Welcome to the Novo Nordisk R&D event in conjunction with the ADA 2022 here in New Orleans in hot, humid June. It's great to see you all here. We have a very nice R&D presentation coming up. I'll have to remind you that this event is being broadcasted. The setup is that we'll do a presentation of some 40 minutes or something like that, followed by Q&A. We'll have a small social event afterwards. That's kind of the format. As usual, I have to remind you, especially when we talk about R&D, that there will be a number of forward-looking statements. The future does not always pan out as we predict in our internal modeling and forecasting. Hereby warn appropriately. Today, we're a team of three from management in Novo Nordisk. Starting with myself, Karsten Knudsen, CFO of Novo Nordisk, for a little bit more than four years now. With me, I have Martin Holst Lange, EVP and Head of Development, and Mads Frederik Rasmussen, Senior Vice President and Head of Clinical Drug Development. These are the two gentlemen who will do most of the presentation today, and who will be able to field all the key questions around our clinical trial outcomes, design, logic, and so on. Looking forward to that. This is the program. After a brief introduction, Martin will be digging into a number of our obesity trials, the STEP trials, the SELECT trial that I'm sure you all know about. Mads will be looking at what we do in our GLP-1 diabetes trials and the additional label indications we're pursuing with Ozempic. Martin will continue with our most recent results on insulin icodec, our once-weekly insulin. Followed by Q&A. Starting out, I brought our strategic aspiration slide from Q1. I'm sure you've all seen it. It has not changed since our quarterly results. Just reminding you all, we're showing extremely nice progress on our ESG, what we call purpose and sustainability, both on the environmental side, social side, and also on the governance perspective. In terms of commercial execution, we continue to take value market share in diabetes, as you see, up 1.2 percentage points compared to a year ago. Doubling obesity care sales compared to Q1 last year. Really very solid momentum on obesity care. I think we all sense here at ADA the drivers behind what's happening in the obesity landscape. Rare disease is also growing 3%. Of course on financials, one of the strongest quarters in recent history of Novo Nordisk. A 2% top line growth and 8% profit growth and corresponding strong cash conversion and capital allocation to our shareholders. I'll skip the innovation and therapeutic focus. We'll come back to that. I brought one slide on what's happening and the most recent market share trends in diabetes. Here on the left-hand side, I brought a slide showing the monthly market share development on global GLP-1 volume market shares. As you see, as of March 2022, Novo Nordisk are now at 59% global volume market share on our total GLP-1 franchise, counting both Ozempic, Rybelsus, and that of Victoza. Furthermore, you see that now Ozempic is the global market leader, the biggest brand measured on global volume market share, again on a global scale, exceeding 40%, now at 41% global volume market share. So very strong momentum on the back of a market at the market that is growing more than 30% measured in volume on a global scale. On the right-hand side, this is the graph that we also discussed in conjunction with our Q1 results and the key drivers behind us raising our outlook for the full year in connection with Q1. We see a U.S. GLP-1 market that's also growing north of 30%, and we've seen an acceleration in new patient starts here in the beginning of 2022. Moving from, I would say, to the tune of 20,000 new patient starts, new scripts per week on the back of Ozempic to now approaching and even exceeding 30,000 new scripts per week on Ozempic. Clearly very strong momentum behind that of Ozempic. As denoted on the slide, now we've also launched Ozempic 2.0 in the U.S. market. This is just the final slide of our strategic aspirations before I hand over to Martin. We've set ambitions for both innovation in diabetes, obesity, rare disease, and furthermore expanding our presence into other serious chronic diseases. Remember, with the sales growth we're looking at as a corporation, then of course we have a key obligation and a key opportunity to step up on investing even further in our R&D efforts. Basically expanding our pipeline and also diversifying our pipeline towards more diverse therapeutic categories. A lot of investments and activities happening there. I think that's the best segue to you, Martin. That's perfect. to cover what is happening in especially obesity care these days. Thanks very much. Yeah. I think you all know me, so I'm not gonna introduce myself. Maybe a little bit on Mads. Mads has almost 20 years in Novo Nordisk and has been in development most of that time. He's had a stint in the U.S., just so he doesn't have to introduce himself. He is one of the most experienced drug developers, not only in Novo Nordisk but also in industry. Really, you should ask him some tough questions because he knows how to answer them. All your friends. Before I jump into our obesity discussion, I just wanted to remind ourselves that this has been a fun and busy year for R&D in Novo Nordisk, also speaking to the fact that we are investing more and more in R&D. Maybe also calling out that while we are investing more in terms of numbers, we are also accruing a lot of efficiencies. In reality, we get more out of our investments. It allows us to continuously increase both the breadth but also the depth of our pipeline. You see us initiating during the course of 2021, but also during the beginning of 2022, a number of both phase I, II, but also in particular phase III trials. I'll show in the next slide, and just as a reminder, we are in phase III within all eight disease areas that we have defined for ourselves, so that is obviously super. Just to call out a few, and I promised the team not to talk about all of it, and then Jacob very nicely pointed or highlighted what I was supposed to talk about, and that's approximately half of the slide. Which is gonna be a little bit of a problem. We have 52 slides, and I promised Daniel to spend a lot of time on trial design. I'll do this fairly quick. Indication, we almost sometimes forget to talk about the Alzheimer's indication. That is still something that is very, very exciting in our pipeline. We think that that is gonna make a tremendous potential difference for patients, but certainly also in the treatment of Alzheimer's. This is currently in the midst of recruiting for the Alzheimer's trials with an aim to finalize recruitment within this year. Then just as a reminder, two years of treatment before we start to see a readout of those trials. You know, obviously the oral semaglutide for both diabetes and obesity, we initiated the diabetes trials before we did obesity. That means that we will expect a readout of those trials during the course of 2023. Z iltivekimab I think also requires a little bit of a shout-out. It's super exciting. It's innovative treatment of ASCVD, specifically, with an anti-inflammatory approach. As you'll recall, we acquired the ziltivekimab molecule slightly more than 1.5 years ago, and we are in the midst of recruiting for phase III in a quite advanced ASCVD population with both established cardiovascular but also chronic kidney disease. We went on to acquire Dicerna. I've discussed that with quite a number of you. Obviously our purpose with that is to acquire a platform that can complement our proteins and peptides platform within all of the disease areas that we move in. Specifically, RNA-based technology allows itself to not only rare disease but also actually looking at targets for the diabetes, obesity to cardiovascular disease, which complements our research efforts very, very nicely. We're super happy about obviously the go approval in Europe. You are asking a lot about when are the first launches in Europe coming, and we're obviously aiming to have the first launches towards the end of this year. Karsten talked about the Ozempic approval for 2 mg in the U.S. You've seen the impact of that on our sales. Really high aspirations for that offering. We are in a place where