Novo Nordisk A/S ($NOVOB)

All right. Good evening, and welcome to the 2026 Novo Nordisk Investor Event in connection with the American Diabetes Association's Annual Meeting here in New Orleans. So my name is Michael Novod. I'm heading up the IR team at Novo. And I'm just going to run through a bit of practicalities -- apparently not. I just want to throw a bit of a practicality. So we're going to start with having a short presentation and then also followed by Q&A. And then the event is going to have a duration of 50 minutes before we're going to conclude. And with -- all right, I should also say that we do expect to make forward-looking statements, and they may differ from expectations. So read that just as a reminder. Today's speakers on the stage is our CEO, Mike Doustdar, he's going to give some brief introduction and is also Martin Holst Lange, Executive Vice President, Head of Research and Development; and also Chief Scientific Officer; and then also for the Q&A will also be joined by Karsten Munk Knudsen, our CFO. So with that, Mike. Thank you.

Thanks very much. So also on my behalf, welcome to ADA and to this session. I'll start with the slide that you have seen a number of times. I will not spend too much time on it. But we are quite proud that when we walk through the halls of the ADA, actually, this congress is no longer just about diabetes, but obesity, I would say, 10 years ago, we were the only one echoing the voice of people suffering from obesity. And today, it is nice to see that so many other companies are with us in that journey. Connected, of course, to these 2 conditions, there are a lot of other comorbidities, MASH, CVD, chronic kidney disease. And in all of those, we are a proud owner of assets and build -- we would like to build upon that heritage as we go forward. We also have, of course, our rare disease franchise where I will not get too much into it today. Now this week, we also made an announcement about how we are doing with our pill, which has been one of the most talked upon assets of Novo Nordisk and the launches recently. I think at the last quarterly meeting, we talked upon -- we talked about how the pill has become the best product launch of -- within the category of GLP-1 and perhaps within the whole category of launches in U.S. We are quite happy that we announced just a couple of days ago that we have now reached more than 3 million prescriptions. And I have to put that in perspective, we are now in week 22, I believe. It took us 10 weeks or it took us 12 weeks to get to 1 million prescriptions. And in the last subsequent 10 weeks, we have done 2 additional million prescriptions. That's in light of competition having arrived in the latter part. So if that is not acceleration, I don't know what is. I think it's been going very well. And we are also very happy to see that the pill is creating a halo effect on the whole franchises of Wegovy on the back of Wegovy High-Dose, Wegovy HD, of course, the original Wegovy. The pill is really causing us now have around 60% of the NBRxs in U.S. under the brand Wegovy compared to our competitors. So this is something we are very, very proud of. Then I also thought I shared this slide with you before I pass it to Martin to go in through the details. One of the most questions that I get on the pill is why are you doing so well, especially in the light of competition having arrived because I guess I am speaking on behalf of most of you, that very few had anticipated that. And the reason, I think, is a combination of, of course, the efficacy that you see here, 16.6% versus 12.4%. That's some 34 percentage difference in efficacy of the pill versus what we are competing with, the tolerability happens to also be at least compared to our competitor better when you compare the number of people that dropped out of our trial versus in their trial -- respective trial. The MACE and the label of Wegovy is helping a lot. This is a product that's not just reducing weight, but is giving you the cardioprotection that Wegovy is synonymous with. So that is also another reason why the physicians are prescribing this medication. The safety profile of it on the back of 50 million patient lives is also something physicians speak to us about. And maybe last but not least, when you compare it to our competitor, is the least restrictive medication, which is the part that most people have ignored and/or did not speak to for maybe good or bad reasons. Yes, I think I'll be the first to say we have one restrictions compared to our competitor, and that's that you have to wait 30 minutes before you take food with the medication. You take a sip of water and then you wait 30 minutes, has not been a problem for millions of patients that are on the pill right now. Meanwhile, against that single restrictions, we can see where the restrictions for my competing peers are. It is quite complicated and restrictive to take the other medication. And that's the fact of it and then that's what the physicians and the patients are trying to, of course, find a way around. And perhaps this combined with good sales and marketing is really the reasons why we feel very comfortable that we are on a good path. We have launched a product now in UAE 2 days ago actually, and early data, and it is really early data, gives me also very good hope that, that will be an equally good launch. And then more of that to come as we go forward with more launches, which we will announce going forward. Now it has been, I think, I'm subjective, but I think it has been a good ADA for us with some 40 different abstracts accepted. 100% of the abstracts that we submitted has been accepted by ADA amongst which, of course, the products that you see. We have had 36 presentations and 4 oral presentations covering more than 15 different clinical trials. And Martin will now speak to some of the highlights of those things.

