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

Welcome to the Novo Nordisk R&D event in conjunction with the 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 the pleasure to have this webcast. So just when we get to the Q&A, this is being recorded and webcasted. So we have a great lineup for today. But before we go through that, then talking about R&D is really talking about the future. And as we all know, the future may play out differently than what is being predicted by different forecasting models in R&D. So do note this is a forward looking warning and statement. So 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 conference, right? So we start out with the diabetes and then we have a big section on our pipeline in obesity and the unmet needs in that space. Great. So on the introduction, it's just a delayed clicker. Can I have the next slide, please? -- right? So when we start out with our strategic aspirations that I'm sure you've all seen before, then 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. And that's exactly what we're solving for with our innovation efforts in R&D, making better products available for our patients suffering with their diabetes at a global scale. And then 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 Knudsen, CFO of Novo Nordisk. Then with me, I have Martin Holst Lange, our EVP and Head of Development and then 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. So with the reorg we did over the last few months, we have created a dedicated unit for portfolio -- and portfolio strategy. So some of the other units that used to be in corporate affairs and commercial strategy. They 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. So that's a lineup for today. And without further ado, Martin, I'll hand to you, and good to see you. And then we move into diabetes.

Thank you very much, Karsten. So you heard both me and others in the company talk a lot about what drives our innovation is on that needs. And I'm oftentimes being asked the question I was done with innovating in diabetes? There can 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, maybe not so surprising because that's correlated to the increase in obesity that we also will speak to in just a minute. But even in type 1 diabetes an increase in both incidents and prevelance 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 is typically in the shape of cardiovascular. That could be stroke, that could be myocardial infarction, that could be cardiovascular death. But it's also chronic kidney disease and peripheral artery disease. If you want to think holistically and how you go about a broad chronic serious noncommunicable disease that is associated with these comorbidities and I will say the same thing for obesity in just a minute. Then obviously, we need to develop drugs that not only talk to treating this glycemia in diabetes patients in a safe way, addressing comorbidities but also trying to look towards prevention and cure. In the space of diabetes, that's both for type 1 and type 2 diabetes. And that's basically the innovation that we want to bring. So Karsten's point. We have a lot of innovation also at ADA that we will not present today, which actually anomaly 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. But we have to acknowledge your focus primarily is on the incretin space today. So we'll talk to that. In the incretin 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 and GLP-1. We know from type 2 diabetes that is not correct. At this point in time, 7 outcome studies has been performed in type 2 diabetes, 2 of them shown zero benefit on cardiovascular events. A couple of them showing around 12% MACE reduction on cardiovascular events. And then there's a magnetite with 26% risk reduction. There was also a apiglutide, 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. So what we do is obviously to show we have the best drug for improvement glycemic control in diabetes. And we've done that a lot with semaglutide. And then we look at the comorbidities. You've seen the outcomes and they are being presented at this year's ADA of the FLOW trial, the SOUL trial, the STRIDE looking at kidney disease, cardiovascular outcomes with Rybelsus and on functionality in patients with peripheral artery disease. And across the board, if I could have the next slide. 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 an oral semaglutide rebuilds on the cardiovascular effect. And then obviously, the STRIDE trial showing improved functionality in patients with peripheral arterial disease. Thinking holistically around how we address type 2 diabetes with our inventions.

Absolutely. Talk a little about what it means from a profile perspective. First of all, thank you very much. Good morning, some of you. Others may be 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 6 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 metabolic franchise, the whole DAPA program being 1 of the examples and then move from diabetes to chronic kidney disease and heart failure at the time. So I am back to the roots in a sense. Semaglutide has produced the most -- the widest comprehensive body of evidence for GLP-1 and type 2 diabetes. What Martin said for me is absolutely critical, there is no class effect. Each molecule is different. And what you can see here, based on the subcu 1 and 2 milligrams or the oral one, you have a wide set of outcomes that is actually second to an unrivaled in the market. Of course, the glycemic control might be the 2.2 with the same [indiscernible] the MACE outcome. You mentioned -- 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 as hard in [indiscernible] something in PAD 13% the body weight, the kidney outcome is 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, body weight, 9.8%. I just got that number for you to have in mind, 9.8% on the weight loss with Pine and the MACE outcome, with -- so all this is quite unrivaled and it's quite unique. And honestly, from a width of comorbidities associated with diabetes, it's really unique. What does this mean? And if you got maybe the next slide, thank you very much is that we are the market leader in GLP-1 diabetes. And there is still a lot of growth potential -- the growth potential in the U.S., we know there's a growth potential around the globe. Ozempic was launched in 80 countries. As you can see, this 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, a positive opinion from the CHMP on Friday, just on our way on the plane to ADA. And of course -- and we started, as you can imagine, to repromote again in IU after thanks to the increased supply. Rybelsus, 45 countries, the first and only oral GLP-1 in appeal. And I remember that when I left AZ, the whole debate was is it still feasible or not? And the jusry is still out at the time 6 years from now. I think the jury has said the answer to that, and the sole trial this isn't expected by H2 2025. So again, global market leader, market share of around 60% and potential worldwide. In the U.S. and in IO 70% only -- 77% only of the overall prescriptions or GLP-1. So there's a lot of debt in that market that we need to continue to explore with Semaglutide.

