Welcome to this Novo Nordisk Fireside at the 61st edition of EASD here in Vienna. Welcome to all of you in the room and also welcome to those listening in online. Today's call will focus on the R&D and the pipeline, and we're here today with Martin, who will take us through some of the developments later. Before we get into it, just the usual word of caution in terms of the forward-looking statements and that the future is unpredictable. That pertains in particular when it comes to the pipeline. In terms of the format, Martin will spend a few minutes on some opening remarks. After that, we'll turn it to you in the room, where we go around with one question each, and we'll take the discussion where you'd like to go. As said, we'll focus the call on the pipeline and R&D events, both pertaining to the EASD but also to the pipeline overall. With that, welcome, and over to you, Martin. Thank you very much. Basically, I'll just talk a little bit about the new R&D organization that has been created in Novo Nordisk. As you know, for the last five years, we've had two distinct organizations: research and development. Back in August, we decided to re-merge those two areas. This was done to create the strategic, but also, and maybe primarily, the scientific synergies that we see from early research to the later stage development. More importantly, also actually feeding the clinical data that we generate back into research, driving not only new targets and target discovery, but also supporting some of the propositions that we are developing in research. I have to say, a little bit of an efficiency gain by collapsing two organizations. From an execution perspective, we can see already now that we are making faster decisions. We are progressing faster in terms of not only our research, but also our clinical pipeline. Obviously, having the new organization in place already, it was announced mid-August. It's been in place in approximately a month. That is quite gratifying. You also heard it from Mike, and we discussed it a little bit at the roadshow in August. Our strategy has not changed. We are a diabetes, we are an obesity company. Our key research, but also development focus, will be in the obesity in the diabetes space. We've received some questions, "Are we then walking away from comorbidities?" We are not. We are very serious about not only understanding, but also treating the comorbidities that are related to diabetes and obesity. We allow ourselves to say when we are, for example, looking at cardiovascular disease, there are more than 200 distinct diagnoses in cardiovascular disease. If you have cardiovascular disease, but not obesity, maybe that's not where Novo Nordisk will do innovation. We'll focus on addressing the cardiovascular, the renal, the kidney diseases that are related to and typically stem from diabetes and obesity. That's our focus. Obviously, we also have our focus on rare disease. I guess we'll not discuss that too much today. This has been a very exciting EASD for us. It, to an extent, reflects our obesity, our diabetes pipeline. We have, at this EASD, shown new data on semaglutide. Our pledge will continuously serve patients suffering from diabetes, from obesity with semaglutide and generating new indications, but also generating new offerings, in this case, in the space of higher doses of semaglutide. We've now shown that we can accrue a full 21% weight loss with semaglutide in obesity. That, together with a well-known safety and tolerability profile, and obviously the CV benefit, the MASH benefits, we believe creates a unique offering in the space of obesity. This has been filed for European regulatory approval already as we speak. As was disclosed yesterday, I think by me, we also have a plan and intent to do U.S. regulatory filing during Q4 this year. We are disclosing the details of the oral version of semaglutide for obesity later today. That is still, I don't think it's out yet. That is still under embargo, but you heard me talk about the data. 17% weight loss, well-known safety and tolerability profile. Obviously, with the current U.S. regulatory review, part of our review process is discussing with the regulators if the CV benefits that we know with semaglutide, subcutaneous semaglutide, can also enter the oral semaglutide label in obesity. We're moving beyond that. All of our CTs are obviously very exciting, and you have been kind enough to show a lot of interest in those. You have also oftentimes asked, "How does that translate into real-world evidence?" We have, at this EASD, seen a number of real-world evidence studies, some most focusing on the cardiovascular benefits of semaglutide still, some using a standard of care comparator, and then there's one study using an active comparator. In all cases, confirming the benefits that we know from semaglutide. Also a little bit what we've discussed before. From a numerical perspective, semaglutide does seem to stand out in diabetes. That's where we have the most comparative data with a 26% CV risk reduction. In obesity, we would expect to see the same, but we also have to acknowledge that at this point in time, semaglutide is the only molecule in the obesity space that has established CV benefits. All of that being confirmed by real-world evidence, which is obviously really, really gratifying for us. We've shown data from