one excluding PTSD, and one including. I'm just trying to think a little bit here about the upside potential, and we think about the progress to the 8th of February PDUFA, just thinking about your confidence on an approval and whether or not we could potentially see an ad comm related to this indication, just given the kind of variability in the results seen. And then just second on Vyepti, again, looking at the kind of peak sales, I'm just wondering if you could provide any geographic breakdown of that, what proportion of those sales could be reliant on positive Asia data?

Great. So let's talk about maybe Rexulti PTSD, Johan, maybe more the view of...

Yes, maybe I can start, and then Tom, maybe you can talk about it. So for our confidence, yes. It's there, right? Because in the rule of the thumb in psychiatrists, you need 2 positive trials. Now we have a third also, the Phase III trial, in the pot. I'm cautiously optimistic about this, but we're not putting this into our guidance because it's at that level. And why am I cautiously optimistic? Because FDA really like to work with us on this. We did actually -- we delayed a little bit the submission of the sNDA to do more analytical work they requested. I also like to add that Lykos had a little story this summer, right, hammered by an ad comm. We don't think we get an ad comm for this. We might, but we don't think so, because this is extremely well-established drug with a completely different profile. I don't think there's any read through what happened to Lykos for this.

And Tom, maybe your question -- in the question more also as we see a success scenario of PTSD, how do we see that also play into our current resource, leveraging our field force?

Yes. What I think is really interesting about the PTSD indication is that it really fits into our current footprint. If we look at PTSD, only 23% of patients are diagnosed but 80% of those patients are treated within the psychiatry specialty. So we can cover that opportunity within our current Sierra sales force, which also covers MDD. And because of the familiarity of psychiatrists with Rexulti already, we believe that there's an opportunity both from a PTSD standpoint to expand the utilization of Rexulti, but also it will have a spillover effect to strengthen our competitive position in MDD. Did you have an Asia Vyepti?

The second question was Charles' question around the contribution of our outlook for Vyepti from the rest of the world. So maybe, Michala, you want to comment, especially Asia as well?

Yes. So my confidence depends on Johan's confidence. But of course, Asia represents a sizable opportunity because there is a huge unmet need, and there is, of course, a significant patient population. And then, of course, there's pricing that's different. So I think I'll say it's a sizable opportunity. When you look at the graph, you can see EU and international operations delivering more than it has. And of course, Asia represents a big part of that.

Yes. I think, Charles, the -- you saw on the slide, certainly equal populations, probably, in terms of U.S., ex U.S., but we see, at this stage, 1 billion coming from the U.S. and 300 million from the rest of the world. So that's based on price differences as well. So that gives you some direction. Thank you. Michael?

Michael Novod from Nordea. Just cycling back to the patients switching in migraine. So most of the patients are switching. So how do you see the potential for actually patients starting on an oral moving straight on to Vyepti at some point in time as well as the potential for combining PACAP or anti-PACAP with Vyepti also to drive increased persistency and thereby also sort of having patients much, much longer on a large base of sales for Lundbeck? And then secondly, to amlenetug, how do this specifically differentiate from potential competition in the area of MSA or other related diseases?

Thank you, Michael. So let's talk about patient switching.

So as I stated in my presentation, what we're seeing is a positive market dynamic as it relates to the evolution of the treatment paradigm. We are seeing Vyepti moving up the treatment paradigm, where previously it was reserved for fourth or fifth line, and now we're seeing it used much earlier. One can imagine a market dynamic where you go from orals to Vyepti. And we do see that in some physicians that are broad loyalists. But I would say it's more common for a patient to go from an oral to a subcu to Vyepti. But we see that evolving and changing.

Yes. And then I think there was a question really from Michael around our views on fixed combinations or the combination of Vyepti PACAP. Johan, you want to comment on?

Yes, I said that one of the fun things is to get the proof-of-concept positive. What it is also fun that you unlock new opportunities with validating biology further, right? And we are not far into that idea to do various combinations here and build on this biology further. We have not talked so much about it, but there are many opportunities here. You could do various things or combination therapies, of course, Vyepti PACAP. That depends on whether you show that you really have a different biological spectra you reach into, which we, of course, hope we will see with it.