Welcome. Welcome to the Novo Nordisk R&D event in conjunction with ADA in Chicago here in June 2025. It's a pleasure to see a lot of people here in the room, and we also have a pleasure to have this webcasted. Just when we get to the Q&A, this is being recorded and webcasted. We have a great lineup for today. Before we go to that, talking about R&D is really talking about the future. As we all know, the future may play out differently than what is being predicted by different forecasting models in R&D. Do note this as a forward-looking warning and statement. The agenda for today is, as you see here, a brief introduction from my side. Then we have a section on diabetes. This is the American Diabetes Association's conference, right? We start out with diabetes, and then we have a big section on our pipeline in obesity and the unmet needs in that space. Just clicking now the clicker, right? Okay, great. On the introduction, it's just a delayed clicker. Can I have the next slide, please? Right. When we start out with our strategic aspirations that I'm sure you've all seen before, our focus is truly about raising the innovation behind diabetes. We all know about the significant unmet need in diabetes, as we'll see later on also. That's exactly what we're solving for with our innovation efforts in R&D, making better products available for patients suffering with diabetes at a global scale. The same goes for obesity, delivering superior treatment solutions in the obesity space for people living with obesity. For today, just a brief introduction from my side. I'm Karsten Munk Knudsen, CFO of Novo Nordisk. With me, I have Martin Holst Lange, our EVP and Head of Development. Finally, I have Ludovic Helfgott, EVP of Product and Portfolio Strategy, which is a new name for what we used to call commercial strategy, where Camilla was running that unit before. With the reorg we did over the last few months, we have created a dedicated unit for product and portfolio strategy. Some of the other units that used to be in corporate affairs and commercial strategy have been moved to other areas, meaning that Ludo is running a pure play unit focusing on product and portfolio strategy, focusing on upstream pipeline input to R&D, and then driving products through from a commercial point of view and preparing them for the markets and for commercialization ultimately. That's the lineup for today. Without further ado, Martin, I'll hand it over to you. Good to see you all. Now we move into diabetes. Thank you very much, Karsten. You heard both me and others in the company talk a lot about what drives our innovation is unmet needs. I'm oftentimes being asked the question, are you done with innovating in diabetes? There can't be more unmet need left. I just remind you, the prevalence, the incidence of diabetes is still increasing. That goes actually both for type 1 and for type 2 diabetes, which is a little bit surprising. Type 2 diabetes may be not so surprising because that's correlated to the increase in obesity that we also will speak to in just a minute. Even in type 1 diabetes, we see an increase in both incidence and prevalence, which we need to understand better. This is our legacy, and this is where we try to drive innovation still. Importantly, these patients are still living with a much higher risk of both mortality and morbidity. Mortality and morbidity typically in the shape of cardiovascular. That could be stroke, that could be myocardial infarction, that could be cardiovascular death. It is also chronic kidney disease and peripheral artery disease. If you want to think holistically about how you go about a broad, chronic, serious, non-communicable disease that is associated with these comorbidities, and I will say exactly the same thing for obesity in just a minute, obviously we need to develop drugs that not only talk to treating dysglycemia in diabetes patients in a safe way, addressing comorbidities, but also trying to look towards prevention and cure. In the space of diabetes, that is both for type 1 and type 2 diabetes. That is basically the innovation that we want to bring. To Kasim's point, we have a lot of innovation also at ADA that we will not present today, which actually annoys me a little bit. We have once weekly insulin that is heavily presented here at ADA. We have Icosema, and we have more innovation that actually helps patients with both type 1 and type 2 diabetes. We had to acknowledge your focus primarily is on the increasing space today, so we'll talk to that. In the increasing space, obviously, as you know, we are very, very happy with what we've seen with Semaglutide. Again, I'll just remind you, I hear a lot about it, and GLP-1 is a GLP-1. We know from type 2 diabetes that is not correct. At this point in time, seven outcome studies have been performed in type 2 diabetes, two of them showing zero benefit on cardiovascular events, a couple of them showing around 12% MACE reduction on cardiovascular events, and then there's semaglutide with 26% risk reduction. There was also a big glutide, by the way, that gave no weight loss, no good glycemic control, that gave a 23% reduction in risk of having a MACE event. Speaking to the fact that these molecules are different, they work in different ways, both on ability to introduce good glycemic control, on weight loss, and on cardiovascular comorbidities. What we do is obviously to show we have the best drug for improving glycemic control in diabetes. We have done that a lot with Semaglutide. We look at the comorbidities. You've seen the outcomes, and they're all being presented at this year's ADA of the FLOW trial, the SOUL trial, the STRIDE trial, looking at kidney disease, cardiovascular outcomes with Rybelsus, and on functionality in patients with peripheral artery disease. Across the board, if I could have the next slide, thank you. We obviously, and you've seen those data being presented before, really, really substantial reductions, not only in the kidney disease, but actually also in the cardiovascular space in patients living with type 2 diabetes and kidney disease. Very strong reduction for oral semaglutide Rybelsus on the cardiovascular effect. Obviously the STRIDE trial showing improved functionality in patients with peripheral artery disease. Thinking holistically around how we address type 2 diabetes with our interventions. Ludovic. Absolutely. It's so great that way you mean for that. From a profile perspective, so first of all, thank you very much. Good morning, some of you. Others maybe less so. My name is Ludovic Helfgott, and as Karsten said, I'm now running the product and portfolio strategy. I've been in the company for six years. I joined in 2019 in the rare disease world, but prior to that, I was working with AstraZeneca, and I was actually running the whole cardiovascular, renal, and metabolic franchise, the whole DAPA program being one of the examples, and then moved from diabetes to chronic kidney disease and heart failure at the time. I am back to the roots in a sense. Semaglutide has produced the most, the widest comprehensive body of evidence of all GLP-1 in type 2 diabetes. What Martin said for me is absolutely critical. There is no class effect. Each molecule is different. What you can see here, based on the subQ, one and two milligrams, or the oral one, you have a wide set of outcomes that is actually second to none and unrivaled in the market. Of course, the glycemic control, the 2.2 with SUSTAIN FORTE, the MACE outcome, we mentioned it a few minutes ago with SUSTAIN 6, the PAD outcome, and I've been myself investigating medicines in PAD, and I know at heart it is to actually show something in PAD, 13%, the body weight, the kidney outcome, a fundamental outcome when it comes to the cardiovascular, renal, metabolic universe, and of course, the all-cause mortality. Oral semaglutide is the same. Glycemic control, body weight, 9.8%. I just put that number for you to have in mind, 9.8% on the weight loss with PIONEER PLUS, and the MACE outcome with SOUL. All this is quite unrivaled and is quite unique. Honestly, from a width of comorbidities associated with diabetes, it is really unique. What does it mean? You should have maybe the next slide. Thank you very much. We are the market leader in GLP-1 diabetes, and there is still a lot of growth potential. There is growth potential in the U.S. We know there is a lot of growth potential around the globe. Ozempic was launched in 80 countries. As you can see, it is the broadest label across the board, including in the U.S. CV, CKD indications. Again, comorbidities top front and center. The PAD now being submitted and received, I think, positive opinions from the CHMP Friday, just on our way, on the plane to ADA. Of course, we started, as you can imagine, to re-promote again in EU after thanks to the increased supply. Rybelsus, 45 countries, the first and only oral GLP-1 in a pill. I remember that when I left AZ, the whole debate was, is it still feasible or not? The jury was still out at the time. Six years from now, I think the jury has had the answer to that. The SOUL trial decision expected by H2 2025. Again, global market leader, market share of around 60% and potential worldwide. In the U.S. and in EU, 7% only of the overall prescriptions are GLP-1. There is a