our pipeline, CagriSema, Amiglutide, and so on. Very, very exciting. It doesn't stop there. We'll have a busy year. Moving towards the end of the year, we'll see the CagriSema readout for type 2 diabetes, the Reimagine program. I just want to caution you because that will always create noise. The first study to read out is Reimagine Free. That is add-on to insulin, and that's maybe not the first study where you will see a good indication of what CagriSema can do in type 2 diabetes. Just to level that, the first pivotal study will read out actually after Reimagine Free, and that's basically the duration of the studies that is driving that. Just to call that out. Obviously, very interesting also in the space of type 2 diabetes, we'll see the readout for Amiglutide. Obviously, that is also going to be very interesting. We primarily see Amiglutide as an obesity drug, but given the biology of both amylin and GLP-1, it's prudent to investigate the diabetes potential as well. We are aiming to do the resubmission of once weekly icodec in the U.S. As you know, this has been approved in a number of countries outside of the U.S. and actually also launched outside of the U.S. The U.S. resubmission is, from a patient-centric perspective, very important to us. In the obesity space, I almost don't know where to start. Obviously, the regulatory approval of the oral semaglutide so that we, as per plan, can launch oral semaglutide in the U.S. Q1 of next year. That is going to be interesting. The Redefine full results and regulatory submission in the U.S., that's not so much for this year. Maybe at least the Redefine full results, that's for Q1 of next year. That is also going to be very exciting. I think this year, cagrilentide phase III initiation, I saw some interesting sort of speculations on what does that mean. Just to spend two seconds on that, I know Jana wants to go into Q&A. I sometimes get a question, "Why would you launch a drug that only gives 12% weight loss?" That's very, very clear, and some of you have heard me talk about that before. We see obesity as a complex disease, a disease where individual patients have individual needs. Just to give you an example, if you have BMI of 30, a 25% weight loss will get you to a BMI of 22, and that is maybe not what patients want. Maybe that patient would like to have the 12% weight loss with fewer side effects. We know from redefined one that cagrilentide in monotherapy gives exactly that 12% weight loss, at least at that study, and approximately half of the gastrointestinal side effects that we saw with the GLP-1 analogs. We do believe that there is a substantial proportion of patients living with obesity that will benefit from that treatment. The way we think about it, Wegovy or semaglutide is for slightly higher weight loss and a focus on comorbidities. From a pipeline perspective, moving into the higher weight losses with CagriSema, with amiglutide, with our triple agonist, and also focusing on comorbidities there. I think it's important to call out there is room for a moderate weight loss, low gastrointestinal side effect drug in the obesity space. What we take a lot of comfort in is that we can actually serve all of those, or that broad spectrum with our portfolio. Both, as we just discussed, for semaglutide, but also for amiglutide, the oral offering. Just to point that out, when we initiate phase 3 for amiglutide, the program will contain both subcutaneous, but also oral subprograms. We pursue both. We'll see later this year phase I results from our triagonist. That's going to be the first readout. Just a disclaimer, this is not developing as we did for amiglutide, so it's going to be a reasonably small study. It will lead to a phase II program because I cannot conclude definitively because it is a small and short study. I cannot conclude definitively on dosing, on efficacy, and safety. We'll go into phase II there, just to call that out. Obviously later, we'll see the readout from the other triagonist, and I hope all of you know the difference. The first triagonist is GLP-1, GIP, amylin, and the second one, the UPT asset, is GLP-1, GIP, and glucagon. Again, filling our pipeline with a differentiated range of molecules. Obviously the newly acquired LX-9851, which is the acute coenzyme synthase inhibitor. I really am tongue twisting myself here, which is also going to be interesting. We see that as a potential play. It's a small molecule, so that would be an oral offering also in the space of obesity. Similarly, in rare disease, I think Ludovic is now covering the full spectrum of our portfolio, but he still has a heart for rare disease, so he's looking forward to the submission of Mymate. He's been waiting on that. Obviously, we are very, very interested in seeing the readout first with the Evoke trials in Alzheimer’s disease. Jacob wants to caution me, and I agree with him. This is high risk. The attrition in Alzheimer’s by definition, because of the nature of the disease and also the nature of how we are allowed to do clinical trials, is high. The risk is high. Obviously, we are very, very interested in the data. We are also looking very much forward to Cynthia Beckman readout in 2026. Exciting times ahead. At the same time, with my new job and new title, I’m obviously also focused very much on building the research pipeline and portfolio. I don’t