we're being asked a lot about responses to tirzepatide. We are actually of the opinion that from an efficacy perspective, there's not a big difference in terms of glycemic control between tirzepatide and Ozempic. As you all know, with a tolerability profile comparable to that of 1 mg, this is a super attractive offering, as we also see from the uptake already. Mim8 and concizumab in rare disease, we are in the midst of doing a rolling submission for concizumab for patients both with hemophilia A and B with inhibitors. We will be finalizing the study, phase III study for patients without inhibitors during the course of Q3. Then we'll do the regulatory submission for the full population in short order. At the same time, we aim to initiate phase III for Mim8 during the course of this year. I'll come back and talk about icodec and ONWARDS 1, 2, and 6, so I'll not go into that. That was a really, really fast run through what actually has been super exciting and really, really busy year. The end message is partners allowing us to invest more in the clinical space. You also know we invest a lot in the research space. Matt has lost most of his hair because he's responsible for the clinical trials. As you will see, when we started in 2019, we had 17,000 patients in clinical trials. We are today close to 50,000, and we intend to exceed 50,000 during the course of this year. That's obviously a reflection of a great number of activities, and just the fact that we are in phase III, which we were not two years ago in all of our disease areas, is obviously talking to the progress of our R&D pipeline. Maybe just one word of the risk profile of what we see here. We actually see a nice combination of high reward, low risk projects within the diabetes obesity, and maybe also a little bit rare disease space, combined with maybe some higher risk in our new therapy areas, where the reward is also similarly high. But again, giving us a very, very nice and balanced profile for our phase III program, and this is the approach that we intend to take also in the future moving forward. Moving to obesity. Most of you have commented that this is about diabetes, and everyone is talking about obesity. It makes a lot of sense because as you obviously know, obesity is basically the starting point for type 2 diabetes in the vast majority of patients. There are outliers, there are patients with type 2 diabetes that may not be obese, but the vast majority of type 2 diabetes patients start with obesity and then progress to more severe comorbidities. Everything in the cardiometabolic space starts with obesity. Therefore, it's super prudent, even at a diabetes conference, to talk about obesity, the treatment of obesity, and the use of anti-obesity approaches, anti-obesity medication to prevent not only type 2 diabetes but also other comorbidities. This is why you see us, but also some of our competitors talk about the cardiometabolic space, but also talk about NASH cardiovascular disease in the context of obesity and diabetes. Obviously, our approach is not new. We believe that we have been among the front runners in this with our focus on obesity that will allow us to talk about the many comorbidities that are associated with obesity. You hear some, including our customers, talk about more than 200 comorbidities associated with obesity, some of them more prevalent than others. Obviously, if we look at what weight loss will introduce in terms of improved outcomes for patients, very, very clear that even with smaller weight losses start to touch about, touch some of the early aspects of the cardiometabolic syndrome, for example, hypertension or hyperglycemia. This is important also because we know that some of the later-stage comorbidities are actually driven by hypertension that goes undiscovered for years, or hyperglycemia, maybe not with diabetes, but hyperglycemia that goes undiscovered for years. The rule of thumb, I think I can say that, is that type 2 diabetics maybe has five to 10 years of undiscovered, hyperglycemia and diabetes before they actually are being diagnosed. That obviously speaks to a long period of time where these patients are dyslipidemic, hypertensive, dysglycemic, allowing them to develop the comorbidities. The weight loss that we can introduce, starting with maybe the smaller weight losses moving towards 5%, 10% and then maybe even 15%+, that's where you see the impacts of the outcomes. Now, the data to support that are sparse. I'll obviously come back and talk about the SELECT trial and why we are super excited about the SELECT trial. But already with 5%-10% weight loss, we know that we can start to talk about defatting of liver, maybe decreasing the cardiovascular risk, certainly talk about potential improvement of glycemic control and prevention of diabetes. We do believe, obviously, that with more and more weight loss, you can introduce better and better outcomes for patients and really impact the more severe comorbidities. That was probably my stopping sign and moving on to the next one. It's Investor Relations. Exactly. Very briefly, and we've presented this data at this year's ADA. Obviously, we want to look at the circumstantial evidence for the weight loss that we can introduce with a compound like semaglutide. You know, we reduce in excess of 15% of body weight in the treatment with semaglutide in obesity, and that is consistent across all of our trials. Rule of thumb, if you're on semaglutide, you lose 17% of your body weight. You may remember STEP 1, that was the pivotal trial for Wegovy. Semaglutide 2.4 mg versus placebo, patients randomized two to one. Fairly standard study in our hands 68 weeks with a seven-week follow-up. STEP 4 is a little more complicated. Here we wanted to look at the impact of stopping anti-obesity treatment. Patients are run in onto semaglutide for 20 weeks, accruing a certain weight loss, and then being randomized to placebo or semaglutide, allowing us to look at what happens in terms of obviously continuous weight loss with continued semaglutide treatment, but also weight gain with when being switched to placebo. That allows us then to obviously look at the weight loss and we reported on that, and as you know, 17% body weight loss. That was interesting. What we can also do with these studies is to look at risk factors. One way of looking at this is the cardiovascular disease scoring, which talks about the risk of developing diabetes over a 10-year period. Looking at factors like sex, age, ethnicity, BMI, blood pressure, blood glucose, and triglycerides and HDL cholesterol, we can do this risk score and then predict the patient's risk for having or developing diabetes over a 10-year period. What we see is that regardless of looking at the STEP 1 trial or the STEP 4 trial, being on semaglutide is associated with a quite substantial almost 60% risk reduction in using this score, suggesting that patients have a 10-year lower risk of developing diabetes if being on semaglutide and accruing that semaglutide-induced weight loss. Obviously, very, very strong data. They're not proof, but a suggestive evidence of the impact of semaglutide treatment. Therefore, it's obviously also suggesting that if you stop semaglutide treatment, your risk score goes back up. Again, a suggestion for some of you are asking from time to time, is semaglutide or is weight-lowering treatment a chronic treatment, or is it something that you do to introduce a weight loss and then you stop? Our clear interpretation of this data is suggesting that continuous treatment, chronic treatment, is probably what is required when we talk about weight management. I think that is an important conclusion going out of this. I think you've also heard the analogy. I've also talked about that a couple of times with some of you. When you talk about dyslipidemia treatment, when you talk about hypertension treatment, you don't ask, "Is this chronic treatment?" You know it's chronic treatment. 