lot of depth in that market that we need to continue to explore with Semaglutide. Perfect. Now to obesity. I'll give the same song and dance. Huge unmet need. We, together with our competitors, our peers, are treating less than 5% of patients living with obesity in the U.S. That means we are treating a very, very, very small proportion globally. We expect to see the incidence, the prevalence of obesity still be on the rise. Our commitment is to work with society, but obviously also with treating physicians on how to break that curve for the treatment, the prevention, and potentially cure of obesity. The last is obviously a long-term aspiration. Right now we're focusing on treating obesity and treating comorbidities. The comorbidities that we are talking to are many. Depending on which review you look at, you can see lists from somewhere between 150-250 comorbidities associated with obesity. Great number of those are cardiovascular in nature. Some of them are just related, knee osteoarthritis, for example, to the weight that patients have to carry around. Some of them are maybe more difficult to address from an intervention perspective, for example, cancer. Still, our aspiration is to think very holistically, how do we address obesity and its related comorbidities? At the end of the day, living with obesity is again associated with a dramatic decrease also in outcomes, i.e., increased mortality. Therefore, we have just seen in the last couple of days, ACC adopting to their guideline that GLP-1 should be considered in patients who have established cardiovascular disease and need to lose weight. Yana wants me to speed up, but the clicker does not work. The way we think about this, and you've heard me talk about it a couple of times, is we are building a pipeline. We're building a portfolio of drugs that caters to different patient needs at all times. You've seen it many, many times being presented before. Some patients need to lose some body weight, but have no comorbidities. They just do not want any side effects. Some patients have to lose weight and focus on comorbidities. I'll show in just a minute, and you've heard me talk to it before. Wegovy is that drug. It's still the only obesity drug with an increasing base that has proven CV benefits. Then some patients will need to lose more body weight and still focus on comorbidities or maybe not. Always with a view of gastrointestinal and other side effects have to be catered to. It has to be a differentiated profile across the comorbidities because no patient is alike. As you also probably heard discussed at the ReDefine symposium this morning, there will be a subgroup of patients who have different requirements, not because of their physiological needs, but simply because in their segment, losing 25% is not desirable, or losing 15% is too little. Being able to cater to that in a holistic way, that's the pipeline that we're building. You'll hear us speaking, and then you can sort of guess where Ludovic is going to position them. Speaking to Cagrilintide monotherapy, Wegovy and monotherapy, CagriSema, amycretin, and our triples. That's the broadest and the deepest pipeline that we can see at this point in time. This is the pipeline. This is just a snapshot. Obviously, our researchers and our colleagues in research, but also our business development. By the way, I think both Lars, Kasim, and Ludovic forgot to mention, Ludovic is also heading up business development. We are working very hard to source both in and external innovation to build that broad and deep pipeline. I think we can agree that at this point in time, this is just the clinical pipeline. We are going broad and deep. We have assets that obviously are leading in the incretin space, but we also have assets, and I should in this context actually mention Ambient Biology, that goes beyond the incretin space. Kasim, he loves strategy. It is a poor strategy to continue competing where everyone else is, and most of our competitors are moving into the incretin space. Our philosophy is we win the incretin space, but then we also win what comes after the incretins. I'm not going to show SELECT, I think for the first time in a long time, because now we have real-world evidence data. That also speaks volumes to what semaglutide can do in real world. This is from the SHAPE study. We actually see that the weight loss seen with semaglutide as compared to tirzepatide is more or less the same, 14% versus 16%. We can obviously speculate why that is, but this is a 10,000-patient study, almost 7,000 patients with semaglutide and 3,000 patients with tirzepatide. Reasonably robust looking at a weight loss achieved in the real world. It is also interesting, you remember the 20% risk reduction of MACE in SELECT that we showed in real world through the SCORE trial, we see 42% risk reduction of MACE being on semaglutide versus not being on semaglutide. Just confirming what we already know from our clinical trials. You will actually remember in clinical trials, Wegovy introduces a 17% weight loss quite consistent with the real world. Obviously, we have to say real world on cardiovascular outcomes is actually besting the RCT that we did, 42% versus the 20% that we showed in SELECT. Really, really strong data coming out of real-world evidence. This is obviously something that Ludovic and his colleagues can speak to. Absolutely. It's not you yet. Sorry. Yeah, lots of data. Super sorry. I want to say on comorbidities, obviously in obesity, we look at cardiovascular outcomes as defined by MACE, but we also look at heart failure. You've seen the dedicated data from the STEP-HFpEF studies where we did one in obesity, one in diabetes. On average, 69% risk reduction for hospitalization for heart failure, death from cardiovascular death. Obviously, in less dedicated heart failure studies, i.e., the FLOW trial and the SELECT trial, we see somewhat lower numbers, but still a significant benefit of reducing risk of hospitalization for heart failure or death from cardiovascular disease. This is on the regulatory review. You've heard us talk to that. We expect to see outcomes later this year. The same thing for MACE. At this point in time, the strongest data that we've seen in phase III in the space, a 62% or 63% risk or reduction in steatosis and a 37% reduction in fibrosis. These are non-placebo adjusted, so you just have to subtract for that. Nevertheless, really, really strong and robust data that have prompted the FDA to give us a priority review. A speedy review that will hopefully lead to a readout in Q3 of this year. Step up is our attempt to show also that semaglutide actually has the potential of in monotherapy as one biology giving the same weight loss that we've seen elsewhere. Around 20%-21%, 20.9% to be specific, with more than 50% losing more than 20% of their body weight. That's with semaglutide 7.2 mg. The interesting thing is this can be done without compromising on safety and tolerability, at least when we look at the gastrointestinal side effects. I had to call out, and I expect to get that question also when we discuss amycretin, the dysesthesia where we actually see more dysesthesia events with higher doses of semaglutide than what we've seen with 2.4 mg. It is also important to call out, and that is the same thing for every biology being tested, ours and other sponsors, and you've probably seen it from other sponsors as well. This comes with strong biology. It is transient, and it does not lead to withdrawal from the studies. Therefore, obviously, we are investigating and we are trying to understand it, but it is not seen as a detriment to the overall risk-benefit of the offerings. I just wanted to call that out. That's where we actually see a difference between 7.2 mg and 2.4 mg. And now it's you. Thank you very much. Thank you, Martin. From a commercial perspective, taking a step back, of course, the left-hand side of that graph shows you the immense potential of the obesity market today, where essentially 4 million out of 934 are actually on treatment today. It is a super, super deep market to be in across the world. Again, in that logic of obesity, a bit along the same view as what we saw in diabetes, the breadth of the evidence and the outcomes demonstrated by semaglutide is really unique. We talked about the weight loss. We talked about both in RCTs and in real-world evidence. We actually just talked right now about the 7.2 mg, the 21%, 20.7%, which is very important because we perfectly understand that right now the market of obesity is marked by a short-term preference on the dimension, the magnitude of weight loss. It's the way that it's seen today. I think that's the way the market sees it. We need to respond to that need. That's why you can clearly see that we are stepping up with semaglutide with this 20.7%, which is extremely competitive versus what is there in the market today. The MACE outcome, again, uniquely positioned right now, all-cause mortality. These two are the benefits which are going beyond the weight. That, again, is the demonstration that we are really trying to address the whole set of comorbidities of patients, the HF outcome, and the liver benefits on MASH. We believe that, by the way, incidentally, this MASH benefit is certainly one of the main attractions why