know why I was about to say something I was not supposed to say. In the not-so-distant future, you will hear more about what we plan to do with the research pipeline and how we progress that. I think with that, we're ready for the Q&A, Martin. Yes. Thanks a lot. Here in the strategy organization, the EASD program, and then also the pipeline, as well as the clarification in terms of optionality for 7.2 submission. Let's move into Q&A for the next 35- 40 minutes. One question per person, please. Let's start on the front row with Mr. Parkoi. Sorry, Martin Parkoi from SEB. Could you maybe set the scene a little bit more on the expectation for the Evoke trial? Maybe with the outcome in the baseline and what would be the normal progression of such a patient and what will be good data? Yeah. Now you're asking for a super complicated answer, and I apologize for that in advance. The primary endpoint is a regulatory endpoint. That is basically the gold standard from a regulatory perspective in both the U.S., but also outside of the U.S. It's called CDR sum of boxes, clinical dementia rating. It consists of six domains in which each domain you can get a score from zero to three, zero being normal, three being substantially cognitively impaired. You basically then get a sum, hence the name CDR sum of boxes. The highest sum that you can get is by inference 18, so six times three. That would basically indicate a very, very, very cognitively impaired person or someone suffering from severe dementia. Normally zero. That basically also means that any delay in progression from zero towards 18 is clinically relevant. That means that how I measure success is statistically significant. That will lead to a label update. That will be clinically meaningful to a patient. I mean, let's say I tell you that I see a 10% improvement of CDR sum of boxes over placebo. It doesn't make sense to you. If I tell you that I can delay the progression by, let's say, 0.5 or a full point, that's actually clinically meaningful. That's the difference between moving from mild cognitive impairment to mild dementia to more severe dementia. If we can show that study is powered to show a difference of 20%. Again, you know what 20% of 18 means. That basically means that's what we've powered the study for, but we also now know that we can actually detect to the low teens in terms of statistical significance. Based on our dialogue with treating physicians, that's still very clinically relevant because it implies a delay of progression to the next and more severe level of dementia. Sorry, long answer. That's very clear. Thank you, Martin. Let's move to Michael, also on the first row. Thank you, Michael Novod from Nordea. Just trying to figure out, Martin, how is the thinking around the different CagriSema, CagriSema co-formulation, and then comes Amiglutide? What happens to CagriSema in its normal form, dual chamber? If co-formulation is successful, how fast can you progress it? From now on, we know that you're sort of through the first step. The overall split going forward between those three drugs, I would say. Absolutely. It's also a little bit of a talk that you need to have with Ludovic after this. The co-formulation is to allow us flexibility in terms of how we scale. As you know, we are already planning to scale the dual chamber device quite substantially. We are prepared for a full-scale launch when we get the approval, starting with the U.S. That being said, we also know that the dual chamber device is a single-dose device. If we can co-formulate and have that co-formulation in our PDF-290 or FlexTouch, that will give us more flexibility. That basically means that these two offerings, maybe not in the same country, but that remains to be seen, these two offerings can co-exist. They basically will allow us a global flexibility in how we scale our production. Amiglutide in the base case, Amiglutide will have the same safety, tolerability, efficacy as CagriSema. It's still a very valuable offering for us because it's one molecule. It definitely goes into a single chamber device because it is only that one molecule. It's one API. From a scalability perspective, at the very least, it's one API versus two APIs, and it can for sure go into whatever device we need it to go into. These early days, we don't know the clinical profile of Amiglutide. You've seen the data today. I wasn't yesterday. We presented the data. Both the data. 60 mg, 36 weeks, 24.4% weight loss. That holds a promise of a substantial weight loss with Amiglutide. I don't want to sit here and say I think it's going to be better than CagriSema, but there is that possibility. It doesn't seem that we need to compromise on safety and tolerability going to that weight loss. There is a really, really strong base case for Amiglutide, but there is also a very exciting upside that we need to show in phase III. Thank you, Martin. That's very clear. For dual chamber, base case is launched with a relevant upside for co-formulation. I'm sure we'll get back to the amaze program later if I know this audience well. Karsten. Thank you. I'm guessing many of us were just at an overgriping presentation, but also a commentary in the end about patient dropouts and how it has become increasingly difficult to keep patients on clinical trials. I've heard that too. Yeah, yeah. I can recognize that. I