'Cause we've established that through chronic treatment, we can improve outcomes. Going back to the SELECT idea, we intend to use SELECT to also say chronic treatment will improve outcomes. We sort of close the discussion, is this chronic or is this just temporary treatment? Something that you may not have seen, which is a study that we finalized a couple of weeks ago and reported at least internally a couple of weeks ago. We obviously wanted to look at obesity in children, in this specific case, in adolescents. This, we believe, is very, very important. Broadly speaking, when we talk about prevention of obesity, but also obviously when we talk about prevention of diabetes and other comorbidities, early initiation of intervention is important. I don't think realistically we can talk about today there's almost 700 million people living with obesity on a global scale. I don't think it's realistic to talk about treating all of those. If we are to break the curve, we have to start talking about prevention. One way of starting to do prevention is obviously to intervene early, and that would be in childhood or adolescence. Therefore, we conducted what we call STEP TEENS. STEP TEENS is a fairly small study, 200 patients with quite high obesity, age 12 to 18 years of age, being randomized to semaglutide 2.4 mg or placebo and treated for the usual 68 weeks. What is interesting is that the results are almost boring because we see the usual almost 16-17% weight loss. Nothing new here, but super consistent with semaglutide. You can probably imagine that if we can do that in children, then we can start talking about preventing adult obesity. We can start talking about preventing the comorbidities that adults develop. Therefore, we think this is a really, really interesting approach because apart from being really, really effective in the body weight lowering arena, it was really well-tolerated. Despite the fact that these children are obviously slightly lighter than their adult obese peers, we actually did see a safety profile that was almost more attractive than what we see in adults. This is maybe also reflected by the fact that we see a statistically significant but also clinically relevant improvement in quality of life in these children. For us, really exciting. I think, you will see us use this data to talk about how to initiate early intervention. To move to more obesity prevention, diabetes prevention, and also other comorbidity preventions. Just a few words on the SELECT trial. Again, this is something that we discussed for a couple of months. You heard us talk about this at our Capital Markets Day. SELECT is a big study, 17,500 patients being treated, again, with semaglutide or placebo, with a primary endpoint of 3-point MACE, looking at cardiovascular outcomes. As we also discussed previously, we will be looking at other outcomes than cardiovascular, but the primary endpoint is MACE. We will do an interim analysis. There's no questions asked, we will do an interim analysis. The consequences of the interim analysis, however, is what we can discuss. I just want to remind you that our internal prerequisite for the interim analysis is basically that we have accrued a sufficient number of events, and an external DMC will then look at the data. The study, the full study is powered for 17%. Without going into the numbers, and you will ask me, I know, you should expect that when the DMC look at the data, they will be looking at something, or they should be making their decision based on something that is more than 17% difference. We have specifically asked them not to recommend to close the study if, and again, I don't wanna mention the number, if the point estimate that they're looking at on the primary endpoint is not actually quite substantially beyond 17%. That also means that you should not be disappointed if we continue the trial, because there's a risk that then the point estimate is then between, let's say, 17% and 19% or 17% and 20%. That's still super good. We will be very, very happy with that, but we will continue the trial. The reason why we will continue the trial is that even though Mads is super good and he has a very nice team, closing down a study with 17,500 patients, that will take time. That will actually take approximately three months. In those three months, we will accrue approximately 115-150 events. That basically means that we have to think what could that 150 events do to the results. Even very, very good data could still mean that we continue the study. We have to have a point estimate that is quite substantially better than 17% before we decide to close the trial, or rather the DMC decides to close the trial. I just point that out so none of you become disappointed if we're doing the course of this autumn, continue the trial. I can see already now Martin has some questions. Also gonna be very, very interesting, obviously from our perspective, is we intend to use the SELECT trial to the fullest. That is obviously both to inform us about comorbidities in the obesity space, impact the long-term impact, the potential legacy impact of weight loss introduced by semaglutide, but also potentially to look at comorbidities that could have a regulatory bearing. We intend actually to extend the SELECT trial with a 10-year observation period, looking at obviously both the placebo patients, but also the semaglutide treated patients that have accrued a substantial weight loss, and the impact of that potential weight loss on outcomes in a 10-year period. Seeing from UKPDS that there is a legacy period of having good glycemic control or a legacy effect of having good glycemic control for a long period of time, we do believe that there's a potential that weight loss introduced for a prolonged period of time could also introduce that legacy period. We intend to follow up on that. We don't think all 17,500 patients will go into that extension trial. It will be somewhere between 5,000 and 10,000 patients, but still a substantial number. Now obviously, we'll be looking at some of the same endpoints, but we will actually also allow ourselves to look at, for example, diabetes prevention. Just talked about what we saw in STEP 1 and four, where we saw indicators that potentially the weight loss could be associated with a 10-year improvement in risk of developing diabetes. Looking at the SELECT trial, we can actually, in the extension, look at potential diabetes prevention in regulatory grade settings, allowing us to potentially interact with regulatory authorities on diabetes prevention. The regulatory requirement for diabetes prevention is off, an off-treatment period of at least three to six months. Here we are providing them 10 years, and that obviously will call for a good dialogue. Really, really exciting. Overall, just to conclude on the obesity part, we do believe that being on semaglutide is potentially associated with a decrease in risk of developing type two diabetes. That we have established through risk score looking at STEP 1 and STEP 4, indicating a potential 60% decrease in risk. But as we also discussed, we intend to follow up with the SELECT-LIFE over a 10-year period to potentially establish that diabetes prevention. We're super excited about the STEP TEENS being able to introduce not only a substantial but also a safe weight loss in adolescents, holds great potential for prevention of obesity and its complications. Obviously, again, the SELECT interim analysis is gonna be a very exciting end of this year. With that over to you, Mads. Thank you, Martin, and thank you also for introducing me and my hairline. Yeah. I'll try to do this paper another time. Yeah. That will not be for another 10 years. I'm here to tell you about GLP-1 in diabetes. You're probably well aware that we are investigating the use of semaglutide well beyond glycemic control and weight lowering. We've initiated these four clinical trials, FOCUS, SOUL, FLOW, and STRIDE, with either subcu or oral semaglutide. Today I'll just remind you about the two trials related to chronic kidney disease, the FLOW trial and the STRIDE trial, our trial investigating potential benefits for peripheral arterial disease. First, a little bit of background about chronic kidney disease. You hear about it all the time here at the ADA, and that's not by chance. You can see on the panel to the left that the association or the number of proportion of patients with either type 1 or type 2 diabetes that also have chronic kidney disease to a certain extent is around 30%-40%. If you visit a dialysis clinic, you'll notice that approximately half of those who have end-stage kidney