we actually believe we're going to grow with Wegovy over the next few months and years. This MASH impact is really second to none. It's better than anything on the market. It's also helping us to both accelerate the penetration of Wegovy in the obesity population as much as expand it as the diagnostic rate will be picking up. It's something here that I think one should not underestimate. It's quite massive. Altogether, 30 launches. The MASH indication, as Martin said, any heart failure label decision expected in the second part of the year in the U.S. Of course, we've submitted, and sorry, we'll be submitting the 7.2 mg in Europe in the second part of the year as well, which is really important. Again, widening and going back on the turf, on the ring of efficacy, because we believe that we have the data to support that efficacy. I've seen great data being put to good use. Thank you. All right, oral semaglutide. There's a lot of focus on oral increases at this moment. We believe that we have what is, if not the best, then very, very, very good offering in this space. Actually, the weight loss that we've seen with oral semaglutide is 17%. Completely comparable to that of the subcutaneous offering. Again, 15% weight loss reduction seen in more than 55% of the patients, 20% weight loss reduction seen in 35% of the patients. Very, very strong weight loss data with an oral offering with a very well-known, oh, sorry, with a very well-known safety and tolerability profile that I will show you in just a minute. Before that, I just want to show you that, and this is maybe not surprising, you've just seen the data from the SOUL study. Again, it's down to semaglutide exposure. We see some really, really nice benefits as measured by waist circumference, HSCRP, and systolic blood pressure on the cardiovascular biomarkers. To the tune of something that you actually heard from some of the clinicians today, this for semaglutide is impressive. We're going to show you slightly more impressive data from CagriSema in just a minute. As I said, the gastrointestinal side effect profile is very comparable to that of what we know for semaglutide from the subcutaneous space, and obviously also what we know from Rybelsus in the diabetes space. Super happy that. Absolutely. Same graph on the left-hand side, same depth of market. Certainly with oral semaglutide, the opportunity to address a new population that right now is not yet contained within the growth. It is one of the best ways we believe to expand the obesity market. From a performance and efficacy perspective, again, 16.6%, 17% equivalent to the cousin, the injectable cousin, and the MACE outcome, the potential, of course, if there is a bridge between 14%-20%. You have here something which, again, weight-wise is best in class from an oral perspective. From a MACE perspective, bringing additional benefits, widening that market. That is what we really need to do. We will talk about it later on without spending our own thunders. We will talk about it later on, widening that market and that penetration. To be submitted, so it was submitted actually in Feb, expected decision by the end of this year, full-fledged launch in the U.S. Interestingly, API production, tablet manufacturing, and packaging in the U.S. Very interesting. Of course, the scaling of supply is happening as we speak, and the U.S. are really getting ready for a super, super, super strong launch of oral semaglutide 25 mg. Again, first, oral, super competitive, and something that we really are impatient to bring to patients. What annoys Karsten most when he goes to results presentations in the clinical space is the 30 minutes that he has to endure on methodology and statistics before he actually gets to see the results. I feel we're doing a little bit the same with you. Now we move to CagriSema and CagriL Insight. I think you saw this very nicely described also today. The amylin biology is complementary to what we see with GLP-1. It acts in some of the same, but also different cells and areas of the brain, leading to what in animal models were shown to be additivity. In humans, it's at least more benefit than what we see with the monotherapies. You've also seen that a lot of players are moving in this very complex biology. The receptor system of amylin biology is such that you have always a calcitonin receptor, and to that binds one or three RAMPs, they're called. And that's then the amylin receptor system. That also means that it's very, very difficult to find something that never binds to calcitonin, but they can have different receptor selectivity depending on what you are aiming for. At this point in time, no one really knows exactly what is the right analog backbone. Do you want to go more towards amylin or do you want to go more towards calcitonin? No one knows really exactly where you want the receptor selectivity. There's a school of thought saying if you really want the efficacy, you are more on the calcitonin side or you are at the very least in the middle. There is also a school of thought saying if you do that, then you get more side effects. The important thing for us, again, back to the holistic pipeline is we have everything. You are seeing right now we're testing two amylin analogs in monotherapy in phase one. We already have CagriSema. That's sort of a dual acting on the receptor system. You should expect that the other two are maybe on either side of the spectrum so that we actually test what we have for our different biologies and then we know exactly where to put our money. Cagrilintide in monotherapy has actually already now shown that it's a really, really effective drug. 12% weight loss speaks to the spectrum that Ludovic will also come back and talk to where we differentiate and where we position our drugs. Importantly, those 12% weight loss, that is actually very, very decent for people who have moderate obesity and a focus on not too many side effects. We do not have too many side effects. We actually have substantially lower than what we see with Wegovy. Sorry, I should just say we expect to start Cagrilintide in monotherapy in phase three later this year. Obviously, it is full speed ahead because this is a segment of patients that no one really addresses at this point in time. Obviously, we have the potential to be first with a really, really strong offering in this space. CagriSema, I do not think I can do it more credit than what was done today. You know the trial design, CagriSema versus semaglutide versus cagrilintide versus placebo in a skewed randomization, so 21 to 3 to 3 to 7. Obviously, you probably also heard today there was a speculation. Obviously, I can a little bit confirm that speculation. We do know that men loses less weight than women. In this study, we saw slightly more men than what we've seen before. Same thing for Asians. Therefore, there is maybe something in the ReDefine population that could drive the results that we. You know from the last figure, if you start to add all of those up, that could also be interesting to look at. You've seen the weight loss, obviously, 22.7%. This again with a differentiated of how many patients went to the highest dose. Just for the mathematics, it's also important to call out that if we had had an additional 13% of patients that went to the top dose, so they were comparable with semaglutide, they should have lost 34% of their body weight if they were to drive a 25% body weight loss for the population. That is not the issue. It is basically the fact that patients are still losing weight at the end of trial, 68 weeks. You also heard some examples today of this is probably a too short trial. I'll come back to that in just a minute. Importantly also that we see 40% of patients who lose more than 25% of their body weight. We actually see almost a quarter of them losing more than 30% of their body weight. What is also interesting is that we look at body composition. We actually don't see anything new. That's either because we didn't do the right assessment or because CagriSema actually doesn't lead to a differentiated effect on body composition as compared to semaglutide. What is more important is, and you also heard that today, that's not a concern. That is the proportional weight loss that you see with normal body weight loss. Regardless of if you do diet and exercise, if you do gastric bypass or you do medicinal intervention, approximately 30%-35% of your weight loss is attributable to lean body mass. We see that also with Semaglutide and other in-market therapies. What really, really gives me a lot of confidence then in the weight loss that we here introduced is we know from Semaglutide that we improve lives. We reduce mortality. We reduce morbidity. As you have seen, if you have seen the striped slide, we improve functionality. You actually also saw that from the CagriSema presenters today with the quality of life questionnaire, improved functionality despite obviously this body composition. The most important thing to call out is actually because you lose 2/3 of your weight through fat mass, you improve body composition anyway. This caught some interest. This is what I have been trying to talk to you about for the last six months. There is a big group of people, actually the majority of patients who titrate to the full dose. They get to a level of BMI 30 at the end of trial. They are actually as a group, all of a sudden in the close to non-obese space. There is another group that is also a substantial group. It's not 50%, but it's lower than 50% that lose weight very, very fast. They are actually approaching a BMI below 27, i.e., they are not obese and they are close to even not being overweight. The speed of that weight loss seems to be driving them turning down or dialing down on dose more than gastrointestinal side effects. It should be mentioned that the first group, the big group, have a really, really, really attractive safety and tolerability profile. So adverse event rate that are actually lower than what we see at Wegovy. The other slightly higher, but not high enough to drive the reduction in dose that we see. Clearly driven by the speed of the weight loss. As you also heard from the investigators today, that can be mitigated by slower titration. That was both from the questions, but also from the speakers today. That is basically how they see the solution in the obesity space. Another clicker does not work. You have also seen the impact on cardiovascular biomarkers. Again, sorry, this is not treated time. I am sorry, I am mixing up the slides. It is actually really, really interesting. 