was just interested in hearing your opinion on that. I have to say, we all run trials in different ways in different countries and at different sites. We are obviously happy with our model. We've not seen, and I think this is important, at this point in time, including compounding, we are maybe treating 3 million patients in the U.S. total. That means that an argument of patients dropping in and out because there's availability of in-market drug in a space where we are still not treating just in the U.S. more than 100 million people, I'm not sure I fully recognize that. We don't see that in our own trials. You've seen us report on trials all the time. I don't think that we've seen that. I don't want to rule it out. I just have to say at this point in time, I cannot recognize it. Very good. Let's move to the next question. Let's go to Carrie and then to James afterwards. Thank you. Carrie Hoffman-Burbank. I've seen that they've evolved more positively for cagrilentide and clearly now progressing the phase III monotherapy. Can you talk about how you plan to progress in manufacturing of that product? It has, I believe, previously been manufactured or planned to be manufactured externally. Is that now changing? If so, if you're thinking of now bringing this in-house, how do you balance it with the demand of cagrilentide? Yeah. I don't want to go too much into detail. You're absolutely right. We have started out by producing cagrilentide outside of our own facilities. As you also know, we've invested heavily in building facilities over the last couple of years. That is exactly to get the flexibility across. I just showed you some of the, or basically the late-stage pipeline. With the ambitions that we have from research of also moving more into the clinical space, obviously, we need to maintain that flexibility. That means that we will continue to produce, I would say, more and more because we get more and more capacity in-house. I do not want to rule out that cagrilentide or some future molecules will, at least in the beginning, be produced outside. Exactly. That's clear. Good. Thanks, James. Thank you, James. Cody from Goldman Sachs. Just picking up, we'll just continue on the theme of cagrilentide monotherapy into the phase III. Could you give us a flavor of what the phase III design could look like? How many trials? Whether you plan to do a CVOT? I mean, obviously, offering a grip on doesn't have one. It doesn't seem to matter in terms of the commercial execution at the moment. To sort of pick up again on Karsten's point, I think one of the reasons why the discussion that said the clinical trial dropout rate was higher was also because of the forced up-titration. Will that happen in your trials, or will you have more of a CagriSema type? I got beaten up a little bit on redefined one because of not doing forced titration. The wonder of it was actually the patients who were allowed to do flexible lost more weight. People tend to forget that. I think you will also see for amiglutide, but certainly also for cagrilentide, we will not use forced titration. This is exactly the reason. In redefined form, we had one of, if my memory serves me correctly, actually the lowest discontinuation rates in this space. Considering a 23% weight loss, that is pretty amazing. That's basically because patients were allowed to titrate. They, one, actually lost a lot of body weight, but two, also could manage the speed of that body weight loss. Three, and that's to your question, also could manage the gastrointestinal side effect. Just to give you that example, in redefined one, we saw with cagrilentide approximately half of the gastrointestinal adverse events that we saw with the GLP-1 analog. For CagriSema, we saw the same gastrointestinal side effects as we saw for the GLP-1 analogs. This works not only from a clinical trial perspective, but also from a, I would say, real-world perspective. We're trying to mimic what we know is happening in the real world. I just want to remind you, the patients who used flexible titration in redefined one, they lost 26% on CagriSema. We believe that works. That is something that we'll continuously adjust. I mean, we listen to treating physicians. We obviously also listen to key opinion leaders, but we also listen to patients. We're trying to understand exactly with different offerings, what's the best way to treat. I think Ludovic and I share that hobby horse of being patient-centric in how we both develop our drugs, but also how we approach our patients. To your question, the initial trials are actually quite simple, aiming to get a very fast approval. We will build on those trials, also maybe testing higher doses. We will also generate data in more subpopulations. It's too early for me to say if we will do a cardiovascular outcomes trial. I think what you're hinting at is that there has been a notion that CV benefits is a class effect. I think recent data suggests that it's really, really not. I don't belittle that most GLP-1-based therapies have CV benefits. I'll just remind you, 26%, and we only have comparative data for diabetes. 