Yes. Thank you very much, Mike. So -- good lord. Yes. Can we turn the volume down? So I'm going to focus, obviously, on you've seen top line data on CagriSema and type 2 diabetes. I'll remind you, we also did REDEFINE 2, which was -- it is part of the obesity program. But today, I'm going to focus on the REIMAGINE program that is the dedicated type 2 diabetes program, a secondary endpoint of weight loss. I'm going to focus on Zenagamtide in type 2 diabetes. And then I'm going to show you some details also on UBT251 -- the highlights -- all right. So very briefly, Actually, I had to say the sum of Julio Rosenstock and Donna Ryan are tough act to follow. And you probably attended most of you the session that was just finalized. You've seen the data. It is 3 studies basically comprising the spectrum of type diabetes from very early type 2 diabetes in REIMAGINE 1 through advanced type 2 diabetes in REIMAGINE 2 to late-stage type 2 diabetes in REIMAGINE 3. So when we talk about the very early type 2 diabetes, the average duration of diabetes was actually less than 2 years in that population. The 3 studies have reasonably similar design. So comparing CagriSema 2.4 milligram to 1 milligram in all of them -- in all of them also a placebo arm in REIMAGINE 2 also comparing to the mono component of semaglutide and cagrilintide. In all 3 studies, less than 50% females. Obviously, you've seen a couple of times during this ADA. You also have heard us talk about it before. We do know that, that impacts the weight loss observed in the studies that we do because we see bigger weight loss with women that we do with men. We have a mean BMI in the 2 first studies of around 35 and a mean BMI in the last study of 31. Again, important when you interpret the data. And that basically is reflecting a mean body weight around 100 kilos in the first 2 sides and 90 kilograms in the last study. The weight loss you've seen and REIMAGINE 2 at the highest dose, 14.2 percentage point weight loss with an A1c lowering of 1.9%. I do want to mention, if I placebo control that, it's going to be 2 percentage points, which obviously, in this basin, you've seen other diabetes data being presented at this years ADA glycemic control does actually still matter in type 2 diabetes. Obviously, we want the big weight losses, but the first license to operate is good glycemic control. So approximately 2 percentage points lower A1c in this specific study, combined with a 14.2 percentage point weight loss. For consistency, we basically see around the same 14% weight loss in the REIMAGINE 1 and the REIMAGINE 3 studies and around 2 percentage point lowering in A1C. Obviously, there's a range. It depends on the specific population, but again, if your placebo-controlled somewhere between 1.6 and 1.8 lowering in A1C. So really, really robust and consistent data. There were a lot of discussions of the tolerability profile of CagriSema. We talked about it. You also saw it today. You see improved glycemic control, superior glycemic control vis-a-vis semaglutide in monotherapy, better weight loss vis-a-vis semaglutide in monotherapy, but comparable adverse events rates as compared to semaglutide in monotherapy. So better -- basically we get better weight loss, better glycemic control, but with the same safety and tolerability profile and no new safety events occurring in the space of these studies. Just want to point out, we are not ready to do regulatory submission of type 2 diabetes for CagriSema because we are awaiting the cardiovascular outcomes data for basically both the type 2 diabetes, but also the obesity. We're doing that in one trial called REDEFINE 3 and that will read out next year. What will also happen next is obviously that we do initiate the higher dose of CagriSema. As you've seen, we've successfully established that we can increase the dose of semaglutide in monotherapy to 7.2 milligram without compromising on safety and tolerability as compared to lower doses of semaglutide. We intend to leverage that and initiating higher dose CagriSema studies later this year. Turning to Zenagamtide, just reminding you that in obesity in the same time span of the study, approximately 6 months, we saw in obesity 24.4 percentage point weight loss. Obviously, we expect to see something slightly lower in type 2 diabetes. And specifically, we saw almost 15% weight loss in type 2 diabetes. We do know that there is a little bit of a resistance to weight loss in patients with type 2 diabetes. So it is expected to see a slightly lower weight loss. But as you've also seen during this year's ADA, a 15% weight loss in 6 months is quite impressive in type 2 diabetes. In particular, if we combine that with, again, I was about to say almost the usual approximately 1.6 lowering in A1C. Again, this is at 6 months, not in the longer studies. I know that at least one of you will ask into the safety and tolerability profile. And I do want to spend a little bit of time if I can get the slide on the withdrawal rate of what we saw with CagriSema. You obviously see the nausea rates, the vomiting rates based on what we've seen during this week's ADA, it's not a surprising data in a Phase I/II trial. But there has been some concern expressed about the high withdrawal rates, 34% in the highest dose. This is simply because of trial technicalities because with this very powerful biology and an attempt to really push the dose escalation, we basically withdrew patients from the study if they did not want to dose escalate, which basically meant that people who felt that they had already lost more than 20% of their body weight, they did not need