40% loses weight, so they are below BMI 27 at 68 weeks. You have a waist-to-height ratio that is below 0.53 in 36% of the patients. In almost 30% of the patients, we see a combination of the two. These are really, really interesting measures because they are probably a little bit in combination stronger as a treat-to-target measure. They are also reflective of cardiovascular outcomes. This is something that we want to explore more. The fact of the matter is we see the strongest data that we've seen with CagriSema. Obviously, we intend to pursue that as we move further. Now I'm at the cardiovascular biomarkers, waist circumference, systolic blood pressure, HSCRP. I don't think apart from dedicated anti-inflammatory drugs, we've seen a 70% reduction in CRP. It's really, really stellar results. It obviously speaks to our sort of aspiration of showing strong CV benefits with CagriSema. We are currently conducting ReDefine 3. Obviously, with that kind of data showing that these biomarkers are better than what we see with semaglutide, we could hope to see something that is maybe even better than what we've seen with semaglutide. I've already spoken a little bit to the gastrointestinal side effects. As a group, the side effects were similar. Sorry, those are the gastrointestinal side effects. The events are similar to that what we see from Wegovy. In the patients who titrated to the full dose, the events were actually lower. In the patients who titrated to the higher dose, the events were slightly higher. Again, speaking to these patients need a slightly different titration, probably longer intervals between their titration steps. ReDefine 2, again, super strong weight loss. You heard sort of the statements from the stage today. I cannot repeat those. I do not think I am allowed to do that. Really, really strong weight loss data. Obviously, when we look at glycemic control, and I know that there is going to be a question or two on that, you cannot, and you also heard that from stage today, you cannot assess glycemic control without an active comparison. The good question is, why is there not an active comparison? That's simply because this is a regulatory obesity study, it's not actually a diabetes trial. That being said, 2% lowering in this space is really, really strong and gives us a lot of confidence in what we expect to see when we do the REIMAGINE trials and see the readout from the REIMAGINE trials. Specifically, you get a little bit of a pointer when you see how many patients achieve the A1C target. That's more than 80%. That's reasonably strong. Obviously, when we look at time in range, I don't think I've ever seen data like that. We saw them actually in phase I and II, but now we've also seen it in phase III. That is a very, very strong time in range. That should give us confidence that we'll see really strong data when we see the readout. Again, a gastrointestinal side effect profile that is similar to what we saw in the non-diabetes space. Obviously, really, really excited to take all of these learnings and take them into ReDefine 11, where we will, and you heard a statement of, and I'm trying to calculate, I'm not always too good at that, of we need at least 90 weeks of treatment. Our assessment is actually for accruing most of the weight loss, we'll need 80 weeks of treatment, but we're extending the file. We can continue to see up until 150 weeks of treatment. Optimization on obviously how we titrate and how we guide for titration, but also maybe one point that we can all think about. It is somewhat unrealistic to believe that a patient who has BMI 30 or 27 wants to lose 25% of their body weight. If you do the calculation, they end up at an end-of-trial BMI that is basically too low. In this trial, and you'll also see the same for some of the CagriSema trials, we will not include patients with a BMI below 30. Those patients will be addressed in the cardiovascular outcomes trials where we can address lower BMIs together with comorbidities. We'll do it in a slightly different way, obviously aiming to show what kind of weight loss potential we have with ReDefine. Good or weak? Absolutely. As you can see, we're really trying to address two different objectives. The first one is really to exploit the full potential of CagriSema from a weight loss perspective. Because again, ultimately, weight loss matters. That's why you're seeing the ReDefine 11 trial, longer trial. It is really important that we are really, it is very clear that we are really focusing on that. The second thing we are trying to do is we are trying also to understand, and again, it is a segue to what we are going to talk to in a few minutes, we are really trying to understand how the drug can be used with different patient profiles. What about the maintenance dose, for instance? We all know that the way people will be on maintenance dose might differ, their choices and preferences. Some want to be titrated longer. We saw the lower curve. Some might want to have even a longer duration of treatment. Addressing the efficacy first, but already moving to what we believe will be the next step in obesity treatment, which is more customization of the treatment journeys of patients. If you summarize, overall, we have with CagriSema a first set of successful pilot trials for those who were there this morning. It was, I think, quite clear. We continue to investigate with what we believe has the potential to be really the best in class in this category, bringing not just the weight loss, but also the potential to bring the other benefits, including cardiovascular benefits. This is really for us the direction we're going, efficacy first, because that's the name of the game today, already anticipating what will be tomorrow. Amycretin, not usually to talk too long about a small phase one trial. It was actually more complex in the setup than what we are showing here. Also testing the 60 mg dose that you have seen results of the last couple of days. That was fast. At the end of the day, I thought we had something about weight loss and this comes up. Sorry. Obviously, we see a gastrointestinal side effect profile that is not really what you want to see when you do phase II and III, but in phase I, this is what we had to expect. As the good Dr. Park just pointed out, these patients are actually hospitalized a good part of the trial. Obviously, in that, you collect a lot of data that you would normally not collect. Also, we're now taking the learnings from ReDefine 1. The titration was being pushed quite hard. We do believe that, and as you've seen in the recent announcement, we discussed this also with the regulators, that with the right titration and with the right focus on how to titrate, but also allowing some of the things that we've allowed in the ReDefine program, we can actually mitigate the side effects and bring it to be comparable to that of CagriSema. With the weight loss potential that at 20 mg at 36 weeks suggested 22% weight loss. At the 60 mg dose, also at 36 weeks and up to 24%, actually 24.3% weight loss. Really, really exciting days. Something that is big potential. We have to get the dosing right. We have to get the titration right so we mitigate the gastrointestinal side effect. You can clearly see the weight loss potential is interesting and attractive. Obviously, if we again think about the spectrum of obesity, amycretin, CagriSema will not be for everyone. It should not be for patients with BMI 27. If you have severe obesity and a lot of patients have that, I think it's around 20% of U.S. patients who have BMI above 40. CagriSema, amycretin with this kind of weight loss would be really, really an attractive offering. The logic follows the same thread. On the one side, you can see the current MACE program. That's what you have on the left-hand side right now. This is really the weight loss in obesity. Of course, you have the type 2 diabetes for regulatory purposes. You have already some comorbidities interesting in MACE 5 