26% in diabetes for semaglutide. Second best is dulaglutide and liraglutide, and now tirzepatide with 12%. There is a couple that is even below that. From a numerical and from a volume of the benefit perspective, there is a difference. There is always the joke that I love to mention, albiglutide that was taken off the market. Didn't give a very good weight loss, didn't give very good placebo control, but a 22% reduction in CV mix. That speaks to there's something in these GLP-1 analogs that we don't understand that is not generic for GLP-1 analogs. We believe that semaglutide stands out. I hate to quote Martin Parker, so he can do it himself. That he will do. Thanks, thanks Martin. Thanks, James. One reminder on trial design is, of course, a keen eye on dose re-escalation as part of it. Let's move to the left-hand side and Richard Vosser, please. Hi, Richard Vosser from JP Morgan. Actually, on cagrilentide again, and Charles Simon, but also Amylin 355. Just with cagrilentide, your competitors are doing some maintenance trials, I think, with their oral small molecule. One area where you could think about that may be with cagrilentide monotherapy as well. Just your thoughts there on maintenance and probably link to James's question. If you're going to do maintenance, do you have to prove a CV benefit for payers? Because that's what they really want. Just Amylin 355, just your latest thoughts on what the best approach to Amylin is, calcitonin balance. Yeah. For better or worse, until I see that readout, I have to give you my usual answer. None of us really knows. I really want to see in our hands that differentiated approach. As you know, we have more focus on Amylin, and then cagrilentide is a dual acting. That's going to be interesting. On maintenance, I actually agree with you. That's also, again, why I'm really, really happy with our portfolio. We can think about cagrilentide as a maintenance therapy. I don't want to rule out that CV data will be required in that space. We can think about, and again, in that context, oral semaglutide as a maintenance therapy. We can actually also think about just lowering the dose. I do want to call out, and I'm doing the same thing. Most of us think about maintenance in obesity as less intensive than the weight loss therapy. If we compare obesity to, let's say, diabetes, hypertension, dyslipidemia, also metabolic and progressive diseases, over time, more intensive therapy is required, not less. What we need to prepare for, for these are early days in obesity, none of us really know, is that maybe there is a time where you have to do less intensive therapy because that is okay the first couple of years. We cannot rule out that over time, we will also be thinking about more intensive therapy. A differentiated portfolio with drugs that could potentially be added on or be switched to a more intensive therapy, we believe that's the way to go, and that's the way that we serve the full obesity population, not only now and next year, but also for the longer term. Thank you, Martin. Thank you, Richard. Let's move to Mattias here on the second row. I think Richard has another question or a comment. Thanks so much, Mattias. I'm from Handelsbanken. In the New England paper on amycretin, the authors make clear reference to therapies that generate a weight loss of more than 10% obesity correlates with a CV benefit proven by the SELECT study with semaglutide. How do you think about that comparison, almost hijacking your data? At what point will CV benefit really matter for patients and physicians? It doesn't seem to be the case yet. First of all, I'll just return to what I said before. No GLP-1 is the same when it comes to CV benefit. It's interesting that I think, unfortunately, and I hate to be cheeky, but I hope the authors have read the literature also on the SELECT data. We have very clearly communicated that the weight loss is not the only driver of CV benefit. Actually, it's only explaining, I don't think we've communicated the proportion, but it's less than 30% of the CV benefit that is explained by the weight loss in a mediation analysis. That statement factually makes no sense. The only way that you can talk about CV benefit for a GLP-1 is to generate the data. I think our competitor has just done that for their GLP-1 GIP analog, and they've showed there is a CV benefit to the tune of 12% risk reduction. That is to be differentiated from semaglutide, which is 26%. I have no idea what a small molecule GLP-1 will do. Absolutely. Thank you, Martin. Thank you, Mattias. We will move to Bank of America. Question on the Evoke trial and the beta amyloid drop-in. Do you have any expectation or sense of what% drop-in and how balanced that could be between the arms? I think how stringent the criteria to permit the drop-in of beta amyloid would be. I think more broadly, given we're seeing obesity trials with the placebo patients realizing they're either not on GLP-1 from weight loss or lack of GI tox, how do you avoid placebo patients accidentally unblinding and requesting beta amyloid drop-in? A very short second one, you have a slot at CTAD, that high confidence in data before December 4th. I have no idea what the data will show. We have that slot because we want to communicate the data. Trust me, they have me in handcuffs, and I don't know what. I have no idea what the data will show. At this point in time, nor does anyone in Novo Nordisk. In terms of the drop-in, given the penetration and given where this has been marketed, we're not that concerned about drop-in. On drop-in in the placebo arm on GLP-1, we cannot