disease have diabetes. It is a progressive disorder, meaning that one in 10 patients who have a diabetic kidney disease of one level or another will actually progress all the way to end-stage kidney disease. There's definitely an unmet need here that is worth addressing. In our already conducted cardiovascular outcome trials, we have a focus also on collecting data related to progression of chronic kidney disease. In the two trials, the SUSTAIN 6 trial with semaglutide, a two-year trial, and LEADER with Victoza, that was somewhat longer, close to five years. We actually did see an attenuated effect or loss of kidney function with our GLP-1 receptor agonists compared to active controls. A rule of thumb is that the diabetes patients with chronic kidney disease will decrease their glomerular filtration rate with approximately 1 mL per minute per body surface area per year. The effects that you see here, even though the numbers are not that great, are actually clinically meaningful and something that is worth substantiating through dedicated trials in patients with chronic kidney disease. Even more encouraging is that you can see, to the right up here that the effect seems to be greater in patients that already have established a moderate chronic kidney disease indicated by an eGFR less than 60. The so-called FLOW trial is a trial dedicated for patients with type 2 diabetes, with either a very low GFR, with or without urinary albumin excretion, or somewhat higher eGFR, but with more urinary albumin excretion as indications of chronic kidney disease. It's an event-driven trial, expected to last for five years or more, with a primary endpoint of collecting a composite endpoint of either, things associated with chronic kidney disease, renal death, renal replacement therapy, dialysis, or cardiovascular death. That's the regulatory endpoint. In addition, we'll also be looking at standard MACE. This is a really diseased population with a lot of comorbidities, and that is something that you may have stumbled over in one of the posters at this year's ADA session. The population, the baseline characteristics of the population included in the FLOW trial. The age is somewhat similar to many of our diabetes trials, but you can see that the diabetes duration is somewhat more substantial, close to, or just over 17 years here. But if you look at the diabetic comorbidities, you'll notice that close to half of the patients actually also have either nerve complications, microvascular complications, or diabetic retinopathy complications. When we calculate a CKD progression risk score, you can see that is actually more than two-thirds of patients that are at the very high level according to this KDIGO kidney disease improving global outcomes score. That's the name of it. We didn't in the population that we've included here see an association with either A1C levels or duration of diabetes with the progression risk score. We very much look forward to see the outcome of these data that should substantiate a label claim. This is the first and only kidney outcome trials conducted with a GLP-1 receptor agonist. This is not something that will extend, you could say the population that we can target with Ozempic, but it will be something that we use in promotion and certainly something that we can use towards both physicians and the patients as another reason for why to use GLP-1 receptor agonists. Another disorder associated with diabetes is the peripheral artery disease. Atherosclerosis in the limbs instead of in the heart or in the brain. There's clear association with with diabetes, so approximately 20%-30% of people with PAD have diabetes. And that is associated with either long-lasting duration of diabetes, older age. There's an unfortunate link also to the microvascular complications of peripheral neuropathy, giving rise to diabetic foot ulcers, something that we've actually in our LEADER trials seen an effect on with Victoza. Part of that is actually what has led us to initiate a study here. There's also a really substantial unmet need in peripheral arterial disease. It is a complication of diabetes or atherosclerosis that hasn't seen a new treatment come to the market for the past more than 20 years, since 1999. These days, many of these are left on their own with the symptoms of claudication that lasts until they actually need surgical intervention. That's the background for designing the STRIDE program, phase III trial with a functional outcome. A six-minute walking test on a treadmill. The inclusion criteria here is that the people should have what's called intermittent claudication of a certain degree, meaning that they have pain if they walk more than 200 m. To make it practical, they shouldn't be able to walk more than 600 m because then it takes too long to see an effect. The idea here again is to actually get a label claim that we can improve intermittent claudication in patients with type 2 diabetes. Another great reason for using GLP-1s in patients that have this complication. The overall takeaway is that we still see a lot of good things that GLP-1s can do for patients. We have evidence based on trials that we've already conducted that has led us in the direction of these two complications, along with, of course, what we're doing with the cardiovascular outcomes in our SOUL and SELECT trials. You'll also hear more about the FOCUS trials once that has read out, but that'll take a little bit longer. The two trials that I've shown today should have a readout in 2024 at the latest. With that, I'll invite Martin and all his wonderful hair back to the stage. All right. Thanks very much. Some of you have written about this today because there was a super nice session by Thomas Pieber on the risk of hypoglycemia with insulin icodec. It's been a long-standing discussion. When we introduced degludec 10 years ago, there was a lot of discussions about prolonged risk of hypoglycemia. We know now that that is not the case. Actually, degludec is associated with the lowest risk of hypoglycemia we've seen in basal insulin treatment so far. Nevertheless, it's a concern. It's something you guys ask about, but maybe more importantly, regulators also ask about it, and treating physicians ask about it. Therefore, it's good form to conduct a study to investigate the risk of hypoglycemia with one insulin versus standard of care. What is the way to go about it is that you introduce hypoglycemia by overdosing patients. That's a really good test. In this specific case, some of you have seen the presentation by Thomas Pieber today. We randomize patients to either icodec or glargine. They're being run in on a standard dose. Twice during the treatment period before the first crossover, they are being dosed by either double the dose to introduce a glycemic level which is below 54 mg per deciliter or 3 mM. If that is not sufficient, you give them three times their normal dose, and then you still attempt to achieve that level of hypoglycemia. The patients are being planned to ensure that they don't go too far or too low in terms of hypoglycemia. That's obviously dangerous. The whole idea is to look at not only the actual response, so looking at glycemic control, but also looking at the counterregulatory hormones. You look at four hormones in response to the introduced hypoglycemia. It's standard. It's the way to do it, and we've done it with all of our insulins in recent years. What is really, really interesting, despite a half-life that is 7x or actually more than 7x longer than insulin glargine, the comparator compound. With the doubling in dose, we actually saw that approximately 40% in both treatment arms reached a level below the 54 mg/dL. With the tripling in dose, we actually see that less or fewer patients with icodec reaches that hypoglycemia level as compared to insulin glargine. That obviously is a super comforting finding for us. You heard me talk about ONWARDS-2, that we did not observe any prolonged hypoglycemias. I can already now disclose that we didn't see that for neither ONWARDS-1 nor ONWARDS-6 either. What is also important obviously is that we, in ONWARDS 2, at this loading dose, and eight patients actually inadvertently took the loading dose for the duration of the trial, and none of them had severe hypoglycemia. In our