Perfect. And now to obesity -- and I'll go give the same on huge unmet need. We, together with our competitors, our peers are treating less than 5% of patients living with obesity in U.S., and that means that we are creating a very, very small proportion globally. We expect to see the incidence, the prevalence of obesity still be on the rise. But 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. But last is obviously a long-term aspiration. So right now, we're focusing on treating obesity and treating comorbidities. The comorbidities that we are talking to are many, so depending on which way you look at it, you can see list from somewhere between 150 to 250 comorbidities associated with obesity. A great number of those are cardiovascular in nature. Some of them are just related new knee osteoarthritis, for example, to the weight that patients have to carry around. And some of them are may be more difficult to address from an intervention perspective, for example, cancer. But 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, again associated with a dramatic decrease also in outcomes, i.e., increased mortality. And therefore, we've just seen in the last couple of days, ACC adopting to their guidelines, the GLP-1 should be considered in patients who have established cardiovascular disease and need to lose weight. Jan wants me to speed up, but the clicker doesn't work. And so -- the way we think about this, and you 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 comobidities. They just don't want any side effects. Some patients have to lose weight and focus on comorbidities. I'll show in just a minute, and you have heard me talk to it before we go with that drop is still the only obesity drug with an increase in base that has proven CV benefits. And 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. And 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. So being able to cater to that in a holistic way, that's the pipeline that we're building. And you will hear speaking and then you can sort of guess where Ludovic is going to position them speaking to cagrilintide and monotherapy we go in monotherapy, CagriSema, amcretin and our triples. And 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. And by the way, I think both Karsten and Ludovic forgot to mention Ludovic is also heading our 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. And we have assets that obviously are leading in the incretin space, but we also have assets. And I should, in this context actually mentioned ambient biology that goes beyond the incretin space. Some strategy. It's a poor strategy to continue to compete where everyone else is. And most of our competitors are moving into the incretin space. So 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. And that also speaks volumes to what semaglutide can do. in real world, and 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%. Now 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. So reasonably robust looking at a weight loss achieved in the real world. What 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. So just confirming what we already know from our clinical trials. And you will actually remember in clinical trials, Wegovy introduces a 17% weight loss, quite consistent with the real-world -- and then obviously, we have to say real world on cardiovascular outcomes is actually besting the ICT that we did, 42% versus the 20% that we shown in SELECT. So 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. 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 and one in diabetes. On average, 69% risk reduction for hospitalization for heart failure deaths 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 under regulatory review. You've heard us talk to that. We expect to see outcomes later this year. And the same thing for MASH. 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. But nevertheless, really, really strong and robust data that have prompted the FDA to give us a priority review. So 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 milligram. And 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 have 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 milligram. It's also important to call out, and that's 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, is transient and it doesn't lead to withdrawals from the studies. So therefore, obviously, we are investigating and we're trying to understand it, but it's not seen as a detriment to the overall risk benefit of the offerings. But I just wanted to call that out. That's where we actually see a difference between 7.2 million and 2.4 million. And now, it's you?