rule that out. We see that in most of our studies, and all of them are powered to handle that and take care of that. Thank you, Martin. Thank you, Charlie. Goes to Conor. Hi there. Conor MacKay here from BMO and MMGR's team. The discussion at the Chamberlain presentation today made a point about the need for active comparator arms in some of these studies. How are you thinking about that in the context of the development of some of your earlier stage clinical assets? If you were to plan to incorporate active comparators, what would you use as that comparator? First of all, I think that that's a thought that is very close to our line of thinking. I think we do still need to do placebo-controlled studies, but I also think that we need active comparator studies in this space of obesity. If you want to look at cardiovascular benefit, the only relevant comparator is semaglutide. Don't misunderstand me. From my perspective, if I show non-inferiority to semaglutide, I can claim a 20% benefit in obesity. If I show superiority to semaglutide, then obviously that's a good thing also. From my perspective, that is okay. If you want to do an active comparator for weight loss, you can either do tirzepatide or you can do Wegovy. You are already seeing us do that. With CagriSema, there are two studies already running with head-to-head against tirzepatide, and we are considering that also for the MAIS program. Very good. Fifteen minutes left. Let's move to Rune and then Emily behind afterwards. Yeah. Rune Dahl from DNB Carnegie. You talk about speed to market, and you've been somewhat slow with cagrilentide, and maybe also CagriSema going to market. How do you see the new initiative from the U.S. government to speed that up, impact the market? I think that is great. I think speed to market is important. It's about serving patients with huge unmet needs. We want to have our medicines reach patients as soon as possible. I also have to acknowledge that you have a point with both cagrilentide and CagriSema. For CagriSema specifically, we very clearly communicated we wanted to have a robust supply chain so we could have a full-scale launch. We don't want to run into a discontinuity of care for patients if they cannot access the drug. Now we have that supply chain, and therefore we do the launch. That, I think, is the more patient-centric approach. Of course, it would have been wonderful to just go full speed ahead, but I think it's the right approach because now we can do a full-scale launch. For cagrilentide in monotherapy, you also heard me say we wanted to see what cagrilentide in monotherapy could do, both in terms of the efficacy. There has to be a minimum of weight loss for this to be relevant for a patient and in this space. More specifically, in terms of the safety and tolerability, we were actually very happy to see the safety and tolerability profile with cagrilentide. As you've also seen from other players within the amylin space, it's not a given that you have a clean amylin safety and tolerability profile. We demonstrated that. Therefore, you could say we could have started the phase III a year ago, but it's prudent to look at the data and sometimes to take an informed decision rather than sometimes. We do both. Sometimes we take a higher-risk decision to move fast ahead, and sometimes we decide that we want to look at the data. Super. Let's move to Emily. Hi. I'm from Barclays. With Emily, could you please comment on any updated thoughts on the clinical relevance of the weight loss quality, please? We haven't really seen the lean mass preservation in the human studies for amylin, but we did see today there's proportional more fat loss in the upper glycerin attempt when data versus, you know, other obesity studies. We're just wondering how clinically relevant it is, and also is there any reason that, you know, upper glycerin showed a differentiated impact on this matrix versus the peptide? I actually haven't seen those data. I have to admit that. That being said, there's always a disproportional fat loss as compared to lean mass when we lose weight. There have been some really, really good publications outside of the drug-induced weight loss suggesting it's the speed of the weight loss that is driving fat versus lean mass. The faster you lose weight, the more proportionally you lose lean mass rather than fat mass. That's also why you've heard me talk about many, many times fast titration is not smart. It's not good for lean body mass preservation. It's not good for side effects. From that perspective, we always focus on that. Based on the data that I have seen and that I can speak to, which is obviously semaglutide and actually also other of our competitors, that disproportionate more fat mass than lean mass weight loss takes place. You do lose lean mass, but you lose more fat mass. That basically means that you improve your body composition with semaglutide. You also do that with our competitors' drugs. The important thing here is, and we've actually had two pieces of data at this EASD on that, is that patients do not lose muscle strength or functionality. We've actually established maybe most prominent from the step-up trial where we see the biggest weight loss. Again, we see a lot of fat loss. We see a lot of lean or some lean mass loss, but the muscle strength and the functionality is fully