Novo Nordisk A/S (NOVOB) Earnings Call Transcript & Summary

A very warm welcome to the Novo Nordisk 2024 Capital Markets Day. My name is Lars Fruergaard Jorgensen. And together with my management team, I'm very excited about hosting all of you here today. We're excited because of our unprecedented growth. We're excited about the strategies, the progress we're making in building capacity, expanding our pipeline to sustain a very attractive growth going forward. And this is obviously all about serving more patients, and we believe we can serve many more patients in the future. We would like to start the meeting by actually inviting an individual who has been on in one of our trials to learn a bit more about what it means living with obesity and also heart failure. So [ Isabel Davis ], please join me here on stage. Please. So Isabel, thank you so much for joining us today and accepting to share a bit with us your experiences. And I would like to ask you by helping us to understand what does it mean to live with obesity and also heart failure?

Well, I was very overweight and initially just put down the breathlessness to being overweight and not been able to do very much. But however, when I get diagnosed with heart failure, I realized that the weight was exacerbating things. So yes, I mean simple tasks like going upstairs by the time I got to the top of the stairs -- if I got to the top of the stairs before, I started getting out of breath, really quite breathless doing simple chores around the house. Could only do so much and then need to sit down and get my breath -- it was...

And you always describe to me how the pandemic did not help.

Pardon?

You always describes me how COVID-19 did not help at all.

The pandemic -- the coronavirus, as you became much more sedentary. So you were sitting about a lot more in those days. And then when -- as I said, when you start to move about, I was feeling, as I said, very breathless.

And then you had an opportunity of being enrolled in our STEP-HFpEF trial? So what happened there?

Well, I wait for an echo and get told that I had heart failure. And I was asked if I would take part in a drug trial, which having been overweight most of my life and tried various diets, I said yes, right away and I would do this, I would try it. So then I started on the trial in 2021.

Yes. And what happened when you got enrolled to the trial?

Well, I was monitored pretty closely, which was a good thing, especially when you get told you've got a heart failure, you kind of quite taken aback at that you don't think things like that. So when I went on the trial, I was going monthly to the hospital to get -- to partake in the medication. And very quickly, I saw a weight loss. So at the end of the trial, I had lost a lot of weight. I just think along the lines of think of your suitcases when you're carrying 30 kilos, that's more or less what's come off me, and I could lift 30 kilos now, but I was walking about with that.

So how has been on [indiscernible]

Well, I go upstairs, and I'm not having to stop at the top of the stairs and go like that. And when I went shopping, I'd maybe get halfway into shopping and think I have had enough. But no, I can just go and I finish my shopping and do more household chores that I didn't -- wasn't really able to do to the same degree that I can now. And last year, my granddaughter was over from Australia with her 2 little girls aged 2 and 4, so it was nice because we could go to the park with them, but it's really nice being able to help with the children. My granddaughter left myself and the other granny to look after the children for ready. So that was good.

You talked about aged 2 and 4 so that's a bunch to keep in control?

Yes, yes. With us, I don't think I would have coped before with...

So when you think about your life today and the alternative, so how do you think it has changed your life?

I think it's made a great difference. Unfortunately, though, I had a hip replacement last year, and I've been recovering from that. So I don't think I would have got the hip replacement to begin with because I had such a lot of weight and I would have had to be still be in pain. So this year is a new year for me, and I feel as a new lease of life. I'm looking forward to better weather in Scotland, which is not often there. So that I can get out more, yes, and be more active.

Isabel, thank you so much for sharing your story with us. It's a great inspiration for all of us working in Novo Nordisk. I can promise you we'll keep on doing research and...

Well, I'll be 78 this year, and I feel as I got a new lease of life.

Thank you so much. Thank you, Isabel. Thank you, Isabel for sharing that story with us, and I could not think of a better way to actually start a Capital Markets Day and a better way of bringing our purpose to life, which is really to drive change, to defeat serious chronic diseases. And we live at a time with aging populations, more and more people living with one or more chronic diseases like we heard Isabel tell about. And this is turning into the biggest, say, cost burden for the health care systems. And in many health care systems, around 80% of the cost burden is actually linked to these chronic diseases. So this is the strongest and the most motivating purpose I could think about for our company. The purpose is in the center of our strategy. It's surrounded by the Novo Nordisk way, stipulating how we work in Novo Nordisk, our culture, our values and our commitment to being a sustainable company. I'll get a bit back to this later on. Our strategy, our corporate strategy remains the same. It's striving for leadership or expanding leadership in diabetes, obesity, rare diseases and then the change in the slide is that we have reworded other serious chronic diseases. It was not so motivating to be other into cardiovascular disease and emerging therapy areas. And we also do that change because we are very pleased with how we are actually shaping up our pipeline in cardiovascular disease, and we look forward to sharing that with you later on today. I would also say from a corporate strategy execution point of view, we are very pleased in how we are executing on our strategy. We see a strong growth, we see a pipeline shaping up and we're tracking in expanding our manufacturing capacity. So you can say that our strategic aspirations for 2025 is serving us very well in guiding our strategic execution. And based on that, we are not going to change our strategic aspirations today. They will expire end of next year, and we do not see it as meaningful to change them this time about. We do acknowledge that we have achieved 2 of the aspirations, our diabetes aspiration of getting to above 1/3 of the market. We have checked that. It does mean that we're holding back. We think we have tremendous growth opportunities sustained in diabetes. And we've also achieved aspiration of getting to more than DKK 25 billion in Obesity sales. And again, it doesn't mean that we're stopping there. We think we have a tremendous runway in obesity. So the strategic aspiration serves us well and they stay as they are. The key focus for us is to do what is on this slide, and I actually showed that slide last time we had the Capital Markets Day. So really sustaining the growth opportunity we have based on semaglutide across a number of therapy areas. We have a wealth of clinical data, solidifying our position both in diabetes and obesity, and we see a very, very strong opportunity for driving sustained growth there. In parallel, we are also building breadth of pipeline to further accelerate and sustain growth in the coming years from these new areas. So in essence, what we are solving for here is really to strengthen and broaden our pipeline. It's to build the capacity needed to bring these products to many more patients going forward, and it is to evolve the organization to support that innovation and scaling of the company. And you could say this is really the essence of the Capital Markets Day. This is the agenda for today, will unfold a bit more of the corporate strategy, then we'll go in and do a deep dive on where are we in research and early development. We will address how we're building capacity. And then we go into deep dives on our therapy areas and we have breakout sessions where we look at some of the markets in a bit more depth, and we're also going to unfold how we seek to bolster the company performance and innovation based on digital tools, artificial intelligence, and we wrap up with financials, growth in the markets, the P&L and return to our shareholders. So this is a plan for today. And we have put in Q&A sessions around the agenda, so there will be ample opportunity for you to engage with us. We will, throughout the day, be making forward-looking statements. I think you the slides by heart. So please be careful what we preach from stage might turn out to be different. So please pay attention to these forward-looking statements. You'll see this slide a number of times, but we don't talk to it once, so that was now so now is to take it to heart. With that, I would like to invite Dave Moore. Dave Moore is Executive Vice President of Corporate Development. You might recognize Dave. Dave worked in NNI, our U.S. operations as Head of Commercial some years back, left to explore a career in biotech and private equity, but came back 1.5 years ago to lead our corporate strategy and business development activities. So over to you, Dave.

Thank you, Lars. Thank you. Such a pleasure to be back at Capital Markets Day and really happy to kick things off and spend some time with you to talk about our corporate strategy. As Lars mentioned earlier, our purpose is a center point of our corporate strategy. It's anchored there. And we're here to defeat serious chronic diseases. It's what drives us for people like Isabel, who we just spoke to this morning. We have 4 focused areas that comprise our corporate strategy. Diabetes and obesity are the #1 priority. Diabetes is our heritage. It's where it all started. And we will continue to be the leaders in diabetes into the future, that includes both type 1 and type 2 diabetes. We are also the leaders in obesity. We have been since the beginning. That is not going to change. We will strengthen our leadership position in obesity, and we will shape the future obesity market. In our Rare Disease franchise, we also have a position of strength. We've been in these businesses since the 1970s and 1980s, and we will use that position of strength, that strong history to expand to the new areas as well. As Lars mentioned, cardiovascular disease is now a new focused therapy area. And we've put extensive work into building a competitive pipeline in cardiovascular disease. It's an adjacency. It aligns well with our history in diabetes and obesity. And we're also working on some emerging therapy areas such as chronic kidney disease and liver disease. So when we execute on this strategy, it goes right back to our purpose. We're now at a point where we're adding millions more patients every year that we're serving like Isabel. And that is what will continue to drive us into the future. One thing that has served us well over our long history is a clear and focused strategy, and that will continue. That's the way we operate. And we wanted to share with you some of the considerations, some of the choices that we make when we think about our focus areas and we think about our strategy into the future. So on the left, what you see here is the external view. The things that we take into account when we're thinking about moving into an area or strengthening our position, we have to understand what's that market look like? Where is the real potential, the value that exists? Is it growing? Are we able to participate in that growth? And can we lead? Secondly, is there a real need? Is there a place in therapy that we can own differentially to compete. Once again, our focus is to be a leader if we go into an area. And then lastly, what's the level of risk? What's the level of innovation that's required? We are an innovation-based company. If an area doesn't require new innovation, it doesn't really line up with who we are and our history. And then what we do is we take those external views and we marry them up with our company. As you see, we don't go into areas that don't work for Novo Nordisk. Where is our position of strength? Do we have strengths that we can leverage to compete in that marketplace? Our internal capabilities, what's our R&D capability in that area? Can we supply the market? And is our commercial execution at a place that we can leverage that strength as well. So what happens when we work through these considerations is we have a good understanding of where we will play and how we will win in the future. And we believe strongly that strategy is about making choice. We can't be everything to everyone. We must prioritize. So this is what it looks like when we prioritize even within our focused areas. As we mentioned, diabetes and obesity, priority #1. And we'll remain that way for some time. And we wanted to give you some words to characterize what does that mean to be the top priority here. Well, from an investment standpoint, it means that's our key investment area. It means the most time, energy, resource will go into those therapy areas. It also means if you think about the R&D pipeline, it's broad, it's also deep so that we understand the future segments, we're shaping that and where these diseases are going into the future. The second priority is now cardiovascular disease and rare blood disease. And what that looks like is we want to go after multiple targets in the key segments within those therapy areas. The investment focus is we're building competitive pipelines for the future. So those future launches take these therapy areas to the next level. The third priority is the emerging therapy areas MASH and chronic kidney disease as well as rare endocrine disease. So this is a little bit more targeted, a little bit more focused. We're looking for those synergies that exist within the organization. Those adjacencies when we're building pipelines for these therapy areas. And lastly, when we do work in indications like Alzheimer's disease, Parkinson's, these are not focused therapy areas for us but they're still important diseases with high unmet need, and that is a targeted investment where we're really looking for opportunities. It's trigger-based based on how those programs progress. So when we take our focused areas and how we think about it in terms of an R&D pipeline, we then break that down into near-term and long-term focus. And if you think about near term, it's really about executing on the strategy. That's our focus, right? So if you take each one, in diabetes, what's our near-term focus? Maximize CagriSema and maximize insulin icodec. That is near term, right in front of us. In obesity, it's also about maximizing CagriSema. We really like it when one of our programs can serve more than one therapy area. In cardiovascular disease, it's about maximizing ziltivekimab and in rare blood disorders, it's Mim8. Those are very clear. The long-term focus on the bottom is about building those pipelines for the future. And here is where that work really matters. Where is this therapy area going? How do we see it evolving? What's the competitive landscape? Let's take obesity as an example. What will it take for us to be the leader into the future? What's the innovation height that we're going to need to bring? What do those future market segments look like? That's what we think about in terms of the long-term focus. And I also wanted to spend a couple of minutes to share some insights and thoughts around external innovation. As you've seen over the last couple of years, RBD M&A activities have increased and you should expect that to continue. And it will continue in a focused way, just like we've been talking about. We're looking for research and development stage assets that we can add to the pipeline where our internal R&D capabilities can add value. That's what makes sense to us. We have dedicated search and evaluation teams for each one of these therapy areas that are out there looking for that opportunity that we can add to the pipeline that complements our internal R&D capabilities. We have a pretty high bar internally. We're looking for things that are better, that are in modes of action, that are different than we might be working on. In addition, we look for technology platforms that we can leverage across these TAs, and that work will continue into the future. So now we've given you idea of where we focus, the choices that we make and then also how we're building for the long-term growth. And I'd like to turn it back over to Lars.

Thank you, Dave. And in my opening, I mentioned that I will just get a bit back to what it means to be a sustainable company. So before we get into R&D and manufacturing capacity, just allow me a few slides to address this. So I mentioned that we're committed to being a sustainable company. We are very pleased with our ownership structure. We have the ultra-long perspective from the foundation being a safe anchor for the company. And we have, in addition to that, the day-to-day, say, discipline that the capital markets push us on. I think that's a very, very attractive ownership structure. Our shareholders have in our Articles of Association adopted the triple bottom line principle. So we have to be a socially responsible company. We need to be an environmentally social responsible company and obviously, a financial responsible company. We'll get into the finances later on today. So allow me just a few comments on how we look at the social and environmental responsibility. Starting with the environmental impact. We have committed to be, say, a net zero company by 2045. We're progressing on that. We have a commitment to be also 0 in our emissions from our own operations and transport by 2030. Short term, we are building a lot, and we're growing a lot. So that has an impact but doesn't change our long-term commitment to this agenda. We are proud about how we have taken initiatives to actually deal with the waste that come from use of our devices. We have the remit program where we are now live in 4 countries where we take back plastic devices for recycling. And since this is a bigger challenge than just one company, we've also invited our competitors and peers in, and we're glad to see that more companies have joined this effort. We're now increasingly focusing on biodiversity. I personally feel this is a bigger challenge for society than CO2 emissions, which perhaps can be solved by innovation. So it's important for a company like Novo Nordisk to focus on what is our biodiversity impacts and how do we mitigate that. From a social responsibility point of view, obviously, our largest contribution is the innovation we provide to patients. But when you look at access and the fact that we treat now a bit more than 40 million patients, it's good to understand that close to 7 million of those are actually benefiting from some kind of access program from Novo Nordisk. There's a lot of focus on the African continent and access to medicines. So I'm also pleased that we have formed a partnership with Aspen Pharmaceuticals to bring local filling of insulin vials to Africa, something that can be scaled and reach many patients in the coming few years. And we're also tracking and helping more than 50,000 children living with type 1 diabetes and getting access to free insulin and those children would have quite difficult life on this, we have provided that. Prevention is also on the agenda. You can say dealing with obesity is actually preventing type 2 diabetes but we're also looking at, say, the broader societal aspects, we have now 47 cities involved in our Cities Changing Diabetes program to drive health benefits in these big cities. We have renewed our partnership with UNICEF and we have established an obesity transformational prevention unit last year. So these are some of our elements of our social commitment. I'd like to finish up on compliance and ethics. I know it's something that's been a keen focus area for many of our investors. So I just share with you that when we look at the Novo Nordisk way, a key element is actually compliance. So we guide all our employees to follow 10 essentials. One of them is never to compromise on quality and business ethics. It's involved in our code of conduct. It's involved in all the training efforts we do. We do audits, we do trending and risk management for all of these aspects. And of course, when you approach a new disease area like obesity with some inherent dilemmas, this becomes even more important. So we are taking initiatives to both communicate to health care practitioners in what is the correct use of our medicines according to label. We have done a lot of work in making sure that our employees are keenly aware of how do we interact with HCPs, how do we interact with the stakeholders even when we bring a patient on stage here and what can we talk to as a company. We have beefed up resources. So as we increasingly roll out our obesity portfolio in various countries, there will be dedicated people to secure that we stick to compliance. So as the CEO, I just wanted to make you honestly hear from me that I'm very comfortable in the program we have. It does mean that it's -- there will not be mistakes from time to time, but I feel we have a really, really strong compliance program. So with that, we'll close the strategy session, and I would like to invite Marcus Schindler our Chief Science Officer and EVP of Research and Early Development Stage. So Marcus, over to you.

Thank you, Lars. Great to be back after 2 years and in a full room and to all of you out there. Good morning, good afternoon, good evening. And a lot of things have happened, a lot of things have changed over the last couple of years. What hasn't changed, as Dave and Lars has said, is our aspirations, right? And they hold true because they talk a lot about pushing the boundaries, they talk a lot about as an innovation, providing meaningful impact to patients in large chronic diseases. And I think that is actually sort of our Northern Star here that we're following in research and early development, and with spare heading this because our core job is to generate data, make new hypotheses, make new molecules and test those. And this is how it all starts. And we do this, of course, and I think Isabel was a fantastic reminder that on an individual level, a, we make impact, but, b, the job is far from done. 20% relative risk reduction still means that 80% are untreated. So there is a significant unmet medical need in the big chronic diseases we're working in and on a population scale, on a global scale, the numbers are rising. And probably, as I speak, the numbers I have here on the slide are already out of date. Just a couple of days ago, a publication, The Lancet estimated the number of obese people in the world, including a staggering number of adolescents to be in excess of 1 billion, way outperforming malnutrition as the #1 issue on the globe, right? But you, of course, know all of it. So how can we make an impact? This is ultimately the field we're working in. But I think Dave has also said very nicely. It's one thing to know where we want to play, but how can we be uniquely positioned actually to make a difference in this? So how do we in research and early development actually translate those corporate priorities, our corporate strategy, the unmet medical needs that we're seeing into reality and how do we actually run R&D. We are, we maintain, but we will also continue to drive leadership in Diabetes and Obesity. There is no doubt in this. And I often get asked, so are we at the end of innovation with obese -- with insulins or GLP-1s? And the answer is, of course, no. This field, whilst it has a tremendous success, was even seen as the breakthrough of the year by the science magazine, is still at the beginning, scientifically, and there are many more things we can learn from, and I'll share a little bit about this later on. There's also so we set to go beyond those 2 molecular classes, which have served us in the patient population well. Novel mode of action, driving actually down in different biological pathways, which are complementary or that might actually uncover entirely new biological paradigms in the diseases we're working in. And it is about not only losing weight or lowering glucose. It is about achieving outcomes. And I would already at this point in time, highlight that for us, it is really important to take this conversation beyond weight, beyond glucose. We have a staggering number of data through a lot of outcome trials where we show that people live longer, healthier and better lives. And I think this is all what matters at the end of the day. So it means also understanding and dealing better with comorbidities and outcome endpoints that we're maybe not yet addressing fully. And one thing, I think, which I know is high on your radar, but most certainly is on our is -- so how can we turn this from interesting scientific discovery for molecules or even therapies that are suitable for a few million patients to an entirely scalable version? And Henrik will touch on this, but it is actually in the molecular design when we're starting our programs that we're now thinking about, is it scalable? How can we ever get to tens or hundreds of millions of patients with the chemistries that we're dealing with. So that for us is the next innovation hurdle or barrier or actually sort of a stimulating factor for all our scientists that we go after. At the last CMD, I spoke about the concept of human-centric drug discovery. So really focusing on the one species that is relevant for us, the one species that we would like to treat today. I can share with you some really exciting news on how we are working with this. We've nearly tripled our investments in access to human databases to human cohorts and those cohorts actually are relevant for obesity, diabetes, cardiovascular and other diseases, kidney diseases. But very deliberately, we are also dealing with a larger diversity, ethnicity, a global setting where we simply want to learn more about the people around the globe and whether there are commonalities or differences in the disease etiologies and potentially the treatment opportunities that we can see. So that remains an important cornerstone for us. And why is this even relevant today because we now can interrogate large data sets with this immense rising computing power and sophistication. We're actually able to unravel very, very complex systems. And for those of you who have signed up to the digital and AI breakout session this afternoon, we'll have you give you concrete examples but also talk to you how the quality and the access of data and how we actually deal with data also in a compliant and ethical way are fundamental to everything that we do. And it's, of course, not enough to have access to the data and to interrogate them, but how do we actually turn data into knowledge. What systems are we actually using to move those to new drug projects? And this is actually what we call the target discovery engine. Which is a composite of a platform that interrogates large data sets, so through computing power, through artificial intelligence. But it is also a system where we use human model system, microphysiology systems, in vitro systems when we can and when we need to actually test those new hypotheses. So we start with human data, and we interrogate those human data through human systems and then we validate our targets. And why is that a good thing? Because it will give us better targets, those targets that we actually explore, we have higher confidence that they will make a difference in late-stage clinical development in Martin Lange's organization. Just 1 year in action for the target discovery engine, we have nearly doubled the number of projects and targets that we actually have progressed through this and this is honestly just the beginning because we have designed this engine, this machine as being entirely scalable. So we are thinking about interrogating thousands and thousands of targets and actually fast tracking them onto the clinic. So this is something we can do with publicly available databases where we joined consortia and some other groups. But there's one particular data set we are very, very excited about, and that comes obviously from our own SELECT trial, a 5-year data on cardiovascular outcome in the patient population that matters to us. 17,000 people were in this trial, and we have an opportunity, of course, analyzed and blinded to interrogate those data. And those data points can be genetics. There can be blood biosamples and actually from 11,000 of those, we even have proteomics data available to us. And that is not only a rich source of information, it is actually a unique proprietary and we feel competitive advantage to us to have this data set. And what are we going to do with this? First of all, of course, from a scientific discovery point of view, it's very interesting to see what actually happens because we have longitudinal data points. What happens with treatment? What systems are changing? Which molecules are contributing actually to semaglutide effects on those phenomenal outcomes? It will help us also to understand disease progression, maybe also different patients subpopulations. But it will unravel novel biological systems and thus novel targets for us. So an incredibly rich source. So the first pillar is where we look into human data externally available. The second pillar is we look into human data to our own clinical trials, SELECT being the first one out of the block. The third pillar for anything that we do novel disease understanding, but also novel targets is through partnerships. And I would say we've come a long way over the last couple of years. And I won't read through all the numbers, but it's an impressive cadre of collaborations, different collaborations around the globe, where we talk about new biologies, new modes of actions, fundamental biology, but also a significant number of those partnerships actually delivering to the pipeline. And this is a nice opportunity for me also to give you a nice glimpse and insight into what we do in cardiovascular and rare disease. With Heartseed, we're working on a cell therapy product for heart failure where we generate cardiomyocytes and inject those into the heart of patients with severe heart failure. And that trial, that Phase I started some while ago, and that trial is actually ongoing. 2seventy Bio, formerly bluebird bio, we are collaborating on a gene therapy approach for Factor VIII. And really excitingly, we've achieved in primates a proof of concept where we could see relevant -- physiological relevant levels of factor VIII being produced through this gene therapy. So we're very excited, of course, to take this into humans soon. Inversago, our cannabinoid receptor inverse agonist, I'll spend a little bit more time on in 1 minute. But let me also speak to Ventus, where we work on the inflammasome, the NLRP3 inhibitors. And this is actually a very important fundamental node in biology where many inflammatory pathways come together and we believe that potentially blocking this pathway could have therapeutic benefit. We see this in the greater franchise of what we're already doing with ziltivekimab on IL-6. It has potential in cardiovascular disease, MASH, but obviously, also other opportunities here with this exciting biology. So let me spend a few minutes on the cannabinoid receptor system. Why are we actually excited about this? And wasn't there something there that didn't work out so well a few years ago? Absolutely, and that is all true. What I think is fantastic here, we have a very clearly formulated, differentiated hypothesis for this new class of molecules that the company Inversago has discovered and developed. And what did they do? They realized, obviously, there are cannabinoid receptors in the brain. They regulate some of our reward system, but there are actually more cannabinoid receptors throughout the human body. And they seem to play a role in kidney disease, in cardiometabolic disease, and other important physiological systems. So what if we could actually selectively target these classes of cannabinoid receptors that are beneficial without potential running into those side effects that we have seen in the past, which were of psychiatric nature. And they with laser precision actually design those molecules to do exactly this. And this brings us to a very exciting class of molecules. Monlunabant, Inversago-202 is already in clinical trials, and Martin will touch on this in a minute and how we're also progressing with this. Very exciting for us that there's also -- and it does look promising. There is a follow-on compound 347 that you see on the right-hand side, which we have in-depth profiled in our preclinical species. And I hope you agree with me that the weight loss we're seeing here in this particular species in excess of 30% is promising. So we would like to show with this follow-up compound more efficacy probably than what we already have and potentially also working on a different pharmacokinetic profile. So it's not just a single molecule. It's a class of molecules. And through this acquisition and partnership even we're really exploring this space and continue to be excited about this. Last time we spoke about Dicerna Actually, 2 times ago, we spoke about Dicerna partnership. So it's a red line here whenever I come. So from partnership to acquisition and now we're actually fully integrating this platform. This is the siRNA platform that gives us unique access to intracellular targets. And as a reminder, it helps us actually to target genes with extreme precision, will knocked out the genes that we want to knock down and nothing else. And the very cool thing is that effect actually usually lasts for a significant long time, months, quarters and even longer. We've made significant investments over the last couple of years in CMC, but also into the platform and that will actually enable us to not only work on as it has previously done liver targeting through the GalNAc system, what we call the GalXC platform but actually go beyond liver targeting. And you might remember that was our aim that we target different tissue types in the human body, and we call this the GalXC-Plus platform. And this platform actually is a collection of different chemistries for different target organs. So why is that important? Because now we can actually make those molecules target specifically a gene of interest and then deliver it actually to the target organ of interest with high precision, right? And the first one of those molecules are actually now out of the block. Just to remind you, Dicerna, even before we acquired it, to this very day has delivered 11th first time in humans. The platform is derisked. So it's really why we see this as one of our core elements now. We now have also our very first siRNA launched onto the market, Rivfloza. And we're now also seeing the first extrahepatic targeting moiety is already in clinical trials. So we have a lot of confidence in this platform even to say that 50% of our pipeline will actually be about nonliver targeted and moieties. It will make a big impact to our pipeline, 50% of Dicerna of siRNA projects will be in obesity and diabetes. And I think now we are seeing actually the beauty of integrating this because now the unmet need, the deep biology expertise in obesity, diabetes and other serious chronic diseases comes at play and is combined with this platform. And that actually also keeps us confident that we're already in play with what we see as an average annual 3 first time in humans. So this becomes our workhorse of intracellular precision medicine. And that leads me to this overview of platforms that we're using. And why is that important? Because at the end of the day, we do not want to be limited too much when we see novel targets, when we see exciting biology that we don't have the right tools in hand. We're now broadening our toolbox. And of course, we come from an extremely strong heritage on protein peptide therapeutics and we continue to innovate in this space. And that will stay like this. There's much more to be done. We were the first ones out of the block with oral biologics, and we're leading the way. You'll hear later on this afternoon actually how we are changing from antibodies to minibinders, totally changing molecular formats. And that, of course, is applicable in all our therapy areas. We see siRNA having a similar potential, and that makes us really, really confident also to further invest into this. Cell therapy, I gave you the one example on cardiomyocytes on heart failure, our Parkinson's trial with our partner Lund University is actually ongoing, and we continue to work on our beta cell program, which is actually a collection of different programs to tackle this really, really big problem. We have a small but significant number of small molecules now in the pipeline from discovery, but also to late stage, including Phase III. And Henrik can touch on that as well. It is not yet our core, but we are actually committed to gain expertise, knowledge and depth into this particular molecular entity to be a significant player in this. And then we're actually starting to get serious about gene therapy, gene editing. We're using [ Rare D ] as a platform to experiment here. Obviously, also with an aim to see are those technologies one day suitable for larger patient populations. So consequently, that has actually impacted the distribution of modalities of our pipeline. As you can see on this slide here, siRNA takes a bigger chunk than just a few years ago and so do small molecules. And that is actually a really nice distribution that we're seeing here. It helps us to tackle as many targets as possible. Sometimes, it also helps us actually deploy different technologies and modalities to the same target and then we'll find out which of those modalities is actually best. It could be an siRNA, could be an antibody. And I think that flexibility is very, very useful. And of course, all of this has enabled through our ability to interrogate those targets and technologies in a much faster way through automation and in silico capabilities. The pipeline consequently has significantly grown. This is just the number of net projects, so to speak. We obviously also have the diligence to stop projects if they don't fulfill our criteria, and our bars are incredibly high, incredibly high. So whatever makes it, you'll see on this graph here, you see diabetes and obesity still being a sizable portion, and that will remain so and we'll continue to provide breadth and depth, but cardiovascular and rare blood disorders play a more significant role than before. So let me just give you a short quick deep dive into some of the programs that we have, in particular, in diabetes and obesity. So in diabetes, one of our must-win battles continues to be glucose-sensitive insulin. I shared last time that we have achieved the first human trial. We actually showed that our concept proved to be true. We could also show that we have different approaches and chemistries to actually tackle this very, very serious problem. So that remains a big, big important piece for us to be working on, and the next molecules are coming out of the block now. In frequent dosing, in particular in diabetes, but also obesity are big topics for us. And we're excited about it once monthly. It's early. It's in Phase I. Once monthly GLP/GIP combined molecule. It's actually a single molecule, Where we feel that will add significantly to convenience. In obesity, I spoke briefly about the Inversago molecule, the cannabinoid receptor molecules, oral amycretin. And you, of course, will remember this is a single molecule that combines efficacy and affinity to the amycretin, to the amylin receptor as well as the GLP-1 receptor. And this molecule, we have first tested in an oral presentation utilizing the SNAC platform as a once daily oral. But why we're actually really excited about amylin, why do we believe that amylin is a key competitive edge for us because? It's not an incretin. It is a hormone, but it's actually released from beta cells in the pancreas. And the interesting thing when we look at it, actually, GLP-1 and amylin act in concert, they work together. They're entirely complementary, not only what we see on weight, on glucose, but potentially also in other interesting comorbidities. And you, of course, are fully aware of the data we've generated with CagriSema. So the question for us was what if we not only had 2 molecules in 1 syringe but actually had a single molecule combining those 2 pharmacologies. We might actually get to a point where we see significant weight loss and then those potential benefits of amycretin , as I've shown you on the right-hand side, also on lean body mass. And let's start with the efficacy data. So in 12 weeks of amycretin, we actually saw a body rate reduction of 13.1%. So we believe that is actually not only competitive and interesting, but it actually also confirms everything that we have predicted that we saw, both from animal species but also what we know about the combination of amylin and GLP-1 in a single molecule. There was nothing new, and that is the good news in terms of side effects. We've seen things which are entirely consistent with 2 classes and we also see a very benign pharmacokinetic profile. And Martin will actually get later on into how we're actually taking onwards CagriSema both in diabetes and in obesity. So these are the kind of data really interesting, exciting data for us when we push the boundaries of science. So you'll see us to continue to do, as Dave has said, maximize the GLP-1 franchise, learn more about GLP-1, make better molecules, make less frequent dosing, more scalability, maximize the value in incretin and amylin biology. One example I gave you here, right? And then actually build out a broader pipeline of novel mode of actions, biologies that we don't even understand yet to really push the boundaries of science. Within the next 12 months, you will see us pushing a new tri-agonist, 3 different biologies that we're exploring in a single molecules into first time in human testing. So we're very excited about this, and we see very, very promising preclinical data. We continue to innovate on amylin because we are absolutely not done here, right? And so much more to learn. One great example, you also here in the breakout session this afternoon. And you'll see a new amylin molecule also in clinical testing throughout this year. And then, of course, we turn our attention to not only managing food intake and energy expenditure but also looking into weight maintenance. The importance of lean body mass preservation, but I would actually say rather than lean, I would say, functional body mass, and then how we can do this in a sustained, but also from a portfolio point of view, sustainable way, and that is very important. So all these investments in the portfolio the new signs that we're tackling, the target discovery engine and our cutting-edge technologies and leadership in biology and in obesity and diabetes actually leads us to continuing our aspiration on tripling the first human doses. Had a good year last year and even better the year before, and we'll continue this growth in '24 and '25. So that actually gives you not only I hope, a status of where we are today, but actually also what you can expect from us in the coming period. We'll continue with our core capabilities and technology and science, but we also grow those. We have unique tools to do this. And the new frontier for us is really to think about how we take this out to many more patients. So scalable as a new innovation, scalability and that is probably a good segue over to Henrik Wulff. Thank you very much.