Thank you very much. Thank you, Martin. So 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. So it's a super, super deep market to be in across the world. And 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 milligram, 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 is seen today. And I think it's -- that's the way the market sees it, and we need to respond to that need. And 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 have come, again, uniquely positioned right now, all-cause mortality. And these 2 other benefits. which are going beyond the weight. And 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. And we believe that, by the way, incidentally, this MASH benefit is certainly one of the main attraction why we actually -- we 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. And 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. So it's something here that I think one should not underestimate. It's quite massive. So altogether, 30 launches, the MASH indication, as Martin said, and the heart failure label decision expected in the second part of the year in the U.S. And of course, and we've submitted -- sorry, we'll be submitting the 7.2 milligram in Europe in the second part of the year as well, which is really important. So again, widening and going back on that -- on the turf on the ring of efficacy because we believe that we have the data to support that efficacy.

Not seeing great data being put to good use. So thank you. All right. oral semaglutide. There's a lot of focus on oral incretins at this moment. We believe that we have what is, if not the best, and very, very, very good offering in this space. Actually, the weight loss that we've seen with oral semaglutide is 17%. So completely comparable to that of the subcutaneous offering. And the -- again, 15% weight loss reduction seen in more than 55% of the patients, 20% weight loss reduction seen in 35% of the patients. So very, very strong weight loss data with an oral offering with a very well -- sorry, with a very well-known safety and tolerability profile that I will show you in just a minute. But before that, I just want to show you that -- and this is maybe not surprising, you've just seen the data from the SOL study. Again, it's down to semaglutide exposure. We see some really, really nice benefits as measured by width 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. And then as I said, the gastrointestinal side effect profile, 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. So super happy that...

Absolutely. same graph on the left-hand side, same depth of market. And certainly, with oral semaglutide, the opportunity to address a new population that right now is not yet contained within the growth. And it's one of the best way we believe to expand the obesity market. From a performance and efficacy perspective, again, 16.6%, 17%, equivalent to the causing, the injectable causing and the MACE have come with the potential, of course, if there's a bridge between 14% to 20%. So really, you have here something which, again, weight wise is best-in-class from an oral perspective and from a MACE perspective, bringing additional benefits, widening that market. And that's what we really need to do, and we'll talk about it later on without spelling our own thunders. We'll talk about 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. And 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 overall semi 25 milligram. So again, first, oral, super competitive and something that we really are impatient to bring to patients.

So 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 are doing a little bit the same with you. So now we move to CagriSema and Cagrilintide. 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 1 or 3 ramps, they call. 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. But there's 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. So you are seeing right now, we're testing 2 amylin analogs in monotherapy in Phase I. We already have Cagrilintide. That's sort of a dual acting on the receptor system. But you should expect that the other 2 are maybe on either side of the spectrum so that we actually test what we have for our different biologics 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, speak to the spectrum that Ludovic will also come back and talk to where we differentiate and where we position our drugs. But 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 don't have too many side effects. We actually have substantially lower than what we see with Wegovy. So sorry, I should just say, we expect to start cagrilintide in monotherapy in Phase III later this year. And obviously, it's full speed ahead because this is a segment of patients that no one really addresses at this point in time. And obviously, we have the potential to be first with a really, really strong offering in this space. CagriSema, I don't 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 [indiscernible] randomization, so 21 to 3 to 3 to 7, and then obviously, you probably also heard today, there was a speculation. And obviously, I can a little bit confirm that speculation. We do know that men loses less weight than women. And in this study, we saw slightly more men than what we've seen before. Same thing for Asians. And therefore, there is maybe something in the REDEFINE population that could drive the results that we -- and you heard from the last speaker, 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. And 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 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. So that's not the issue. It is basically the fact that patients are still losing weight at the end of trial, 68 weeks. And you also heard some examples today of this is probably a too short trial, and 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, and we actually see almost 1/4 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. So 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. But 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. So regardless of you do diet and exercise, if you do gastric bypass or you do medicinal intervention, approximately 30% to 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 introduce is we know from semaglutide that we improve lives, We reduce mortality, we reduce morbidity. And as you've seen -- if you have seen the slide, we improved functionality. And you actually also saw that from the CagriSema presenters today with the quality of life questionnaire, improved functionality despite, obviously, this body composition. And 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've been trying to talk to you about for the last 6 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. So they are actually as a group, all of a sudden in the close to non-obese space. But there's another group that is also a substantial group. It's not 50%, but it's lower than 50% that lose weight very, very fast. And 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 those 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 rates that are actually lower than that what we see at Wegovy. The other slightly higher, but not high enough to drive the reduction in dose that we see. So clearly, driven by the speed of the weight loss. And as you also heard from the investigators today, that can be mitigated by slower titration. And that was both from the questions, but also from the speakers today. That's basically how they see the solution in the obesity space. And now the [indiscernible] work. You've also seen the impact on cardiovascular biomarkers. Again, sorry, this is not [indiscernible]. I'm sorry, I'm mixing up the slides. So it's actually really, really interesting. 40% loses weight, so they are below BMI 27 at 68 weeks. Who have a weight to height ratio, not a treat to target ratio, weight to height ratio that is below 0.53 in 36% of the patients. And in almost 30% of the patients, we see a combination of the 2. These are really, really interesting measures because they are probably a little bit in combination stronger as a treat to target measure, and they are also reflective of cardiovascular outcomes. So this is something that we want to explore more. But fact of the matter is this we see the strongest data that we've seen with CagriSema. And obviously, we intend to pursue that as we move further. Now I'm at the cardiovascular biomarkers, waste 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. And it obviously speaks to our sort of aspiration of showing strong CV benefits with CagriSema. We are currently conducting ReDefine-3. And 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 effect. 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. And 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 the titration steps. ReDefine-2, again, super strong weight loss. You heard sort of the statements from the stage today. I cannot repeat those. I don't think I'm allowed to do that. But really, really strong weight loss data. And obviously, when we look at glycemic control, and I know that there's going to be a question or 2 on that. You cannot -- and you also heard that from stage today, you cannot assess glycemic control without an active comparator. And then the good question is why is there not an active comparator? 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 achieved the A1c target. That's more than 80%. That's reasonably strong. And then obviously, when we look at time and range, I don't think I've ever seen data like that. We saw them actually in Phase I and II. But now we have also seen in the Phase III, that is a very, very strong time and range, and 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. And then 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, we need at least 90 weeks of treatment. Our assessment is actually for accruing most of the weight loss, we will need 80 weeks of treatment, but we're extending the trial. So 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. So in this trial, and you will also see the same for some of the amycretin trials, we will not include patients with a BMI below 30. So those patients will be addressed in the cardiovascular outcomes trials where we can address lower BMIs together with comorbidities. So we'll do it in a slightly different way, but obviously aiming to show what kind of weight loss potential do we have with REDEFINE.