as an example. That's really interesting. Of course, this is just part of the program. We are considering developing and enhancing this program to better match the various comorbidities that patients with severe obesity could actually face. Multiple maintenance dose, very important. Of course, the comparison between the subQ and the OPS and the oral and/or different presses and different comorbidities, which essentially is enriching the amycretin program to make sure that we're really answering not just the comorbidities, but also the way to be treated, as you can see, ASCVD, heart failure, CKD, the knee, the osteoarthritis, the sleep apnea, which we believe is also one of the main problems that the obese patients are actually facing today. Widening that program to make it stick and fit with the reality of the diversity of our patients over and above what we're doing today. I've already shown the slide. Now the clicker is doing me one over again. Here we go. Trying to address a spectrum of obesity. It's super, super complicated. A couple of years ago, there were people in the company discussing early obesity versus late stage obesity. It's not like that. You can have early obesity with a BMI of 40. You can have BMI 40 with no cardiovascular events. You can also have BMI 27 with a lot of cardiovascular risk. We know from SELECT, those patients also benefit from treatment. The complexity of that requires maybe also, I don't want to say a complex, but a comprehensive pipeline. Right now, we and everyone else is playing to win in the incretin space. Based on the data that we've shown you on cagrilintide, which is not an incretin, GLP-1, Wegovy in combination with cagrilintide, and obviously with amycretin addressing those same two biologies, we believe that we have a great first step into how do we serve patients in a broad spectrum of obesity. We also have to acknowledge we are not done there. Innovation has to come more in the incretin space. Innovation had to come more just back to the complexity of the amylin biology in the biology space. Innovation also had to come with new mode of actions. As you can also see, we are already now in the clinical space investigating novel mode of actions because we think that is where we can truly address the unmet needs. That complexity is interesting. It requires both in and external innovation from our perspective. We will just give you some examples. Some of these are one internal. The triagonist combining the GLP-1, the GIP, and the amylin biology in one molecule. Some of it is external. The other triagonist, which is, I do not want to say a conventional, but a well-known combination of glucagon, GLP-1, and GIP. There is a completely new mode of action, first in class. I really resent you if you will ask me what ACSL 5 stands for, because I can only say it in Danish. It is acetylcoenzyme synthase, inhibitor 5. Try to look it up in English. It is much, much, much easier. All of this obviously speaks to a differentiated approach to how to address obesity. We expect to see really, really big weight losses, but also impact on comorbidities with the first two. Maybe slightly less weight loss, but a more differentiated then approach to other subpopulations of obesity with the ACSL 5 inhibitor. Exciting times and really something that we want to pursue with everything that we have. I'm trying to push. Here we go. Absolutely. Maybe trying to represent what we're doing in product and portfolio strategies to make sure that we're connecting the science with actually what the market needs are today and what they will be tomorrow. A couple of slides now to explain to you from a patient perspective, some say customers, some even say consumers sometimes. What does it mean to have a full portfolio and really be relevant in the world of obesity? On the left-hand side, I think Martin shared that with you, the BMI categories. You still have a significant amount of proportion between 27 and 30. Look, if you sum up your 30-40, you actually have more than half of that population in that grade. That is going to go up, which means that there is definitely a lot of space for the advanced agent. There is also a need to be relevant in that space as well. The wider we are with our medicines, the better we can actually really exploit, fully expand that market and exploit that market. On top of it comes the comorbidities. Are we talking ASCVD, heart failure, the MASH fibrosis? You can clearly see that the variety of patients and the variables are quite high, but we need to match that. That is what you see on the right-hand side. Next, please. This is what you saw earlier on with Martin. He shared with you actually this idea that there are three elements that we fundamentally are considering, or four elements, sorry, that we're considering when it comes to our portfolio and the breadth and depth of our portfolio. Of course, the efficacy of the weight loss. That is the right to play. And we need to continue pushing the full potential of our medicine. That's what we're doing with CagriSema, with amycretin, with the trial. We're really pushing as hard as we can know to make sure that we can really exploit and test the limits of what we can do. But then three things are actually very important. The first one is the differentiated treatment goals. We all talk about the reduction of weight in percentage terms, but think about the absolute, which explains, by the way, why some people that are starting with a lower BMI might not want to get down to below the 27. Look at the absolute weight reduction. It's actually quite impressive and sometimes daunting for patients. The way you want to be treated, you want to have a very fast weight loss reduction and then maintenance over time, or do you rather want to be quite progressive and then have your side effect being managed? Second element of differentiation between the patients is the comorbidities you have. We're talking cardiovascular, but MASH is one, or even your arthritis or a knee or women's health, for instance, which is extremely important when it comes to the different patient needs. Last but not least, of course, safety and reliability. If you multiply and if you combine this, not by pushing our science towards the market, but rather understanding what the market really wants. Starting from the patient and the customers, you could clearly have the need to have a wide set of medicines covering all these needs. Why not starting, for instance, with Cagril Insight? That tolerability profile is actually super, super good. You saw it that morning again when you saw the lines that were showed by the presenters. Of course, semaglutide, the backbone of what we do, both subQ and oral. Then you escalate. CagriSema, amycretin, subQ, oral, and of course, the triagonist. This is only what is in development today. We also have other assets that are of different modes of actions, including more than seven BDDs on the topic over the past year. Really enlarging the width. That is what we believe will be the, we believe could be the winning ticket in terms of obesity, is having that breadth of products to make sure that we are respecting these profiles and we are really on the gender, lifestyle consideration, and the oral clinical profiles relevant for patients. That, I think, roughly concludes our discussion. We are very happy to answer questions. Summary, high unmet need in diabetes remains. You have seen that. Still low global penetration rates. Complex disease for obesity. Different treatment options. We have that with Wegovy, oral sema, amylin, CagriSema, and amitriptyline. Of course, committed to continue the development of a portfolio with superior treatment outcomes. Thank you. All right. Thank you to Martin. Thank you to Ludo. Now you got a comprehensive review of our portfolio. Now it is Q&A time. I see now it is not phones going up. Now it's hands being raised at an equally fast pace. To control, I think we start here from the front and then we move backwards and then back. Richard Vosser, and if you could please state your name. And then one question each. One question each. Hi, Richard Vosser from JP Morgan. One question on amycretin. Martin, you mentioned sort of thoughts about slower titration and different doses. Given the data you've got on the phase one, do you need to do more trials? Did the diabetes trials give you enough information? How can you tell which doses and which titration, given it's a different molecule to CagriSema and there's not a lot of data there? We have to say that the biology is very similar to what we know from CagriSema. The side effect profiles are also quite similar to what we saw in phase I. We know by adding one more dose by allowing, and again, going back to the CagriSema analogy, you have to be careful you do not optimize for the minority. You rather have to optimize for the majority. The majority in ReDefine 1 actually titrated well. They lost 22% of their body weight, and they had very, very low adverse event rates. You should not ask the entire population to start to titrate slower, but you need to allow the patients who do, and for better or worse, there was some speculation today. We cannot predict based on baseline phenotyping who will be a super responder and who will be a normal responder. We