Thank you, Marcus, and good morning or good afternoon on where you are in the world. So advanced molecules, broadening the toolbox, more complicated molecules. You need to stay very alerted when you are in manufacturing, in particular, when you combine that with the number of patients that we want to serve. So it should actually be a dialogue up here with Marcus and I will have to say these days, been working with manufacturing development and manufacturing in this company, the requirements around that is that you stay very alerted. You are very interested in what is going on already in preclinical in Phase I and in Phase II because if you're not prepared, then you will not reach the many patients we want to reach. So you saw the numbers of insulin patients, diabetes patients, and Marcus also showed the number of obesity patients. The combination of what they're doing in R&D, actually early research and development. And what we are trying to do in manufacturing is to take all the complications, all the advanced molecules and make it as simple as possible because that served more purposes. And I will come back to that. I also have forward-looking statements. So just to start with some perspectives of how we are doing in the scaling part. And we have actually served 5 million more patients in just 1 year last year. That's by far the most -- the highest growth of patients in Novo Nordisk ever in 1 year. How can we do that? I brought some simple numbers on the right-hand side, we are increasing our organization significantly. So we have moved in just 2 years from 16,000 employees to 25,000 employees in just manufacturing. They need to be trained. They need to be educated. They need to fulfill CGMP requirements before they go into operations. We do this worldwide, all sites, it's not a trivial task. Secondly, we have now scaled our CapEx organization so that they in '21 could handle DKK 6 billion in CapEx investments a year, now in '23 they could handle DKK 26 billion, and you saw the number for this year, and I will come back to that later. We have moved the number of Ozempic pens. We have moved that 3x up since '21 and our API manufacturing output, here, we just picked semaglutide. I think it's relevant for you, that's 4x up in 2 years. So there is a significant scaling ongoing. And then you also know that the announcements, and I will come back to that, you also know the announcement of our CapEx programs that we have done last year. They are, of course, not in operations already now. So they are part of our future scaling. Let's talk about volumes. We are the clear leader in the world in diabetes volume. We are the clear leader in the world in diabetes GLP-1 volume. We are the leader in obesity GLP-1. How do we do this? And how do we plan to continue this? We have more than 50 years of experience in high-scale API manufacturing. We have used many, many years of experience to build, to optimize, to utilize existing knowledge into new products and new molecules. It is a very, very important task that you keep this vehicle running in everything you do in manufacturing because the key is, in particular, if you base your product on our existing platforms, then we are up to a head start when you continue your growth. So in particular, within API, it's process industry. Many of you will go to the site tomorrow, you will get a glimpse of what we are doing. You will be impressed. And this is the example of accumulated experience in our business, how we have worked with this so that we can scale even faster and even bigger with smaller footprints. We are not done with the API. The API needs to go into something. So the biggest platform that we have is fill-finish classes, liquids. We have a significant installed -- already installed capacity worldwide on cartridges and vials, and we are building the syringe and you also know, we started a few years ago with actually moving our semaglutide API into a tablet technology. We have also, for many, many years, been producing our own devices and scaled our own devices in different generations. So we have noticed the interest about volumes and scaling. So that we will focus on that. But I would just have to say, manufacturing and scaling and volume is nothing without product quality and compliance. So that's very, very important. It start with patient safety, it start with product quality and it start with living up to the expectations on CGMP regulations that are ever increasing. So that's also a game. The large part of the game is having a sound and ever improving productivity. Why? Because, first of all, it served the financial circulation of funding back to Martin Lange and Marcus area in research and development, bringing innovation even higher up in Novo Nordisk. Secondly, of course, it's a competitive edge of manufacturing having the lowest possible unit cost with the highest possible quality. Our manufacturing, it looks pretty smart when you see it on a slide like this, it looks like we designed it this way. It's, of course, evolution, it's also evolution. And you all know this is a Danish-based company. We started the business in Denmark. We have kept on expanding our capabilities in the country. So we have a massive presence of API manufacturing in Denmark. We have 3 sites producing API for our products. And then lately, since 2015, we started planning expansion in North America. So there we have 2 sites. We have, by far, the largest platform on yeast. That is the platform that we use for diabetes products and obesity products. Then we actually -- the medias are not paying that much attention to that, but we have actually quite a significant expansion ongoing for cardiovascular and emerging technology capacity also here in Denmark, also on API. So that's also important, and it speaks back to what Marcus talked about, the potentials of other platforms than yeast. So we're also expanding that. Then we have E. Coli and synthesis that we also need to use. The CapEx investments are focused on scaling API, and we will continue optimizing those with better yields and expansions. Another important task here is that when we sneak around and listen to their R&D folks, what they are doing, it's really important to try to get it into the installed capacity and the expansions that we are doing. And what we try to do is to build in flexibility so that one example is that we cater for whether the company wants to use the capacity for the oral compounds or they want to use the API for the injectables. It's even more important when the next generations of obesity medicines kicks in. Then from API to fill-finish, our global footprint is now expanding due to our wish to buy the Catalent sites, 3 Catalent sites. We are now expanding from 11 sites to 14 sites. They are placed across the world. And now we call it them a little bit. So you can see where the Catalent sites are placed, but all the sites that we have already, they are all expanding. The newest site that we have is our island site that we actually bought for tablets. We have both manufacturing development people there, but we also have manufacturing there. We also intend to expand that both for our oral semaglutide tablets but also, for example, Inversago. So we have expansions ongoing all places. We try to balance this so that we have regional suppliers, and we are serving as close as possible to the markets. Let me just talk through the 3 Catalent sites. There is one major site in Indiana in U.S. There is a smaller site in Belgium, and there is a significant site in Italy. Why do we want to buy these 3 sites? So first of all, the sites, they are already operating. So for us, that means that in this case, there's 3,000 well-trained employees already in the sites. They speak the same language as us. We can talk manufacturing, we can talk optimizations. We can talk CGMP compliance. Their buildings are there, well maintained, and they are operating. This is, of course, a significant advantage compared to pick a greenfield somewhere in the world, starting finding the people, starting finding the construction and then start from there. So that is what we want to do with these 3 sites. And it's also important to repeat, and we also said that in the announcement, we do not plan to interfere with the contracts already in these sites. These sites are going to serve the existing contracts to the existing customers in the sites. Our plans are made on top of this. So that's important. Finally, from fill-finish to the patients. There is some significant elements in choosing the right devices and choosing devices or platforms to scale. So now I just took some well-known pictures of devices. So from the left-hand side, you see our well-known connected durable device for insulin patients. So I only need to produce one of these for a full year consumption because they get the cartridge and they get the medicine. The vials, normally, they are designed so that you need 1 per month. Our FlexTouch pen is also approximately 1 per month because the cartridge is designed so it can take 4 doses. Then come, the famous single-dose device. That's 1 dose. And in obesity medicine nowadays, it's 1 dose, 1 week and then you throw the whole thing out. And of course, the tricky part here is how to scale this and what to select if you want to scale new opportunities? So it's really important back to Marcus' presentation that the molecules are designed so that they can be scaled but it's also important that the delivery systems are chosen both -- absolutely both from an environmental point of view, from a CapEx point of view, but of course, also, please remember the patients they need to stack these pens up in the fridge. So the smaller it is, the better it is for everyone. We will step up our CapEx investment, of course, also in this area to follow the pace of the API expansions. We will, in this case, utilize CMO partnerships that is not possible in the API space. We are the only one producing this kind of API. But in this field, there's many people out there you can team up with that can help you producing. We will try to push again, together with R&D for less frequent dosing. And again, in this area, we will do whatever we can to design and build for flexibility in case that we changed direction over time. What does it sum up to? There's a very simple overview of how we are trending in our CapEx program. We have doubled the program from '21 to '22 from '22 to '23. And then we have also almost doubled it from '23 to this year. So I can tell you, and you will also see that in Kalundborg tomorrow, those of you that are going there, there's major activities ongoing many, many places in Novo Nordisk. We have just summed up our announcement. You see many of these with API until now. And of course, fill-finish will follow. Please be reminded that when you're using DKK 45 billion in CapEx in 1 year, then you are not done in that year. So it takes us a significant time to build advanced manufacturing, get it validated, get it approved. And it's not only one approval. We want worldwide approvals. We want approvals for all the countries in the world. So you need to go through all the countries and all the authorities to get the factories approved. That's very important. Sometimes you forget why don't you just build a factory and then produce. You cannot do that in pharma. We need to get it approved, the products and the facility. Then if we take another look and we take on the most famous brands that we have, then you will notice on this slide, and that's what I tried to illustrate here is that we intend to use the same manufacturing technologies, the same setup across these drugs on API. So Rybelsus, Ozempic, Wegovy, soon to come, CagriSema, potentially amycretin, we plan to use the same setup, the same type of manufacturing technologies for these kinds. So there's major synergies in getting this right from the get-go. On the below side of the slide, we are still expanding our tableting technologies and capacity. We are, of course, expanding our FlexTouch. That's our main pen for Ozempic and Wegovy. We are expanding our single-dose device for, in particular, Wegovy in U.S. We are now designing our dual chamber pen for the launch of CagriSema and then we will continue utilizing our existing device platforms. So when you look at this, one thing that you need to take away is that we are extremely disciplined in trying to get as many as possible compounds, medicines and opportunities for Novo Nordisk into the same API systems because that holds a major advantage within scaling, regulatory approvals, competencies, et cetera. And then we are more flexible on our fill-finish and on our devices to basically scale. Final slide. We have used 100 years in Novo Nordisk to get to around 40, 42 patients. And with the CapEx plan that we have in place, the understanding of the potentials of the molecules and the brands in the market, the patient reach, the relevance in the market, our abilities to scale, we are planning to serve significant more patients the next period. So what you need to take away from this session is that we believe that we have the expertise, the scalability within biologics. We think that's a significant competitive advantage for Novo Nordisk. We will continue our CapEx investment programs to serve the potential that we have in the market, the many patients and certainly also to move even earlier in the R&D pipeline to make sure that we serve a broader and bigger Novo Nordisk also from a science point of view. We have plans in place now for serving many more patients in the next period. Thank you.

And then I will invite for a Q&A session with those that has already been on the scene, including the CFO now.

That's important.

That's very important.

I see a good energy here, a lot of people raising their hands. So with limited capacity, then I think we'll have to do it based on some house rules. So we'll do 15 minutes of Q&A. So now it's for you to work. And please state your name, and please restrain yourself to 1 question per person. So we go with the sun. The sun is almost out. It's Denmark. It's March. So we go from the window here?

Rajesh Kumar from HSBC. Just on the CapEx plans, thanks for explaining how you're scaling up. If you could give us color on how fungible the investments are to next-generation products like when you move from Ozempic to CagriSema. Can you be -- still be able to use the same facilities? And within that piece of question, you mentioned that Catalent plants will continue providing to the existing customers, the contracts, when the contracts and can they be repurposed?

So there's 2 questions. So we are very -- so which one do you want? #1 or 2.

The first one.

Okay. The first one, [ CagriSema ] in our factories.

Yes, we have stiff eyes on CagriSema, of course, because that's the next generation of obesity medicine in Novo Nordisk, and we can use the same facilities.

Great so we move here. Seamus?

Seamus Fernandez from Guggenheim Partners. So really the question is on that scalability question and the way that amycretin can actually slide into the subcu formulations over time? It seems like that's something that can move very easily into the overall FlexPen device over time. So I just wanted to get a better sense of that strategy.

So now we are close to the forward-looking statements because we are very early, right? So that's important. But the way that we see it right now, it's actually exactly the same answer as before. We think we can use the same facilities and the same devices that we are scaling right now.

All right. Thank you. Then we'll move to Pete.

Pete from Citi. One question. The last slide, Henrik, you're starting with 40 million patients, and we know the market is going to be 1 billion. If we took it illustrative, you have illustrated on the slide. If we took that away, I mean, we all know you're going to supply it to hundreds of millions, but the scale of your ambition in terms of how much of the market you can supply? Any ballpark figures you could give us there would be helpful.

Yes. We have not prepared for that question, right, Karsten? We have prepared for that question. So -- I will try to give you the most flavor that I can because the products are also different. So it's also a matter of which product we decide to produce in the facilities. Let's assume that we have the box that we have now announced. So that's important. There's -- for me, there are some differences. What is the strength, what is the yields and et cetera, et cetera. But is still within the same sort of ballpark. You probably all know the dynamics between oral and injectables, but let's just talk about the injectables. And then I'm back to my slides with the missing figures. What we are doing here because we, of course, have all seen now the potentials in obesity. That is we are taking the accumulated knowledge that we have in all the facilities that we have within insulin. And then we have redesigned the whole thing, so that we on the same footprint, can scale much higher. That's our plan. And what it leads to, that is that depending on the sort of the portfolio of the products that we decide to put in the facilities and, of course, also the scalability of the equipment.

Great. I think that's as close as you get Pete. So -- Sachin...

Sachin Jain, Bank of America. A question for Marcus on the amycretin data you've put, I'm sure you're expecting this. So questions on what's not on the slide. So what dose is that data at? Could you flesh out the safety in any more detail relative to CagriSema? And then I just wanted to be super clear on the profile that you interpret to us, it looks like a little bit better than CagriSema, which was, I think, 10% in 12 weeks and a decent chunk better than Lilly's orfo, which is about 6% or 7%. Just wanted to confirm my understanding is correct.

Yes, whether that classifies still as one, but let's talk about amycretin. So obviously, we'll share much more detail on amycretin actually on the molecule, but also on the trial and what we know preclinically in due course. So you'll get a deep dive on this. What you see here is obviously what makes us really excited in terms about the dose. As you know, it is really hard to compare across trials and how long patients have been on top doses and so forth. But all I can say is we feel, a, this is a very competitive profile; b, the slope of the curve looks promising. So at this juncture, no sign of plateauing? And third and maybe also as a scientist, that makes me really comfortable, it fulfilled nearly all the predictions that we made from preclinic and everything that we knew from CagriSema and the individual components. Yes, so percentage points up or down, we feel this is a really, really good place. And keep in mind, for the first time we combined here 2 separate entities into a single molecule and additivity of these effects was not necessarily given when we set out to design the molecules. So we're very, very pleased with what we're seeing.

Thank you, Marcus. Then we move to Mark Purcell.

A question on GLP-1 fill-finish. Catalent has provided some road map effectively going from a unit of 1 to roughly 7 '23 to '26 and then doubling that to going from 1 to 7 to 14 units of fill-finish capacity behind GLP-1 medicines by 2030. Could you help us understand your own ambitions using those 3 steps? And how important you are -- how reliant you are on Catalent to make that progression?

Like plans for Catalent, customer commitment and...

First of all, customer commitments, and we have been in looking at that. And we have also been in to see what is the potential of these facilities compared to how we run our own facilities 24/7. And they will play a part of our capacity build also a significant part of it. That includes -- and that's why we can fulfill the customers' obligations in there. That, of course, includes that we are installing more equipment in those facilities. And the technology that we are moving in is the same technology as we are moving in across our own sites. So there is no sort of -- it's a linear flow. If you take the whole sort of global picture of fill-finish that we look at, whether it's CMOs, whether it's the Catalent side, whether it's our internal expansion, you see a fill-finish that will follow API expansions, right?

Thank you, Henrik. Then it's Michael. We can have mic to Michael?

Michael Novod from Nordea. Maybe for Marcus on the technology that is used for the once a month GLP-1 GLP. Is that sort of also a universal technology that could potentially be applied also to a once-monthly Amycretin?

So we are exploring a number of -- I mean, infrequent, maybe to start back infrequent dosing for us, I think, is an important area because we feel actually that will open up a new innovation space. And whether it's once monthly or beyond, I think we'll need to see. So one thing is obviously we have different technologies, right, with siRNA, for example, is in the core molecules that we see very long-lasting effects. When we have incretins, obviously, we're using different chemistries then to prolong those effect of those incretins. We are obviously very interested and maybe that is the core of your question, in technologies that are suitable for a number of key molecules out there, that if we wish to do so, we can deploy this technology. And those technology investments for us will take precedence over just solving for a single problem.

Then we move around the table -- Martin?

Martin Parkhoi, SEB. And for last maybe on one of the first slides of the day with the illustrative graph of the sales development long term. Could you elaborate a little bit on your thoughts behind the development of semaglutide post the LOE? What is your thought process? Is it due to [ Henrik's gap ] or whatever?

But it's clear that I think we have one of the perhaps largest categories ever in, say, the pharmaceutical world, both in terms of number of patients, but also in terms of number of units to be produced. And bear in mind, as long as we look at injectable therapy, these are highly complex presentations in high volumes. And when you start mapping the world, there are very few products like that. So it actually takes a lot to serve those patients. So we feel that we'll probably see a long period in front of us where we'll be launching these products. So the classical modeling of say, 4, 5 years of uptake, plateau and then decline, I believe, will be much different for a molecule like semaglutide. And it takes -- it would take, say, a disruptive technology to change that. And I don't see that around the corner. So we'll be building capacity to cater for many more patients going forward. And we believe we are the best suited company for also serving those patients after [indiscernible].

Thank you, Lars. Then this is a very active table, Richard?

Richard Vosser from JPMorgan. Maybe one back on amycretin. I saw it at the top of the slide, the format of oral and subcutaneous. I think at the top of the production slide for amycretin. So just to confirm that you'd be looking to move both formats forward, it seems very good as an oral, but obviously, flexibility within injectable, but just to confirm that.

So there, you will have to hold your breath until Martin Lange comes on stage in some of the later sessions. Sorry about that. So we go to Simon. Okay, Florent, you take it and then we move back to Simon.

Florent Cespedes from Societe Generale. A quick question on the monthly GLP-1 GIP. Do you see anything different on safety and efficacy profile? And could you use this platform for maintenance treatment.

It's too early to say, to be honest, whether there's anything untoward. We don't expect this, of course, but it's early clinical testing. So we would be monitoring. You've seen on my slides that I think weight maintenance is one of the 3 dimensions, I think, for innovation. One is efficacy. The other one is scalability and sort of weight maintenance, quality of weight loss are important elements for us. So anything that is infrequent and makes it easy for patients and/or prescribers actually to do this, I think, is certainly in play.

Thank you, Marcus. Simon?

Simon Baker from Redburn Atlantic. Another one for you, Henrik, on Sema. You very hopefully gave us index levels of API capacity at 2 time points. So I wonder if you could give us the same indexed levels on semaglutide yield? So where are we -- where were we before? Where are we now? Where could we go to? And just as a point of reference, where is mammalian yield compared to yeast because that's the most likely route by which biosimilar competition will come in rather than trying to emulate your yeast process?

So Simon, before Henrik, I'll start out, then we'd rather not get into detail on specific yields. So Henrik, perhaps if you can speak about the platforms and why we believe that the yeast-based platform is highly competitive, generally speaking, for proteins and peptides and our approach vis-a-vis yields on the mammalian platform also.

Thanks, Karsten. You just saved me. So I'll give you another perspective actually because the interesting part of us expanding quite heavily both on the mammalian platform and on the yeast platform is actually we run it the same way, meaning that the technologies and our base core competencies, we use that both within mammalian and within yeast. So one data point is why do we expand mammalian capacity in-house when there's so much mammalian you can buy? Because it's too expensive to buy compared to my unit cost. So that's also about yields. And it just shows that our technology and the way that we operate these technologies in large-scale continuous API manufacturing, they are quite competitive. Even if there is installed capacity out there only on mammalian, not on yeast, we still are expanding ourselves and we are -- and now with the new products coming in from R&D also within cardiovascular, that is a competitive advantage for us. And if you -- sorry, for the long answer, anyway. So if you combine the sort of the buildup on the unit cost and the full manufacturing cost then API is our core technology and the scaling of the API is a smaller part of an injectable medicine no matter what we use it for. So that's my answer on yields.

And then we move to -- yes, yes.

Steve Atkins with Polen Capital. I'm curious what as semaglutide continues to expand usage, what you've learned about patient adherence and how to improve patient adherence, whether through devices or patient education?

I think we'll get back to that later on.

Let's take it under the TA sessions. So now we'll have to do the final question for this session because we all need a break. So last question here.

Hopefully it's quick. Emily Field from Barclays. On amycretin, you've long said that the bar for amycretin is CagriSema, which I've interpreted as good as based on the data that you've seen in the Phase I thus far, do you think it can now be better?

Yes. I wouldn't want to speculate on Phase I data. As I said to a previous question, we feel it's in a very competitive place and it's really consistent with what we've expected. So obviously and now the cliffhanger here, Martin will share with you a really exciting progress, how we take it actually through clinical development onward. And I think then we have much more solid data to, at the end of the day, answer your question.

And we don't set bar for efficacy, so...