Absolutely -- so as you can see, we're really trying to address 2 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, and that's why you're seeing the REDEFINE-11 trial, longer trial. So it's really important that we are really -- it's very clear that we're really focusing on that. The second thing we're trying to do is we're trying also to understand, and again, it's a segue to what we're going to talk to in a few minutes. We're really trying to understand how the drug can be used with different patient profile. 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. So addressing the efficacy first, but already moving to what we believe will be the next step in obviously, treatment, which is more customization of the treatment journeys of patients. So if you summarize, overall, we have with CagriSema, a first set of successful pivotal trial. For those who were there this morning, it was, I think, quite clear. And 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. So 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 easy to talk too long about a small Phase I trial. It was actually more complex in the setup than what we are showing here, also testing the 60-milligram dose that you have seen results of the last couple of days. That was fast. At the end of the day, I thought we heard something about weight loss in this that comes -- 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. Parkhoi just pointed out, these patients are actually hospitalized good part of the trial. And obviously, in that, you collect a lot of data that you would normally not collect. Also, we've not taken the learnings from REDEFINE-1. So 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 effect and bring it to be comparable to that of CagriSema. And then with a weight loss potential that at 20 milligram at 36 weeks suggested 22% weight loss. And obviously, at the 60-milligram dose also at 36 weeks and up to 24%, actually 24.3% weight loss. So really, really exciting days, something that is big potential. We had to get the dosing right, we had to get the titration right, so we mitigate the gastrointestinal side effect. But you can clearly see the weight loss potential is interesting and attractive. And 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. But if you have severe obesity and a lot of patients have that, I think it's around 20% of those patients who have BMI above 40. CagriSema, amycretin with this kind of weight loss would be really, really an attractive offering.

And 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. So 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. But of course, this is just part of the program, and 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 subcu and the oral and/or different presses and different comorbidities, okay, which essentially is enriching the amycretin program to make sure that we are really answering not just the -- the comorbidities, but also the way to be treated, as you can see, ACVD, heart failure, CKD, the knee, knee osteoarthritis, the sleep apnea, which we believe is also one of the main problems that the obese patients are actually facing today. So 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.