hands, or at least in our current assessment based on these data and the data I'm gonna show you now on ONWARDS 2, 1, and 6, I think we can conclude that from a hypoglycemia profile perspective, icodec is actually quite safe. That's a nice segue into the ONWARDS development program. We talked a lot about ONWARDS 2 already. I'm gonna repeat the data in just a minute. Today, we're also gonna talk about ONWARDS 1 and ONWARDS 6 that we reported on last week. We are still waiting for ONWARDS 3, and we are still waiting for ONWARDS 4 and 5. ONWARDS 3 and 4 will read out during actually the course of July, and ONWARDS 5 will read out in Q3. Still very exciting times. Just to remind ourselves, the trial designs are fairly simple. ONWARDS 2 was the first to read out. Patients are being randomized to either icodec or the comparator, in this case degludec, in a 1-to-1 manner. ONWARDS 2 was a 26-week trial, so a fairly short trial. The idea was to look at switching from already insulin-treated patients from their previous basal insulins to either icodec or degludec. Sorry. I'm taking so. Yeah, sorry, that was correct. Therefore, we introduced this bolus dose as the first dose, and then we had sort of regular titration after that. This is the titration schedule. You will notice obviously this is super simple. Our key purpose with icodec is to introduce something that is simple for patients to use. Once-weekly treatment obviously is one thing, but the other thing is a very simple titration schedule. Based on SMPG values either being below 4.4 millimolar, between 4.4 and 7.2 or above, patients are being asked to adjust either by decreasing, maintaining, or increasing the insulin dose. Very standard and not different from what we would do with a once daily insulin treatment. You've seen the results. Saw a very nice decrease actually in both treatment arms, but superior with insulin icodec as compared to insulin degludec to the point of approximately 0.2 percentage points difference. There was no difference between the treatment arms in terms of level 2 hypoglycemia, so fairly low doses, 0.73 with icodec, 0.27 with degludec. I'm often being told that is a numerical difference. That is absolutely correct, but no statistical difference. Again, with the low rates, that actually corresponds to our patients had to wait 1.5 years to have a hypoglycemic event with degludec. Sorry, icodec, is suggesting that this is indeed a very, very hypo-safe insulin. Also interesting to note that the only severe hypoglycemic events that we saw in that trial was on degludec and not on icodec. We talk a lot about quality of life. We've never been able to show an improvement in quality of life with one insulin over another. We could actually do that with icodec as compared to degludec. For us, that is obviously super exciting. Maybe not surprising that a once-weekly is superior to a once-daily in terms of quality of life. Nevertheless, this is something that we from a regulatory, from a payer perspective, and from an access perspective can use in our discussions. ONWARDS 1, equally simple trial. Patients being randomized 1-1 to either icodec or in this case glargine. This is a bigger study, approximately 1,000 patients, and being treated for 78 weeks. The data I'm gonna show and talk about now is at 52 weeks, so we are continuing the trial for another half a year, and that is basically to live up to the regulatory guidelines. The first readout and the primary readout was at 52 weeks. These are insulin-naive patients, so slightly different in terms of how to initiate insulin icodec. Here we do not give a bolus dose, we just give the expected treatment dose and then use the same titration algorithm that was also used in ONWARDS 2. The data also becoming a little bit boring, the same 0.2 percentage point difference. This is statistically significant, and therefore we can claim superiority with icodec over insulin glargine. This is obviously very, very nice. I will remind you that this is treat to target studies. We do, I mean we spent 100 years doing treat to target studies, so we know how to do them. If you look at the SMPG profiles, they are completely superimposed also in this trial. That basically mean that we can claim proper treat to target. Therefore, also be able to claim superiority on overall glycemic control is actually quite a feat, and is speaking to that insulin icodec is giving better glycemic control during the day. This is what we show here in the color slide, than insulin glargine. This study is probably the first where we can see a difference between two insulins in terms of time in range. Some of you may ask is 72% really better than 67%? That is a difference of approximately 5%. If you try to calculate that more than one hour a day, it's actually an hour and 15 minutes per day that patients are in better glycemic control. This is not only statistically significant, it's also clinically relevant. Therefore, also a reflection of the flat and stable profile that we see with insulin icodec, and the reason why we can claim HbA1c superiority as well. The one hour in better glycemic control is actually something that people can take home and say, "This is really a better insulin." It's probably also one of the reflections of the improved quality of life that we observed in ONWARDS 6. I told some of you about the analysis on being in good glycemic control without hypoglycemia. I think it's interesting for us to see that even looking at A1C without hypoglycemia compared to the standard of care, we see superiority on that. The really interesting thing is, if I look at the same proportion, just A1C being reached, A1C below seven being reached, it's 54%. Talking about the very, very low rate of hypoglycemia that we see in this trial. This is actually what is reflected here, 0.29 for icodec at level 2, and 0.15 for glargine. Even in a 1,000-patient study, this does not become statistically significant, speaking to the very, very low rates of hypoglycemia that we actually see with both insulins. The analogy here is that a patient needs to be treated with icodec for three years before he or she experience one level 2 hypoglycemia that is and not severe hypoglycemia. Again, speaking to the hypo safety of this compound in insulin initiation. One event of severe hypoglycemia with icodec versus three events for insulin glargine. Again, nothing to talk about in terms of statistical significance, but a very, very nice piece of evidence for us to see that, there's no risk of severe hypoglycemia in this space, and no risk of prolonged hypoglycemia. ONWARDS 6, now I can see Karsten, I need to hurry up, is again a super simple trial, 52 weeks. You need some more training. Patients treated with icodec or in this case degludec, approximately 600 patients being randomized, and this is a basal bolus treatment. What we also see here is this time we don't see superiority. We didn't expect to see superiority. We actually see complete parity between the two insulins in terms of glycemic control. We do, however, see as some of us also discussed, we expected that a little bit higher risk of hypoglycemia with icodec as compared to what we saw with degludec. The rates are really low. You may recall from the degludec program that in that program, we saw rates approximately at the 35-40 events per patient per year level. Here, we're looking at events of 10-20, so low rates of hypoglycemia, but still they are statistically significant. Severe hypoglycemia, there is a numerical difference. This is not statistically significant. For better or worse, and obviously super annoying for us, one patient was experiencing 33 events of severe hypoglycemia, or at least reporting 33 events of severe hypoglycemia, driving the numerical difference. If we exclude that patient, which obviously we can, then there's actually a lower risk of severe hypoglycemia with icodec as compared to glargine. Overall, in conclusion for insulin icodec, we remain to be very, very excited for icodec. We have established in a dedicated hypoglycemia study that there's no increased risk of hypoglycemia with insulin icodec as compared to insulin glargine. ONWARDS 1 and 2 have established that this appears to be the best basal insulin that we've seen so far, superiority on glycemic control, no increased