Great. Thank you, Marcus. That concludes this part of the agenda. And now it's time to stretch legs. It's 15 minutes. Catch management, if you didn't get the answers to all your questions and then looking forward to be back on the TA sessions. [Break]

So welcome back from the break. And now we're going to move into the therapy area sessions. We'll start with diabetes, where we have the longest history but we will talk to you about how we are going to continue to expand our leadership, both from a commercial execution point of view, but also from a pipeline point of view. And we will start, of course, we're taking a look at our current leadership. You remember, we said the targets last set. We've already met it. We are not going to stop here. We will continue to innovate in this space, and we also will talk to you about our commercial execution. The problem with diabetes is still huge. As you will recall, today, 1 in 10 has diabetes. And in the future, we expect that it will be 1 in 8. And it's not just living with diabetes that it is the problem, it's actually also the comorbidities that are related to diabetes. You see here that it results in a life expectancy that is 8 years shorter. We also know that around 30% of people living with type 2 diabetes are also affected by cardiovascular disease. And if we take chronic kidney disease in its broader sense, we know that 40% of people living with type 2 diabetes are affected by chronic disease -- chronic kidney disease as well. So the unmet need is still huge, and there's a lot more we can do to Marcus' point, innovation is not over in this space at all. Looking at our leadership, you see that we have expanded it to 33.8% of total diabetes. This is, of course, primarily driven by our GLP-1. The GLP-1 of total has actually doubled in the last few years, as you see here on the right-hand side. And this is, of course, primarily driven by the fact that GLP-1s can address not only sugar levels but also cardiovascular risk, especially with Ozempic, you've seen the results. But of course, also a very convenient treatment that is a once-weekly treatment. So we are going to continue to expand our leadership into these segments. We are looking to explore innovations that goes beyond just HbA1c, also more into the cardiometabolic space that you heard earlier from Marcus and we're also going to look at how we can do preventative potentially in the future curative treatments. The prevention starts with obesity knowing that obesity is the leading cause of type 2 diabetes. Of course, we're also going to work with digital solutions, how we can support patients making it a lot easier to live with type 2 diabetes but also type 1 diabetes when it comes to more intelligent devices and when it comes to also supporting dosing regimens. On the right-hand side, you see how we are competing with very significant brands, very well-known and recognized brands, both in the oral space, in the injectable GLP-1 space. And then we are, of course, looking forward to launching the world's first weekly insulin in not too long from now. We look forward to expanding also further, and Martin will talk to that in the future into each of these segments with our innovations and further developments of the pipeline, as you see. But let's just dig into one of these innovations, Icodec for a moment. When we look at Icodec, we know that there is a huge potential in the basal segment. It's the biggest of the insulin segments. We have a market share around 30%. And we know that there is a potential of around DKK 40 billion in this segment. We expect, as you see here also that Icodec make a real difference in the dynamic segment. The dynamic segment is basically people who are new to basal treatment or people who are willing to switch. And when we are asking physicians and patients whether a once-weekly insulin that has slightly better efficacy and comparable safety, whether that is interesting? We get very strong answers to that. That is certainly very interesting. More than 80% of physicians would say that just a once-weekly approach to insulin is the reason to change insulin. So we expect that this dynamic segment will continue to expand from the 30% that it is today to an even more dynamic segment in the future because of the advantages of a once-weekly insulin. We know also from patients that it's a very cumbersome to be treated on a once-daily regimen. And of course, while it's not exactly comparable to GLP-1s, we know that once-weekly just have many advantages for patients. And here, we have seen from our trials, slightly better efficacy and similar safety, which is, of course, very relevant when it comes to insulin. The other focus we have is, of course, on GLP-1 and expanding into more you can say, of the comorbidities related to type 2 diabetes. Here, you see what we call a Venn diagram and you will get all of this later, so you don't have to write down all the numbers in the bubbles. But what we will show you throughout the day. Within the cardiometabolic space, we will show you the overlap of patient populations here from the U.S., we call it a Venn diagrams. It's based on statistics from the U.S. national health surveys and you will basically see the overlap between both diabetes, type 2 diabetes, of course, obesity, cardiovascular disease, chronic kidney disease and so on. And in each of the sessions today, we will speak to some of this overlap because that's, of course, relevant for many of the trials that we have done with semaglutide. You see on the right-hand side where we have completed trials to show what are the benefits for people living with type 2 diabetes in terms of cardiovascular benefits, and Martin will show you later more about the flow data in the renal space and so on. So it's not only about glycemic control and weight management, but it's even about the broader, you can say, comorbidities reductions that we can see with semaglutide. So just an example, if we look at chronic kidney disease, not in a broader sense, but in a smaller sense, you see here, chronic kidney disease Stage 3, that is not exactly the same as what we had in the FLOW trial, but almost, so you can say, similar. You will see an overlap of 5 million out of the 35 million patients living with type 2 diabetes. So there is a significant relevance here for having a molecule that can work on the comorbidities. And in the end, we also know that those are the costly aspects of type 2 diabetes. When we then look at how much is GLP-1 and utilized, you see here the trajectory over time of GLP-1 and you see that today, it's only 6% of the scripts in diabetes that is -- or the usage of GLP-1 across the globe. If we look at the U.S., it's 16% of the scripts. If we look at some of the other regions, it is less because we have rolled out later and so has the competition. But it is fair to say that whenever there's been a new launch into this segment, we've seen an increased usage, but of course, also with the data that I just mentioned before, and then Martin will be talking to later, we know that this is, of course, relevance for using GLP-1 treatment and especially with the data we have on Ozempic and Rybelsus. When you look at guidelines, they have also changed. They have now included GLP-1s as first-line usage. And this, of course, means also that there is increased support for physicians to use these products. So overall, it means that with 6% of the scripts today, the potential remains very big in this space. And this is, of course, what we are also embarking on when we are expanding our, you can say, life cycle management of Ozempic with more and more indications, as you have seen the data and will be seeing in the future. So with that potential in mind, I would just like to now hand over to Doug Langa to hear how we are executing on that in North America. Thank you.

Thank you, Camilla. It's great to be back at Capital Markets Day. I was reflecting this week that this is my fourth one in this role. I'll get back to that in a minute. So when we think about diabetes care in North America, you can see that we've had strong performance over the last several years. And we're very proud of that, putting more and more patients on our products. What we saw in the last 2 years was really a step change in performance, and that came on the backs as you also see on GLP-1, namely Ozempic and Rybelsus. And I'm going to get into that in a second. What we also see and Camella alluded to was a category that is still underutilized. Now in the U.S., the category grew by 50% last year. And as we indicated, what we saw in the fourth quarter was probably more indicative of what we'll see this year was in that 30% range. But it still is a growing category that is still underutilized, and we still feel like we have the best brands to produce in that category. So back to my Capital Markets reference. So my first Capital Markets Day was in 2017, and we did it that year in November for those of you that participated. And during that Capital Markets, I had Dave Moore with me and Dave, we had recently hired as sort of the Chief Marketing Officer. And part of the hook I had to get Dave to come was this product called semaglutide, and we're hopeful for an approval and a month later, we got it and 2 months later, we launched. So if we look back from '17 to 2023, how did we do? And I took some notes this morning in my hotel room when I was so excited I didn't want to forget any. So I'll share some of these data points with you. And see if you're as excited as me. So last year, we had over 4.5 million patients on Ozempic. 2023, we're a 9x blockbuster, adding DKK 63 billion, adding DKK 24 billion to that -- to sales, which equated to a 67% growth year-over-year. Even with intense competition, we are still the NBRx and TRx leader. And I can say this with confidence, I ask my marketing team again on the latest date to use. We are the best known, most preferred diabetes drug in the category today. So we're really proud about that. But what we're also proud about is that what we still see is 80% of the category is still coming outside of GLP-1. Or if you look again, it's 50% is either naive or generic. So we're seeing it, used early in the treatment, and we're seeing at least and consistently 80% of that coming outside of GLP-1. What we also see is a stay time of roughly 4 years. And also importantly, we're seeing almost 60% of the patients that start on the product or staying on the product. So we feel really good. We feel really good about the products that we have in a growing category, and we're extremely confident. Now I would be remiss and not doing my job if I also didn't talk about the opportunity that we've had, that we will have with insulin icodec. And we do hope to get a regulatory decision this year. And why we're excited is I don't have to tell this room that in the U.S., we've had challenges with insulin over the last many years. I think we've managed them well. But in my mind, there is no better company and there is no better place to launch this innovation into a market that desperately needs it. So we have the plans in place, and we're excited about what this product can mean for patients and providers. And we also think there is an opportunity. If you look at the U.S. market, it's about DKK 10 billion in terms of opportunity and half of that is still with insulin glargine. So there still is an opportunity and we are really excited about this opportunity and what we can do and what it can deliver for patients. So with that, I'm going to turn the mic over to my good friend and colleague, Maziar Mike Doustdar.

It's good to see Doug excited.

I am excited.

I can say that equally, we are also really excited in International Operations. The diabetes business in IO has had a really good double-digit growth for the last 5, 6 years and continues to do so. It really is on a basis of a solid insulin business that we have been building for many, many, many years, and it's quite stable, albeit growing much lower than the GLP-1. And then, of course, the more recent years with the launch of Ozempic in 2019, seeing what Doug just alluded to, a massive growth across various different geographies in IO with the GLP-1 products. If you take that growth area, the GLP-1 and turn them into customers, patients, then you see the slide on your -- the part of the slide on your right-hand side. There are around 6 million people in International Operations that use GLP-1 products, ours and our competitors. And that number is around double as much as it was just 2 years, 3 years ago. So this is really fast growing. Yes, 6 million may be right now is still a small number when you think about the totality of people that need diabetes products, but it's really growing fast. And you can also see that the money that is generated, the financials that is generated from those 6 million people, 71% of it comes to Novo Nordisk. That's our market share, and it's growing. You see 2 lines that's growing, that's Ozempic and Rybelsus; 2 lines that's declining, that's Victoza and one of our competitors; and then another line that's hardly to see at this point. Just facts. Then I want to touch upon Rybelsus because I'm actually quite happy about Rybelsus. In the first year that we launched this product, it's a blockbuster for us in IO. And that we don't see. We actually don't because prices are different, dynamics are different. There are very seldom where you see first year, first launch of any product in International Operations, ex U.S. where you see a blockbuster status. We saw that with Rybelsus. I'm also super excited, of course, about that one. Now when then you think about the dynamic of GLP-1. And I will have one slide on GLP-1 and one on insulin next. The dynamic of the GLP-1 really goes back to, so how many patients are there in International Operations that possibly can use some of these products. And Pete, I think you asked a question to Henrik, where he showed you 2 data points: one, he actually had the number of the products that we had, 40 million, 35 million of the [indiscernible] IO. The other one he did not show you. I have numbers on my slides. They say the sky is the limit. And honestly, if you take the time into the future, and I don't know how long into the future, that other data point for me internally is that there are 480 million plus individuals that can possibly at one point or the other, become part of our customers, at one point or the other. And that, of course, super excited. Actually, when you think about IO externally, I always refer to as International Operations internally, we think about this as immense opportunity. When then, of course, you dig deeper into the numbers in the middle, then you also see -- and I think Camilla also a little bit alluded to it, that right now, all the people who are not taking insulin, they're taking actually some of the more modern medications happens to be GLP-1 and/or SGLT2 and DPP-4 in the tablet format. Then 4% of the totality, so you see that in the middle, 4% of the totality of the market, diabetes market right now is taking a GLP-1 product. It is a small number, but it's growing so rapidly. And it's growing on the back of, again, a number of fantastic products that we have a really strong footprint. And maybe the single difference in IO between us and our competitor is our footprint on how and where we are with our organization. Ozempic is available today in 78 markets. That's a lot of markets. Rybelsus in 47 markets. And that's actually a competitive advantage that we have. And no wonder why also we have a relatively high share of growth when it comes to both value or volume of these businesses. And again, coming back to Rybelsus here, has 29% of the value share of growth, 20% of the total diabetes value that is generated in International Operations comes from Rybelsus. That's quite impressive. Then, of course, insulin, we don't forget that in IO because, as I mentioned, 30 million of the 35 million we serve in IO are still on insulin. And they are very dear to us. So it's absolutely important that we innovate for them and we continue treating them regardless of where they are across the world. We have still a solid business with our modern and human insulin business. Many people cannot afford some of the products that are coming to the market right now. But we have actually fantastic drugs for them in human and modern insulin, and we'll continue to serve them. Next-generation insulin also gives us many patients around the world, we continue serving them. But of course, before I leave, I have to say I'm super excited that we're getting very, very close to the launches of our 2 next insulin products, Icodec and IcoSema. They're going to be fantastic predominantly also because the segment they serve, the basal segment is the largest where we don't have yet leadership. So market share gain in that segment with the weekly best-in-class product excites me immensely. And then hopefully, soon after that, many more things and who better to say that than Martin.

Thank you very much, Mike. So you've already heard it a couple of times, we work in areas and in disease areas where there is a huge unmet need. We still see that in type 1 diabetes. We still see that in type 2 diabetes. And that basically means that we will continue to innovate in those disease areas. We have a strong pipeline. Looking at what we're doing currently in both the subcutaneous but also the oral incretin space. we have a leading pipeline. Obviously, building on semaglutide, where we are now not only focusing on glycemic control, on weight loss. And weight loss is also incredibly important in type 2 diabetes. But we are also focusing on comorbidities. We know for a couple of years that Ozempic is associated with a 26% decrease in risk of cardiovascular disease. We just released the FLOW data, and we'll continue to look at other aspects of comorbidities related to diabetes. But we'll also do innovation. And it's very, very clear that combining the base of GLP-1 specifically is semaglutide, where we've seen these amazing outcomes with novel biologies is leading to next generation of innovation. You've seen the amycretin data for Marcus this morning. I don't think it's a secret that we in this company like the amylin biology. Amylin is boding incredibly well in the obesity space. We'll come back to that, but actually also in the diabetes space. And having 2 assets, one in Phase III and one in Phase I, already at this point is a really, really strong proposition. In particular, when we combine them with Henrik and his ability to scale, we believe that we can have a truly differentiated and very, very competitive pipeline in this space. We also have to say there is still room for innovation in the insulin space. You've heard Camilla, Doug and Mike talk about Icodec. We have very high aspirations for Icodec. It is an incredible innovation in terms of efficacy, combined with good safety and at the same time, it's more convenient than ever for the patients. I can say the same thing for IcoSema. And therefore, we are very, very proud of the continuous innovation that we will bring to our patients. And Marcus and his team are working hard on also getting our glucose-sensitive insulin back into human testing. But we also have a keen eye on type 1 diabetes. We've heard it also from Marcus, one of our focus areas is to change the trajectory of disease, either preventing or maybe even curing disease. We have that outlook in type 1 diabetes, both actually the prevention part but also the potential for curing part through cell-based therapies, obviously, incredibly exciting. I'll do a few deep dives now starting actually with what we're doing with semaglutide, the FLOW trial. If you remember from Camilla's Venn diagram, there's a big overlap between type 2 diabetes and kidney disease. A big number of patients suffer from chronic kidney disease if they have type 2 diabetes. This leads to detrimental outcomes, both kidney-related but actually also cardiovascular-related outcomes. And we had to remember both in chronic kidney disease, but actually also in liver disease, the biggest reason for premature mortality in the space is actually cardiovascular mortality. So the FLOW trial was designed in an outcomes manner where we looked at semaglutide 1.0 milligram versus placebo. And the primary endpoint was a 5-composite endpoint looking at time to first event in either kidney-related or cardiovascular-related endpoints. We are really, really happy about the data. So the primary endpoint that evaluated 5 components free related to progression of chronic kidney disease to the either risk of kidney mortality or cardiovascular mortality. And combining those 5 end points, we saw a 24% decrease in risk. I think it's important to call out that this is on top of standard of care. At the end of the trial, more than 30% of patients were actually on an SGLT2. And still, we see an amazing 24% decrease in risk. I think it's also important to call out that both the CKD and cardiovascular components contributed to the primary endpoint. And I may want to call out, I can't give you the number because we still have to publish it, but I do want to call out that if we, for example, look at cardiovascular disease, we see a significant decrease in this population, specifically for cardiovascular disease. That's actually quite amazing. I don't think we've ever seen that before. And we take a lot of pride in what semaglutide can do in this space. But it doesn't really stop there because if we allow ourselves to just spend a little bit of time on the secondary endpoints, the confirmatory secondary endpoints, these are actually quite amazing. So obviously, we have a very nice head, 24% risk decrease on the primary endpoint. That's a composite endpoint. But we also look at the change in GFR, glomerular filtration rate and that's a measure of kidney function. And what we can see is that the semaglutide changes the slope delaying the progression towards end-stage renal disease. Importantly, and that's the third confirmatory endpoint. Semaglutide significantly reduces the risk of having major adverse cardiovascular events, that's stroke, that's myocardial infarction, and that's cardiovascular death. And finally, we also see that semaglutide decreases the risk for [ all-cause ] mortality. All of this is statistically significant and obviously, in this trial, clinically exceedingly relevant. I just want to remind you, it's the second time in a matter of a couple of months where we showed that semaglutide decreases all-cause mortality in diabetes, but also in obesity. So really, really strong offering and very excited about the data. We continue that journey. A lot of patients who suffer from both diabetes but actually also obesity, suffer also from what we call osteoarthritis. That's not what I'm going to talk about here. I'm going to talk about atherosclerosis. So I apologize for that. A big unmet need also in this space is obviously the part of cardiovascular disease that is peripheral arterial disease. More than 200 million patients suffer from this globally. It is closely associated with atherosclerosis. You've seen in our previous trials that semaglutide can actually reduce, and these retrospective analysis, can reduce the risk of having peripheral arterial disease. It's big and there's a huge unmet need because there's no treatment available. 25% of all cardiovascular disease has the nature of peripheral arterial disease. This is debilitating for the patient. They can have less functionality. And therefore, if we can change that outlook, obviously, we need to do that. STRIDE will read out during the first half of this year. We're looking very much forward to that. It's, again, a simple trial, patients randomized to either semaglutide 1.0 milligram or placebo for 52 weeks, looking both at the primary but also secondary endpoints of functionality, improving functionality in these patients, but actually also looking at the harder endpoints of what we can do in this space. I want to go back to my secret love, and that is amylin. Maybe it's not so secret anymore. You've seen these data before. This is what makes us excited. In a reasonably small type 2 -- Phase II program in type 2 diabetes, we see that amylin combined with semaglutide improves glycemic control significantly and clinically relevant 0.4 percentage points after 32 weeks. We also know from amylin biology that, that improves over time. So we do actually have a potential for aspiring for even better glycemic control when we do more than a year-long study. But what is even more exciting is the weight loss that we see in type 2 diabetes. Currently out there, you see weight losses around 13% at the max in type 2 diabetes. Based on these data, we can safely say that CagriSema holds the potential of delivering maybe more than 20% of weight loss in type 2 diabetes, clearly differentiated, and this is why we love it. We also see more than additivity. We actually see synergy on cardiovascular markers of risk. So we are taking semaglutide into Phase II in diabetes. We still haven't seen -- sorry, amycretin. CagriSema is currently in Phase III. So this is obviously something that we are very excited about. We will see a readout of that next year. But going back to my previous point, we are also excited about what can amycretin do not only in obesity, but also potentially in diabetes. We haven't seen diabetes data for amycretin yet. And that basically means that we are now conducting a Phase II trial. And you're asking me how long that will take. I will just point you back to the CagriSema days where we also did a Phase II trial for type 2 diabetes. And we did that, I think, faster than I've ever seen a Phase II trial being conducted before, and we intend to do the same thing for amycretin. It doesn't really stop here. We also actually have some really, really nice data for our GLP-1 GIP. You saw from Marcus that we are working both on a once-weekly, but potentially also on a once-monthly. That holds back potential also. We see some very strong data on glycemic control, some very strong data on weight loss, maybe not fully to the tune of what we see with CagriSema and amycretin, but still very exciting. We're very excited about what we see in our pipeline, both in the clinical space, but certainly also what is coming in from Marcus in terms of novel biology. And we believe that is required because the number of patients who suffer from both type 1 and type 2 diabetes is increasing. There is still room for innovation because there's still a huge unmet need. We believe that part of that need can be addressed by incretins, may be combined also with amylin biology. And given that around 6% of patients globally today are on a GLP-1 analog with type 2 diabetes, there's a big growth potential. But there's also a big potential for innovation. And obviously, we are very proud and happy with what we do with Icodec, IcoSema, CagriSema and amycretin. So with that, I think we will invite both the presenters but also Lars to modify our Q&A.

Thank you, Martin. And let's get our colleagues up. It was easier in the old days when there was only 1 molecule in development. So now we have to keep track of all of them.

So even I get confused.

So maybe we start from this side this time? Yes, yes.

Peter Welford, Jefferies. I wanted to ask you a question on what excites you the most, amylin? Curious, in particular, you talked right actually, it was before the presentation before, you talked about a new amylin in the pipeline. Curious, what is it you see that potentially could be bettered on cagrilintide? And what is the rationale, therefore, for pursuing in your mind, a better or a newer amylin?

So we know already from the GLP-1 space that you can always improve your approach to the biology. We've seen that going from Victoza to semaglutide. And obviously, we want to pursue the best possible amylin monotherapy. At this point in time, it's exploratory. We're really, really happy with what we've seen obviously with cagrilintide, but we are specifically also very happy with what we've seen with the mono component -- sorry, the molecular format of amycretin. So currently, we are adding to our pipeline, but it also allows us to choose because as both Marcus and I have spoken to, we'll not bring not differentiated products to the market. We don't think that's who we are, and that's not helping patients. So obviously, allowing ourselves the flexibility of choosing is an important part of what we do when we double down in both diabetes and in obesity.

Thank you. Here...

It's Harry Sephton from UBS. On the FLOW data, can you talk about the SGLT2 use? Can you specifically show an additive effect over SGLT2 with Sema in this study? Is that a subgroup that you're going to look at specifically?

So these are early days at the baseline of the trial, we saw 15% of patients being on SGLT2 more were added in during the course of the trial at the end of trial, approximately 30% were on an SGLT2 and actually more on placebo than in the semaglutide arm. And this is probably to be expected. What we also see is actually that the number of events because it is the smaller population is lower when we combine GLP-1 and SGLT2 and therefore, we should be a little bit cautious to interpret the data. I think it's very, very clear specifically on the cardiovascular end points that we see that the benefit of combination or rather the benefit of semaglutide is there on top of SGLT2.

Martin?

Martin Parkhoi from SEB. Just to Martin. Maybe you could elaborate a little bit because we saw you highlighted that we'll see superiority on [ all-cause ] death. But comparing to SUSTAIN-6, which, of course, also why wherein therapeutic patients, that was actually -- it was actually 1.05, as I recall it on the hazard ratio. So what's the difference between these 2 trials that you can end up with 2 different results?

So you've heard me say this a lot a good number of times, I'm really concerned always comparing across trials. I've also heard some comparisons to SGLT2 trials and their outcomes. The difference is in population. So duration of diabetes, how many patients have. And in SUSTAIN-6, not all patients had chronic kidney disease, only around 40% of patients had chronic kidney disease. Here, obviously, all patients had chronic kidney disease. There's a difference in the level of cardiovascular disease. In FLOW, these patients were very, very sick with established both heart failure, previous MI, previous stroke, established peripheral arterial disease. There is a difference in the background medication. And we actually see that the FLOW trial has a very high level of RAS blockers, a very high level of hypertension, very high level of dyslipidemia, all of those to the tune of 90% plus. And that basically means that you can't really compare neither to SUSTAIN-6 where the actual end point also was different. So the composite endpoint that we have in FLOW is different what the endpoint described in SUSTAIN-6 is. Can't really compare across. If you really want to know, you had to do the head-to-head.

Thank you, Martin. Richard?

Richard Vosser from JPMorgan. Maybe just going back to the GLP-1 GIP. I mean you've talked about amylin very passionately, but you're doing a monthly version of GIP/GLP-1. What's different, I suppose, in the biology that doesn't allow you to do a monthly should we expect that for amylin? And sort of why pursue GIP, you've talked about cardiovascular, maybe not as good. So just why even pursue it?

So GLP-1 GIP is not bad. We believe that from a weight loss, from a glycemic control, but potentially also from a cardiovascular perspective, amylin plus GLP-1 is better. But we do see and you saw that in the slide, we do see good weight loss, and we do see good glycemic control with GLP1 GIP. When Marcus then has the opportunity to investigate a less frequent dosing in this case, once monthly. In that biology, then obviously, we take that opportunity because it's not a bad biology. We just believe that GLP-1, amylin has a bigger potential.

Michael, and then we move backwards.

Michael Novod from Nordea. So Martin, can you say in 5 years from now, where do you stand in terms of generational wise on the SNAC technology and the ability to significantly increase by availability? And in that respect also, is there a way for this technology to reduce the food and water restrictions?

So specifically on water restrictions or fluid restrictions, we don't see a big impact on that neither in our clinical trials nor in the market. I think Mike spoke to the success of Rybelsus. So that's really not a big concern for us. Obviously, we're looking into this, but it's not our biggest focus area. On the generation and the bioavailability, we see continuous progress. You've already seen us moving into the next generation. I think Marcus is currently working on Generation 7. Not all of those will be taken into the clinical space because, obviously, again, it has to be not a minimal but rather larger stepwise improvements in what we see in terms of bioavailability. But we see that continuously thereby also supporting Henrik and his endeavors.

Simon?

Simon Baker from Redburn Atlantic. I'll give Martin a breath on this one. This question is essentially for everybody else. Tying back to what you said in the presentation this morning, Lars, that we've seen a lot of data today and previously showing tremendous growth of GLP-1, whether it's in diabetes or obesity, but still very low penetration in the grand scheme of things. So I was wondering, as you've demonstrated more on the benefit of GLP-1 across both indications. How has the cost benefit discussion with payers evolved? Because I'm assuming it's getting incrementally a little bit easier as they see the benefit we're still at a very low point. How has it across different regions changed? Do people get it more than they used to a few years ago? And how should we then think about where we're headed in light of that?

Thank you, Simon, maybe Doug and Mike's perspective on how you see, say, the payer action and maybe why you think about that, Camilla, you can allude a bit to the overall health economic perspective we see for this type of medicine.

Yes. So as a starting point, we're still at over 95% access for both Rybelsus and Ozempic, so that's extremely positive. I'd say part of our job is always to demonstrate the value of our brands. And yes, to your point, as we see increase in indications and the potential penetration benefit into other comorbidities? I don't know if the conversation is getting easier because the flip side of that is that the size and scale is getting larger. But certainly, those are more robust conversations as we're having them with vertically integrated health systems. So yes, I think it's a benefit for us the amount of data.

I think on the penetration question, you have to separate the Generation 1 and Generation 2 of GLP-1. If you think about the Generation 2, Camilla showed a picture that penetration is around 15% in U.S. where we are in first and lower because simply, this has been just a few years, not mentioning COVID was in the middle of the whole thing as well. Having said this, within diabetes across the world, GLP-1 to a large extent, is reimbursed right now. So people have understood the benefits of products like Ozempic and Rybelsus. It's our job now to bridge that into the obesity, of course, and make sure that, that continues.

Yes. And on that point, in the health economic models in the beginning or a few years back, we saw mainly a focus on HbA1c and then a modeling in terms of what would that mean in terms of risk of other serious complications. But now we actually have the exact data. So we don't need to rely on DCCT, if some of you remember that in UKPDS more than 20 years ago, even 30 years ago too. So we actually have that data now, and that goes into these models and the discussions. To Doug's point, cost effectiveness remains very important. But of course, budgetary impact short term is equally also an issue. But of course, here, some of the data that we also generate, we can also show impact on hospitalization and other things that are sometimes quite immediate even.