So I've already shown this slide and now the clicker on over, okay. Here we go. Trying to address a spectrum of obesity. It's super, super complicated. There were -- 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 40. And you can have BMI 40 with no cardiovascular risk. You can also have BMI 27 with a lot of cardiovascular risk. And we know from SELECT, those patients also benefit from treatment. So the complexity of that requires maybe also, I don't want to say 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 2 biologics, we believe that we have a great first step into how do we serve patients in a broad spectrum of obesity. But we also have to acknowledge we are not done there. Innovation has to come more in the incretin space. Innovation has to come more just back to the complexity of the amylin biology in the biology space. But innovation also has to come with new mode of actions. And 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 an external innovation from our perspective. And we'll 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 don't want to say a conventional, but a well-known combination of glucagon, GLP-1 and GIP. And then there's a completely new mode of action, first-in-class. And I really resent you if you will ask me what ACSL5 stands for because I can only say it in Danish. It's [indiscernible] inhibitor 5. So try to look it up in English. It's much, much, much easier. But 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 2, maybe slightly less weight loss, but a more differentiated than approach to other subpopulations of obesity with the ACSL5 inhibitor. So exciting times and really something that we want to pursue with everything that we have. And I'm trying to push. Here we go.

Absolutely. So 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. And a couple of slides now to explain to you from a patient perspective, some say customers, something, even say consumers sometimes, what does it mean to have a full portfolio and really be relevant in the world of obesity. So on the left-hand side, I think Martin shared that with you, the BMI category, you still have a significant amount of proportion between 27 and 30. But look at -- if you sum up your 30 to 40, you actually have actually more than half of that population in that range. And that's going to go up, which means that there's definitely a lot of space for the advanced agent. But there's also a need to be relevant in that space as well. So 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. We're talking ASCVD, heart failure, MASH with fibrosis. So you can clearly see that the variety of patients and the variables are quite high, but we need to match that. And that's what you see on the right-hand side. Next, please. So this is what you saw earlier on with Martin. He shared with you actually this idea that there are 3 elements that we fundamentally are considering -- for [indiscernible] 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 do with CagriSema, with amycretin with the tri. We're really pushing as hard as we know to make sure that we can really exploit and test the limits of what we can do. But then 3 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. So the way you want to be treated, you want to have a slow -- 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 urthritis or knee or women's health, for instance, which is extremely important when it comes to the different patient needs. And last but not least, of course, safety and tolerability. So if you multiply and if you combine this not by pushing our science towards the market, but rather understanding what the market really wants. So 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 cagrilintide that tolerability profile is actually super, super good. And you saw it that morning again when you saw the lines that you -- that was showed by the presenters. Of course, semaglutide is the backbone of what we do, both subcu and oral. And then you escalate CagriSema, amycretin, [indiscernible] and of course, the triagonist. And this is only what is in development today. We also have other assets that are of different modes of actions, including more than 7 BD deals on the topic over the past year. So really enlarging the width. And that's what we believe will be the -- we believe could be the winning ticket in terms of obesity, having that breadth of products to make sure that we are respecting these profiles, and we are really on the gender, lifestyle conservation and the RSV clinical profile is relevant for patients. That, I think, roughly concludes our discussion, and we're very happy to answer questions. Summary, high unmet need in diabetes remain. You've seen that still low global penetration rates, complex disease for obesity, different treatment options, and we have that with Wegovy, oral sema, Amylin, Cagrisema, Amycretin and, of course, committed to continue the development of a portfolio with superior treatment outcomes.

All right. Thank you to Martin. Thank you to Ludo. Now you've got a comprehensive review of our portfolio. So now it's Q&A time. I see now it's not phones going up and now it's hands being raised at an equally fast pace. So to control. I think we start here from the front and then we move backwards and then back. So Richard Vosser, if you could please state your name and then one question each.