basically had to allow them to start on the first dose. We also know in that first titration step, that's actually when they start to see the weight loss. That's maybe when they had to think about moving from titrating every four weeks to every eight weeks. If they do that, then I had to do a longer study because then all of a sudden, it's not 16 weeks or 20 weeks to reach the top dose. It's something more. To get data from state to state, we do longer studies. We're reasonably confident that we can do that. We've had a lot of discussions, obviously, with external experts, but also with authorities. Based on everything that we have, we think that we can do that. Obviously, it's something that we monitor closely because, as we just spoke to, we want to win the weight loss, but we also want to have a gastrointestinal adverse event profile that is attractive and competitive. Thank you, Martin. Matt, and then Michael afterwards. Thank you. It's Matt Weston from UBS. Can I come back to CagriSema and the ReDefine program? One thing that I'm sure we're all going to get asked about next week is the suicide rate that we saw in both studies. It was clear from the experts. They stated that there was no causal link to the drug that had been suggested. Given that we've already had the discussion previously about liraglutide and suicidal ideation, how confident are you that that is not a signal that's going to emerge and challenge when it comes to regulatory review? I'm reasonably confident. I don't think there's anything in this biology that should speak to this. I would remind you there was one event. It was not a great number of events. There was one event in ReDefine 1. The most important thing is we had questionnaires looking at suicidal ideation. They did not show any signal at all. I will just remind you these chance findings, when you randomize 21 to 3 through 7, any statistician will tell you that one event will happen where you had the most patients. We had to do select to get 20 events of suicidal ideation, semaglutide versus placebo. They were distributed 10 to 10. Based on everything I know, that would not be my biggest concern. Obviously, it is something that we continue to look at. We will continue also to employ these questionnaires so we understand exactly what is going on. Thank you, Martin. Michael. Michael Novod from Nordea. Martin, also one question on the DEXA scans we saw in the supplement. Can you talk a bit to that? Because it seems like there's a bit of disconnect between how we thought amylin would drive weight loss mainly through fat mass, but it doesn't seem to be the case from the DEXA scans. First of all, there's a lot of volatility in DEXA scans. You have to look at all of the methodology biases that you have in a study like this. You have to drive a phantom around between the sites that do DEXA scans to have sort of calibration every time they do this. Therefore, DEXA scan is maybe not the most robust measure. That being said, my current assumption is in humans, biology is slightly more complex than it is in animals. So I'm not 100% certain that we will see a lean mass preservation above and beyond what we've seen already with semaglutide and other molecules. Again, for me, that's not a concern because I know the weight loss is normal as compared to diet and exercise, as compared to gastrointestinal bypass. I also know from Semaglutide that that weight loss reduces risk of death, reduces risk of cardiovascular morbidity and mortality, and it actually improves functionality. Based on what we just saw today from the questionnaires, it appears that CagriSema weight loss is the same. We will continue investigating this. It's not because I think we have to have slightly more sophisticated methods of investigating this. I would also say looking at the biology of amylin, I would probably also be looking at bone health as a higher likelihood of seeing true differentiation. Good. Thank you, Martin. We will move one row back to Carsten. Thank you very much, Carsten from Danske. I'll try to see if I can pronounce it correctly. This is DCIA. Yeah. Some of us have seen tests for glutathione and we are a little bit allergic to allergic reactions. How certain are you that these are not the sort of hypersensitivity signs or something like that? What we do in our development programs is that we also measure antibodies. There is no correlation between antibodies, i.e., approximate for allergic reactions, and this. The important thing is the events are transient and they go away while patients stay on treatment. Most of them, apart from one, were mild in nature in the amycretin program, for example. Again, something that we have seen before, others have seen it as well. If you look at what, and it does not appear to be related to an immune reaction. Okay. We move to the other side, Pete. Thanks, Peter of BNP. Just a question on R&D strategy for you, Martin. Yesterday, we heard there are 50 non-peptide oral GLP-1s in the clinic. Sorry? Yesterday, we heard there are 50 non-peptide oral GLP-1 assets in the clinic. Today, we hear about tailoring medicine, sorry, personalized medicine for obesity in terms of dose selection. The question is basically, does Novo need, in your view, an oral non-peptide GLP-1 in the portfolio? Number two, when you think about phase III, thanks for the extra information on amycretin, but how are you managing all these multi-doses and escalation, de-escalation, and not ending up with a result like ReDefine 1? It's a really good question and obviously something that we're looking at. Actually, the dose changes are almost easier with an injection device. Obviously, we also had to cater to that with tablet-based treatment, as do anyone else. Our philosophy is that with semaglutide as an oral in obesity, we have the best weight loss that has been seen so far and with a very well-established system solubility profile. If we can scale that, and that's what I hear from, it's not Kasim who's scaling, but he's telling me that we can scale, then we would have to make an acquisition on something that could be scaled with competitive FMC and scalability, and then a very well-established safety profile and a really good efficacy profile. We haven't seen that. You've also seen our recent announcement on Sapturna, where we actually looked together with Sapturna on what I would call next generation, not peptide incretins. There the chemistry lends itself not only hopefully to the good efficacy and safety, but actually also to the scalability. That's sort of our approach. I don't want to buy a small molecule just for the principle as long as we still think that we can scale oral semaglutide. Obviously, if we can find something that can be scaled at a reasonable FMC, that's where we go. Sapturna is our first shot on goal there. It's the same philosophy with the ACSL5 inhibitor molecule. That's also an oral. I think we're in the equivalent of DPAP over here now. The idea is that you're a signal where there's incretin or incretin or objective, or we want to broaden the mode of action that we have in order to make sure that we cater for the various needs. It might be very early if we want to progress that as we just got to the final point. Yeah. Good. Martin. This is Martin Parkhøi from SEB. If we look at the SMART-1 data and now the detailed data today in ReDefine 1, and then we'll all look towards ReDefine 4, how much do you think you can win by prolonging the trial, by the baseline characteristics as we've seen today with the high exposure to patients, and also having the same flexibility in the two arms of the study? It's a good question. I think we have to wait and see. Based on what we know from CagriSema and ReDefine 1, extending the trial will give us slightly more weight loss. That I think is okay. Whether it will show statistical differentiation, we'll have to wait and see. The true proof for CagriSema is ReDefine 11. Yeah. That's clear. Jeff? Hi. Hi, Jeff. from T-Rowe. On this analysis on the sort of people who dosed down and responded better, one thing that struck me is that their weight is about 10% lower than the other. There's this difference at the start. The BMI is different. The BMI at baseline is two percentage points different. One was at 39, the other is at 37. At end of trial, obviously, there's a big difference. It implies that there's like a mid to high single-digit difference in weight, assuming they're all the same height at the beginning of the trial. Just the question is, have you seen in any other trials that maybe the starting weight of the patient determines the tolerability or anything else just because they're getting a higher sort of milligram per kilogram of body weight of dose of the drug? The second part to this is, it doesn't look like it was documented, but when you're looking at the reasons behind dosing down or not escalating, was it more driven by tolerability? Is it more driven by concern about what BMI the patient has got to? Just answering the last question first, as you also heard from states today, we didn't really collect it. Based on everything that we can deduce from the data, it actually seems more like it was the speed of the weight loss and the approaching sort of the magic line of BMI below 30 that prompted them to slow down