That perfectly closes the Q&A session on diabetes. So we now have a slightly shorter break for 10 minutes, so please be back after a short break. Thank you very much. [Break]

Even today, we see misconceptions. We see statement around obesity. We are also a little bit happy to say that spearheaded by Wegovy, supported by SELECT, the dialogue of -- is obesity a disease? Does it need to be treated? It's changing. I think that's supported by numbers. We know, obviously, obesity is increasing and that is globally. And a lot of countries are trying to catch up to the U.S. in a bad way. And when I -- in the slide show that we are expecting to exceed [ DKK 1 billion ] by 2030; actually, numbers are coming out suggesting that we are getting there already this year. So it's big. And we also know that obesity is associated with a great number of comorbidities in the metabolic space, in the cardiovascular space, but also in the mechanic space, so to speak. Life expectancy, if you suffer from obesity is substantially and fundamentally decreased. This is exemplified on the right hand of the slide. If you are age 46 today, livelihood if you have normal BMI of reaching age 70 is 80%. If you just have BMI between 35 and 40, it's down to 60%. And if you exceed 40 in BMI, it's down to 50%. This is a serious chronic disease in need of intervention. The overlap between obesity, I think from pathophysiological perspective, if you really try to simplify it, obesity is the starting point. That basically means there's a huge overlap between obesity and diabetes, but also obesity and cardiovascular disease, obesity in this space also heart failure with preserved ejection fraction. But we will later in the day also show other comorbidities, including chronic renal disease and kidney disease. Our focus has and will be on weight loss. That's the fundamental or first intervention of obesity. We started out with Saxenda, then we went on to 17% weight loss with semaglutide. And obviously, we've already -- a little bit discussed what we believe the amylin biology can do starting out with CagriSema. But on the other side of the slide, the outcomes becomes incredibly important for the individual patient, for payers, for regulators and for broader society. If we boil it down and include the comorbidity. So obesity is one of the most expensive diseases that we have in society today. That's why we like SELECT. A lot of you have talked about the primary endpoint of SELECT, we saw a 20% decrease in risk of myocardial infraction, stroke or cardiovascular death. We can talk a lot about that. And there were some questions on number needed to treat. I think just looking at the primary endpoint, it is honestly too simplistic because -- we also, in select, saw a decrease in cardiovascular death, albeit not statistically significant. A substantial decrease in half a year, almost 20% and almost 20% decrease in risk of all-cause mortality. And more than 20% reduction in kidney risk that basically means that we can assume kidney benefits for not only patients with diabetes, but also for patients for obesity. And a 73% reduction in diabetes. It doesn't really stop there. In SELECT, we also look at more comorbidities, but these are maybe some of the big items also from a health economic perspective. In a postop analysis, if I am allow myself to pool this, we can actually show a 37% risk reduction being on semaglutide versus placebo. If you want to translate that into number needed to treat, after the first year, number needed to treat is 45 people on the primary endpoint alone -- sorry, 45 people after 4 years. But if I look at the composite endpoint, after the first year, it's 20 people. If I look at 4 years, which this is what constitutes a chronic disease, it's 9 people. These are staggering numbers. We can make a true impact for patients living with obesity with a really, really great intervention. It's no doubt that SELECT is an incredibly strong tool. We also received a question on that in the previous section. But we've seen this in more than one trial. I've talked about the STEP-HFpEF trials a couple of times. I'm again, not allowed to show you the actual data from just the STEP-HFpEF trials because we are still aiming to publish those in a prestigious journal. But if I allow myself to just show you the pool of STEP-HFpEF and SELECT, STEP-HFpEF has a really -- a very well-defined population. In SELECT, we pool heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. But in STEP-HFpEF we only look at heart failure with preserved ejection fraction. But if I allow myself to pool the data, we show that we can reduce the hospitalization, very expensive hospitalization for heart failure with 58%. If I look also at cardiovascular mortality, we look at a 39% reduction. These are really, really strong data. And those of you who go into the numbers can probably imagine what we will actually see coming on from the individual STEP-HFpEF trials. This is why I'm doing product development. You saw Isabel this morning. She had heart failure, more specifically she had heart failure with preserved ejection fraction. That's a disease that is closely associated with obesity. And she described what being on this drug meant for her in terms of her everyday life, but we can now also tell us that we can reduce the risk of going to hospital, and reduce her risk of premature death. This is why we do business. And to talk about how we do this in the commercial space, I'm super happy to invite Camilla to the stage.

Thank you, martin. Yes. Thanks a lot, Martin. And there is no doubt that with Wegovy and the data that we have provided from clinical development and research, we have been able to truly unlock the diabetics market. And we have also been able to reach our strategic aspiration, as Lars mentioned this morning, and this will not stop us from progressing further. As you see now, Wegovy and Saxenda together is 18% of our total sales -- and at the same time, of course, we are also looking at what is the total unexploited potential. You see here, and Martin talked to it, there are more than 800 million people living with obesity and we are treating around 1 million. So there has been a number of changes that we have been working on before the launch of the Wegovy, but that we've also seen materializing after the launch of Wegovy. And I'd just like to take you through sort of 3 elements of that. With regards to patients, before the launch of Wegovy, we saw that patients were in doubt, is there a help to get? Should I just exercise more and eat less? Is that all I can do? They were used to that message from physicians. But now we know that the obesity market is driven by people showing up at the physician's office and a big, big part of the prescriptions are driven by patients asking for more help. So that is a significant change. We also saw before that the stay time and adherence was relatively low with Saxenda. But we see now because of expectations to longer weight management had because, of course, also affordability, access and also about the efficacy in itself that there will be a longer and longer stay time and we see very significant and very good improvements in that. At the same time, with prescribers, it's not long ago that not every physician was reflecting on whether to prescribe obesity products or not. They mainly will not be doing that. But since we -- after the launch of Wegovy just in 3, 4 years, we've seen that the number of physicians prescribing are up fivefold approximately. So it's just to say that more and more physicians are now truly considering prescribing Obesity medication. And the guidelines are also still improving; yet, of course, that takes a little longer time. When it comes to payers, Doug and Michael will be talking to this in a minute about how, of course, also access has significantly improved in many parts of the world not only with Wegovy, but we've even seen it accelerate also with Saxenda in recent years. So the understanding of why to treat obesity is much greater than what it was just a few years back. As I said, this should not stop us and think that we will be able to solve all problems in terms of potential. We are going to continue to expand our pipeline we now have the only molecule that has cardiovascular proven benefits in Wegovy. We are looking at pipeline innovations, of course, also that Martin will be talking to a little bit later, both in injectables, but also in the oral space. And then in addition to having a great pipeline and great innovation, great efficacy, great convenience for patients, what is equally important due to the size of the numbers in the obesity space is the ability to scale, is the ability to bring this product to many, many, many patients. And you heard from Henrik this morning how we are planning to be able to do that. And that in itself is, of course, in this space with such a big potential, a strong competitive advantage. We are also aware of the fact that some people, they are living with obesity, are not able to pay for some of the innovation. So when we are rolling out the Wegovy and when we are reflecting on how we can support them best, we also have allocated volumes to the most vulnerable patients. And of course, we're also looking to seek reimbursement in more and more countries, not for everyone, but for part of the populations and segments where we have a good dialogue with players on the cost effectiveness as we spoke to earlier. And then we are adjusting our commercial model to also reflect on how can we better support patients when this is now a pool market, a patient-driven demand that is out there. And this, of course, also has to do with online opportunities and other ways to support patients. And then finally, before I hand over to Doug, just wanted to share with you that we know from SELECT that the cost effectiveness of treating with semaglutide 2.4 milligram compared to our Saxenda population and the STEP 1 population is significantly better and up to twice as effective. And we also see that when we then look at subpopulations from the SELECT trial, we see that the cost effectiveness is even stronger than that. So of course, when we are looking to having these discussions with payers and policymakers, then it is very important data to have. And as you see on the bottom here, we talked about it earlier in the diabetes section. The questions around cost-effectiveness now do not only look at weight loss and target endpoints but truly look at some of the events that we have very clear and significant data on. So CV events, fatal events, hospitalization and so on and the sustained weight loss. So all of that means that we have a great starting point for having discussions with payers on the SELECT population, of course. And so with that, I'd like to hand over again to Doug to explain a little bit about how we are doing this in the U.S.

Thank you, Camilla, again. So maybe as a starting point, I'd tell you that in over 30 years in the life science industry, although challenging, this is the most, I'd say, exciting and rewarding disease state that I've ever participated in. And I said that whether it's coming from family members that are impacted or the concern I have actually for my own country, as Martin alluded to, with our population growing to in the next couple of years could be almost 50% of the population that is clinically obese. It's a health crisis that needs intervention, and we have a product that can help. It's called Wegovy. So how did that product do in the U.S.? So even with supply constraints last year, Wegovy performed extraordinarily well. You could argue it was one of the best launches that we ever had in the U.S. It's the second largest contributor to growth. As you can see, it added DKK 23 billion, and we're very pleased with the performance. What I was also happy to indicate on the full year earnings was that we started releasing more product into the market at the starting doses. As you all know, something that was critically important to us last year was continuity of care. So to make sure that patients that started on Wegovy could stay on Wegovy. So we reduced the starting doses into the market. So we're very happy to rerelease them in early February. In the first couple of months of February, we've seen an impact already NBRx, and we're excited about that. But it is about patients. So whether we heard from Ms. Isabel or 2 years ago, if you remember, Lars interviewed a patient called Lisa, who participate in our clinical trials. And although they always reference weight, some of the things they also talk about are the simple things in life. Climbing up to this top of the stairs. Lisa talked about playing tennis again, going for a walk, things that many of us may take for granted. So for us, the narrative is moving away from just absolute weight into more health and life. And we feel confident and you've heard this all morning about the hard outcomes data that we're going to see or are seeing in SELECT that we have the product that can talk about that. That can no -- it could not only help the patients, but it can be a competitive advantage for us. It's excited to get that out. Now these are the characteristics of what we see in patients today and what I'll have you zoom in on is the comorbidities. Again, maybe another proof source here. Which is if you look at the Wegovy patients today, again, it's skewing toward female. You can see the average age, the BMI, but over half the patients have 2 or more comorbidities. And the third have 3 or more. So we know we have to take this discussion beyond just absolute weight and that's what we're doing. But we also see -- I know we get a lot of questions, so maybe I'll just address it now and stay turned. Because of the supply constraints that we've had, it's very hard to get to an exact number. But what I can tell you is that Saxenda is at 4 to 5 months. Wegovy is greater than 6 months, so it's directionally in a good place, and we believe that will get better over time. But we also see importantly that over 30% of the patients are staying on the product for over a year. Now some of the 3 pillars that I've talked to you about over the years have been activating patients and Camilla alluded to that, we see more patients being activated. It's market access and reimbursement, and it's also prescribers. We just simply, over the years, we've needed more prescribers. So last year, we more than doubled our footprint in the U.S. and in essence, doubled our call plan. And you can see, if you go back to 2022, we had about 90,000 prescribers and then 2023 is 179,000. So we are making progress. Now you hear a pull market a lot and as evidenced by the middle of this, we do see that the prescriptions coming from, in essence, non-called-on are greater than what we see in called-on. So the good news is more patients like Lisa and Isabella are getting encouraged to go speak to their physicians about weight and what they can do about it. So that's good. But what we also know and what we see from the data is that we're seeing twice as many prescriptions come from the called-on doctors. So what that tells us is that dialogue that we're having around education and all the components within that are still very important. So market development and education is important. That's why we have field sales teams, medical educators, medical liaisons and market access teams, et cetera, which we will continue to deploy. What we also do is we don't leave the non-called-on universe alone. We have a lot of information we give both that's in the -- for consumers and HCPs, and we will continue those efforts. One of them is we think obesity. It's a nonbranded campaign for awareness for HCPs. I'm happy that recently, we hired a, I'd say, a top executive last year from a competitive life science company to come in and continue to transform marketing. And these programs and services will continue in our called-on and our non-called-on universes. And we're proud of the efforts that we're making there. So lastly is market access, something that is near and dear. We are pleased, and we've said this over time, with the 50 million patients that currently have access to Wegovy today, what that correlates to, as you can see, is 80% of the patients are paying $25 or less. So it's working. Are we satisfied? No. We're going to continue these efforts. As you can see, we're going to have some opt outs. Unfortunately, that does happen, and that's not good for patients. But we're seeing a lot more opt-ins. And so the net effect is we're adding more lives year-over-year, and they are coming in various federal channels as well as states and certainly commercial market. And lastly, what I would say is that we do believe that with Select, this does add to the body of evidence that we have, that body of evidence we use all the time to the question I just got earlier. We are going to use it with Medicare, I'm not saying that Medicare is going to reimburse overnight. There may be an opportunity through CV. But it does add to the body of evidence. So we're very pleased that we have it, and we're going to continue to make sure that market access is front and center. With that, I'm going to turn it over to Mike.

Thank you very much. Doug's numbers are so good, he starts stuttering. I hadn't seen that before. I -- actually, in that context, as he was showing in his numbers, I was a little bit trying to think how can I excite you with my numbers. He showed EUR 29 billion worth of Wegovy sales, and I have 2 only. And then I thought the way actually to look at this slide, it's almost a copy and paste of Doug's slides on the left-hand side. The way to look at this is that although the bonds are much smaller in number and the colors are reversed. Look at it in the context, again, of IO and maybe Saxenda. Saxenda was launched in 2015 in IO, and we have it in 76 markets. And in 2021, we did 3 billion with that. Wegovy in the first year, launched with capped volumes in less than -- less than a handful hit 2 billion. So as we get going with Wegovy as the supply will come as the launches will be released from their caps, this is going to get big. It's going to get very, very big. Where we have actually Wegovy now, are the 8 flags you see, the 8 markets where we have launched them. They are very special launches. We don't have a big launch event like usual. We don't go to all the different targeted doctors. We segment which doctor, which institute, which hospital should be prescribing the medications and we really make sure that the right people get the product first and foremost as we launch and go forward with this. I could not bring all the examples of all the markets, as there is not enough time. But I thought that actually, in order to give you a bit of a contrast to the U.S. picture that Doug showed, I take this bucket, Denmark, and give you a bit of an insight on how the product is available in Denmark. Then you could see on one side of the slide, of course, the TRxs per month that you can take a look at. But the 7%, I think, is quite important to look. 7% of the obese population in Denmark right now is on Wegovy. Or you can make the calculation differently. If you take a total population of Denmark, 1.5% of Denmark is on Wegovy. We have never seen a product like that ever. Then on the other side, their numbers very similar to Doug's, a little bit up and down. The 71% female is a little bit less than what Doug showed, the 36 BMI, I think, Dough showed 38. Very, very similar. 8% (sic) [ 80% ] comorbidity is also very similar. The difference is on the last part of the slide. Fully out-of-pocket payments. Wegovy right now is out of pocket in international operations, 7 or 8 markets that we have launched. People are willing to pay for it. So there is, of course, a lot of pressure on the healthcare professionals, on the GPs that have to prescribe these products. And then there is this other thing that is inequality in health where we really need to pay attention to as we expand in IO. Inequality in health, because even if you take Denmark, a highly developed, high GDP per capital country and look at their prescriptions, then you see some differences. A lot of the prescriptions are coming from North of Zealand, where the more affluent people are living. So as we go much, much broader into emerging markets with this, we have to really make sure that we don't leave anyone behind, and we cover everyone. And one way to do that is to really make sure, besides, of course, acknowledging that out-of-pocket will play a very big role in this type of a product for a long, long time, we need to double down on reimbursement. With Rebels -- sorry, with Saxenda, we actually did pretty well. 20% of the population that was getting Saxenda in IO was reimbursed. 80% was out of pocket. Early signs with Wegovy are also good. We have made a good forward leap in our dialogue and discussions with the government of U.K. Actually, last week, Switzerland reimburse the product, and we're in good dialogues with the other countries as well, and we will do so as we launch into more and more places. And of course, what will help reimbursement is data, SELECT is fantastic starting point to have the discussion with the various different people. And more data and more pipeline will excite all of us and who better to talk about that than Martin.

Thank you very much, Mike. Obviously, we can't talk obesity without also talking about the clinical pipeline. You heard about our philosophy on doing research development approaching obesity from Marcus. Obviously, we have to look at the weight loss. We had to look at the comorbidities. We have to look at the healthy weight loss, during that we are preserving the right proportion of lean body mass. We have to look at maintenance. And then obviously, we have to discuss safety and tolerability. I just want to make one comment that I didn't make before on SELECT. The amount of safety data that we have on the semaglutide molecule from diabetes and obesity at this point in time is second to none. And every time we do a major placebo-controlled outcomes trial, we confirm the safety profile of the semaglutide. That is in and of itself, an incredible differentiator. And obviously, we aim to continue that journey having a very high focus on safety and tolerability of our anti-obesity medication. Marcus also talked to the dosing frequency and we'll discuss that more also at later meetings. We are really, really happy with having a broad, deep and differentiated pipeline. I'm going to come back to discuss my love for the amylin biology also in this space. But just on this slide, I may want to point out, first of all, that we expect regulatory approval in U.S., but also in Europe for the SELECT label update that we submitted during second half of last year. And that will happen in a not-so-distant future. I also want to count out the 7.2 milligram that will read out in second half of this year. Our model tells us that without compromising with safety and tolerability, we can actually expect around 20%, 21% weight loss with 7.2 milligrams of semaglutide in the obesity space. So a step of in and of itself, not to the level of CagriSema or Amycretin, but still a step-up. Now I get to talk about osteoarthritis. And osteoarthritis is a debilitating condition in obesity. A lot of people -- and we've talked about that live with the cardiovascular risk with the renal risk, with the liver risk. And we heard from Isabel that having heart failure with preserved ejection fraction impairs her functionality. A big proportion of patients living with obesity also have impaired functionality due to osteoarthritis. So we conducted STEP 9. It is an exploratory study, so a reasonably small study, 400 patients, where we compared semaglutide 2.4 milligram to placebo. And investigated in a co-primary endpoint, obviously, the weight loss, but then the functionality and pain associated with osteoarthritis. And we are really, really happy with what we see. Because in this small study, we actually show not only statistically significant but clinically very relevant decrease in what is called the WOMAC score between friends, as they said, functionality and pain in these patients? So again, taking the holistic approach to obesity just as we did in diabetes, we actually conserved the patients in the best way. And we've already talked about the results coming out of the SELECT trial and STEP HF trials. And combining that with the STEP 9 trial, we continue to add to the evidence pool that we have for semaglutide. My next [ love ] is obviously CagriSema. You've seen the data a couple of times in obesity. We know that it holds great potential. At least 25% weight loss with a safety and tolerability profile that in Phase I/II was similar to that, are we going? So we get more bang for the buck, so to speak, without having to compromise on safety and tolerability. If we can show that in Phase III, that's really going to be a game changer. We also discussed the potential obviously, on the cardiovascular system. We've seen more than additivity on some of the biomarkers for cardiovascular risk, blood pressure, dyslipidemia, but actually also inflammation. And that holds a big, big potential for what CagriSema can do. We'll see the first readout from REDEFINE 1 later this year. And as you can also see in the slide late this year. That's going to be incredibly exciting. That's our pivotal study. It's a 26 -- sorry, 68 weeks study in 3,400 patients. And if I can use a proxy for future success of a molecule, it's typically -- how easy is it to recruit into a trial? We actually recruited these 3,400 patients several months prior to our schedule. And then obviously, again, at least in my mind, and it is a proxy as to speaks to the potential of CagriSema patients, and these physicians appear to like CagriSema. REDEFINE 2 is a type 2 diabetes study as we've already discussed, big overlap between diabetes and obesity. Good number of patients, almost 80% of patients with type 2 diabetes have obesity and establishing weight loss in that population is incredibly important. And as we discussed in the previous session, CagriSema appears to, in type 2 diabetes, introduce weight loss that is second to none. So again, a key differentiator. I've talked about the cardiovascular potential of CagriSema, we're investigating that in REDEFINE 3. REDEFINE 3 is a hybrid trial in the sense that we've been allowed to investigate patients with obesity as well as patients with diabetes and obesity. So REDEFINE 3 serves not only for the obesity program, but actually also for the diabetes program. And then obviously, a lot of you have put attention on REDEFINE 4, which is a head-to-head against tirzepatide, we do a similar study in the diabetes space. And again, based on what we see so far, we're really, really confident that CagriSema will show some very, very convincing data. The potential of CagriSema also warrants us to take this maybe even further. Obviously, we'll investigate obstructive sleep apnea, but we'll also specifically go into heart failure, chronic kidney disease, non-alcoholic but also alcoholic liver disease. We saw additional aspirations in the diabetes space. Again, we have really, really high aspirations and high confidence in this biology. But it doesn't stop here. These days, we do both in and external innovation. Monlunabant or INV-202 is an externally acquired asset. As Marcus alluded to, there's even a follow-on INV-347. But right now, we are currently investigating Monlunabant in clinical trials. These are actually published data. And we can always discuss how convincing is a placebo-controlled 4% weight loss. You have to consider this is after 28 days. So when we put that into our model, we expect around 15% weight loss, and that is in a tablet form. And if we -- to Marcus' point, can rule out [ neuropsychiatric ] disorders, it also appears to be very safe and tolerable. Really, really big upside. When we then also combine that with [ Henrik's ] ability to scale because we think about that, and we believe that we have a competitive edge there, this is a very, very strong offering. You've already seen this data. At the very least, amycretin has the potential of showing same efficacy and safety as CagriSema. And we have the ability to bring that to the patients in either an oral or subcutaneous format. We are currently investigating the subcutaneous format in Phase I. That will read out sometime in 2025. And then we'll look at the data, and we will figure out how to go into what I would call an ambitious further development program. This is high potential. And it is something that we will investigate in a very diligent manner. I've been asked a couple of times if we will skip Phase II. I will not rule that out, but it has to be contingent on the data that we see from Phase I. And just to get it out of the way, what I want to see in Phase I is differentiation between doses on efficacy, on safety and on pharmacokinetics; if I see that, then we'll have that dialogue. So to sum up, it's very, very clear, we are changing the outlook for obesity, Wegovy has unlocked obesity care market, but we still see a huge unmet need and a huge need generation. I think we have established both over the last couple of months, but also with more data today that SELECT is a key differentiator. Wegovy is the only anti-obesity medication with cardiovascular and other data available to support its differentiation. And obviously, a keen eye on a differentiated competitive pipeline, and at the same time, the scalability and the supply to support that. We believe that we will continue our leadership in this space. So with that, I'll invite my co-speakers but also Karsten to the table to moderate Q&A.

Thank you, Martin. I see a lot of very quick hands, but just to mix things up and keep us all awake, then we'll do slightly different this time. Now the sun is out. So we cannot use that one anymore. So now we'll start with Q&A on commercial strategy and commercial execution. So -- and then after that, we'll do the development questions. So -- so commercial, Martin, you are the fastest. So commercial strategy and commercial execution, Martin?

I hope my question is in the right category. But you showed the slide with the -- of course, we've seen all the strong data from SELECT and so forward. And then you go to the payers and then they showed you the slide from Capital Markets Day that only 32% of patients are on treatment after 12 months. How will you convince them to pay for something that people potentially never will experience?

So I think that goes for Camilla first and then Doug, perhaps a comment on the 30% in the U.S. and the supply constraint selling?

Thanks a lot. It's clear that the more we learn about the obesity treatment, the more we know that it's a serious chronic disease. So it's basically, again, back to the SELECT data saying that -- of course, if you drop off the treatment, then you don't get the benefits and your weight will increase and you may lose some of the longer-term positive effects on the comorbidities. So it's about that pattern. And actually, I think you know well also, Martin, that we have done the [indiscernible] after 20 weeks, people on Wegovy and Placebo and after 20 weeks, we -- or both on Wegovy in the first 20 weeks, we let people move on to placebo. Immediately, the change in the curve was different and people will regain the weight. And of course, from SELECT, Martin would also say, and maybe Martin should talk to that, that it is not only the weight benefits, of course, of semaglutide that drives the cardiovascular risk reduction, but these are very important data to show that adherence to treatment is important. And we are, of course, working also on how we can support patients the best way, maybe Doug and Mike can say something about that.

I'd say more on the scorecard is the access today and every major PBM has covered it, and we've had really, I'd say, encouraging dialogue with payers. Our job is to describe the value proposition and we use data to do that and to bridge beyond just weight into chronic other kind of conditions in disease states. So we'll continue to do that and use the data to our advantage. And then I'd say lastly, in the supply-constrained world, we had intermittent stock outs. And so I have to say the stay time and the 30%, there's an asterisk to it with what we had to face last year. So as that improves over time, as we indicated, it will, I think we'll see a different number.

Thanks Doug. Then move up to Seamus.

So just 2 -- 1 very quick question, so I only had one. The [indiscernible] (197:15)Amycretin strategy as part of the commercial strategy, how important is an improved tolerability profile? And can you help us understand the percentage of patients that are actually dropping off specifically for tolerability-related reasons versus reimbursement or other dynamics?

Thanks, Seamus. So Camilla, will you take that? What do we see there?

Yes. So the majority of the drop-offs actually happened in the first 12 weeks, approximately where we see most people dropping off for tolerability reasons. And we see that with Wegovy compared to Saxenda, I think Doug showed you some -- the curves there is a big difference even there as well. So -- you can imagine when that happens in the beginning. Then in parallel, of course, is also the expectations to the efficacy of the treatment. How long will that continue and people are likely to stay on to the treatment as long as they continue to see improvement. So this part of our tolerability is, of course, important, especially in the first phase of the treatment. But we've also learned that management by the physician to manage expectations that this will -- this is a likely you can say, drawback initially, that helps a lot and people get used to it.

Thanks, Camilla. And Seamus, you asked about amycretin. So this is what we see in the market on Wegovy and the beauty of CagriSema that we have in Phase III, as you know, is that we see additivity on weight loss, but not additivity on tolerability. So I think that's really the promise of CagriSema and then Amycretin remains to be seen in later clinical trials.

Great. Then we move to Pete. Peter?

Just one question to address to -- sorry, Doug and Mike. Just on the commercial footprint that you have. I know you're not going to talk about numbers, that's commercially sensitive. But in terms of being rightsized boots on the ground, I mean, we all know the top line is going to be moving. But with all this innovation, do you really need another salesforce here or other salesforce there, particularly in the U.S. Just the -- I realize you can't talk to numbers, but the rightsizing in terms of your current commercial footprint in both IO and U.S.

Yes. Thanks, Pete. Doug first then, Mike.

Yes. Thanks, Pete. It's a rigorous process we go through every year and we look at sizing, spend and control and what we need for each brand, and we'll continue to do that. So I'm not going to get into specifics of our strategy. But I would say is we view life cycle management, new indications, things of that nature, we size appropriately to the opportunity.

And with regards to international operations, that's probably the last thing I'm worried about. We have a really strong footprint compared to all of our competitors, ex U.S. And I think we continue to, of course, assess and continue to add. And I think we have a huge advantage over others that, that is not going to be the biggest problem.

Thank you, Mike. Now we move to pipeline and of course, commercial. So -- but now we'll open it up to pipeline and as Sachin being fast.

I prepped a commercial. So I just another commercial person okay. So just a really big picture. As you think midterm question I ask very frequently, how do you think about split of the obesity market oral versus injectable and within that oral, you're now thinking about 2 molecules at least biologic and small molecules. So geographically, how are you going to position twin oral strategy?

That sounds like commercial strategy. Camilla?

Yes. So no doubt that there is market for orals as well as injectables, there also no doubt that efficacy is really very important in this space. When it comes to how we are going to divide sort of or think about our opportunities, it comes down to commercial tactics, I would say. So I'd rather not go into the details of that, but no doubt that we feel that across, we have a very, very strong pipeline, we showed the segment earlier also and we are going to optimize, of course, the utilization of that to help as many people as possible. And I think that's the closest I can get to that now. It's a relevant question, no doubt, but also a very competitive one. .