Richard Vosser from JPMorgan. One question on amycretin then. Martin, you mentioned sort of thoughts about slower titration and different doses. Given the data you've got on the Phase I, 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 and the side effect profiles are also quite similar to what we saw in Phase I. So we know by adding one more dose by allowing -- and again, going back to the CagriSema allergy, you have to be careful you don't optimize for the minority. You rather have to optimize for the majority. And the majority in REDEFINE-1 actually titrated well. They lost 22% of their body weight, and they had very, very low adverse event rates. So you should not ask the entire population to start to titrate slower, but you need to allow them the patients who do -- and for better words, there was some speculation today. You can -- we cannot predict based on baseline phenotyping, who will be a super responder and who will be a normal responder. So we basically have to allow them to start on the first dose. But we also know in that first titration step, that's actually when they start to see the weight loss. And that may be when they have to think about moving from titrating every 4 weeks to every 8 weeks. And if they do that, then I have 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. And to get data from steady state, we do longer studies. We are reasonably confident that we can do that. We've had a lot of discussions, obviously, with the external experts, but also with authorities. And based on everything that we have, we think that we can do that. But 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.

Matt and then Michael afterwards.

It's Matt Weston from UBS. Can I come back to CagriSema in the REDEFINE program? And 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. And it was clear from the experts they stated that there was no causal link to the drug that had been suggested. But 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. So it was not a great number of events. There was one event in REDEFINE-1. And the most important thing is we had questionnaires looking at suicidal ideation. They did not show any signal at all. And I'll just remind you, these chance findings when you randomize 21 to 3 to 3 to 7, any statistician will tell you that one event that will happen where you have the most patients. We had to do select to get 20 events of suicidal ideation semaglutide versus placebo, and they were distributed 10 to 10. So based on everything I know, that would not be my biggest concern. But obviously, it's something that we continue to look at. And we will continue also to employ these questionnaires so we understand exactly what is going on.

Michael Leu from UBS. 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.

So first of all, there's a lot of volatility in DEXA scans. So 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. And 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. But 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. And based on what we just saw today from the questionnaires, it appears that CagriSema weight loss is the same. But we will continue investigating this. It's not because -- I think we have to have slightly more sophisticated methods of investigating this. And 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 a true differentiation.

Thank you, Martin. And then we move one row back to Carsten.

Thank you very much. Carsten from Danske. I'll try to see if I can pronounce it correct this dysesthesia.

Yes. We have -- some of us have seen taspoglutide, for example, and we are a little bit allergic to allergic reactions. So how certain are you that these are not the sort of hypersensitivity signs or something like that?

So what we do in our development programs is that we also measure antibodies. There's no correlation between antibodies, i.e., a proxy for allergic reactions and this. And the important thing is the events are transient and they go away while patients stay on treatment. And most of them, apart from one was mild in nature in the amycretin program, for example. So again, something that we have seen before. Others have seen it as well if you look at what -- and it doesn't appear to be related to an immune reaction.

Okay. Then we move to the other side, Pete.

Peter, BNP. Just a question on R&D strategy for you, Martin. Yesterday, we heard there's 50 non-peptide oral GLP-1s in the clinic. 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. So the question is basically, does Novo need, in your view, an oral non-peptide GLP-1 in the portfolio? And 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 any of the 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. But obviously, we also have 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 safety and tolerability profile. If we can scale that, and that's what I hear from -- it's not Karsten is 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 a competitive FMC and scalability and then a very well-established safety profile and a really good efficacy profile. We haven't seen that. But you've also seen our recent announcement on Zepbound, where we actually look together with Zepbound on what I would call the next generation, non-peptide incretins. And there, the chemistry lends itself not only hopefully to the good efficacy and safety, but actually also to the scalability. And 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. But obviously, if we can find something that can be scaled at a reasonable FMC, that's where we go. And Turner is our first shot on goal there. It's the same philosophy with the ACSL5 inhibitor molecule. That's also [indiscernible].

Acquisition of that we announced -- so the idea is that irrespective of whether it's incretin, non-inretin or injectable, we want to grow the mode of actions that we have in cater various needs. might be very early if we want to progress that as...

Martin?

It's Martin Parkhoi from SEB. If we look at the SURMOUNT-1 data and now the detailed data today in REDEFINE-1 and then we 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 agents and also having the same flexibility in the 2 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 a statistical differentiation, we'll have to wait and see. The true proof for CagriSema is REDEFINE-11.

Jeff?

It's [indiscernible]. So on this analysis on the sort of people who dosed down and responded better. So one thing that struck me is that their weight is about 10% lower than the other. There's a difference at the start. The BMI is different.

The BMI at baseline is 2 percentage point difference. One was at 39, the other is at 37 -- but at end of trial, obviously, there's a big difference.