on titration or maybe even titrate back more than the gastrointestinal side effects that were actually not that dissimilar to what we see with Wegovy. From that perspective, that's our thinking. Obviously, in future trials, we will ask slightly more specific questions as to why they titrate or why they maybe not titrate. On the baseline characteristics, it's the million-dollar question. Obviously, we look very thoroughly into this. There is a difference. I mean, again, BMI 39 in one group and 37 in the other group. The challenge is if you look at the variation at baseline, they both go from 27 to 60 plus. The mean is just different. In every study that we've seen, we've seen a little bit of the same picture also in our old semaglutide trials. The issue is you can find that difference between the groups as means, but the spread around the means, this allows you to predict who will do what. We have to do that in the clinical space. As I said, we can reasonably fast predict who starts to lose weight fast or maybe who gets gastrointestinal side effects. They should then be asked to titrate at a slower pace than the ones who actually like what they see, so to speak. Thank you, Jeff. Thank you, Martin. I saw Seamus being fastest before. We go there now. Thanks. Martin, I noticed on the pipeline slide, you've decided to discontinue your GlypGIP, and Novo's decided to advance to bring forward a triple G, and you're advancing another triple agonist. Just trying to get a sense for the next leg of the pipeline. Also, Novo's historical, I guess, our perception at least at Guggenheim of glucagon really kind of being an anathema mechanism. I think there's a lot of statements suggesting that glucagon could be unsafe, but you just licensed in that asset. I'm just trying to get a better sense of how you're thinking about the novel mechanisms that are coming in and what you're most excited about. Thanks. I really appreciate that question. I have to compliment you for actually spotting it. You're absolutely right. We've discontinued our GLP-1, GLP that was in phase II. You've heard me talk to, if we were to progress that to phase III, it should be differentiated on efficacy and safety. What we saw was actually a really, really good and strong weight loss comparable to what we already see out there in the competitive space. From a pipeline perspective, not differentiated to that and not differentiated to what we have with CagriSema, amycretin, and potentially the triples coming in. That was sort of an easy say. I mean, it isn't really a negative because in all of what I just showed you, you should expect to see slightly more attrition. We'll test in the clinical space. And then, I mean, it's not a given that all of our amylin analogs will survive either. We will pick the best, and we'll only progress the differentiated molecules back to Ludovic's point into phases II and III. On the triple, it's a little bit the same. I think we've seen in recent months data coming in that there is differentiation between what appears to be similar biologies. I just gave my take on the cardiovascular differentiation on GLP-1s in diabetes. You've seen one of our competitors having to terminate an amylin asset in monotherapy because of side effects that we clearly don't see with CagriSema. So we've also seen what we would call concerning safety signals with a glucagon. With the right ratio in a triagonist, we do not want to rule out that glucagon could do something. I mean, we do know, for example, in MASH, and as Ludovic said, MASH is very interesting to us also. Glucagon may have an important play. Having that as part of what we investigate, but not necessarily progress to the market, that is super important. The other triagonist with amylin biology, I think that from our perspective and the way we think about this, has higher potential, but time will show. Great. Thank you, Seamus. Thank you, Martin. We move to Thibault. Thank you. Thibault from Morgan Stanley. You mentioned the different sort of supermarket that you want to address. I think one of the things that was maybe not mentioned is the potential for longer duration of action assets. I just wanted to know where you stand here and if in your pipeline you have something that could sort of longer duration of action. I think Ludovic can maybe speak to the commercial lead from a medical perspective. It's interesting, but it's not first on our innovation agenda. First, we look at efficacy, we look at safety, we look at comorbidities. Obviously, if there is a possibility to generate an efficacious, safe, but also from a comorbidity perspective, interesting asset with a longer treatment duration, that would be potentially attractive. It also comes with some flaws because if you have, for example, gastrointestinal side effects and you have a half-life of a month, that gives you other challenges. We have actually made a collaboration where we are testing the potential for once-monthly GLP-1. That will go into clinic, I think, in this or early next year. I think from a commercial perspective, if you look again, the market is an asymmetry, it's very difficult to say. If you look right now at the motivations for these treatments in the various subgroups, you do not see the length of a treatment per se, in terms of exposure to the medicine popping up as one of the top criteria for success. It might be the case in a few, maybe in a couple of years when something is on the market. Right now, we see other either comorbidities or approaches to the treatment that are popping up in a much cleaner and clearer way in the U.S., but also in the Western European market. We have it, as Martin said, as one option. It's not the option that we are now, we believe, is top of the list. We have it again, back of our pocket in case. All right. Thank you. We move backwards. Warner. And then Emily, afterwards. And then Mathias. Yeah. Warner [in Behaviorality] Martin, obviously positive that you're moving amycretin into phase III, but you've been speaking to this opportunity for more than a year. Why does it take until 2026 before you initiate the study? Also, just looking to your main competitor, it seems like they're more aggressive in timelines also compared to filing for when they have initial readouts and when they then file. Can you speak to what you're doing to speed up your processes? Yeah. You've actually seen us when we need to, we can move very fast, both in terms of recruiting into and conducting clinical trials. ReDefine 11 was up and running in two months' time, and it will actually have finalized recruitment just around the end of the summer holidays. That we can do, we can also do very fast reporting. You may remember we did a filing, I think it was four weeks after last visit. When we look at the totality of the pipeline, the portfolio, and also having to consider in particular our production and supply, it's a little bit of a puzzle, and the puzzle master is sitting there. Having the entire, also from a commercial perspective, when do we launch what? I mean, I don't think Ludovic wants to launch CagriSema and amycretin at the same time. I don't know. We think about this in a holistic way. Specifically for amycretin, we actually have to make sure that we have a robust supply chain in place because once we start amycretin program, then it goes very fast. Then our supply people have to be able to have product for launch, not for doing the clinical trials, but product for launch and building that supply chain. We have also seen us actually doing the same considerations with oral semaglutide for obesity. We could have filed that last year, but we wanted to make sure that we had a robust supply chain in place before we. Because we have drugs in the market and because we have a pipeline that continues to push out more data, we can allow ourselves to think about it like that. All right. Good question. We like speed in R&D. Thanks for pushing on that one, Warner. Over to Emily. Hi. Thank you, Emily Field from Barclays. The last speaker today who was obviously very positive on the data did mention that in his clinical practice, he hopes that all these medications can have all doses approved as a maintenance dose given the heterogeneity of the population. Given what you learned in ReDefine 1 and 2, how are you thinking about that as you think about designing future trials and regulatory filings? Apologies, just a very, very quick clarification question. You mentioned filing step up in the second half of this year in Europe. When are you filing in the U.S.? On the first one, you actually saw a little bit on this from Ludovic in one of his lines. ReDefine 9 is testing 1 mg and 1.7 mg. The idea would obviously be to have that also in play from a regulatory perspective. For amycretin, we will aim to have more than one dose approved. Basically addressing those needs, we believe that it's incredibly important to actually cater to what obviously payers and regulators want, but maybe more specifically what patients and treating physicians want. On the filing in the U.S., I think that's more for the focus of the U.S. is on CagriSema and the focus on the value in IO. From a calendar perspective, it actually makes more sense to pursue the U.S. CagriSema venture to be actually a return on the