Scalability is really impacting these states. So I'll now move to this table.

Martin Parkhøi for Danske Bank. For Martin, in light of the SELECT data for how long can you continue to start new CV-outcome trials with placebo as a control in a scenario where you would ask -- would you expect your emerging obesity pipeline to be differentiated enough to be superior to some -- in such setting?

Yes, absolutely. So honestly, not for very long. -- when we start to see label updates starting with Wegovy and for the next 5 years, that's maybe where we will be. We'll have to consider what's the right comparator in this space. Specifically, vis-a-vis semaglutide, the promise of CagriSema is better weight loss, better glycemic control, but also better on markers of cardiovascular disease. So that wouldn't be a concern to us. But right now, actually -- for CagriSema our first trial will be against placebo because when we started the trial, SELECT was not available.

Thank you, Martin. And we'll move back here.

Question, please to Doug on U.S. prescribers. You showed some nice numbers, these are growing quite dramatically. Can you comment on the proportion of those that are specialists versus primary care. I think probably increasingly important given the huge demand and the long waiting list that we have for patients to see specialists. So are you yet seeing broader physician adoption?

Yes, good question. And we are seeing broader adoption as evidenced by the slide. And I would say that, generally speaking, we still see 80% of the prescriptions coming from HCPs and nurse practitioners. And then the other 20%, there's a lot in between that, some specialists. We did deploy a couple of years ago a cardiovascular team. We're happy we did that. And -- we'll continue our efforts across specialty as well as primary care, which in the end is an enormous opportunity for us in terms of that segment.

All right. Then we move here to Mark Purcell.

Mark Purcell from Morgan Stanley. Martin, could you help us understand how you move the physician and payer audience from weight loss to outcomes. And in your CagriSema comments, you talked about using, looking at lower doses of CagriSema, whereas you're looking at high doses of semaglutide 7.2 milligram with pivotal data later this year. So can you help us understand the sort of dose effect in terms of, obviously, weight but quality of weight, CV factors, inflammation, triglycerides, et cetera? .

So I don't think I said lower doses for CagriSema. Currently, we are investigating 2.4 milligram plus 2.4 milligram. And we actually see a potential if the 7.2 milligram of semaglutide pans out to go into even the higher doses with CagriSema in the life cycle management space. So we are investigating everything. But currently, we see the maximum benefit on weight loss on, glycemic control, but certainly also on the cardiovascular biomarkers on the doses that we picked for PHASE III, so 2.4 milligram and 2.4 milligram. I think specifically to your first question, we only allow 1 question but then 1 [indiscernible] Communication sharing of data. We're super happy with the publications that will get out, but also more specifically, the guideline updates and the regulatory updates that, that will entail. It will enable our medical communication, but also when we get the regulatory updates on our commercial communication.

All right. Then we'll move to Michael Novod. ;;

Thanks, Michael from Nordea. A question to Doug. So we see today that Cigna is saying that you have signed -- also Lilly has signed new deals around commercial access to obesity drugs where you also have sort of a financial guarantee and a cap. So can you give a bit more flavor to that? And how does that correlate with sort of a financial guarantee likely driving higher volumes in a world where there's supply constraints?

Yes. Thank you, Mike. It's a good question. What I would say is we're open for business. And what that means is, is that we know that one stop, one shop is not going to be the answer to the amount of patients that we want to serve. Integrated Solutions will be a part of that. So as you see in these partnerships, I don't want to get into the specific details, but we are working across all payers right now on various different programs and services because we know that. What we're looking for is a sustainable market over time, and it's important to us to serve as many patients as possible. So we're off to a good start. We'll continue to keep our doors open for that dialogue. And that's just a number of -- another example of vertical integration or integrated solutions, I should say that is one that we'll continue to pursue.

Thanks, Doug. And let's move to Florent in the next table. Mike, could you pass it.

Florence sees from Societe Generale. A question, Martin, on SELECT. Based on data available so far, have you identified some subpopulation that would benefit the most from the product that's something that could help, let's say, better access and better reimbursement within Europe. So any color on that would be great.

If you think the strength of semaglutide is that as far as -- and we are still looking into the data as far as we can see, if we stratify it by age, by gender, by region, by duration of whatever comorbidity, we see the same benefit with semaglutide. And more specifically, if we look at BMI, so a patient with a BMI 27 to 30 has the same CV benefit as the patient with the BMI above 40.

And perhaps, just adding to what Mike said on reimbursement in Europe, vis-a-vis SELECT, what's the latest experiences in the market?

It's going incredibly well. I just wanted to say that, of course, we've talked to a few markets only. But I can bring news from the discussions we've had with the Swiss authorities, for example, last week. It is really about SELECT. It is really about that there is a so-called secret sauce in Wegovy that goes way above just weight loss. And that should matter. It should matter because as you get older, then you often die from some of these conditions that you speak to, you die from a kidney failure, a liver problem, you die from cardiovascular issues. And that's -- that matters more than if you have 2 kilograms more or 2 kilograms less at the time of death. And the payers are listening to that.

Okay. Sounds good. So unfortunately, I'll have to cut the session now. So now it's lunch break. You can catch the team outside during the break, and then we're looking forward to seeing you back after the lunch break. Thank you. [Break]

[Presentation] Good afternoon, welcome back. Good evening for those that are online, abroad. It's a pleasure to be with you today, and I hope you had a great lunch and sort of great discussions with the management and of course, between you. My name is Ludovic Helfgott, and I will have the pleasure to walk you through what Novo Nordisk is doing in terms of rare disease. I would like to start a bit where we left together a couple of years ago when we did the last CMD. And I would like to frame a little bit what Novo Nordisk is doing from a rare disease perspective and why we are investigating in this area. Let me start with the most important, the unmet need. Right now, today, you have roughly between 8,000 and 9,000 rare diseases in the world, out of which 95% of them don't have a proper cure. It's reduced life expectancy, severe comorbidities and impaired quality of life, long diagnostic lead times and, of course, broken continuous care. We need to do something here. It's also part of our purpose. And in that frame, Novo Nordisk has a longstanding legacy in terms of rare diseases in 2 aspects, particularly first on the growth hormone side since the early '70s when the investigation started. And of course, in hemophilia, since the early '80s with a NovoSeven [ fast ], but then all the subsequent treatments that are now helping our patients Esperoct with Hemophilia A, [ Refixia ] benign in hemophilia B. So there's a need, there's a frame, there's a legitimacy. Second, we really believe that rare disease constitutes an amazing opportunity for Novo Nordisk for 3 reasons: Reason #1 is the strategic portfolio play. When you look at the overall portfolio of Novo Nordisk, a lot of prevalent, highly prevalent disease, and we saw that this morning. Here we have a very specialistic play. Few patients, use unmet needs, very specialized health care base with physicians being both investigators and clinicians. And very specialized frontline teams on the commercial side, on the medical side, a completely different business model. So very helpful from a strategic perspective. It's also a platform to spearhead new trends. as we heard this morning, with rare disease Novo Nordisk is working on new therapeutic platforms like gene editing that we are really, really spearheading for the whole company. Innovative access pathways of course, with early access teams that are multiplying across the globe, not just in the U.S., not just in Europe, but also in China, for example. And of course, new operating models where we can actually cluster some centers together. And doing this by focusing not on the medicine, but on the solution around the medicine, what we call 5D, which stands for digital diagnostic device, drug and data is actually a turnkey solution. that is now important in the rare disease world, was actually important already 15 years ago in the oncology world, and we believe will play a key role going forward even in the prevalent diseases. Last but not least, it's an integrated unit. Mostly dedicated to 2 rare disease early research down to commercial that is really help to work in an able and flexible way. So that's why we believe it's a good opportunity. When we saw each other last time, we were at the beginning of this adventure. And we spent the last few years really building our rare disease strategy. That is based on 3 pillars. First pillar serve more. And by serve more, I mean what are the areas, the disease areas in which we need to focus. As I mentioned, 9,000 rare diseases. It's very easy to get lost. It is very easy to get lost in the maze of rare diseases. So where do you pick your battles. And we decided to move from hemophilia to rare blood disorders. And from growth disorders to rare endocrine because these are the 2 places where there is a high growth over the coming years, but also we were legitimate because we have the biology and we have the platforms. The second pillar is find more. And this is very, very important, again, because find more means 2 things. It means, one, we are actually allowed to pick in the best technology platform that Novo Nordisk has to offer. Of course, the historical peptides and proteins, but also, as you can imagine, silencing RNA, and we have just launched Nedosiran Rivfloza in the U.S., gene editing, I mentioned and small molecules, for instance, with the acquisition of Pharma Therapeutics last year. It also means that we need to grow on both legs, both internal and external. So it's very important to run both dimensions. The last but not least, the third pillar is grow more. Because if we are very competitive in diabetes and obesity, we need to be equally competitive when we're talking about rare disease. There's no reason why patients share and market share are not valid. And I'll share with you examples about that a bit later. This trajectory was built on 3 episodes. The first one was from 2019 to essentially 2022. We had to relaunch the search engine and really maximize the value of the existing brands. The second step in this journey is the fact where we're going to launch the new medicines that we are just bringing to patients today. And of course, we're talking all hemo, in hemophilia A and B with inhibitors. Sogroya in growth disorders, Rivfloza rare haemato-renal disease, hyperoxaluria, just launched recently in the U.S. And of course, the one you're all expecting, I guess, Mim8. We will talk about a little bit later. At the end of the decade, we'll be talking much more about the expansions towards hemoglobinopathy sickle cell disease and thalassemia as an example. So let's quickly get through the first pillar, serve more. And I mentioned to you that the point was yet to find the right balance between fully leveraging our experience and the logical adjacencies with our core areas, like hemophilia and gross disorders, but not spreading ourselves to same. And this is why we came with that approach, we call it the sunshine, ready to Sunshine where you can see that by focusing on rare blood and rare endocrine disorders, we can actually -- we've decided to focus on a few disease areas where we believe that the depth of our portfolio will be very important and on our platforms as well. Out of this sort of 350 million patients suffering from rare disease in the world, this is only 6%, 6%. So if it could seem why it's actually very focused when you think about it. And we're focusing on 3 elements to start with the beginning of the core, the foundation. The first one is, of course, the rare bleeding disorders, hemophilia, Glanzmann's on which we've been already very present. Huge unmet need, very attractive growth over the next -- over the next decade. New technologies coming in, including gene editing, but not just met and we have here with Mim8 a key cards to play. Hemoglobinopathy, the second one in the blood side, sickle cell disease, thalassemia. And this is really an important one. We barely talk about it. But essentially, if you have sickle cell disease, your life expectancy is reduced by 25 years, 25 years less than the average, okay? It was around a bit more than 20 in the early '80s. We now run 40 today. It's a massive unmet need. And on this one, we actually are developing a portfolio in research and in development, to help us tackle what we believe will be a very growing category. Last but not least, the growth disorders, the one we're already on, we used to be with Norditropin and we're now entering with a long-acting growth segment with Sogroya. And let me now move to the second pillar of the strategy, and you've heard a lot about Martin darlings this morning with [indiscernible] meeting. He's going to talk to you a bit more about the other darlings of Martin. So what about -- what's in the pipeline of rare disease, Martin?

Thank you very much. And Ludovic is exactly right. I have 3 kids. I love them all, and I can love more than one drug. So obviously, moving into the rare disease space, I also had my darlings. Ludovic already talked about this in rare disease, broadly speaking, the unmet need is incredibly high. We still see unmet need in rare endocrine disorders, we still see unmet needs in rare blood disorders. From a research but from -- also from a development perspective, what we do is to think about how do we create synergies. By allowing ourselves to stay, for example, within rare endocrine and doing research and external innovation in that space. We can already now see in the preclinical pipeline, stuff coming in from Marcus, that will be very exciting. We do the same thing in the rare blood disorder space. We've been many, many years in the hemophilia space, but building on the synergies, the capabilities that we have in research and development, but also in the commercial space, allows us to successfully build and progress the pipeline. So we moved from hemophilia to now also focusing on hemoglobinopathies. Ludovic talked about sickle cell disease, huge unmet need. Not only in terms of decreased life expectancy, but a life and pain, life with [ comorbidities ] and really a huge unmet need. Rare disease from a research and development perspective is also an area where we can allow ourselves to experiment, both in terms of how we do research. We basically see more technologies applied including gene editing, in this space than what we do in the diabetes and obesity space so far. Actually, as Marcus also alluded to, there is a potential of also using some of these technologies in our broader disease areas. But we can maybe start out testing and learning in the rare disease space. In the development space, we do the same. Mim8 is a good example of that. It's one of the fastest development -- full development programs that we've conducted in the development space 4 years from [indiscernible] dose to [ phase 3 ]. So right now in the rare endocrine space from a clinical perspective, we're investigating new indications for Sogroya. That is incredibly important, big unmet needs in those spaces. In the rare blood disorder space, you see actually a quite broad pipeline, focusing on not only hemophilia, but now also sickle cell disease and thalassemia. I also have to mention, while it's not in the slide, nedosiran our first siRNA approved drug for the treatment of primary hyperoxaluria. In this slide, I want to call out, obviously, Mim8, I'll do a little bit of a deep dive in Mim8, but I do also just want to call out it's a book that talked about the huge unmet need in sickle cell disease. [ Etavopivat ] is an externally inquired molecule and we are very excited about that. While doing development in rare disease, I talked about the speed with which we have progressed Mim8, but we also had to do innovation in terms of trial design. You don't have a lot of patients to put into clinical plans. And therefore, you have to get the best out of everything that you do. So the FRONTIER 2 trial is a reasonably complex trial. It's not the biggest trial in the world, but we are investigating patients coming from on-demand treatment, investigating patients coming from prophylaxis treatment, investigating once weekly and once monthly dosing. Mim8 has the potential to be best-in-class. Obviously, we have to show that in Phase III. And no, I have not seen the data that will come soon. I have not seen the data. But the potential of Mim8 based on Phase II is that it could have best efficacy. So obviously, median annual bleed rate of 0, that is to be expected. But in our position to what we already see out there in the market, Mim8 has the potential of having 0 bleeds and more than 70% of the patients. Obviously, again, I have to show that in Phase III. Has the potential to be very safe, but also a clear differentiation on convenience. So truly once monthly, an easy-to-use device, subcutaneous injections in low volume and therefore pain-free. Also on the convenience side, an important differentiator. And therefore I think Ludovic can work hopefully unlock with that.

Thank you very much, Martin. And I would love to quickly finish by the third pillar. We said, find more, serve more, find more, and now let's grow more. And you're going to start by saying, "Well, grow more what happened last year." And it's a very fair question. If you look at our growth pattern since 2020, we actually grew in '20, in '21 in spite of, of course, a pressure on NovoSeven. And in '22, plus 1%, and we decreased in 2023. And that is actually is due to a product supply manufacturing output crisis that we had by changing an old factory to a new factory, while the demand was actually going extremely fast. And that actually create some disruption from a PS perspective from an out perspective, mostly on the endocrine side, and we hope that the whole production will be stabilized during the course of 2024. The point though is that growing, of course, relies on commercial. I would like to spend a bit of time on what has not been affected by the Norditropin issue last year. It's actually the blood franchise. And you can see that actually on the left-hand side of this slide, where in the investigating segment, we actually were able to double our market share in only 1 year. If you look at our latest launches in terms of EHL, extended half life, the combined growth here is above 30% growth, even 4 years into the launch. So it's really something which is quite impressive, and that attributes to the teams of Doug and Mike. On the right-hand side, something very interesting. Sogroya, new long-acting growth hormone. We launched at the beginning of the summer in the U.S. in less than 6 months, we're the third entrant in the market, we're now the #1. We have actually 6-point-something market share. At the end of the period, we're already #1. And if you look at Japan, if I'm not mistaken, we're also around 8% by the end of the year. So as you can see, the commercial engine beyond is actually very healthy. And this is why we're so really, really confident about the promises to capture the fair share of the rare disease market. So that's the conclusion. Strategy is unchanged, focusing on rare blood and rare endocrine, dedicated rare disease unit with early and late pipeline and launch capabilities to really capture growth. And last but not least, the Mim8 results, Phase III expected in the first half. And if everything is fine, we might have a couple of other opportunities to talk about this later in the year.

The number of darlings of Martin is actually numerous this afternoon, and it's my pleasure to call Martin back to that about cardiovascular side of...

Thank you very much. Now I really start to get into broad as is a good problem to have. And the more balance I can have the better our patients and the better off is Novo Nordisk. So when we talk about cardiovascular and emerging therapy areas, we are very specifically talking about [ cardiovascular ], liver, renal [ and/or ] degenerative disorders. We are active in those spaces from a research from a development but also from an external innovation perspective. This is part of our future growth, an important part of our future growth. And you already saw from Dave and Lars, the priorities that we put in particular on the cardiovascular space. The way again that we go about this in research and development is thinking about the synergies that we can do in research and development, understanding the underlying pathophysiology of certain aspects of cardiovascular disease, liver disease and kidney disease because these aspects are oftentimes derived from the metabolic space. So again, if you look at the diagram, the overlap between diabetes, obesity, cardiovascular disease, heart failure, and we can do the same thing for liver disease and kidney disease. That allows us to create those synergies, building on our capabilities, and we see that as an incredible strength, where we then also talk to [ Henrik ] and secure in good time, a proper supply chain. And again, we see that as a key differentiator moving forward. There's a huge unmet need in this space. And I'm not going to go through every single disease. But we've talked about it a couple of times. Globally, cardiovascular disease is still one of the biggest reasons for premature death. More than 30% of all deaths globally had arrived from cardiovascular disease. Cardiovascular disease has many things, many different diagnosis. But there are pieces of cardiovascular disease that are very closely related to metabolism, our core. That's ASCVD. And there's still unmatched needs in ASCVD or atherosclerosis we still see too many patients with uncontrolled dyslipidemia, uncontrolled hypertension. And we see a huge unmet need in the aspect of ASCVD that is [ derived from ] inflammation. We know that inflammation is a key driver in ASCVD and ASCVD also heart failure. And therefore, our focus on inflammation as part of this is very, very high. You also heard that from Marcus. In the heart failure space, we think about heart failure in 2 different entities, heart failure with reduced ejection fraction and heart failure will preserved ejection fraction. Specifically, heart failure with preserved ejection fraction is, in essence, a metabolic disease, closely associated with obesity, diabetes, hypertension. And a huge unmet need because virtually very few treatments available. Obviously, for us, it's nice to take point of departure in that we have semaglutide. We talked about that earlier today, moving into a new therapy area having a molecule already in the market that decreases the risk of MACE improves cardiovascular but also all-cause mortality, primarily thinking about the ASCVD space is incredible. But I have also today showed you data from the heart failure field, again speaking to the power semaglutide and that's a really, really great starting point when moving into a new therapy area, also allowing us to build on the synergies that we have. But it doesn't stop there. We formulated a couple of years ago our cardiovascular strategy. And it's really, really comforting for us to see that we already now have assets in our pipeline that address ASCVD, dyslipidemia, inflammation and hypertension. Some of it derived from external innovation, some of it specifically semaglutide obviously derived from internal innovation. In the heart failure space, we can say the same thing. And we even allow ourselves to focus on cardiomyopathy, specifically ATTR cardiomyopathy. So a acquired ambitious pipeline already at this point in time. But I also have to say a little bit spearheaded by semaglutide that actually addresses a good number of the areas that we want to be active in. We know from SELECT that decreasing inflammation and semaglutide does that improves outcomes in patients. Ziltivekimab, which is our anti-IL-6 antibody decreases inflammation even more than semaglutide does. In our Phase II trial, we actually demonstrated a 90% decrease in [ markers ] of inflammation. At the same time, in a reasonably large Phase II study, we demonstrated that ziltivekimab is safe. That's a novelty in this space. So we have high aspirations for ziltivekimab. Those aspirations are being exemplified and we are currently in Phase III outcome trials in 3 areas: ASCVD, heart failure and acute myocardial infarction. A few words of ocedurenone external acquisition, small molecule targeting the mineralocorticoid receptor. It's third generation mineralocorticoid antagonists. And third generation means that we can actually see differentiation with ocedurenone on the efficacy side, exemplified here with a 16-millimeter mercury blood pressure drop. But also on the safety side, being more specific, less risk of hyperkalemia, less risk of steroidal side effects. This, obviously, we intend to take fastly into the cardiovascular space. but it actually also holds opportunity in the chronic kidney disease piece. So again, a holistic approach to what we do, a holistic approach to how we can create synergies. And obviously, we intend to do the same in the commercial space. So talking to that, I'm happy to invite Camilla to the stage.

Thank you, Martin. So despite the fact that there's been so many efforts in cardiovascular disease over decades, there is still a huge economic burden in this space and a huge unmet need. You see here the economic burden on the left-hand side in Europe, in the EU was close to [ DKK 300 billion ]. And if you look at the right-hand side, you see we're getting close to [ USD 700 ] in the U.S. on the burden of CVD. So huge implications for health care systems around the world. And we have been in this field also around 10 years. We have probably one of the companies that have done the most cardiovascular outcome studies. Since we met last time at Capital Markets Day, 2 years ago, we have completed 4 trials cardiovascular outcome trials, and we have also decided to initiate 4 new ones since then, 1 has already been started, and 3 are about to start and Martin was talking to some of those. So this is just to say we do built on our existing pipeline to gain significant experience within this field. From a commercial point of view, the way that we are going to make our entry into cardiovascular disease is really to build on our leverage with semaglutide. So you know when we talked to it earlier, how we're expanding the indications with semaglutide near-term. And really also seeing cardiologists, we are approximately seeing 30% of the cardiologists that we expect to see when we launch [indiscernible] later on towards 2027. So the overlap is gradually increasing. And if we at this point are around 30% of the potential cardiologists that would be relevant we, of course, will expect that we can increase that gradually over time so that we are making, you can say, from an investment point of view, a safe entry into the space, getting to know the right people better and better before we launch our new -- either stand-alone products in this space or completely new mode of actions in this space from our pipeline. So this is the way that we commercially are building on what we have getting into a related area. Our strategy is also backed up by a number of studies. Martin was talking to some of them in ASCVD but also in heart failure. And you see the potential in terms of populations below here. So again, a huge unmet need. This is still the leading cause of death, as we talked about. 18 million deaths a year. This is something that we would like to make sure we can use our science and technologies to impact more positively. And of course, we also expect to have differentiators, as you can see on the bottom line here in terms of how we actually are able to enter this market and make a difference that has not been made before, despite that many have been working in this field for many years. So that sort of ends our part about cardiovascular disease for now. We will have a Q&A a little bit later. But before we move away from cardiovascular disease and emerging therapy areas, we'd just like to Martin to please come back up and talk about some of the other emerging therapy areas, especially in MASH.

Yes, absolutely. So we wanted to give you a snippet of what we're doing in emerging areas. And obviously, looking at this slide, you would think I will also -- and Camilla will also move on to talk about CKD and Alzheimer's disease. For better works, we don't have time for that today. It doesn't mean that it's not important. It's a big focus area for us. Not a lot to talk, at least from my perspective, about in the Alzheimer space because we are currently conducting the book clients, they will readout next year. And until then, I will not know any more than you do. So really, really high on our agenda, but not something that we can talk to. And in the CKD space, I mentioned ocedurenone, but we don't have a lot of development activities other than that and flow but while the focus on both external innovation, but also [indiscernible] activities in the preclinical space. But for MASH, we can spend a little bit of time because here, we actually see a rather robust pipeline. And as you all know, this has been a crowded space. If not so anymore. It's safely a quite slim space in terms of drug development, but the unmet need is still huge. Again, this is a disease that people live with that is associated with comorbidities specifically cardiovascular comorbidities, but also that people die from. And from, again, a research and development and commercial perspective, we can create synergies because this is a metabolic disease. Huge overlap with obesity and diabetes. And that, again, allows us to build on our capabilities when we move into that space. Again, we also have to acknowledge, and this is exemplified by the top line, that semaglutide actually offers itself up as a really strong candidate that has the potential to be 1 of the 2 first drugs on the market in this space. It doesn't really stop there. Also here in the clinical space, we do collaboration in this case with Gilead, looking into the more advanced areas of MASH. But we also have early stage assets both in Phase II where we investigate FGF-21 and actually also Concizumab. And we have Phase I assets. Addressing the broad spectrum of the pathophysiology of MASH, metabolism inflammation, fibrosis. Just a few words on why we are excited about semaglutide in this space. In a Phase II trial, we saw a 6% to 7% decrease in steatosis. At the same time, we saw a decrease in fibrosis at a clinically relevant level. That actually allowed the FDA to give us breakthrough designation for this 1 study and agree with those that we don't have to do 2 Phase III trials. We only have to do 1 Phase III trial because the other trial can actually be our Phase II trial. Normally, FDA requires 2 well powered, randomized and controlled trials to approve a new indication. So what we're doing right now is we are in Phase III. The ESSENCE trial. There's 1,200 patients here. That's for the sort of full Part 1 and Part 2 of the study, the regulatory part of the study focusing on steatosis and fibrosis through liver biopsy is an 800-patient 72-week study. So part 1. And obviously, the data had to be there. But that will readout during this year. That will allow us to have a broad palette of semaglutide offerings, moving into not only diabetes, obesity, or based on what Camilla just discussed also the cardiovascular and the liver space. Very, very attractive offering and very, very exciting. And Camilla speak to how we will go into the MASH space from a commercial perspective.

Thanks a lot, Martin. The commercial potential, we expect is around 30 -- sorry, I need to get right, 22 million people from F2 to F4. So 22 million people is a lot of potential. But recently, until there has been no treatment available, the diagnostics has not been very strong. So when we are thinking about how we commercially prepare for this market, it's all about awareness. It's not easy to see if anyone is living with MASH or not, it's different from obesity in that sense. However, there are a job to do on awareness, there's a job to do on referrals to make sure that the physicians we have been talking about before are actually referring patients to hepatologists to get treatment and then the diagnostics. So in the diagnostics space, we are working with a number of other companies in nonexclusive agreements to make sure that we can also support that there is a development of noninvasive tests. So the NITs, the noninvasive tests are important for us because, of course, they are much a lot less invasive than biopsies. And the complementary effects of these noninvasive test is, of course, extremely important for realizing the potential in MASH. So that's why we are working in these partnerships. There's also educational activities, there are guidelines their consortia around this because it is a new, you can say, therapy area or at least the treatment area due to the history of no treatment available. So all in all, this is efforts we are undertaking with a number of other companies to make sure that we can unleash the potential in MASH based on the data we have with semaglutide and are building also for the future in other compounds. So this summarizes our session on cardiovascular and emerging therapy areas. And just in closing remarks in both areas, cardiovascular, but also in MASH, there is a big unmet need and there's a lot that can be done we have the cardiometabolic complementary competencies to launch products into this space. And with the significant unmet need, we believe that both in cardiovascular disease, but also in MASH there's huge potential. And of course, the next thing we're looking forward to this year is the readout on the 2.4 milligram in MASH later this year. So very exciting, and we look forward to that. So with that, we will close this session, but invite the panel up for Q&A, and last will be the moderator, I think.

Thank you to the colleagues. We are ready for the next Q&A session. And let's start here, Richard.