risk of hypoglycemia, and improved quality of life. We meet the primary endpoint for ONWARDS 6, but we also have to acknowledge that we still have to work with the hypoglycemia risk in the type 1 diabetes space. Overall, we believe that once-weekly has the potential to become the ideal starter insulin in type 2 diabetes. Looking a little bit forward to what the rest of the year holds. Obviously, very, very happy with the U.S. approval of Ozempic 2 mg, we already discussed that. If I can just maybe call out that what we are really excited about for the rest of the year is obviously the initiation of phase III for CagriSema. We will see results for the CagriSema type 2 diabetes trial. Again, I have to remind you this is exploratory, this is why we do the study. We are also looking towards higher doses of semaglutide. We've seen some questions on that. We'll actually do a phase II study in type 2 diabetes, investigating even higher doses of semaglutide in this case. This is a little bit of a reflection of we believe that the jury is still out on whether we have maxed out on semaglutide, also reflecting a little bit on what we have seen from our competitors. Therefore, we believe that we can actually serve our patients best by also investigating even higher doses in the diabetes and potentially also in obesity space. With that, back to you, Karsten. I almost made it. Thank you, Martin. You almost made it. Yeah. This concludes today's R&D event presentation here at the ADA. Now we move into the Q&A session, and I think it's a small group, so we do one question at a time, and then we can move around fairly swiftly. Michael, you are first. Michael from Nordea. One question. Is there anything we can read into the sort of timing of your comments now to SELECT, because we're starting to get close. Is it just the normal jitters before getting data, or is it just that we should be more cautious in expectations into SELECT? It's actually simply because obviously we haven't seen the data, but we've seen some of you becoming very excited about that interim analysis. We just want to, I don't wanna say temper or dampen the excitement, but just be realistic about we can still see very, very good results even though we are not being recommended to close the study based on the interim analysis. I think that's a good reminder. An education session. Exactly. Right. Richard? Thanks. Richard Vosser, J.P. Morgan. Just actually not on R&D, but on the Wegovy resupply. We've obviously seen data here for tirzepatide in obesity and their launch in diabetes. Just if you could give us the latest on Wegovy's resupply, 'cause obviously scripts are coming down right now, and it'd be good to get that going back up. Absolutely. We all want to see it coming back up. As I'm sure you've noted, the Saxenda scripts are actually coming back up these days. Actually, not a lot more to comment on compared to what we did at Q1 on Wegovy resupply. Manufacturing is running, including at our CMO. We are producing, and we are building inventories as we speak. This is purely around building sufficient inventories before we make the product available in the market again, which as we said at Q1, we'll do during the second half of this year. No change to previous commentary. Martin? Thanks. Martin Parkhøi from SEB. Just a question, Martin, on CagriSema. Yes, sir. It's not only you are excited about it, you can also see many industry excited about it. You have previously said that you would not be afraid of doing a head-to-head with tirzepatide. If that would be the case, would you prefer to do that in diabetes or in obesity, given that diabetes, Mounjaro of course will be available earlier to make such a trial? A good question. I mean, given that the only data I have on CagriSema right now is in obesity, I have to say obesity. Given that Lilly has gotten the diabetes doses approved at the same level as they expect to have the obesity dose, that actually allows us to do the testing even before they get their obesity indication. That's just a clinical investigation. We can do that if we should so decide. We haven't made that decision yet. If we do it will be in obesity. We can basically do it once we can purchase yeah, Mounjaro. We'll go to Marcus on. Thanks very much. Marcus from Morgan Stanley. Can I just ask about your GIP compound? You don't talk about it very much, where it is in development, and there's been a lot of discussion this meeting about what the GIP component of tirzepatide is providing. Is it expanding the therapeutic window? Has it got activity itself? There was some data suggesting it could have a CKD benefit to what Matt was talking about. Where are we with that program, and what are you seeing with the GIP agonist as a single agent? As a single agent, we do not think that has a lot of room for clinical treatment. We believe that GIP, if it has any role, it has to be in combination treatment. That being said, we are testing our own GLP-1 GIP in both phase I and II as we speak. I went very fast over the trial, but you will actually see our phase I readout already in this quarter, so very soon. That is a safety and PK file, so not a lot of information on pharmacodynamics and efficacy. We'll have to wait until Q4 to look at the readout from our phase II trial in that space. Interesting specifically in the obesity space, we still believe that CagriSema is the way to go, as we talked about, primarily because better efficacy potential, but also because with CagriSema you don't have to compromise on safety and solubility. I think it was Michael from TD Cowen. Thank you. Michael Nedelcovych from TD Cowen. We've heard from a couple consultants that COVID-related cardiovascular disease could muddy the waters of cardiovascular outcomes trials like SELECT. Do you view that as a risk for SELECT, or is that something you've contemplated? Short answer is no. Obviously we've had a DMC looking at this. Our current assessment is if we have had COVID-related cardiovascular events, they will just be counted as any other cardiovascular event. I mean, they increase the risk of having a cardiovascular event, but they will be counted as would anything else. If semaglutide has a positive effect on that will just be a plus. I think it's maybe important to call out because I saw some of our competitors being asked about the withdrawal rates of patients in their studies, in part due to COVID-19. Bas is really good at what he does. Our current retention in the SELECT trial is in excess of 90. Therefore even with COVID-19, we're not concerned about that either. Michael? Yeah, Michael Novod. Regarding CagriSema and the sort of decision to start phase III in type 2 diabetes, can you say what is sort of the bar to start in terms of A1C? And the A1C benefit from adding amylin, does that come from the additional weight loss, or does it come from increasing insulin sensitivity from amylin agonist? On the last part, short answer is we don't know. This is specifically also why we do the phase II study. You could speculate that it's the weight loss. You could actually also speculate that it's glucagon suppression. And in reality, we don't really know. That is why we are doing the phase II study. We will have to show superiority, not only statistically significant, but also clinically relevant superiority over monotherapies on glycemic control for it to be relevant. Historically, the FDA have been looking at 0.3 percentage points to that end, and therefore that will be the bar. To be honest, that is a tall order. You probably see glycemic control from short-acting amylin analogs, and therefore, again, we have to call this experimental and/or exploratory until we've seen the data. I also hear a lot of excitement about this. I'm potentially excited, but I'm also a little bit cautious because honestly speaking, it's theoretical as we speak. Yeah. Thank you. It's Jesper from Carnegie. We've seen here at the ADA many doctors and in scientific sessions arguing that we should treat diabetes with weight loss as a primary target instead of HbA1c. If we see treatment guidelines here in the coming days, either advocating fully or partly with more focus on weight loss, how would you quantify the sales opportunity that opens up to you guys, and how large a penetration do you think GLP-1 