preserved. I think that is incredibly important. I saw an interesting discussion at the conference today on sarcopenia with GLP-1s. The first definition by the discussion was sarcopenia is defined by loss of muscle strength. We don't see that with GLP-1s. It's a little bit of a folly to call it sarcopenia, at least based on the data that we have at this point in time. No one is saying that you are not losing lean mass with weight loss. You do that also without a drug-induced weight loss. The proportion is most often more fat mass, less lean mass. The big driver of that, as far as I can see, is the speed of the weight loss. Thank you, Martin. I believe there's also a poster on oral and 7.2 lean body mass at the conference. Let's move to the corner here. Thank you. Kritika Kalia, JP Morgan Asset Management. The question I had is reverting back to CagriSema. You said today that you're gearing Amiglutide more towards obesity. How confident are you in the ability for CagriSema to differentiate, and do you see it geared towards one or the other? Bigger picture, do you feel more confident in your outlook in diabetes or within obesity? Oh, that was many questions. It's all about my confidence. In general, when we talk about CagriSema and amiglutide, the data that we have from weight loss and obesity is quite confident. At the very least, we see 23% weight loss with a very good and strong safety and tolerability profile. I think that if we continue to see that in our clinical trials and maybe even slightly more weight loss, obviously I'm very confident. The same thing for amiglutide. Best data that we have right now is phase I. It's early days. 24% or actually more than 24% weight loss in 36 weeks is suggesting that that is a good weight loss drug. The amylin biology in diabetes, and I'm fully aware there's a short-acting amylin analog approved for treatment of diabetes, and it has been for many years. For that really to be impactful in a CagriSema or amiglutide perspective, the offering would have to be superior in glycemic control over semaglutide. That's a tall order. You'll not hear me say that's a slam dunk or that's a given. We would not have done phase III without believing in it. We don't have very many data supporting amylin and diabetes and glycemic control. Based on everything that we know, we think that it's a very good proposition, and we'll see the readout later this year as we just discussed. I have to say, REDEFINE 2 did really show that CagriSema reduces blood glucose quite substantially. There was just no comparator in that trial. I don't know whether it's superior to semaglutide. We have time for a few more. Let's move to Martin Parkoi on the first row. Just back to the 7.2 mg. Of course, we have seen what has happened in the UK that they already, you know, all the clinics have started actively promoting the 7.2 mg data already even before it's launched. We would like to see the proof first. Yeah. They have restarted. Has that been a part of motivation also to go to the U.S. to get the marketing angle there? With respect to devices in the U.S., now you also have the Govee FlexTouch device coming. What will be the administration of 7.2 mg in the U.S.? That's not for me to speculate on, but it's a good question. You know it, so don't need to speculate. All right, I will not disclose it. Step one is submission functionality, and then step two is potential launch. Let's move to the next one, that's Karsten. Thank you. I was just hoping that we could take another round on GIP. There was a presentation today with the Sema plus GIP versus Sema versus GIP alone, I think, essentially showing that whenever you use GIP in a Danish trial, you never find anything at all. Yeah, that's one way of putting it. Maybe I can hear your thoughts one more time on GIP because you're also at 88. So. You could discontinue the GLP-1 GIP, you haven't. That discontinuation was basically driven by we didn't see differentiation. We saw really good and on par weight loss with that GLP-1 GIP. It wasn't differentiated, and then it's not for us to push it further into phase III. The question becomes, in a GLP-1 GIP, one molecule, so unimolecular format, is it a really, really good GLP-1? Because either it's just good, or it's dosed right, or it's biased, so the receptor stays longer on the surface. All of those theories are out there. Or does GIP add to the weight loss potential? Based on everything I still know, regardless of Danish studies, we can get the same weight loss with semaglutide 7.2 mg as a GLP-1 GIP can, 21%. That suggests to me that if you dose a GLP-1 right, that's probably where you are going to get. That's also why you need to go to maybe other biologies for co-administration to get even further weight losses. What this means for GIP antagonism, I don't know. I think the jury is still out. I think it's an interesting field. You will also see me continuously pushing both GIP agonists and antagonists into our pipeline because I do believe that until we know, I need to stay curious, and we need to stay curious. If we really want to claim to have the broadest and most diversified pipeline, we need to also be in that biology until it has once and for all been proven it's not really doing a lot. You would probably also have noticed from the study that GIP in monotherapy does a little bit on insulin sensitivity, just