The pressure. Richard Vosser from JPMorgan. Maybe you could talk about the specific benefits with related to MASH on the glucagon mechanism. We've seen some data there that seems to have maybe slightly better data than just semaglutide or just GLP-1. So just your thoughts on glucagon targeting and maybe Amylin targeting with relation to MASH.

So I guess this is really research question. But Martin, do you feel comfortable addressing that?

Yes. So theoretically, glucagon is potentially good in MASH because it has direct effects on the liver. I don't think we've seen data that are hugely differentiated from GLP-1 alone GLP-1, GLP. We are in the 70% in terms of the steatosis reduction. That means that it works. But I would still love to see some safety data. I would still love to see some fibrosis data. I know you would as well. So I think this is a big potential. But it's too early days and we actually believe both from a timing perspective, but also from a functionality perspective, that semaglutide will make a big difference in this space. And then we have higher aspirations for our pipeline as [indiscernible] with FGF-21 and Concizumab.

Thank you, Martin. Peter, will you?

Peter Verdult Citi. Just one question for Martin, just on the MRAs. I had the pleasure of being at the Bayer CMD on Tuesday, which sort of went slightly differently to yours today. But one area of overlap to be fair, is finerenone. I mean they have got good data in CBD and CKD, but they admitted is hard work. And when you speak to the docs, are you really going to see these patients on SGLT2 on a GLP-1 on an MRA. So can you just remind us what is it about ocedurenone that if I pronounced it correctly, that is going to differentiate you versus the second generation from Bayer?

I think it's two things. We actually believe that ocedurenone has a really strong efficacy profile. Obviously, again, we have to show that in Phase III. But specifically, the safety profile appears to be quite attractive and specifically the hyperkalemia side effects. That is a big area with this mode of action. We believe that ocedurenone has the potential to be clearly differentiated.

Thank you, Martin. Any questions [indiscernible] No take Simon.

Simon Baker from Redburn Atlantic. Just continuing on the theme of MASH. You've clearly got a lot of shots on goal and treatment options and potential treatment options there. But one other one I was wondering about was ziltivekimab in MASH because there's been a lot of work on IL-6 implication in MASH? Is that something that you've looked at either alone or in combination with the other options that you're currently developing?

So I think it's a really good question. And obviously, inflammation is a key part of the pathophysiology that we see in MASH. Our belief is that the first step has to be to rectify the underlying metabolic derangement that is basically initiating the disease. And we believe that those metabolic agents should serve as maybe the foundation for treatment. Adding them to that. And you [ actually also ] see that is in our pipeline is potential for inflammation. And we could potentially see us pursuing more than what we already have but then also down the line potential for antifibrotic. But the standing point has to be, in our view, the metabolism.

Are there any questions for ready, yes.

Maybe it's more -- [indiscernible] it's more of a short topic on Rare D because we've seen you have some significant struggles commercially recently due to lack of supply and manufacturing. So of course, it's not a Rare D, R&D question, but more to -- when you're looking into Mim8 and coming products. How do you feel in terms of confidence levels that you have addressed? What you had seen a challenge in the last couple of years on the Rare D side to also make a decent commercial push for new assets in the pipeline?

Absolutely. It's a very good question. We really believe that we are -- we're putting everything we have right now in solving the issues behind our output presence. And I'm sure that later on, if you have questions also for Henrik, we can talk about that. So we really are investing turning around and accelerating the throughput of all our factories in the system on the -- of course, on the Norditropin at first. But what's important to see is that behind that, as I said, the commercial engine is actually very, very, very, very robust. And that's what we are seeing every day out for Sogroya also in the growth hormone element, but as well as in blood.

And Martin, you going to continue? If you still have the microphone at the table? Martin?

He's maybe not so ready, but it's -- I have to go back to the glucagon component Martin, because you have had a GGG in development or maybe not in development before and you decided not to go with that. And now you have a new GGG and I suspect that you have swapped the glucagon with the GLP maybe you can confirm that? And then maybe what the issues, what are your concerns regarding glucagon?

So first of all, I have to acknowledge that other players right now are moving into the glucagon space, and they appear to be successful. Based on what we saw and we observed some safety tolerability profiles and aspects that we didn't really like that was actually reasonably good efficacy, not as good efficacy as we saw with [ concizumab ]. But then we had a safety profile specifically on cardiovascular that was less attractive. We could potentially have overcome that but in a pipeline prioritization perspective it's quite easy to up-prioritize concizumab because it has better efficacy and better safety profile. And then in that aspect, then cancel the glucagon PACE molecule. That, I think, still makes a lot of sense. It doesn't mean that glucagon doesn't work. But in our pipeline, we had way more attractive offerings, both from an efficacy and from a safety perspective. We've actually published the safety considerations on [indiscernible] glucagon. I think it's also important to call out, and none of us know at this point, glucagon is also involved in [ taurine ] metabolism and amino acid metabolism. And when we're talking about preservation of lean body mass, I think I'm still curious to see what glucagon does to lean body mass in a weight loss setting.

Thank you, Martin.

Seamus Fernandez from Guggenheim. So my question is actually on the comment earlier about the interaction between the inflammasome and IL-6. Can you, Martin, talk a little bit about where NLRP3 fits in the grand scheme of things, other people are approaching it in CNS disorders, some are approaching it as you are in cardiovascular disease and then -- more recently, we've seen some pursuit in obesity. Can you just kind of talk about the intersection or the potential intersection of those 3 areas?

I'll give you a super brief answer because I think Marcus is also very well suited to. So maybe if I don't give you the right answer, you can ask it again in the final Q&A. You're absolutely right in most of the disease areas that we move in inflammation has a component to at least the comorbidities. And therefore, we are very, very focused on inflammation. We actually started with semaglutide. Now we will sell ziltivekimab anti-IL-6. and then we have NLRP3. And NLRP3 is higher up in the information cascade. And that has the potential of maybe having bigger efficacy impact, but potentially also something that would warrant a keen eye to the safety aspect. So right now, we are building a broad pipeline that allows us to investigate the different aspects in the different disease areas, starting out with ziltivekimab anti-IL-6 but also moving further up the cascade.

Mark?

Mark Purcell from Morgan Stanley. With CKD, I think one of the challenges is diagnosis. So apart from using open diagrams and using obesity as a trigger to test people for proteinuria and other things to diagnose CKD. Can you help us understand the challenges there? And Martin, do you need [indiscernible] has choose other combination partners with your MRA for a combination approach to keep CKD?

So I think our first approach to CKD is actually starting and we do that with Ocedurenone in the CKD space. It's a good place to start because they are the diagnosis that are actually quite high. The diabetologists have a keen eye to kidney disease. But obviously, moving into the broader CKD space, this is something that we have to work on. As you know, Camilla has some thoughts on that as well because we have the same challenge when we talk about use of CRP for Ziltivekimab or when we talk about diagnosis of MASH. So this is something that we are working quite diligently on. I've seen the combination therapies. And obviously, that's something that we need to investigate. Right now, our areas to first investigate also toward on -- in monotherapy and then maybe go to combination therapies. That's obviously contingent on effects remaining on the lead and obviously also dynamic for the commercial. Sachin?

Sachin Jain of Bank of America. Just back to MASH. You focused on the MASH resolution for [ summing ]. Could you remind us the fibrosis data you had in Phase II and expectations for ESSENCE fibrosis given fibrosis has been a real focus for the competitor data sets in the last few weeks.

Yes, absolutely. So honestly, I can recall the number, but I think we saw around 50% reduction in fibrosis, placebo-controlled, that was less. And that also means that it was not statistically significant, but clinically relevant, that actually prone the FDA to say this is still good if you can show the same thing in Phase III because in Phase III, we'll have the sample size to show statistically significance on that differential. I think more importantly, 75% risk reduction of [indiscernible] the next level of MASH. So progressing from F1 to F2, F2 to F3, which is obviously also very, very relevant when we talk about prevention of progressing to, let's say, cardiovascular disease or end-stage liver disease. Any reti question? Yes. Here in the back. Yes.

Yes. Eric Le Berrigaud, Stifel. One clarification question on [indiscernible]. On 1 slide, we see the blue arrow of the Phase III going into '25 while you're saying at the same primary endpoint where we bought in H1 '24. Does that mean that the complexity of the trial will require that you look more into a subsegment of the data before you're going to file? What's the time between primary endpoint of availability and filing time when we are getting into '25.

Okay. So we never really take that on file time. We have to see the data first that, what we can say that is we'll have Phase III data in first half of this year. So within the next couple of months. And then obviously, we'll do a regulatory filing as soon as we can. To the complexity of the data, honestly, I don't know.

So we'll take a final question down here.

Florent Cespedes from Societe General. Quick question on rare disease for Ludovic. How do you see the dynamic of the real disease business going forward as you have [ Nuplex ] launches, should it be back on the 2021 time frame with a low single digit or something a little bit more dynamic with the new products and some production capacity coming back.

As you can imagine, we're not guiding on forward growth rate, as you can imagine. But what you can see is that we really, really worked hard to create a portfolio with many drugs in sort of efficient indications and many launches to come, which was not the case when in the phase 2022. But that's, again...

I think Ludovic is being a bit humble here. I think you showed that when we have products, we can actually compete and gain share. So I think it has the potential to have an attractive growth profile without getting specific into that. . So that will wrap up this Q&A session and now you have to get a bit access because 2/3 of you will have to move to the neighboring building and some signs here. So if you're in data science and AI, region China, it's the neighboring building, don't worry. It's very close, just on the [ shining ]. And then we have region EMEA in this room. So again, the breakout sessions. [Break]

All right. Welcome back, and welcome to the most popular breakout session. So congratulations on taking the most popular breakout session, which means that you didn't have to go to the building next door. So this is our region EMEA, deep dive. And the way we feel this is through 2 persons. And the reason behind that is that internally in Novo Nordisk, we don't have anything called region EMEA. We have 2 regions. We have CIMEA and Northwest Europe. So that's how we are organized internally, but external reporting, just to make it simpler on the external part, we call it region EMEA. So this really to get a good feel for the commercial execution and operations in EMEA, and I have 2 superstars with me today. So the first one to kick off is Andre Popkowski, who's been in numerous geographies on a global scale with Novo heading up being SVP of of what we call region CIMEA. And then following him, we have to meet last and who is running Northwest Europe. So they'll do, call it, 15 minutes presentation and then we'll go into 15 minutes of Q&A. So over to you, Andre.

Thank you, Carsten. Very good afternoon. I'm super happy that we can share together with a new presentation to the audience, which is expecting to see what are the growth opportunities in EMEA. And I like to start with -- or I will start with diabetes and then Emil will cover obesity followed by the questions. As Karsten mentioned, EMEA is pretty diverse region. It's cafeteria of all the markets. And you can imagine different affiliates, different potential, different population. We cover 30% of the total population of IO, international operations. And of course, we are dealing with very varying local dynamics. What is very common and similar to what has Mike presented, it's all about growth. And we are growing -- we see the growth of the segments. First of all, Diabetes segment is growing and within diabetes, what is growing is GLP-1 where we are gaining market share. And this is a modern oral antidiabetic treatments where we are present and we are then gaining market share. At the same time, if you look at the insulin market, it's flat. But if you dig a bit deeper, it's growing around 5% to 6% a year, and we are holding 50% of the market share. So this is a very important part of the business for us, and we want to continue a successful performance there, especially that we are -- we will be having icodec soon. And of course, we have very high expectation in terms of launch of the product. Obesity, that's all about Novo Nordisk and being -- we are growing the obesity market. So market is growing. And of course, it's thanks to Nova Nordisk force, and we are looking forward to -- for the more and more launches of Wegovy in the coming years. That was market and how we are performing. Please have a look. In the last 3 years, we have started to see significant double-digit growth across all the geographies. Majority of growth is coming, of course, from GLP-1, both Obesity and Diabetes. But as I mentioned, insulin still -- It's, first of all, a big business for us. And secondly, it's still growing. So if you can only imagine if 1 day, we will launch icodec and start to address 10 million of the patients who are now treated with other, let's say, Basal insulin treatments, starts and maybe switches. This is a very, very, let's say, optimistic prognosis for us. GLP-1 market. We have -- we are representing 50% of the total GLP-1 share within IO. So we are pretty important geography -- or pretty important region. So our performance in GLP-1 segment is really critical. If you compare our market share in 2020 to '24, we managed to gain around 10% market share. So market is growing and we are growing market share within the market. If you look especially at the Rybelsus, we are very happy with the performance of our oral treatment. We have managed to gain market share within the growing market. So let me pick [indiscernible] into Rybelsus or oral treatment. We have already achieved 8% of the market share in last 3 years after launch of the Rybelsus, which has been launched in 30 countries in EMEA region, which represents 60% of the value potential of the region. And it's thanks to very strong commercial execution. If you look at several big markets, which we have chosen just for this session and of course, we can discuss during the Q&A. We are very proud and very happy to see that in many of those markets, we have already achieved market leader position. And these are markets where either we have reimbursement or -- there are markets where we are not reimbursed. We are out of the pocket, but we are still performing very nicely. Like for example, Poland having 17% market share in the big oral Polish market. Italy, 28%. I have received data today sort of 27% is from the previous month. So we are growing nicely, and that will continue in the coming years to Emil, now it's time to share news on obesity.

Thank you very much, Andre. And we're still in the similar world, but we are shifting gears, of course, now to obesity. And dots showed some U.S. numbers that I think have impressed everyone, including people inside the company. But -- and Mike said that the numbers are still much smaller, of course, outside the U.S. But what I can share with you is that if you look at the response from the market where we have launched so far, it's overwhelming, and it's like nothing we had the dream of just 1.5 years ago. And if we start a little bit with the outside in perspective, from the launch from the countries where we have launched Wegovy so far, and year than that to the left of the slide. Then you see, first and foremost, that even neighboring countries have quite a different starting point in terms of where are we with the obesity pandemic this year at the moment. These are obesity, numbers of the total adult population with obesity. So quite some differences. But what we also see if we move into the future that in 2030, '35 in all these countries, we estimate that more than 3 out of 10 will have obesity in UAE and the U.K., it will be 4 out of 10. So this is, of course, a Tsunami, that's been going on for a while, and it's not about to stop anytime soon. So that's there. Equally interesting, Also, if you look at differences across and you have the bar below, you will see that we have Denmark, Norway, where right now, we have reached the penetration in the obese population with a BMI above 30, with GLP-1 products. And as you know, that's Novo Nordisk for the moment, and it's mainly in these 2 countries Wegovy go at the moment of 7%. So if you go out on the street here and find someone with high obesity, 7% of them will be on Wegovy the moment in Denmark. If it's North of Copenhagen, you might have 12 or 13 as you average. This of course has been accomplished in the span of just 1 year and a bit. It's staggering. It's not ever experienced before. Come to some of the other markets there. You're down in the low single-digit, maybe even below 1%. But then you will also see later, it's later obesity launches and particularly, it's really Wegovy unlocking this potential. So it's something we worked on for almost a decade. We launched Saxenda. We built the platform since 2015. But in relative terms, the unlocking receive when we had launched Wegovy in Europe is just staggering, and in relative terms like nothing we had really, we're hopeful. So quite something. We also, of course, wonder in Europe if people want to pay out of pocket. It's always been very difficult in chronic care, but this is a different business, willingness to pay is much smaller than we had expected. If you look to the right side, it's just showing that growth from a low base in the EMEA geography. In the last quarter of 2022, EUR 1 billion in sales move on just 4 quarters, EUR 1.7 billion will just launch into a small part of the overall obesity protection in these countries in the large geography. So quite something. Of course, what we saw and what we wanted to learn with Norway and Denmark and Iceland is what happens if we don't restrict volumes in relatively small population settings, and you saw the result we, of course, couldn't keep on launching in large countries given our supply situation unconstrained. So we decided consciously to say, okay, we want to constrain and we want to learn from other geographies. Patients with high unmet needs, will have the opportunity. And of course, we also wanted to build the experience in these geographies. So countries were carefully picked as models if they could manage a constrained supply. For instance, if you gain reimbursement, can you safely the public channel if you have an agreement with government. The whole point, of course, is to drive scientific dialogue for doctors to gain experience for pathways to be built and of course, also to establish field world evidence. In turn, we also had the chance to learn. We had -- in every country, we've launched a Tsunami of media requests. We've had to staff the media teams, it's almost been like a hot line. Patient support has also been, of course, geared up manyfold in these affiliates compliance is, of course, key in this area. So it's really been a getting the learnings, getting up to speed to handle this kind of a pull effect that we have never experienced before as a company. So very, very interesting, very, very positive feedback. And if we go a little bit more granular and we start with unconstrained first 12 months, we've had in Denmark and Norway. What we basically experienced in these 2 countries that are GP driven countries is that in every corner of Denmark and Norway, within a few weeks, we had prescriptions. After around 9 months, 90% of GPs had prescribed, and we were approaching a prescription average step of 8 to 9 prescriptions per GP. We also saw a lot of private clinics popping up with a lot of entrepreneurs, actually taken on quite a bit of market share in each of these countries that traditionally have not had any sort of services in this space. We saw very positively that most of the patients where we have data appears to be a late or sort of the mid-30s, early 30s BMI with the data we have. And we have typically patients with comorbidities. We have a very large real-world database in Denmark that we get once in a while, and 80% of the patients there had a risk factor of comorbidity. So very positively at exactly what we hoped for. Adherence is also trending upwards. It's difficult to talk about adherence because, of course, we've not reached a steady state. But we have kept upping our estimates on adherence and we are looking at around 9 months at the moment, which is very good, given that we are only a little bit more than a year into the Nordics market. If you look to the more kept setting and when I say kept, it's not minute. The U.K. launch is still the biggest launch we've ever had in the U.K. So we would have liked to have more, but it's a very meaningful launch in a country that has a big problem with obesity. But we actually have had good experience Customers were happy. We had very close intact, in particular with the private players in the U.K., setting the expectations, of course, make sure that, for instance, big pharmacy change -- didn't get ahead of where the supply was and did a lot of marketing activities. So it's been a very careful interaction there. So far, we are able to titrate patients exactly as one so that if people start, they can continue to the maintenance dose and stay on treatment. Another positive is a switch from Saxenda to Wegovy because, of course, we have a payence saving there. One of the ways to solve our -- production issue is to move for once daily to once weekly treatment, it's wonderful for [indiscernible] instead of building manifold the production capacity. We can have many more patients with the same number of devices because here, they are shared in the European setting and EMEA. Finally, we have actually had a good start with reimbursement. We have from the very get-go, reimbursement in the U.K. Mike describe that. Here, the limitation is the care setting very much in terms of uptake, takes a very broad population that fits the nice criteria. And we also just got news a few days back that we have a very meaningful reimbursement in Switzerland. So a good start there. And of course, we don't stop. We have the discussions in every country because it's important for us to address that in quality -- in health care that obviously is a concern for all involved. But it's a stepwise approach, and we can also say that the majority of the future growth in EMEA will be driven by out-of-pocket, given the willingness to pay we've seen so far. So in sum, this is really the era of Sema across EMEA, we already have the acceleration in diabetes. It will continue. There's a lot of runway there, and we just got started with experiences that were even better than we did hope for in obesity. And of course, we have that strong market share to build on. We have a strong infrastructure, a strong presence across the geography and that we see as a key competitive advantage. So with that, I think we'll be joined by you, Karsten, for the Q&A.

Yes. Thanks, Emil, and thanks, Andre. So now it's a Q&A. We have 15 minutes. And yes, so we just too along, we go to the back here.

Could you just give us a sense -- sorry, Marshall Gordon, could you just give us a sense of what constrained or cap really means for those launches? And when you think you're going to start either launching more countries or lifting those caps?

Yes, as I said, constraint in Denmark, as you can see, was very flexible. Now we take it more slow in Denmark to also give other countries the opportunity to join. But it's the biggest launch ever in the U.K. And of course, we don't launch in a place where we can't follow through in the following year with that growth. So the idea is now we are building that experience in terms of how do patients titrate through to the higher doses. What is the state time and it's evolving. I can say already now -- so we have more on the -- we order more high doses than starter doses because we want to make sure that we can follow through with the volumes we have allocated centrally. And we already have plans for next year as well. So we will not, of course, tell you where are the next launch countries, and it's something we evaluate quarter-by-quarter based on the uptake and honoring existing patients that have started. So it's a very good growth we have planned we could always start more countries in commercial. We are ready when we get the supply, but it's a very meaningful growth we are planning for.

So in practice, Marshall, it means that at a group level, we allocate a certain amount of pieces to region EMEA into -- if we talk about Wegovy. So Enel and Andre, they know how many pieces of Wegovy will be available this year and instantly also next year. And then that's being allocated on a country basis so that the individual GM knows exactly the number of pieces and then has to commit to based on the criteria you saw before. Commit to be able to execute a launch based on that capacity. So the GM will get no more, no less. That also mean perfection is index 100. Of course, in sales normally you would want to over-perform, but there's no celebration for that at the moment. We don't want to create more demand than we can on, of course.

Yes. Then we move to Jeff.

Jeff Olsen from [indiscernible]. Just because the cash pay phenomenon is a bit new for the pharma industry here, can you just give us some thoughts around will we see price inflation over time on cash base or will be the opposite of what we normally see in these markets or should be our expectation.

That's a good question now with inflation rates intact and so on. So what are the rules [indiscernible] can we change price like in the U.S.

There are many countries involved here. But generally speaking, when we are not in the reimburse setting, there's repricing. So there are opportunities to go down that route. You say our main the win-win, of course, is the more patients we have titrate up to the higher doses because we have similar pricing. The more value we get out of every pen as well, the better the patient experience. So that's our main focus at the moment is early into the launch. But yes, we have in the private market setting some other pricing opportunities than we have usually with reimbursement, where reference pricing also kicks in and becomes part of the agreement.

Can you comment on -- have you taken a price increases on the product -- or what would be the normal algorithm? Would it be at an annual basis, if you'd review pricing just trying to understand.

We do it more often. The only situation where we typically do it where we do sort of this early into a launch is if we have currency developments. And here, we have had at least 1 country that has had a weak currency in our geography. But normally, that is setting. And otherwise, price revisions upwards is typically more in very inflationary countries that we've had South Africa could be an example. Brazil could be another one that has these kind of regulations for that as well.

Yes. [indiscernible] [ Turkiye ], Argentina, Egypt, there are markets where we can -- and we do those exercises.

Peter Welford, Jefferies. Could I just ask with regards to negotiations with governments in Europe, just so far as, a, there are a lot of countries yet, which you had to have the drug even on a private pay. You said there's a willingness to do private pay. So I guess how do you weigh up sort of potentially a government with the negotiating, but then obviously, your supply then get sockets versus on the other hand, actually giving the drug to a country where it doesn't have it yet, where there are patients who are willing to pay for it. I guess there's an economic argument, but I'm thinking out a patient argument as well, how you weigh that up at the moment.

We've given ourselves a challenge that every country where we launch, we would like to have at least 10% of the volume allocated for vulnerable populations. So we sort of have said that should be sort of the -- where we really aim to get everywhere. So that's -- that side, yes.

Isn't like in the U.S., if you like, [indiscernible] people vulnerable is -- I mean, I could -- in the U.K., if you like, if the government is willing to pay for me, I'd be vulnerable, if you like. Is that right?

Yes. But yes. No, 10% -- we're trying to say 10% of our volume, we would like to dedicate to try and see if we could take out the financial part of the care component in a given country.

So 10% will be reimbursed.

Yes, 10% would be reimbursed of the volume. And then that side, yes, I mean, we have, of course, outperformed that already in Switzerland but that's challenge we've given ourselves.

Which links back to what Mike Doustdar was also talking about around health equity and having obesity recognized in society as a serious current disease. So this is really the long-term play. If we don't get that in place or target and we might be able to sell a lot for a period of time. But over time, we need to have it recognized as serious crime disease. Yes, let's move here.

Tony [ Garner ] from JPMorgan Asset Management. And just on -- you said you have 7% of the Danish obsessed market you can supply. You just launched in the U.K. Can you serve 7% of the U.K. obese population? Just give a sense as to what volumes are available?

Not right now. It's -- so we are not at that point at the moment. We are, at the moment, serving around 100,000 patients closing in on 100,000 patients in the U.K. on an annualized basis with these monthly numbers. I think it's 95,000 at the moment. We will, of course, going to increase that, but there's some way given the number of people with the obese in the U.K.

Peter Verdult, Cit. Karsten, I had the pleasure of reading the annual report last week. And in the disclosures, Denmark went up from like point something percent to 0.8%. But when you do the numbers, that implies a growth in Denmark alone was like 400% last year to $0.25 billion. So I just want to make sure when we think about is Denmark, the canary in the coal mine in terms of how it's going to play out elsewhere? Or is it just home market and it's one-off. Can you clarify that? And then if I could come back to Pete's question, just talk us through sort of discussions you're having with the governments in Europe when it comes to reimbursement. What -- where the pushback is, what's resonating? That would be helpful to that.

So thank you for reading the annual report, by the way, and getting into a -- impact to the sales in Denmark. Of course, the math that you know is when you only have 1 decimal and then you multiply it by a very big number. And then, of course, there's some string to the math. But you're correct that we had very strong growth in Denmark. And I would say directionally, yes, the penetration we see in an unconstrained launch with Wegovy is really what's driving performance in Denmark. Ozempic also very, very strong in Denmark, I'd say -- of course, the demographic differences in Denmark in terms of ability to payencealso. So it depends on what you're comparing to. But you could say 7% of the obese population. I don't think that's unreasonable to think that could be possible in other markets also. Yes, Simon?

Simon Baker from Redburn.

Yes. And maybe just to add, I mean, we've seen a very similar trend in Norway, launched a month later, not much different than Denmark in relative terms in terms of uptake, so really a growth driver. And both not with big launch meetings to Mike's point, we sort of -- we had unrestricted supply, but we tiptoed a little bit into it from a promotional perspective. On the reimbursement discussions, we got a little bit of a stamp of approval, we feel from the National Institute of Clinical Excellence in the U.K. already in March last year, actually before the SELECT data, where they found Wegovy cost effective for quite large population group. And again, here, the limiting factor is the setting, the specialist setting in hospitals in terms of the uptake. So that was very important. And cost effectiveness, of course, plays vital role, particularly in Europe. But it's, of course, a balance with cost effectiveness and budget impact. And that's where we also have to make sure that there's ample funding in the system, so we don't found out other important treatment areas. So that is the balance of finding that right population, where it's clinically meaningful, but there's also affordability from a public payer perspective.

Then we'll go to Simon, and then we'll take [ sector net worth ].

Simon Baker from Redburn [ Atlantic ]. Just sticking with the U.K. and you said that you're annualizing at 95,000 patients. The NHS in December in the community setting, dispense 69 Wegovy Pen. So is the market vastly private pay? Or is the second especially set in bumping that up? Or is it even allowing for that? Is it still a market that is heavily, heavily weighted towards private pay?