could go to over time? It's a super interesting question, and given that I have been talking a lot, I would, if Karsten is okay, I would be inclined to ask Matt to answer that question. Matt, if you could start on add-on sales potential. I think it's really a change in direction because initially, if you can recall with Victoza, we were not allowed to talk anything about weight loss. This has really been about getting above a threshold that's clinically relevant, and that likely also drives some additional in type 2 diabetes. To the extent that the GLP-1s are still used very infrequently, I think it's a welcome challenge for us to live up to that. I think for the sales potential, I probably have to leave a little bit of the guessing work for Karsten. I'd say first of all, as we've shown before, GLP-1 scripts out of total scripts on a global basis is 2% or 3%. So we have a very long runway all, and potentially getting improved treatment guidelines that focus more on GLP-1 benefits will of course only amplify the journey towards the highest sales points there. We've seen some markets we're already at 10%, so you can compare for instance being at, call it 25% or so. So to me it's less about, you know, a point estimate in a given year. More, it's more so about a continued class expansion for the next nine years. Richard, I think it was. Thanks. Just going to the SELECT-LIFE trial. Given this meeting and you've said a move towards chronic treatment with obesity treatment would be preferred, how easy is it gonna be to actually recruit that trial, given presumably the patients are not gonna be able to take any weight loss treatment for the 10 years that they're gonna be on it? So yeah, how easy to recruit? How easy to retain patients? And then just an allied question to that. Just, you know, can you go to the regulators after a year with the data and without disturbing the 10-year, just to get a diabetes prevention label? First of all, patients, if they go into SELECT-LIFE, they can actually be on anti-obesity medication. That is part of the assessment. We are specifically because we know that, I mean, based on the data from today and based on what Kasper just said, less than 1% globally is on treatment. A lot of these patients in the immediate future will not be on treatment. For the patients that will go back on either semaglutide treatment or another anti-obesity medication, that will just add to the information level that we can accrue from the trial. We actually see that as positive. We will be able to talk to the agency already after one year. They have previously stated they would be looking for at least three but preferably six months of treatment before they are willing to discuss a diabetes prevention indication. Both we and others have been looking at that with previous intervention and not found anything positive. Based on what we've seen with STEP 1, STEP 4, as we just discussed today, but actually also STEP 5, where we have one year of follow-up without treatment. We believe that if we can see similar data from SELECT-LIFE with a larger number of people, that could be a very interesting dialogue. There would have to be a gap in SELECT-LIFE? Yeah. Between patients treated with semaglutide and patients treated on placebo, and their risk of developing diabetes, yes. Actually, based on the data that I showed you today, you could actually see that gap being maintained. Not all patients go back to a diabetes stage in terms of the risk score. And, uh- Yeah, we'll go all the way to the back. Hey there. Seamus Fernandez with Guggenheim. We saw from the Wegovy FDA docs that there's a differential effect due to both gender and baseline body weight. Curious if you guys are planning a similar analysis for SELECT, and if you would expect a differential effect on the main endpoints based on those parameters? It's a really good question, and the answer to the first is yes. We always have to look at these differences. The question is whether you find them to be statistically significant, or whether they are of clinical relevance. More often than not, we know that they are not of clinical relevance, even though you in these large-scale outcome trials can see statistical significance. All right. Martin? Martin Parkhøi, SEB. Just on the higher injectable and I know there's doses, I think it was on the slide. How many are we actually talking about you investigating? Secondly, I know you probably will not see the actual doses because then we've said it already. Why are you looking for the most improvement? Are they on the HbA1c or is it on the weight or what is it you're looking for? In diabetes we will still be looking for A1C. That is the regulatory requirement. Obviously we'll also be looking for weight. And obviously in obesity we'll be looking for weight. It's the same. Specifically on in the diabetes trials, the phase II trial that we're discussing, we'll be investigating a couple of higher doses. Obviously we are also in light of what we've seen others do, discussing what should be the right approach towards higher doses in obesity. Great. That was as clear as we can get it to stay, I think. We answer Marcus. Thank you. Can I just ask on SELECT? You're very helpful in terms of providing some numbers. You're targeting a 17% MACE benefit. In terms of all-cause mortality and CV death- Yeah. Could you help us understand what kind of benefit you would expect at the end of the study, if it goes hand in hand with the 17? The reason why I'm asking is that obviously if you look at SUSTAIN 6, after 2.1 years you saw a very strong MACE benefit, but the hazard ratio on those other two endpoints were pretty much 1.0, yeah? Small either side. I'm just trying to understand the impact if you were to stop early, how that impacts your discussions with payers and governments when it comes to even harder endpoints than the 3.8. Based on what we know so far, I'll just remind you that for PIONEER 6, we actually saw a little bit of a different picture in terms of the secondary endpoints. Maybe also speaking a little bit on the risk when you talk about maybe one-third of the events as compared to the primary endpoint. Goes without saying that we'll select 75,000 patients. We have better power, but for better or worse, the power looking at the subsegments of MACE, both all-cause mortality but also cardiovascular mortality becomes lower, quite substantially lower. The interesting thing is, and some of you have asked about that also, that power does not increase substantially by continuing the study to the full trial. So we are actually hopeful that some of the secondary or the sub-components of MACE will pan out positively. But our primary focus is on the primary endpoint. That will be more than sufficient for both regulatory but also peer discussion. What level should they expect to see hard endpoints? My sort of knee-jerk reaction would be that you'll see something, and we've seen that with most of the GLP-1 analogs, probably see most on MI. But then I would expect to see, and Mads can also speculate on that, an equal distribution between stroke and cardiovascular death. Yeah, we actually do have the meta-analysis that confirm that the benefit should be almost similar to the 3-point MACE across, I mean, larger GLP-1 programs. Around 15% if you look at the ones that have reported so far. Of course, I mean, with few events there will be differences. Yeah. We're back to Martin Holst Lange. Yes, thanks. Just all these nice trials on, you know, health gains and tenure, in reality is that on Saxenda you've said yourself, people are staying on treatment for four to six months, and you will not even commit that people maybe stay on treatment for 1 year on Wegovy. What will you do actually because it's a pie in the sky with all these benefits if people just stop treatment within a year? What will you actually do to make sure and promote much longer usage? First of all, I think the difference between Saxenda and Wegovy is obviously quite substantial. Sure. With Saxenda, 5% body weight loss, most of people cannot even see that in the mirror. With Wegovy, we see a continuous weight loss, it's substantial. The increase, improvement in quality of life is driving the patients actually to stay longer on treatment. A lot of this also comes down