So it implies something like a mid- to high single-digit difference in weight, assuming all the same height at the beginning of the trial. So just the question is, so have you seen in any other trial 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. And the second part to this is when -- 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?

So just answering the last question first. As you also heard from States today, we didn't really collect it. But based on everything that we can deduced from the data, it actually seems more like it was the speed of the weight loss and the approaching sort of the magic liner 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. So from that perspective, that's our thinking. But 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. And obviously, we've looked 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. And in every study that we've seen, we've seen a little bit of the same picture also in our 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. So we had 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 to go, so we go there.

So Martin, I noticed on the pipeline slide, you've decided to discontinue your GLP-GIP and Novo's decided to advance to bring forward a GGG and you're advancing your -- another triple agonist. So just trying to get a sense for the next leg of the pipeline and also Novo's historical, I guess, our perception at least at Guggenheim of glucagon really kind of being an [enatma] mechanism. I think there's a lot of statements suggesting that glucagon could be unsafe, but you just licensed in that asset. So 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.

So I really appreciate that question. I have to compliment you actually for spotting it. So you're absolutely right. We have discontinued our GLP-1/GIP. 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. And what we saw was actually a really, really good and strong weight loss comparable to that what we already see out there in the competitive space. So from a pipeline perspective, not differentiated to that and not differentiated to what we have with CagriSema and incretin and potentially the triples coming in. So 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 will 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 cagrilintide. So we've also seen what we would call concerning safety signals with the glucagon. But with the right ratio in a triagonist, we don't want to rule out that glucagon could do something. I mean we do know, for example, in MASH. And as Ludovig said, MASH is very interesting to us also. Glucagon may have an important play. So having that as part of what we investigate, but not necessarily progress to the market, that's super important. the other triagonist with amylin biology. I think that from our perspective and the way we think about this has high potential, but time will show.

Great. Thank you, Seamus. Thank you, Martin. Then we move to Thibault.

Thibault Boutherin, Morgan Stanley. You mentioned the different sort of submarket that you want to address. And I think one of the things that was maybe not mentioned is the potential for longer duration of action assets. So 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.

So I think Ludovic can maybe speak to the commercially 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. But then 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. But we have actually made a collaboration where we are testing the potential for once-monthly GLP-1. And that will go into clinic, I think, in this or early next year. But I think from a commercial perspective...

If you look again, the market is it's very difficult to say. But if you look right now, the motivations for these treatments in the various subgroups, you don't see the length of treatment per se, i.e., 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. But 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. So we have it, as Martin said, as one option. It's not the option that we are now, we believe it's top of the list. [Indiscernible]

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 '26 before you initiate the study? And also just looking to your main competitor, it seems like they're more aggressive in time lines also compared to filing for when they have initial readouts and when they trial. Can you speak to what you're doing to speed up your processes?

Yes. So 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 2 months' time. And it will actually have finalized recruitment just around the end of the summer holidays. So that we can do. We can also do very fast reporting. You may remember, we did a filing, I think it was 4 weeks after last patient last visit. But 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 mat is sitting there. So having the entire -- also from a commercial perspective, when do we launch what? I mean I don't think Nudvig wants to launch CagriSema and amecretin at the same time. I don't know. But 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. And 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've also seen us actually doing the same considerations with all 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 -- and 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. But good question. We like speed in R&D. So we do. So thanks for pushing on that one. Over to Emily.

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. So 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? And then 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.?

So on the first one, you actually saw a little bit on this from Ludovic in one of his REDEFINE-9 is testing 1 milligram and 1.7 milligram. And the idea would obviously be to have that also in place from a regulatory perspective. For amycretin, we will aim to have more than one dose approved. So 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. And then on the filing in U.S., I think that's more for...

The focus of the U.S. is on CagriSema and the focus on IO. And from a calendar perspective, it actually makes more sense to pursue the U.S. CagriSema venture to be actually on the market. That's what we're really trying to achieve speed to market and then we are dividing and conquering these 2 potencies.

Yes. Then we move to Raj, we have carriers just to get some exercise [indiscernible].

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. But you and I very well know that this market has gone out of our hand, and it's a lot more consumer now, right? So 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 other to come and eat your breakfast, just to be sure. And in that context, can you help us understand how oral sema is going to compete with orfoglipron 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?