A few things about the U.K. We launched in September. So it's very early days, and the private market has really been waiting for the product. We had several hundred thousand patients on waiting lists. So that was just a catch-up effect waiting to happen there. It took off. In the NHS setting, as you might be also familiar with, there's the national approval. And then there is a follow-through locally. And actually, in each local setting, there is also a pathway that has to be approved, et cetera, et cetera. We estimate that the capacity when it's up to speed in the U.K. for treating overall obesity patients is maybe around 50,000 patients at the moment in the hospital specialized obesity care setting where you're talking quite -- I mean, a lot of clinics, but not that many for the population side. We have it -- there's a lot of waiting list there for consultations overall. It's been the same with biotic surgery, et cetera. So again, it's not the scope of the population, but it's the treatment capacity. And that's also why it's so important to get started even in a constrained setting.

So just before we move to your setting then I think we should just hear from Andre, how you're preparing for Wegovy in some of the less affluent markets and through what you're doing on Saxenda now and your perspective on Wegovy when volumes are coming that way.

We have several countries where we have been extremely successful with Saxenda, gaining a lot of patience. And of course, we are waiting for opportunity to launch Wegovy. And I think what gives us comfort is that, of course, we have created already infrastructure, which is critical for the proper launch. And what I mean by proper launch is that, of course, you need to talk to the right customers, right doctors who are well trained, right nurses. And of course, you have to go to the right clinics where they know their stuff, especially when you will provide, let's say, limited volumes compared to what explosion could be. But it will be still very precise launch where we will make sure that all the patients who will be enrolled on the treatment, they will continue for months to go. And then gradually new starts will happen. And then, of course, we will secured the growth, which will be like year-by-year ongoing with the decent uptake of new patients, but hopefully no stock-outs, which are very concerning for everybody. And that's why we have to have this very precise surgeon type of approach. But we are pretty well prepared because we know exactly our staff because, of course, Saxenda was launched in many, many countries.

Thank you Andre. And then the last question for you, Sachin.

Sachin Jain, Bank of America. Just coming back on reimbursement. And how are you thinking about outcome-based contracts with single payer systems? And is that becoming a discussion? And I can just take 1 other one. ex U.S., you're getting a lot of out-of-pocket usage. So what -- I mean, this is not typically a former question, work you are doing on price elasticity of what price point will generate substantial out-of-pocket demand?

Yes, so what was the first question you said?

Outcome space.

Outcome space, yes. Okay. It's like happened to also for Saxenda in the past is successful and what we're looking at now. That's more a volume risk-sharing approach I would say, payers are typically more [indiscernible] because we in corporate are concerned about certainty public payers are even more around not breaking their budgets if I have to be completely on. So it's typically more volume risk sharing where after a certain cutoff point you go to the price of a comparative treatment at a lower level? Or you have some other mechanism there to rein the well cost. That's where it's mainly going. Outcomes, should you say, so would be so logically, but there's still some more controls built into that, and it's just not been where the interest have been so far and also based on Saxenda experience.

And the last part.

Price elasticity.

Yes. Right now, you could say with -- it's not difficult selling at the current price points. So of course, over time, over the very long haul, of course, that will be in potential if you want to go to some emerging markets, et cetera, et cetera, there will be opportunities there. We also heard discussions about being flexible on presentations, et cetera. But right now, it's more from in a quality and health perspective that we believe sort of entertaining price discussions and from selling the volume we have at hand for the many in a foreseeable future.

Great. Thank you. That concludes the EMEA session. Thank you [ Emil ] and Andre for good questions. Thank you. And then I believe we have a rotation. So with [indiscernible] and -- so unless they're so good, you want to listen in again, then you have to move.

[Audio Gap] So even if we are very, very successful with reimbursement, it's very hard, I think, for the foreseeable computer -- or future in relative terms to compete with that willingness to pay in our [indiscernible].

I think it will be the same situation to sum out. The -- my part of the world when we will get Wegovy. Most of the sales will come from the out-of-pocket. And of course, we have this ambition as a company that wherever we launch, we would like to secure around 10% of the patients who will be getting product reimbursed with this special reimbursement system established, thanks to Novo Nordisk effort and governmental willingness. Because we would like to make sure that even in the places where we launch and patients can pay, those who really cannot afford. And they have comorbidities and certain life situation, they get help and we'll be able to treat this disease.

Thanks, Andre. And I had a second question. It was that price differential between diabetes and obesity, [ Xiaping ] so What was your second question?

Sorry, it's exactly that. I mean, I think you answered the question that most of it is going to be out of pocket. But I think there's some reasonably big price differentials when we sort of try and think about a typical U.K. price discount. It looks like out of pocket might be twice as high as the price net you get from government channels.

Yes. First and foremost, U.K. In out-of-pocket setting across most countries, we -- there's repricing from our side. In the U.K., there's also free pricing for the private pharmacy chains that drive a lot of the sales. So of course, their pricing is also very dependent on supply. So in current situation, their margins are going up. They also provide a lot of services. They live a big part of the health care provision burden and do it quite well and professionally. But we do foresee that the prices will go down as supply increases at the customer level. On the differential between -- and maybe our willingness, of course, in the public channel, you could say, I think [ Doug ] mentioned that we always open to talk. But of course, in the supply situation, there's a limit to the flexibility. The attractiveness of reimbursement is, of course, that the state time is likely to go up, they will have more patients on the higher doses which then maybe leaves room for some flexibility because it's a higher price per ton given the higher dose average.

So our starting point is, as we presented earlier, it's really important for us to establish [ BCC ] as a serious chronic progressive disease. And part of that is also to work with government's to get it into local treatment algorithms, local reimbursement government health specialties and clinics and so on. And part of that is to make certain contracts for that specific population. And I think by doing so, we really established our brands, our products in the appropriate way in society. So that's the balancing factor we're doing.

Richard?

Richard Vosser from JPMorgan. Maybe you could talk about the -- in the U.K., of course, the night has a stay time of 2 years, and then you stopped treatment post-select maybe you could talk about the conversations you're having to try and lift that time limit in the U.K. and other markets, in EMEA.

A good point because, of course, there are cost [ effectiveness ] pool was before select. So of course, we're having those discussions. But in the U.K., we also, of course, have to get started first. It takes some time from the NICE approval to trickle down to the local care setting. So that's what we are focusing on now and creating that real world experience because, of course, we want to show this day time, show that the hard outcomes in the real world and then hopefully, we can also address the 2-year limitation down the road. But it's really a matter of getting started also in the U.K. on the ground in these specialist centers.

And it is a time-bound contract with the NHS, right, which goes both ways in reality. So they learn how the product works in that setting. It generates real world evidence. And then, of course, we understand how this channel works in the U.K. market.

Yes. [indiscernible].

[indiscernible]. One question. How do we handle off-label use of Ozempic in obesity in the markets where you are not launching Wegovy?

We have, of course, people in the field and who very, very clearly described and educate on the correct indication. And we have no -- I mean that it's a big issue. We have also had a lot of general managers who've been very vocal in the media on addressing this, and we worked with authorities in every way to educate if we see, let's say, private clinics providers, et cetera, that are not living up. It could also be in obesity, by the way, to the indication. Then, of course, we also notify authorities. So we are quite proactive there. It's important for us to know the exact share of sales that are -- where this is happening. But our impression is it's quite limited. And of course, -- the best solution long term is to launch Wegovy and have that option as well to where we should have the real discussion around serious chronic care of [indiscernible] obesity.

The complication, of course, being that we can control the market until distribution, and we can control all our communications around the product and education around the product for appropriate on-label use. And then from there, it's really a medical assessment about a specific patient and whether any given product is appropriate for that specific patient. And then if we see data that is indicating miss use, then of course, we report that. But it is ultimately a medical evaluation.

Yes. Claus.

Claus Johansen at Global Health Invest. Just maybe you could help us to understand when you engage in a dialogue with the European authorities in each country, we have to select data, but what is the second most or the third most important [indiscernible] how to save costs for the same? We have the 20% reduction, but what is the second and third most important?

First point, so what's our best health economic argument, I mean, when you talk to the different countries. And then Andre, perhaps you can cover in your [ market efforts ].

I think it's a very strong argument that the decrease the risk of diabetes where we have a very well sort of understood cost setting for people who develop diabetes on top of the cardiovascular events. So reversing the risk factors and prediabetes is one of our key arguments. We also very much, of course, want to get into a discussion on productivity. It's not always that authorities are receptive to that discussion as we would like because it can also be a bit siloed between, let's say, ministries, but that, of course, is one we would very much like to drive with the real world evidence, what is the attachment to the labor market because we think they are very, very strong arguments. But that takes time, and it will also take real world evidence to really take that discussion home. And then I would say the other part, as I said is, it's very much budget impact, of course, understanding that, making sure that on both sides of the table, we are comfortable with the volume uptake, so we can honor it. And of course, payers can afford it.

Andre.

Maybe anecdotal -- one anecdote from Italy. Recently, Italian government is focusing on obesity and we don't have Wegovy on the market, but they want to discuss obesity, and they want to discuss this because they recognize that it's [indiscernible] from a health perspective, but in a labor perspective as well. And they call us to the table, and we are now and entertaining discussion about future reimbursement for the cohort of patients which needs to support mostly. But that's a good moment because we have to establish those small groups of patients where they get support from the government. Then of course, real world evidence will kick-in, and then we can enlarge groups in the future.

And I would say that based on [ SELECT ], we have updated our health economic modeling and looked at on above what was in the step trials. How does SELECT impact and some of the bigger impact is really on the benefits in terms of progression to diabetes in terms of health economic modeling, heart failure and hospitalization. So they really drive improvement in when you look at our own internal health economic modeling. And of course, that is what we are using when we talk to the different countries about how do they get the biggest bang for the buck, so to say, and how do they control kind of the budgetary impacts in terms of the appropriate patient segments for with [ save reimburse ].

Thomas Bowers from Danske. Well, actually, just to follow up on the health economics. So -- so will you potentially be looking into actually sharing some of the financial risks with governments, and to secure coverage in the longer term?

Yes. So first of all, we are open to many models in this respect, but it takes 2 to [indiscernible] say in that context and find a meaningful model. So right now, I know -- I mean and -- and you've had some real-world experiences in terms of how it works on the other side also. So what works in practice? .

But that is exactly we have looked at, we've also done it in the past with center some sort of volume relatively simple, but volume is [indiscernible] agreements. And of course, it's the size of the volume. It's the thresholds before you, potential discount. And of course, it's a comparator, you discount to, that we are debating, but it requires that we can be comfortable with that, of course, and we can see the state time go up as part of the model, so there should be a good care setting, as we discussed. And it, of course, also requires that authorities could give us some comfort on how many patients would go into that setting that we are discussing. So it's sort of a mutual risk balancing, but it will be one of the tools going forward, no doubt in these discussions.

If you allow me to answer this slightly differently because amylin is responsible for Europe. I've been traveling the world and most -- in most of the markets it's out of pocket, which is driving the growth for Novo Nordisk. And for SUSTAIN, it's only out of the pocket, which I was dealing with in Latin America and now in [indiscernible] . This is the first time in the, let's say, in my career when I see that patients in Europe, they are willing to pay out of the pocket. And I think that's very important factor we should not forget that the growth of the obesity business will be immense, and there will be more and more patients who are willing to address this disease. If there will be no reimbursement, they will be paying this from the pocket. The way we work with the government, is I think it's our responsibility to find the right patient groups, who really deserve this treatment and cannot afford, and then they should get support. But I think we should not really focus only on reimbursement because I see your questions with reimbursement, how do you play with the select? I mean we will do it. But please remember that humongous army of patients who are really waiting for the opportunity to have product and together with physicians address their disease.

That was a really nice way to end. Thank you Andrzej, thank you, Emil. And this concludes the EMEA breakout session. So now I think we all just have to break. So thank you for listening in.

Thank you. [Break]

All right. Good afternoon, and welcome back. Hopefully, everybody still has enough energy for us. And even though Mike insulted me earlier, I've decided to join the stage with him. Thank you, Mike. I appreciate that.

Make less [indiscernible] you don't stutter.

We are very good friends, but we're also very competitive. So we're going to close this up. Now probably a lot of what you've heard today from us, you're going to hear a little bit again, and I know that we're all excited to get to Karsten in the financials. So we'll be brief. But Mike and I are excited to -- we've seen this, get to close up this section, North America operations. So, what we've talked about today is really strong performance over a period of time. And I've mentioned a few times going back to my first capital markets in 2017 and participating in '19 and then into '22, I think one of the things that I'm proud of amongst many, many things is the fact that we've accomplished what we've set out to do and what we've told you. So I think Lars in that original Capital Markets Day, he talked about improving commercial execution, making sure we're best-in-class in launches. So that's what we set out to do. And over this period, I think we've demonstrated that over many, many different products. What we're also very, very proud of is the fact that we now have over 10 million patients that we're serving in North America. So we count patients. And in our world from a -- when you look at it, I think Henry gave a number earlier, it took us about 40 years to get to 5 million patients and it took us about 1.5 years to double that. So really a step change, and we're very proud of that. Now it has not been easy, and I think you'll hear some of this from Mike. We share in some of these challenges and opportunities. So we have had and we'll continue to have Health Care reforms. That is not anything new. We just in a conversation, a minute ago about every president that I can remember has always run on some sort of reform, and I'm sure it will happen again in just a few months from now. It's happening now. But we've been through that, and it's part of doing business in the U.S. What we also know is we're going to have to continue to manage supply, and we've been doing that now for several years. And I think as you just heard in some of the breakouts, especially in IO, and we're getting very, very good at that. Not easy, but we're getting good at that. And I think around the world and certainly in the U.S. since we're a country that usually launches first, there will always be intensifying competition. Like us, they put a lot of marketing muscle and sales muscle into launch brands in the U.S., but we're used to that as well. But more importantly is our opportunities. As I said earlier, we really do believe that with this health crisis in obesity, we have an incredible product. It's really a gift from R&D to us to be able to commercialize it and to be able to change the lives of really, hopefully, millions and many more millions of patients. And as we heard from some of the patient testimonials, it really is changing lives, which is incredibly important and meaningful to us. We do believe there's still an opportunity in diabetes, and you heard that. We have strong momentum in the U.S. with Ozempic in particular and with Rybelsus. Last year, we reported 42% growth year-over-year so we also like Mike, very proud of that product and what we're doing and what we're delivering. And, in the end, we're also excited about and sort of an internal tagline that I'll say at many, many company meetings is that there has never ever been a better time to be at Novo Nordisk. Because when we think about where we've been over 100 years and the opportunities that we have moving forward, we're moving into new disease states. We're in the right disease states now, and we have the right brands. So it's incredibly exciting. So just lastly, if you go back to all way to 2003, we faced Health Care reform in the past. This is not new, all the way through to the RRA, which is now. We've managed that. We'll continue to manage that. It's a part of doing business in the U.S. And as I've mentioned in several occasions now, we're proud of the transformation that's happened in North America. That was the commitment early on back in 2017, we would stabilize the business and then we will return to growth. What we're also seeing is not only in the return to growth with some of these launch brands, we are building for the future. So maybe, Mike, I would say and before I turn it over to the best is yet to come.

Is that because I'm on right now?

Maybe.

I shared the excitement, of course, with that I've seen many of you in previous Capital Markets Day. And if you go back to actually the beginning part of the slide, there was a period where International operations was very proud to have a sustainable business at 4% to 6% growth rate, and we had it actually in our corporate aspirations for a number of years. Then our new boss kind of force us to strive for a bit more and then get to double-digit growth. And then we did, I would say. And the graph again shows this. And then the last period, despite, I think, supply challenges, that we've had, despite shortages, despite that launching, which is the blood line of our organization has gone to a lesser number per year. We have been able to increase the growth rates even though the numbers are larger. And I think we are very, very proud of that in IO. We're also very proud that the bars are becoming more colorful than a single color one. It's almost like a table that has multiple legs, and that, of course, provides the sustainability that we need in the international organization setting. And I say that because when you're dealing with a lot of different countries, it is not unusual that you wake up in a given day. and then there's a challenge somewhere. I often talk about opportunities, but I do want to touch upon some of these challenges here, some of which are exactly the same as Doug mentioned, in North America, making sure that we manage the supply situation, making sure that we manage our competitors. And our competitors are actually some of the ones you know, the famous ones internationally, but we have a lot of competitors, a lot more actually locally that we operate with when it comes to IO. But that last piece, macroeconomics and political instability, I also like to a little bit touch upon. As we enter this year with 2 wars around the world, I have a lot of colleagues in my organization that are basically operating under very difficult circumstances, trying to get the innovations that you saw from Marcus and Martin slides, into the hands of the patients, although their life is very different than the ones we live under. Any given point of year, there are earthquakes. There are other issues that we need to manage. And it goes unnoticed, it doesn't hit the news and the numbers continue to develop and grow. And I'm very proud that, of course, we can do that under the radar, but I thought it would be important that, of course, you recognize that as beautiful, the numbers are, it's not walking a park. What gives us motivation, of course, are the opportunities that are mentioned here. We are building the obesity market around the world. And no matter where we speak to this, there's a huge excitement that we're part of a new revolution. We are finally able to tell the world what we have known for a long time ourselves that obesity is not just a lifestyle issue, that there is much, much more to it. And there are, of course, ways to help and treat so many people in need that have tried on their own for so many years and have not succeeded. GLP-1 growth, I showed it's incredibly exciting everywhere. And of course, I hope that many of you guys had the chance to join the China breakout session, as a single country you cannot -- yet not excited about China. U.S. is exciting, but China is also.

It was a very good session. I was in it.

And then of course, when we put this in really the context of IO in a single slide, then you come with the so-called market fit approach that we have been telling you about for some time now. Regardless of what geography you're looking at, and again, we had a good session on EMEA and in China, but even the rest of the world, the Asia Pacific and the Latin Americas of the world, follows some of this overall strategy. Now if you look at the near term, then you see 3 logos predominantly, Ozempic, Rybelsus and Wegovy. Near term for us is 1 or 2 years. As you move into the midterm, then you see a lot more Wegovy logos there because we're delayed with the Wegovy. So we have to basically get as many markets on Wegovy within this period. And obviously, then in the longer run is everything that you heard about today and some of the specificity of the various different regions, call at play here because while IcoSema could be incredibly exciting, let's say, in China, it might be less so in another market. But we have other, of course, engines to use as we go from one geography to the other. None of this will matter unless we turn that into some financials. And who better to explain that, the Chief Financial Officer.

Thank you, Mike. Thank you, Doug. While an amazing performance, we're talking about historic sales growth in Novo Nordisk, these days, and this is really a pleasure to be able to present the financials on the back of that. So first of all, when we look at what has happened for the -- during the past 2 years since we had the last Capital Markets Day -- just try and click again here. So we had the last Capital Markets Day 2 years ago. And when we look at the acceleration in top line growth, remember, last year, we delivered 36% top line growth. So almost during 2 years, we have doubled the top line of the company. 2 years. We have quite tripled the CapEx spend over 2 years. And by the way, we're going to double it from this year to next year or from '23 into '24. And the R&D investments that you've heard from Marcus and Martin, the step-up, we're doing there, is even faster than the acceleration in our top line. And that's on the P&L. Layer on top of that, the execution you heard from Dave in our business development efforts and acquiring external innovation into our pipeline. So really a period of unprecedented historic acceleration for Novo Nordisk. And then you say, what does that matter? It's only Novo Nordisk. And these are only the absolute numbers. So we also need to look at it in a relative perspective for a similar period of time. So when we compare to the industry, then the pace of our average sales growth during that period of time is more than double up compared to that of the industry. Our margin significantly higher than that of the industry, our operating profit margin. And do remember, we are reporting clean numbers. So there are no adjustments in our financials, as you recall. So we are not adjusting EBITDA and the core earnings and all that, this is what you see is what you get. And talking about what you get, cash return to shareholders. And so one thing is to deliver operating profit growth, but of course, it doesn't really matter unless you're able to convert that into cash flow, free cash flow and return that to shareholders. And that's what you see in the third bar. So really, the cash return to shareholders also significantly higher than that of the industry. And then the last data point, and this is just a 2023 data point. Return on invested capital, 89% 8, 9. So that is when we do our benchmarking compared to that of the industry, number one, clear, number one. So also very, very efficient capital utilization and return on invested capital. So that's history. So what are we going to do moving forward? This is really about how we allocate the resources we deploy in the company. And the starting point there is simple. We started with the corporate strategy. You heard that from Lars . And then we are super disciplined in investing in -- behind the corporate strategy, in what drives profitable growth in the future. And we're investing on multiple time horizons. And that's what you see on the right-hand side, this is really about driving the in-line assets, the on-market assets today, driving growth, diabetes GLP-1. That's the first growth wave. The second growth wave really comes from obesity and then hopefully also from my mate at a slightly later point in time, obesity is really taking off now. So investing in obesity, and then the third wave is what you heard about from my R&D colleagues and from Camilla on cardiovascular and emerging therapy areas, as well as our early pipeline. So really investing in that. So we get into the third growth horizon. So really investing into growth on multiple time horizons. So boiling that down to kind of the super, super simple version is, invest in obesity care market developments, invest in expanding supply chain and invest in pipeline. I think my job is simple sometimes, but on a daily basis, it gets slightly more complicated. So -- but double-clicking on our resource allocation. So how do we allocate our commercial resources into the company? I think Doug and Mike and Camilla really explained and Ludo, around how we drive the assets we have in the market. And our starting point is we have huge unmet needs, big commercial opportunities and highly competitive assets. And that's what we're investing against in our commercial investments. So we are stepping up our commercial investments mainly based on investing in obesity and the obesity opportunity that is by far the biggest investment driver in terms of our resource allocation internally. On top of that, of course, we are gradually moving into cardiovascular disease. It's mainly in our research and development pipeline right now. But of course, we are prepared in terms of our commercial footprint, as Camilla was explaining. So it's a gradual targeted approach, which, of course, is being accelerated based on R&D pipeline readouts. And then on mesh, same principles being driven by pipeline readouts and of course, a targeted approach, utilizing our existing footprint and then going focused on some of the specialty segments like hepatologists. And then lastly, on Alzheimer's, as Martin alluded to, no news today. So that's why we call it a targeted approach. Now we're really awaiting the results from the evoke trial come next year. So when you put all that together, then yes, we're going to invest more in commercial investments because we had the opportunities, in terms of driving growth, short and medium term. But at the same time, we do have the commercial infrastructure in place. So we don't need more GMs in the different markets. We are already present in 80 markets today with our own employees. We have the CRM systems in place et cetera, et cetera. So we have a lot of our commercial infrastructure in place. And based on that, then, of course, we are able to increase our commercial investments at a lower pace than we increase our top line. So we get gearing or leverage on that front and hence, and what we call an S&D ratio coming down in the coming years for that reason. Then on the contrary, in R&D, you heard about the opportunities we have in R&D, really about the unmet need in society within the therapeutic categories where we are operating. And as a consequence, we see those opportunities really justifying significant investments into pipeline because if we are able to solve these unmet needs then the commercial opportunity is very significant. And hence, the return in terms of R&D investments very, very significant. So you should expect us to continue to increase our R&D investments or and above our top line growth and hence, driving a significant step-up in R&D investments. Again, it's device through the corporate strategy, the priorities you saw earlier today. So really increasing investments in Tier 1, diabetes and obesity pipeline opportunities. Tier 2 cardiovascular and rep leading disorders. When it comes to mass rare endocrine and chronic kidney disease, we believe at this point, we are rightsized its selective targeted investments we're doing. But with our current investments, we believe that will not be the big moving piece in the coming years in terms of investment levels. And then for Alzheimer's, I put in here that is decreasing and it is decreasing for the simple reason that with Evoke reading out next year, then, of course, then R&D spending is going down for that simple reason. We don't have a big portfolio of Alzheimer's projects for good reasons. But of course, with that magnitude of step-up in terms of R&D investments, then we need to do that in a recent way. We need to ensure that we are comfortable that this will generate an attractive return on investment for our shareholders. Whereas on commercial investments, it's simpler because it's more like a profit sentiment itself, when you allocate on commercial investments. So in R&D investments, I've taken 3 pillars, and it links very nicely to what you've seen before. So on research and early development, Marcus showed it, this is really about expanding our early pipeline for the third growth horizon I explained before. So expanding the early pipeline, you saw Marcus presenting an ambition about tripling the amount of first tumor doses. And of course, this is not only a numbers game about quantity, It's really, really about quality. But it's just to say that we are very focused on expanding our early pipeline. You've seen it doubling almost over the last years as Marcus presented and with the ambition of tripling for tumor doses. So we do that. We allocate according to the priorities. And then, of course, we continue to focus on productivity, whether it's through AI or other means, as well as speed from a start-up research until first tumor dose. In development, given the more mature nature of the projects, then what we are looking at there, we have, I would say, a fairly straightforward governance approach, where we have a stage-gate approach. So when a project enters Phase II, then, of course, there's an evaluation about the opportunity behind a certain project. And with that also comes financial assessments. And the same when we go into Phase III or Phase IIIb, then the financial assessment coming together with the Stage-Gate passage. And as a consequence, we have the financial assessment around the viability of our late-stage projects. And then at the same time, as in research and development, then we have productivity metrics and speed metrics in development with Martin and the team that we monitor and benchmark on an industry level. And then for business development, that Dave covered and the step up there. We have a good governance model where it comes to approval. So we have a certain evaluate. And then when we see something that we might like then it gets into a governance setting, where we assess this is something we want to pursue. And the assessment is basically linked to strategic fit. So does it fit into our therapeutic strategies that you just saw earlier today, Scientific attractiveness? Do we believe that this is a competitive technology that we're pursuing. And then thirdly, do we believe that the price required close deal, do we believe that, that also generates value for more shareholders. So that's how we're governing our investment on our step-up in terms of R&D investments. So that, of course, yields a profit for the company and that we're very focused on converting into free cash flow and the free cash flow and in terms of our capital allocation of our cash flow generated, there we have a chaired approach, also our priority approaches. Our preference is to invest in the company. And of course, we only invest in the company, if we believe that the investments we do generate an attractive return. Secondly, after we've done that, we are focused on returning capital to shareholders through a consistent dividend approach of around 50% of net profit per year. Thirdly, feed the investments into pipeline linked to what I explained before. And as the last point, we have a flexible share buyback approach. So our share buybacks, you should see as the residue of when we've done the first 3 and then what is required in terms of financial reserve requirements on our balance sheet. So that may vary between years. And then you see the development over time on the right-hand side of the slide. So then a small bragging slide in terms of capital return to shareholders. So this covers the last 2 decades of capital return to shareholders. So over the last roughly 20 years, we returned DKK 500 billion to shareholders. So I think a lot of people, they would have liked to own Novo's shares at that point in time and then sit on them. So just to say a very consistent approach around 50% dividend payout to net profit and then the residual approach on our share buyback program. And then the '23 Novo, with the dividend is what is proposed for the upcoming AGM, which totals DKK 940 dividend per share, which is a 52% increase, compared to the preceding year. So a significant step-up in dividend per year compared to 2022. So that's the capital allocation to shareholders. And then net-net, what does that drive in terms of margins in the company, when you put all this together? First of all, gross margin. So in the coming years, with '23 as a baseline in the coming years, gross margin, we expect will be flat, excluding Catalent, which -- and I'll come back to that, so a flat gross margin over the coming years from '23 based around 84%. The puts and takes behind why it's flat is we have favorable product mix. We have some negative price. And then we have impact from the elevated level of CapEx that we're running right now. So some of our CapEx projects for most of our CapEx projects, not all of the spending goes to the balance sheet, some of it filters down into P&L. So putting all that together, neutral -- broadly neutral gross margin over the coming years. Then in the light blue arrow, what you see is that assuming that the Catalent transaction closes later this year, then in the coming years, gross margin will go down. And the reason why it goes down is basically linked to amortizations and depreciations linked to Catalent. So both on intangible and central assets, there will be a significant step up, compared to before. And noncash, and that is what is driving gross margin down. S&D cost ratio, I explained going down, R&D going up. Admin continuing to go down simply due to the top line growth combined with a platform already in place. Putting all that together yields an operating profit margin which is increasing, but not as much, as if we had not done the Catalent transaction, which, of course, we've done for very, very good reasons in terms of scaling our supply base for the medium and long term. So that covers the market development. So in closing, accelerated sales growth, we are delivering top quartile sales growth in the industry. We have an operating profit margin above average in the industry. We have a growth and return focused resource allocation of the company linked to our corporate strategy. And then we continue to have a consistent financial discipline, where we invest in the business while maintaining an attractive capital allocation to our shareholders. So with that, I'd like to invite Lars back on stage.