doesn't do a lot when it's added to a GLP-1. Very good. I see Uma in the back. Thank you. Martin, a couple of questions, if I may. First, one question, then. I'll focus on Evoke. There's preclinical evidence which speaks to semaglutide's blood-brain barrier penetration being lesser than liraglutide, but I don't know how definitive that is. Do we need blood-brain barrier penetration to have the effect in the first place? I'm not aware of those data because actually what I've seen myself is indicating the reverse. We can also discuss the concept of blood-brain barrier penetration, whether it's broad, whether it's local, whether it's actually just activation of neurons that then leads to something else in the brain. That being said, I think some kind of either penetration or activity is required. That is what we see with semaglutide specifically. We've shown in animal models now that semaglutide not only improves the metabolism in the brain, so lowers the glucose levels in the brain, which is an important part of the Alzheimer's pathophysiology, but also improves central inflammation. We do believe that is caused by a semi-direct effect. That being said, we are still exploring, and we are still investigating this because at this point in time, we don't really fully know. Thank you, Uma. Thank you, Martin. Let's take two more before I hand it over to you, Martin, for closing remarks. I saw Michael first, and then I saw Mattias from Handelsbanken. Oh, there was not a hand, perhaps, Michael? No? We will go to Matthias and Richard Vosser at the end. I'm coming back to the New England paper for Epagliptan. It seems to show a plateauing effect around 48 weeks. Could you remind me how it resonates with what you've seen with oral semaglutide in the ACES programs? Do you think the duration of weight loss is likely to be different with a peptide versus a small molecule, and if so, why? I can't answer that. It's down to the dosing. When we talk about the speed of weight loss and how you titrate, I think with semaglutide, we're typically seeing plateauing of weight loss between 40 and maybe 60 weeks. With higher biologies or more potent biologies, and we showed that in redefined one, we need to go beyond 68 weeks to see the plateau. I think it depends on the biology. I think that it depends a little bit on how you titrate, how fast, or how aggressive you titrate. Absolutely. Let's go to Richard for a final question. Just thinking about breaking clinical trials by BMI, when do you start breaking up the trials and doing trials in different subsets of BMI? Do you do that with Amiglutide? Do you do that with Cagrilentide? When also do you go lower, so below 30? We have actually always done lower, but that's the 27 to 30 with comorbidities. That's sort of part of what we do. It's a really, really good question. You will already, with the MAIS program, see that we are in the first trials excluding patients who have BMI below 30. We are actually changing that concept. It's a little bit, again, if we have an aim to lose more than 20% of body weight loss or more than 20% of body weight, having BMI 27 and I ask you to lose 25%, that will leave you to a BMI of 20. That's not what patients want. Therefore, it doesn't make sense to think about that offering for that patient. We'll still investigate 27 to 30 because we'll do that as part of comorbidities. That's different. I mean, if we're just focusing on the weight loss and the sort of bigger weight loss, we need to also then, a little bit to your point, we're probably not doing fully what you're asking, but we're taking the first steps acknowledging that a big weight loss is not for everyone. Therefore, we will only include the people with BMI 30 and above. Do you spread out? Like, do you take out above 40? Do you take out above 40 at some point as well? Because you know we've seen in all CLIP1's trials today, it's sort of bimodal weight loss. Yeah, I saw that. That was interesting. We have been discussing that for cagrilentide, mostly because we acknowledge that the weight loss is in the range of these, I would say, 12%, maybe a little bit more. Therefore, if you have BMI 40, then maybe something else would be required. I have to say we'll investigate everything because, again, there are subpopulations that need something different. I think it's a reasonable thought that if you know that the weight loss is around 12%, you don't include people with a BMI of 45+. Very good. I'll hand it over to you in a minute, Martin, for some final remarks. Thanks a lot for all the questions. We covered a lot of ground, multiple obesity assets, a bit on diabetes, and also Alzheimer's. No CagriSema this time around, but maybe next time. I said CagriSema. I said CagriSema. Read out in 2026. Very good. Final remarks from you, Martin? Yeah. First of all, thank you for being here. Thank you for some really, really great questions and a good dialogue. Thank you for your interest. We see a lot of progress, obviously, in our clinical pipeline, focusing on diabetes, on obesity, but certainly also on cardiovascular disease, kidney disease, liver disease, rare disease. We are focusing very much on pushing the early research pipeline closer to the clinic and into the clinic to make it visible in a not very distant future. Thank you again and enjoy the rest of EASD. Thanks a lot. Thank you.