to data. The more data we can generate to have that dialogue, obviously including SELECT, the better we are off. I think it's too early to speculate. My bet will be that when we have data on Wegovy, we will see a substantially longer stay time. Pragmatically speaking, because patients actually see the weight loss in the mirror, and they see the continued and sustained weight loss throughout. That's what we saw in the clinical trials. I mean, if you look at our retention rate and stay time on drug within trials, it's substantially better for the STEP trials than what we saw for the Saxenda trials. I mean, we have to discuss when we have hard data, but I am not afraid to say I believe that the stay time on Wegovy will be substantially higher than it was for Saxenda, or is for Saxenda. Just adding to Martin's comment there, I think what we're just experiencing at the ADA this year is a completely different understanding and focus on treating weight as a in terms of slowing risk on the entire cardio-metabolic syndrome. I think if that understanding is becoming prevailing, then it's less about individual treatment decisions in a small population, you know, focusing on obesity as a primary point to a broader understanding of why to treat obesity. Yeah, Michael? One of the patients that you had at your Capital Markets Day described the sort of psychological effect of Wegovy, reducing cravings, and controlling appetite. Is that measurable? Do you know if that's higher with Wegovy versus Saxenda? Is that, does that inform at all patient adherence on the drug, the sort of maintaining that psychological effect, or is that more just a kind of a peripheral effect? Mads has actually conducted some clinical pharmacology trials to look into this. I don't know if you wanna talk, Mads. Yeah. I mean, we haven't done direct comparisons, but we've done very similar trials with both Saxenda and with Wegovy that demonstrate, I mean, the different aspects of appetite regulation, whether that be satiety, hunger, but also cravings. I mean, there is a substantially greater effect with Wegovy than we saw with Saxenda. Do you think that is when patient adherence remains? At least anecdotally, that's what we hear, that when the cravings go away, that it, I mean, the ease of control of not eating too much is definitely something that is felt as a lift in quality of life. Mark? Can I ask an icodec question? Firstly, in terms of the 10 severe hypos you saw with icodec, can you help us understand how you treated those, how simple it is, or otherwise? Then just in terms of trial design and ONWARDS 6, what would you do differently? Obviously, it's a very complex problem to solve here. How would you redesign the trials if you were to do so? Are you inclined to do that, to run additional type 1 diabetes trials before you potentially file in that indication? It's not up to us how to treat severe hypoglycemia. More often than not, obviously we look into it. In some studies, we even adjudicate severe hypoglycemia because we know that there is sometimes over-reporting of severe hypoglycemia. Sometimes it's more the inclination of the patient to get up and get a glass of juice rather than someone else to do it. Some of them are obviously truly severe hypoglycemia, and the patient needs third-party assistance. What we can see is that there's no difference in the treatment and the quality of the icodec associated severe hypoglycemia as compared to what we've seen both in ONWARDS 6 with glargine but also in other studies. No flags raised there. We're actually discussing right now, again, taking into consideration that level two severe hypoglycemia, there was really a low rate as compared to what we've seen previously. Also given that one patient, and again, this is subjective, reporting 33 events that appeared to not all be true severe hypoglycemia. We don't think we need necessarily a pre-approval new study in order to do the filing. That's obviously a dialogue that we had to have with the FDA. I think it's fair to say that we will generate more data in this space, because we need obviously to have an attractive offering that is both perceived to be safe and efficacious. What we will do in the after session, we can discuss the technicalities of this because as you say, it's complicated. The problem is a four-week half-life, sorry, a one-week half-life and that means that every time you do a dose adjustment, you have four weeks to next level of steady state. Therefore we think that the dose adjustments probably had to be done with lower frequency than what we did it on ONWARDS 6. Michael? Just to oral semaglutide in Alzheimer's. Can you just remind us, the first possible filing would be on the CDR-SB data you're getting in a couple of years, and if that's the case, are you well-equipped in terms of both manufacturing for semaglutide should there be a possible outcome from the- That was actually a question for Karsten and not for Andy. -situation. The backdrop for all semaglutide in Alzheimer's, as we discussed before, we have a lot of evidence behind a potential benefit based on registries. Therefore, we characterize this as a high risk, high reward type of trial. As to specifics on manufacturing capacity, then I'd say the starting point is whether manufacturing capacity is sufficient. It depends on demand and demand depends on the results from the clinical trial. There are a lot of assumptions put into this. Currently outcome range is huge. I can say we have a factory coming online, you know, as we speak over the coming quarters in a place in North Carolina, being additive to our oral API footprint. We have ample tableting capacity. I'll say we are expanding significantly. We have a big expansion also in Denmark taking place as we speak, so also being very additive to our oral API capacity. I would say I cannot guarantee that there are no limits to capacity, but as you also see in our CapEx guidance of DKK 10-15 billion, and you saw that at the Capital Markets Day, we're running historic highs on CapEx, and a big chunk of that is linked to API manufacturing. Significantly more capacity for oral semaglutide and in general, additional capacity for support. If I can maybe add on that, we hear from key opinion leaders, but we also hear from others that a lot of patients, a lot of families might prefer a subcutaneous offering. We do actually from an R&D perspective intend to secure that we can use both the oral but also the subcutaneous offering in the Alzheimer's space. That from a capacity perspective provides optionality and flexibility. I think that that's the approach you will also see us take moving forward. What R&D is furthermore contributing with is additional formulation trials. Yes. For the oral tablet formulations, which potentially will improve on bioavailability and consequently also on manufacturing capacity. Got to love R&D. Exactly. Now we have time for one last question, and that goes to Jesper from Carnegie. Yeah. Just a question on all the products that you have lined up, icodec, obesity, diabetes. You are also going head to head against Eli Lilly. So how is your filing strategy when you look at potential voucher use? Because it seems to make sense to use vouchers when you can make, say four, six months, earlier headroom to the market. Just some consideration on how you look at vouchers going forward. Vouchers, as you say, is a tool put in place by the FDA. This is a pure U.S. phenomenon, and it's rather simplistic. It yields to the tune of four months of speed in terms of getting to the markets. You can say you have to compare the price of the voucher to the lifetime value of the product, you know, from a financial setting. Of course, you have to bake in competitive dynamics, launch readiness, manufacturing readiness, and so on. There are a lot of factors going into it. I think now we've shown on a couple of occasions that we're ready to use vouchers in the proper circumstances. We don't use it always, but it's one of the tools we have in our toolbox if feasible for a specific project. All right. Thank you so much for great energy and activity and for attending this R&D investor session at ADA. This concludes the session. For the ones attending in person, I think we have a small social gathering next door. Thank you so much.