And I would like to invite, I think, Doug and Mike also to the Q&A on financials.

Florence Cespedes from Societe Generale. A question on margin going forward, do you believe that if at some point, you cross the 50% threshold even with Catalent. What's the risk to see at some point? You talk a lot about access, drive market access. It's important for the patients. But in the meantime, when you will talk with payers, it will talk about budget as well. So if obesity has become really meaningful, very significant market at some point, what about the conversation you could have with payers given the strong improvement of your operating profit margin going forward?

And maybe I'll actually answer that. So we are not having increased margin as a strategic objective, to be honest. We see dynamics right now where there's a very strong growth in our top line. And we are scaling as Karsten alluded to, but it's not an objective of ours to drive margin. It's a dynamic period right now where obesity is being acknowledged as a disease. We're generating the data, we hope we'll create that point at a price point where payers are actually willing to pay for it. But it's also clear that we are scaling our volumes to get to many more patients. And typically, as you grow your business, you get to lower price points, and that could well be at a lower margin over time, but fueled by a bigger volume. So to succeed in serving many more patients, we'll also anticipate lower price points over time. But it's not meaningful to say how low on price now until the disease has been acknowledged. And in some of the conversations I've had with policy makers when they start talking about price and say, okay, let's just align on the disease first and the value of treating patients because unless you see that as a meaningful activity, there's no price point that makes sense. So right now, we have to establish that body of evidence to have the right discussion of what is the future price point. I think that will unlock volumes significantly, and that's what we're preparing for. So a strong business also at a lower price point in the future. And I think that will drive with the societal model that we want to operate within.

Emily Field from Barclays. Doug, you talked about having navigated through multiple iterations of healthcare reform in the United States in the past. Generally, there's an expectation that semaglutide could be added to the Medicare drug price negotiation list for '27. It's obviously a very different product to some of the drugs being added in '26. Can you give us any initial thoughts on potential pricing impact there? Or how you're thinking about that in the context of navigating through the ROA?

Yes...

So it's difficult to predict about the future, but we are getting some experience right now in negotiating with the government.

We are, and I would never predict the future there. That's for sure because it is the government. But what I would say is this, we're getting through negotiations right now with Aspart. We still have a couple of rounds ago, so I really can't comment any further there. But what I would say and what we've generally said is that one of the concerns we've had with the [ ROA ] specifically is that it could limit innovation and choice for seniors downstream, and we think that is challenging. So I don't want to try to predict what products and when and what that impact may be. So I characterize [ that's at. ]

Maybe add to that, of course, compared to the Aspart negotiation, we have now, where there's limited volume opportunity, even at the lower price point in the U.S., there's still a significant volume opportunity. So again, establishing the medical benefits of using semaglutide will lead to say, broader use of the product. And I think that can somehow compensate for also government negotiation.

Yes. Simon.

You'll get a chance [ both of you ] .

Go ahead. Sorry.

Simon Baker from Redburn Atlantic. Doug, you mentioned your first payments back in 2017. I'm just looking at my notes. And 3 of the things you highlighted is principal to success in the U.S. market was to integrate, localized and focus. I just wonder if you could update us on the localized bit. You said back then the market was very heterogeneous and you gave some examples of, I think, actually Boston and [ burning ] and this is very, very different places where it needed a different approach. How has that changed over time? Is the U.S. sort of coaletting into a more homogenous system? Or is it as well as it used to be back in 2017?

It's a good one.

That's a good note. I would say. I think I read those slides and reviewed them with Dave before we got up here. But when we reorganized, we did change part of the commercial structure because we did -- the U.S. has made up of many, many, many different pieces. And still today, I don't know if it's getting any more homogenous. So for us, a little bit like Mike, when we think about markets fit in the U.S., we are -- healthcare is local in the U.S., and we're trying to meet it where it is, whether it's the health system, the employer, the local payer. And our teams, we do get vertically integrated to make sure that we are bringing our best in terms of the dialogue and the communication that we're having in terms of the value of our brand. So I think we're still in that same model to a large degree, and I think it's still been successful.

Steve Atkins from Polen Capital. I had a follow-up for Karsten. On the gross margin, I understand the increased amortization expenses from the Catalent deal, but you should be able to pull forward more revenues than expected, right? Because of the completion of the deal that should be an offset. Are you assuming that? Or is it just because price will be a negative factor that gross margin still may decline?

Yes. So clearly, the reason why we do Catalent is to access more capacity faster. But the margin guidance is for the coming years. So it doesn't fully offset the step-up in amortization. So if you look a little bit further out, then you're absolutely correct.

Yes.

Matthias Häggblom, Handelsbanken. So growing at the pace you are as a corporation, you need to hire a lot more people compared to the pace you've done historically. So during 2023. I think the net number increased by some 17%. I guess the gross number of people prodding was even higher. So how does [ you ] as an organization manage? And does it provide new risks given the current pace of hiring?

Yes. That's a great question. And we'll have Tania Sabroe, who is leading peer organization on the stage later on. So maybe if we could park that question for her because I think she's the best educated person for answering that. So I will keep note of your question. Pete?

Peter Verdult, Citi. Doug, I'm not going to let you get away with sort of the Medicare sort of brush off.

Of course. Why would you do that.

It is [ election year ], I understand there's probably bigger fish to fry, but -- in light of the select data, in light of your competitors being a bit more vocal about, it's not a matter of if but when. Is there anything you're hearing in terms of potential Medicare opening up or the appetite for that bill to hit the floor? Or is it really -- what is your intel telling?

Thanks for the question because it is a very important issue for us to unlock access for seniors in our country for any obesity medications in total. And I think that, I guess, how I would characterize it is my own team, my own public affairs team still has -- it characterizes as if and not, or when and not if. And I think that for us, we still have more signatures, we got to get an appropriate CBO scoring. And I think that as I continue to say that the body of evidence that we're building and select importantly, puts us in a better position for sure.

Of course, short term, we have plenty of patients to target so we can be patient on that. Yes.

Seamus Fernandez at Guggenheim. Just a question on the CapEx side of things, commitment to CagriSegma, complex manufacturing pen, I think in our conversations, you've actually said, Carsten that, this market can only be supplied on the injectable side up to a certain point, but that the FlexPen and multi-dose pens are absolutely critical. Is that possible with CagriSema? Or is CagriSema more of a bridge to the rest of the pipeline?

Karsten, maybe also a perspective on how we see life segment with CagriSema.

Yes. So first of all, what we're looking at now and the scaling we're doing on Sema alone, we're getting a lot of experience, as Sema was covering between single-dose devices, FlexTouch and how to balance our portfolio in that respect. And yes, in Phase III, CagriSema is in the dual-chamber single-use device. And if we can get that into a FlexTouch device, that would, of course, increase scalability of CagriSema. It's not a [ slam dunk ]. But as Henrik showed earlier on, one of the aspects that we're looking at actively right now is a co-formulation of CagriSema, so it's not a dual-chamber device, but a single-chamber device. So we are working on product development and hence scaling of CagriSema. So you should not see CagriSema as kind of a stepping stone to something coming later. But at the same time, I hope what we've shown today is the portfolio we are playing vis-a-vis the pipeline we have in obesity where CagriSema is one play, but we have a number of other plays vis-a-vis efficacy and scalability.

Thank you, Kars. Martin, yes.

Martin Parkhøi, SEB. Just we haven't talked so much about Alzheimer's today. But given that you will see this Medicare price cut in '27, have you appetite for investing in Alzheimer's [ drug, ] which will be hit potentially by the same? And I guess there will be a lot of Medicare patients, in particular, for that patient population.

Yes. I think we can perhaps say that yes, we have because we started, and I think we start down that track before the IRA came about. But as I mentioned before, we are pursuing a volume strategy for semaglutides. And I think the number of indications we can expand into is actually part of also making better attractive business despite negotiating pricing with the government in the U.S. So we need to see the data, but I think that's part of what also makes it attractive despite healthcare reforms.

And as you know, Medicare party is some 25%, 30% of our U.S. business. So it's not like we'll let one channel dictate how we optimize the rest of our business.

Yes.

Just quickly -- Peter Welford, Jefferies. What's the backup plan, I guess if Catalent weren't to go through or if there were to be from the regulatory authorities, certain steps, I guess, why is that you're not anticipating? And just to be clear as well, is the CapEx framework you've [indiscernible]. Does that already include any additional CapEx that needed with Catalent, if you like? Or because I guess your financial outlook had pre-imposed? Just to be clear, is that irrespective really to be always on the magnitude with the Catalent going through?

So I can talk a bit to the strategy around Catalent and fallback and then Karsten, you could talk to the CapEx around that. So we can say all along, we had a plan to build capacity in house. You have seen that we are building significant API capacity. We had a facility coming in line in the U.S. recently. We have 2 undergoing constructions in Denmark. So really ramping up significant API and many of you will have an opportunity of visiting that site tomorrow. And then in parallel, we are building the [ fill finish ] to, say, utilize that API. And there's a plan looking at leveraging our existing sites. And then Catalent being a challenged company then provide an opportunity for us together with Novo Holdings acquiring 3 sites. So it's the [indiscernible] of what we've been able to do in-house. And that is created by leveraging, say, space they have put in filling suites that were already [ ordered. ] So it's accelerating that strategy. So that the plan is that we'll stick to the original plan and build that. And we have additional capacity coming in gradually over the coming years, and that will then just happen at a lower pace. So we feel that's, say, a robust plan and, of course, attractive by accelerating it. Maybe, Karsten, you can talk a bit to the CapEx profile.

Yes. Yes. So just reiterating. So the base plan is that the Catalent transaction closes. And we form that basis on numerous external legal opinions that we did as part of we and the other pieces in the transaction did as part of due diligence. So that is the base plan. And which is, hence, also what is reflected in the CapEx outlook that Henrik explained, and of course, if we diversify from that, then it will entail more CapEx internally and probably also more CMO agreement externally.

Thank you, Karsten. Since we are broadening out the questions, let's invite rest of management up for full panel, and I'll sit over here. And we'll start by addressing the people question. And while my colleagues come up, I'll just introduce Tania Sabroe. We haven't seen Tania on stage before, Tania has a long time over Novo Nordisk has spent many years with Mike in International operations and spent a year or so leading our people and organization team as Executive Vice President. So Tania, there was a question on all the new colleagues who we are calling.

And it is correct that, of course, we are scaling, and I would say, shaping the organization in line with our strategy. So that also means adding a lot of new people. And last year alone, we welcomed around 9,000 new employees. We grew around 17% in our employee base. And year-to-date, we are growing still around 15%. So that is a lot compared to what we have been used to. You saw we are used to single-digit sales growth, and we will also use the single-digit employee growth for quite a while. But in the last 2 to 3 years, we're talking more like 12%, 13%, 15%. And I think that's a great opportunity. The majority of those employees are in Henrik's shop, as you can probably gather around 70% is driven by the manufacturing roles, but also across the board in development, clinical, digital, we are also growing. So exciting, but also a challenge to absorb so many. So we have a keen eye on onboarding on our purpose, on culture and leadership to make sure that we welcome people and also retain them. So not only that they come in, but we can actually keep them for a good period of time.

Thank you, Tania. Pete?

Peter Verdult of Citi Group. Dave, just a question for you. Now that [ everyone in Douge ] is trying to get into obesity. Just the -- I'm not going to ask you to talk about targets but just the environment to do BD now in the metabolic area. I mean, you've done some interesting deals in the last couple of years, but it's intensifying. So just is it -- are you finding it more difficult to find good deals that they are attractive both from a clinical sense and commercial sense and valuation?

Yes. Thanks for that, Pete. It's a dynamic space right now, right? Every couple of weeks, we update our trackers and there's new programs that have been added to that. But our focus is to ensure that it aligns with where we think the obesity market is going and aligns with our internal strategy. And so we're very diligent about does this add to what we have internally. You've seen some of that today. It's a high bar. And the valuations are certainly increasing based on what they see this market. We think there's opportunity for us to still use external innovation to add to our obesity pipeline, and then we'll continue to do that.

Yes, in the back.

Rajesh Kumar from HSBC. You just touched on the point on M&A in answer to Peter's question. If, let's say, the market scenario for your current consensus numbers for your obesity drug plays out. There will be a lot more cash flow coming out of [ no ] notice. Then you can reinvest through R&E, right. One question. Do you have -- would you revisit the thresholds on IRRs you have set for reinvestment into M&A. Or did you compare [ average ] share buybacks? How do you compare with share buybacks in terms of that capital allocation piece i.e., do you stick to your 4 core therapeutic areas? Or do you actually step out because you think that would be in better interest of shareholders than buying back shares or some -- just any thoughts on that would be much appreciated.

Yes. So let me maybe start and then Karsten, you can maybe comment a bit on capital allocation. So we strongly believe in making a strategic choice based on capabilities. And in that lies is also an ambition to all time broaden capabilities. And you will see from [ Marcus' ] presentation that we have a stronghold in the classical Novo Nordisk peptide protein area, and we're gradually expanding that. We also believe there's value in a relative tight focus on disease areas. And we actually believe that we are broadening the options in that space. And it's not likely with a successful execution of that strategy that you'll see us be very aggressive on M&A because we believe the biggest return we can generate for our shareholders is actually doing the value creation inside Novo Nordisk complemented with external innovation like you have seen us do increasingly. And I'm actually pleased with the team's ability to pick assets that at least looks to turn into valuable additions to the pipeline. Obviously, this is a top space with a certain likelihood of success. But I think we can actually demonstrate that we're both capable of coming up with in-house innovation but also complementing that with external innovation that is meaningful and then we deploy our own capabilities to maximize the value. And then maybe, Karsten, you can always debate how smart it is to buy shares back with the price as they are today. So as the CFO, [ will argue ] for that.

No. So I'll say, coming back to my strategic capital allocation tiering that I presented in my slide, share buybacks are #4 and BD is Tier 3. And I'd say we have assessed a lot of BD opportunities over the last few years. And the vast majority of opportunities that dropped off, they dropped off due to strategic or scientific reasons and not due to IRR thresholds. Not said that we don't have the IRR discipline or the valuation discipline, but the vast majority drops off for other reasons. So yes, share buyback, that's the residual that's -- we don't want to have excess cash on our balance sheet then we buy back shares, but that we only do after we invested our business, we paid dividends, and we executed on attractive video opportunities within our strategic therapy areas.

Thank you. Richard?

Just coming back to -- Richard Vosser from JPMorgan. Just coming back to the new formulation of CagriSema. Given we know that the PH is different from the 2 products, I mean, could we just get a bit more detail on how you're going to work through that, given that was, I suppose, previously thought nearly impossible.

Yes. So I don't think we can go into a lot of details around that. I trust you understand that. But it's clear that we don't mention it on the slide on this. We see a way to actually test this out in a clinical trial. So you would assume we'll do that. And then we'll see how that plays out. Thank you. Mike?

Mike Novod from Nordea. Just another one question on oral [ semaglutides ] always last couple of years has been sort of 25, 50 milligrams pending appropriate commercial availability of supply. Where are we standing now on sort of the pending Part 25, 26, when is it appropriate to sort of fully launch 25,50 milligrams?

Yes. Should I give that a crack also because -- so the way we look at it, we are building, say, a really broad portfolio of optionality, and I think also a deep portfolio. So I think we can play to win in the injectable space based on what you have seen today, highest efficacy and also scalable products. And I think we can also play to win in the oral space, but you have to distinguish here a bit between the different technologies we have. If you take the [ stack-based ] innovation oral sema, oral [indiscernible], obviously, it has a lower bioavailability compared to when we go injectable. So it takes more [indiscernible] So we look at that as an opportunity for us to win, say, in, say, higher-priced markets where we can win on efficacy. I think we have the opportunity of demonstrating by far, the strongest efficacy compared to what we see being developed. But it's not a technology that lends itself for being a -- the dominating global rollout that will have to be injectable. That's also why we have acquired in the [ Sage, ] which is, in our view, real small molecule. So something that's really scalable also compared to what you see out there in terms of small molecules [ at ] one place. And we actually believe it will have an attractive efficacy point. Obviously, there's a safety event to be cleared. So when we look at that broad portfolio, we are looking at our options and also how the market will develop. And I also think we have what is required to win in the different segments. But we would like to make the trade-offs as we have the full data set also on the high-dose semaglutide data that we'll be reading out and then play with that portfolio to win in the different markets. Yes. Mark?

I just stalled. Martin...

Yes. We know you might.

Exactly. Just a question for the 2 guys in the middle and you can arm wrestle around the volumes that you get. But it seems like -- has been a big difference between the growth rates in the 2 markets because back in '19, you had to help Doug with muted guidance we can say. And now it's Doug who is in the driver seat. When are we giving -- when should we expect to get more balance between these 2 regions?

Might start selling more? Is that anymore? The good news Martin is that we're both in the same car and only one person takes the steering wheel. So we are going straight. On a serious note, I think what is happening right now -- what happened back in 2016 was a one-off event. And I think it was very nice that Novo Nordisk had the international capability and presence to be able to basically offset some of the loss of prices in the U.S. What is happening right now is not unusual. We launched our products always in U.S., also partially because of regulatory affairs. And then as that launch gets going, European launches starts and then eventually, we go to Japan and China and emerging market follows. We are following the same principle as we've done during my 35 years here. But of course, right now, we really need to make sure that when we are coming to international operations, we're doing it responsibly. I would not like to launch any product on a Monday only to run out of it on Friday. That is not any of my general managers want to do. So we better kind of have that balance, and I do think we have a wonderful balance right now in order to kind of wait a little bit longer and then launch properly in international operations. I think it's balanced.

So Mike always talks more than me. I'll just simply say it's really -- it's nice to work for an organization that puts the patients at the center and we take that into account with allocations as well. So that it's really nice to see.

Thank you. Mark?

It's Mark Purcell from Morgan Stanley. Maybe starting off with you, Martin, but in terms of the new technologies coming through in obesity, siRNA, you didn't talk about that side of your siRNA platform today. I guess, non-GLP1 orals, which lastly, you just spoke about with in [ Visage ] and those antibodies as well. Apart from [ Visage, ] you don't appear to be playing certainly yet in the clinic in these 3 settings. So do you see those as the 3 settings that could be most disruptive to your business? And how do you ensure that you participate in your own disruption in terms of gaining access to these technologies or being a partner of choice as the commercial space gets more competitive as more large-cap biopharmas enter to the obesity space?

So maybe, Mark, if you could talk a bit to different mechanisms. And then Dave, you can talk a bit to how you see us being a partner of choice.

So thanks for that question. Obviously, with the siRNA space, we're opening up that world. And as you know, siRNAs have been deployed traditionally more in the rare disease space, and this is why we also see advanced clinical programs with other companies. But now actually, this next wave is coming, particularly in cardiovascular and liver diseases, and you see MARC1 and LXR in our pipeline. But the next wave we actually expect [ internal ] compounds that make it from obesity and diabetes. Now those could be liver targeted, it could be also extra [ hepat ] targeting. So I actually feel very confident that we're in a good place here and not only have the technology but also the combination with the biology understanding from that technology to be real leaders in that space. So I think what this space, what is yet to come. So I feel reasonably good. And the value proposition here is obviously, again, position the ability to go intracellularly but also to have reasonably infrequent dosing. And I think that is something very important for us to pursue.

Thank you, Marcus. Dave?

Yes. And then I think it just comes down to the way we approach partnering here at Novo Nordisk. And when an external team has an opportunity to meet the folks in Marcus and Martin's group, they see what it was like to work with us. And we're very open in terms of the way we partner, whether it be a collaboration, it could be a license, it could be an acquisition, if that makes sense, but they really see the value of our 25 years of research in obesity. They really see the value in how we run clinical trials and keep patients on for 4 years. There's no question about our ability to supply and bring it to market. And so I think we'll keep getting those calls, and we're going to continue to listen.

Thank you, Yes, at the back?

Eric Le Berrigaud, Stifel. It looks like the market is very happy with you not updating your midterm target. But is one maybe where you could say a few more words. It's the -- over [ 25 billion ] obesity in '25 since in this case, it has been exceeded already, so probably there's been debate internally about to do or not to do push and pulls. Maybe you can tell us what were the pool and push and why we decided not to do? And then since you're doing a very detailed consensus internally, you can see that consensus is already well above the 25%? And so maybe you can say if you're comfortable, very comfortable -- very, very comfortable with the '25 obesity numbers in consensus.

Yes. So maybe, Camilla, if you can talk a bit to how we look at the opportunities without revealing in numbers. And Karsten, you can talk a bit to how we look at providing guidance?

Yes. So if I start on the potential we saw today that there is a huge number of people that are living with obesity. If you look at our pipeline, even what we have on the market right now, we have an opportunity to make a major difference. So that's what we are planning for. And so therefore, to set a specific target towards 2025 when this target expires is maybe a very, very short term, giving the long-term opportunity that this really is -- and we have been -- we just focused on making sure that we continue to roll out what we have in our pipeline and that we continue to build our pipeline, exactly as we discussed earlier in the [indiscernible] session. That's really our focus and getting the exact number exactly right, is less of our focus. We're really driving towards the purpose in terms of defeating obesity. And that's also why we are not just focusing on treatment but also established this prevention unit to use some of our abilities. You heard maybe about AI today also and how we can understand more and more about this disease. So we can truly expand our presence in the field and make sure many more patients are treated. That's our focus rather than a single number.

Karsten, you are head of guidance.

Yes. So a head of guidance, that's a new title. So -- so Eric, of course, we assessed as part of preparing for the Capital Markets Day in terms of our strategic aspirations. And that's also why in Lars in his opening he covered that we are not updating our strategic aspirations. And the base reason is simply that they run until '25. So we believe that's a meaningful time horizon to close them out before we set new ones. So if we updated the obesity target now, then implicitly, it would be guidance for '25 sales, which I know a lot of people would love to have an opinion about whether it's too small or too big. But that's why we refrain from putting in a new number. I trust you sense that we're pushing with everything we have, especially supplies to maximize the opportunity in obesity. And then to your second part of the question, vis-a-vis consensus for '25 and obesity. Then as you know, we provide guidance on an annual basis. And when you look at our growth drivers, it's fairly straightforward. If you think about Ozempic, Wegovy and Rybelsus really explaining the majority of our sales growth as a company, and we've delivered guidance for '24. So I think per definition, then it's only a '25 number in consensus, which I think is more on sales side, so I have an opinion about and that to me at least publicly.

Thank you, Karsten, and thank you to my colleagues. With that, we'll close the panel Q&A, and I'll leave the floor to you, Karsten.

Great. All right. So now we're getting really close to the end of this Capital Markets Day and having been on numerous road shows, I know the toll of taking time to travel and the time commitment to just like to thank all of you for this commitment, and it's really a pleasure to see all of you. So before Lars closes off, then just a few practical remarks. So In a few minutes, then we will have some [ tables ] and a glass of wine or whatever outside. So a good opportunity to mingle with management and ask all the questions that you didn't have the time to ask during the session. So we have a good time after this session. And then for your travels back, then there will be a hard copy of the presentations in a small binder. Of course, it's uploaded to the website for the digital people in the audience, but some people, they still like the small booklet so you can get that. And then for those of you who have a deep, deep interest in Novo Nordisk and also a deep, deep suit case or whatever you take, then we have acquired a number of this book, which is the history book around Novo Nordisk. So it was authored around a year or 2 ago in connection with our 100-year anniversary by a professor at [indiscernible] Business School. So it's an outsider writing the history with a lot of research. So full access to the company's archives and also access to some of the prior and current executives. So it's a really, really nice read that I highly recommend. It's a long read also. But -- so enjoy yourself with the book if you have the space and then I give it back to Lars for closing remarks.

Thank you, Karsten. So we have spent a day in the kitchen of Novo Nordisk, so to say. We started out the day by talking about our strategic choice strategies about making choice. So we made some very deliberate choice about which therapy areas we focus on, we double down on. We then also spent a day on discussing how we play to win in these areas. And I hope it comes across that we are very excited about the opportunities we have and also how we are executing on our strategy. Let's now focus on capacity. And Henrik gave us some of the details behind that. When you look at it, we are the volume leader in the world in terms of high-volume manufacturing of high complex products, biologic medicines in sophisticated devices. So that's a competitive advantage. And we've taken steps to invest significantly in further expanding that. And of course, you could see that as a sign of our confidence in the pipeline we have in diabetes, in obesity short-term based on semaglutide, but obviously also CagriSema [ increasing ] that we can really get through very attractive efficacy levels at known safety parameters. And as you heard, we believe that known and acceptable safety profile also applies for amycretin. So we're very comfortable about the biologies we play with there. And in this, say, scalable manufacturing setup, we can run through these molecules in a very, very attractive way. We're also making a play on, say, the oral route, both with a real small molecule and then with a somewhat more complex snack-based formulation, major breakthrough of biologics that we believe can give us the best, say, efficacy and safe profile in the space. This is a very, very attractive proposition. In addition, we are expanding our research and health development capabilities, as Marcus alluded to. And we're building a broader pipeline both in the rare disease and cardiovascular disease and some of the emerging therapy areas. So when you look at the growth opportunity for Nordisk going forward. We're very confident that we can sustain the growth in the incretin space, we can drive the volumes to serve many more patients and we can add innovation on top of that. and that we can expand in these adjacent disease areas where, again, we can leverage our core competencies across the whole value chain, research, development, manufacturing and into the markets. So it's an unprecedented growth level we are delivering as a company, and we take that as a position of strength to invest in our business to really sustain a very attractive growth projection also for the future. And that is really living our purpose, driving change to defeat serious growing diseases. And I think that is what it also takes to be a respected company and one that is actually seen as a partner for society in all coming some of the most difficult chronic diseases that the world is facing. That is indeed very motivating. So thank you for your time today. We enjoy these opportunities of presenting to you, but also get your questions because that also helped sharpening our senses, so that's much appreciated. So thanks for now, and see you outside for some more mingling. Thank you very much.