market, especially what we're really trying to achieve. Speed to market and then really dividing and conquering with these two potencies. Yeah. We move to Rajesh. Let's see if we have time. We have Kerry afterwards just to get some exercise into installations. Thanks for taking the question. Very interesting map of how you see the competitive market with semaglutide on one side, amycretin. It's a very medically focused competitive landscape where the decision maker is a doctor who is looking at the benefits and then prescribing. You and I very well know that this market has gone out of our hand and it's a lot more consumer now, right? Have you carried out, just this is just a clarification before I come to the question, any other way of looking at the market in which you've not left enough gaps for others to come and eat your breakfast, just to be sure? In that context, can you help us understand how oral sema is going to compete with orforglipron given the ease of use, which I'm assuming a lot of patients would absolutely love. I'm sure the cardiovascular data you have is much better, right? Martin? You're perfectly right. I think that if you're just pushing from a medical perspective, you only see part of the market. We should still do it because I still believe there's worldwide a lot of reasons to use the medical lens to do this. We're also looking at this market as seen, as I mentioned, from the patient. I even said sometimes the consumer, I know it might be shocking to somebody, or the customer if you want, in terms of how do they want to get to their medicine. Many of the consumers today in the U.S. on the direct channels, they just want to get a prescription online and get the medicine home. We are working in those, what I call the preferences, you know, this pink bar that you saw there. We're hardly working on in which way the patient wants to get their medicine. With what price point do you want to get that medicine? If it's cash versus not cash, how they want to access, being delivered home or not home. We are also working on all the modalities through which patients are accessing the medicine. That pink bar you saw is exactly answering your needs. Now, this being said, you still have to make sure that you're relevant from a scientific perspective, hence the trials, or from a commercial perspective, the packaging of the offers, the subscriptions. Do you want to have long subscriptions, short subscriptions? Do you want to include your maintenance or not into your subscriptions if you're going there direct with NovaCare, for instance? That is completely taken into account, both the more traditional way to access the medicine through the physicians, as well as the newer trends on that medicine. It's taken into account. When it comes to oral sema, your second question, when you look at the quality of the data and when you look actually at the profile as well, and when you correct it typically from on the placebo effect, you can actually see that the profile of oral sema is rather competitive with what could be as well coming into the market. Plus, and you said it yourself, the additional benefits you can actually drive from having been based on semaglutide over and beyond the weight loss. We believe we have here a strong contender in the market and a very attractive profile, even for those patients that do not want to go injectable. One last point on that. We really believe that having an oral aspect of that profile will help us expand further the market. I was even speaking MASH earlier on. We discussed how much MASH was important. We believe that having that aspect will help us because beyond the weight, which is already quite 16.6%, if you correct for the placebo adjusted, you will see that actually from an adverse event, it is really, really on par with what you can see outside. We believe that there is a good chance to be first in the market and having a strong position with the oral and also. Great. Thank you, Ludo. Thank you, Martin. Move to Kerry. Hi there. Question for me on market segmentation. In the context of trying to find the right product for the right patient, I'd be interested to understand whether you considered raising the BMI hurdle even higher. If we think about what you've discussed here for ReDefine 11 and you also referenced amycretin, did you consider going beyond 30 plus? If not, why not? It's a really good question. I think also Ludovic should answer that. I think from our perspective, from a development perspective, also thinking into the commercial space, I don't want to rule out that where we come into the really powerful biologies, potentially the triple, maybe even amycretin, we will do specific dedicated studies to investigate this. In that, and that also speaks to a little bit the question from before and what Ludovic talked to, we really had to think good and hard on the maintenance piece because it's not necessarily so that you need to go on that powerful biology and stay on that. Maybe you need to dial down on the dose. Maybe you need to switch to something else. Again, building those data, but also building that pipeline that can cater to that is the way we think about it. You said it perfectly. The surge in treatment is important. The maintenance is equally important. True for your highest BMIs or for the more regular traditional obesity BMI. That is why we think, and back to your question on the consumers, we are equally interested in knowing how you initiate your treatment, how you escalate your treatment, and how you maintain your treatment. This is all part of the studies, and that is why you get the ReDefine 9 program on the maintenance as an example. We are really interested in understanding that better and actually even with a customer or consumer view, not just the medical. Great. Thank you, Ludo. Move to Emmanuel. Emmanuel from Deutsche Bank. Thanks for taking the question. Maybe just a couple of follow-ups on amycretin, please. Firstly, interested to understand your comfort with a couple of other aspects of the safety profile that emerge in the papers this weekend, namely the elevation in headache rates and perhaps more importantly, the magnitude of elevation of BPM. Then secondly, apologies if I missed it on phase III. If you actually confirmed what doses you're planning to take into phase three, are you planning to use flexible dosing? Perhaps you could just remind us why the urgency to rush into phase III if you're confident on CagriSema. Thank you. These studies take time. The urgency is that for better or worse, and you also heard that today, we are moving from six to eight weeks to something that is longer. At some point, you need to start to initiate them because it will take time. We've not really spoken to the doses. You should assume that we will test up to 60 mg as part of this, but it's not necessarily the intended or one of the intended therapeutic doses. We simply just need to make sure that we've tested the full dose range. What we've seen from 60 mg is it gives a really good weight loss, and it seems to be safe and tolerable. We would be remiss not putting it into phase III. You also have to think again then supply. You would need basically three times as much API with 60 mg as you do with 20 mg. All of that has to be balanced, but we're testing it. My current assumption is that 20 mg, two doses lower, will be therapeutic doses, and then maybe also 60 mg. On the side effects, I think you said blood pressure, sorry, heartbeat or heart rate. We've not seen anything that we haven't seen in phase one with other incretin-based therapies. We obviously had a good long discussion both with regulators but also external experts. And we've basically not seen anything that would concern us. We'll continue to observe this and be diligent. But from what we've seen so far, this is in line with previous biologies. All right. Now we got to the last question, unfortunately. I think we got almost the entire way around. James, you got the last question. The mic is coming here. Thank you, James Quigley from Goldman Sachs. You highlighted the shape trial, Martin. Is there anything in the data that would explain the lower reduction in weight for Wegovy versus Zepbound? Wegovy, the drop between the clinical trial and what we saw in shape was about 2-3 percentage points, whereas Zepbound, it looked like it was more like 5-6 percentage points. Is that just dose or any other factors at play here? What does shape mean for the comparator arm in ReDefine 4? Is that what you'd broadly expect, or is it somewhere between that and semaglutide one in terms of where that should land? It's two good questions. I think for the first one, it would be speculative. What we think we see is maybe that in real world, patients may not go to full dose on the comparator arm, but again, I don't want to speculate into that. I think trying to use those data to predict ReDefine 4, that would be a stretch. I'm not going there. All right. Thank you, Martin. Thank you, Ludo. Thank you to all of you for attending this session. A lot of questions. We covered a lot of ground. Thank you to the online participants for participating. Investor relations and management will be around for a few more minutes after this call. With these notes, we hereby conclude the call. Thank you.