Happy to take that. So... You're perfectly right. I think that if you're just pushing from a medical perspective, you're only seeing part of the market. Now we should still do it because I still believe there's worldwide there's a lot of reasons to use the medical lens to do this. But we're also looking at this market as seen, as I mentioned, from the patient. And 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. So we are working in those what I call the preferences, this R&D pink bar that you saw there, we hardly working on in which way the patients want to get their medicine. With what price point do you want to get that medicine if it's cash versus noncash, how they want to access being delivered home and not home. So we're also working on all the modalities through which patients are accepting the medicine. So that pink bar you saw is exactly answering your need. Now -- this being said, you still have to make sure that you're relevant from a scientific perspective and 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 direct with Novocare, for instance. So that is completely taken into account, both the more traditional way to access the medicine to the physicians as well as the newer trends on that medicine is 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 built on semaglutide over and beyond the weight loss. So we believe we have here a stronger contender in the market and a very attractive profile, even for those patients that don't want to go injectable. One last point on that. We really believe that having an oral asset 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 asset will help us because beyond the weight, which is already quite 16.6%. If you correct for the placebo adjusted, you'll see that actually from an adverse event -- it's really, really on par with what you can see outside. We believe that there's a good chance to be first in the market and having a strong position with the oral and [indiscernible] also.

Thank you, Martin. I then move to [indiscernible].

Question for me on market segmentation. So in the context of trying to find the right product for the right patients, I would be interested to understand whether you considered raising the BMI hurdle even higher. If we think about what you've just got for REDEFINE- 11 and you also referenced amycretin, did you consider going beyond 30 plus? And if not, why not?

So 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 when we come into the really powerful biologies potentially the triple, maybe even amycretin, we will do specific dedicated studies to investigate this. But in that -- and that also speaks to a little bit the question from before and what Ludovic talked to, then 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. And again, building those data, but also building that pipeline that can cater to that is the way we think about 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. So that's why we think -- and back to your question on the consumers, we're equally interested in knowing how you initiate the treatment. how you escalate the treatment, how you -- and how you maintain the treatment. This is all part of the studies, and that's why you get the REDEFINE-9 program on the maintenance as an example. So we are really interested to understanding that better and acting upon it with a customer/consumer view, not just the medical.

Thank you, we move to Emmanuel.

Emmanuel from Deutsche. Maybe just a couple of follow-ups on amycretin, please. Firstly, interested to understand your comfort with a couple of aspects -- other aspects of the safety profile that emerged in the papers this weekend, namely the elevation in headache rates and perhaps more importantly, the magnitude of elevation in DPM. And then secondly, apologies if I missed it on the Phase III, you actually confirmed what doses you're planning to take into Phase III? Are you planning to use flexible dosing? And perhaps you could just remind us why the urgency to rush into Phase III if you're confident on CagriSema.

So these studies take time. So the urgency is that for better or worse, and you also heard that today, we are moving from 6 to 8 weeks to something that is longer. So the -- at some point, we 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 milligram 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 have tested the full dose range. What we've seen from 60 milligram is it gives a really good weight loss and it seems to be safe and tolerable. And then obviously, we would be remiss not putting it into Phase III. But you also have to think then supply, you would need basically 3x as much API with 60 milligram as you do with 20 milligram. So all of that has to be balanced, but we're testing it. My current assumption is that 20 milligram 2 doses lower will be therapeutic doses and then maybe also 60 milligram. 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 I with other [indiscernible-based therapies. We obviously had a good long discussion both with regulators, but also external experts. And we're 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. So now we go to the last question, unfortunately. So I think we got almost the entire way around. So James, you got the last question. So mic coming here.

James Quiqley 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. So Wegovy, the drop between the clinical trial and what we saw in SHAPE was about 2 to 3 percentage points versus Zepbound and looked like it was more like 5 to 6 percentage points. Is that just dose? Or are there any other factors at play here? And what does SHAPE mean for the comparator arm in REDEFIN-4? Is that what you broadly expect? Or is it somewhere between that and SURMOUNT-1 in terms of where that should land?

It's 2 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. But again, I don't want to speculate into that. And I think trying to use those data to predict REDEFINE for, that would be a stretch. So I'm not going there.

All right. Thank you, Martin. Thank you, Ludo, and thank you to all of you for attending the session. A lot of questions. We covered a lot of ground, and thank you to the online participants for participating. Investor Relations and management will be around for a few more minutes after this call. But with these notes, we hereby conclude the call. Thank you.