to go to the next dose. Not necessarily because they saw side effects but rather because they basically didn't want to lose more weight. They opted to not escalate the dose, which basically meant that they had to exit the trial. So there's a little bit of technicality in interpreting this data. When we look at the overall tolerability profile where we model what we can do in terms of dose titration in Phase III we assess that we will have a safety tolerability profile on par with CagriSema, which means that is expected to be on par with that of Wegovy. So a really, really strong efficacy profile, both on weight loss glycemic control, but also potentially a very strong safety profile and tolerability profile. We are conducting a quite broad development program, obviously, in obesity as a focus on weight loss. There is also a focus on immediate comorbidities as we see it in AMAZE 3 and 5 which is sleep apnea and knee osteoarthritis focused. So you've seen a combination trial or basket trial from some of our competitors, we've opted to do individualized trials, so some trials focusing just on the weight loss. Some of the initial trials focusing on sleep apnea and knee osteoarthritis. And then obviously -- and I think this is important we aim to show the same weight loss as we have shown with the subcutaneous treatment in an oral space will demonstrate that starting with AMAZE 9, which is our oral Zenagamtide study. It's only one study, and that's basically because we aim to have it on the market at the same time as the injection. And we can bridge the safety data and some of the other data from the subcutaneous program to the old programs just like we've done with semaglutide. And that really calls for a very strong offering. Again, I can only quote the data that we have at 6 months in obesity, 24% weight loss in Diabetes, 15% weight loss and a lowering of A1c of 1.7%. So delivered in both subcutaneous but also in oral profile. We'll have a cardiovascular study. It's not the usual 3 or 4 or 5 AMAZE studies, it's actually a study focusing on heart failure. We do believe that there's too little focus on the impact of heart failure, both from an unmet need perspective, but also in terms of what we've seen with semaglutide in that space. So therefore, we pursue that really very focused with amycretin. And this is an outcome study. It's not a functionality study. It's a true outcome study. And then obviously, we have the type 2 diabetes program as well. UBT251, super exciting acquisition. You've seen the high-level data. Obviously, I have to call out that in this study testing 3 doses of actually 4 dose regimen of UBT251 versus placebo. This is conducted in Chinese patients and in China only that does lead to an expected lower weight loss than what we would see from a global population. We've seen that in our studies, our competitors have as well. Rule of thumb is that you expect an Asian population to maybe lose 2/3 of the weight loss as compared to what you would expect to see in a global population. And therefore, when we do our modeling, just as we've seen for another triagonist during this week's ADA, we expect to see similar weight loss. So the 19% could translate to what we have seen from our competitors. Of course, we had to show that in Phase III, but really exciting weight loss potential. What is equally exciting is that in the face of that big, big weight loss potential, we actually see a safety and tolerability profile that is very, very attractive. So -- sorry, this is the weight loss. I just tend to ramp without looking at the slides. So obviously, a 19% weight loss or 20% weight loss in the highest dose in this population and quite a number or proportion of the patients, 50% of patients reaching more than 20% weight loss in this all Asian population, we expect to see, as I said, substantially more weight loss in a global population comparable to that what we've seen from our competitors. At the same time, you've seen the data today, those of you who went to the poster, a really, really attractive tolerability profile, very low withdrawal rates even at the highest dose, 0% withdrawal rate due to adverse events. A lot of you have said well, maybe there's also a bias in an all Asian population from that perspective. Just want to say, we've done a number of studies, our competitors have done a number of studies in Asia over the years. There are withdrawals also in those populations. So I think this is reflective of a good safety and tolerability profile. And when we look at the actual adverse events, it looks really, really attractive and very competitive. We are currently investigating UBT251 now in a global population, which basically means that we intend to initiate Phase III in short order. We're not giving the time lines, but aiming to have regulatory submissions and launch around the turn of this decade. Briefly on R&D milestones. Obviously, you heard a lot about CagriSema. You heard a lot about UBT. You heard a lot about Zenagamtide. I think for CagriSema, what is next is REDEFINE 11, that is the study where we're taking all of the learnings to really look at the weight loss potential of CagriSema. That study will read out in Q1 of next year, which is approximately a time of launch of CagriSema, expecting the U.S. regulatory approval later this year. we will see a continuous presence and initiation of Phase I study in both type 1 and type 2 diabetes that is not shown in this slide, but you will get more details and information on that if you attend Capital Markets Day. In U.S. for diabetes, we expect to see regulatory approval for 25-milligram of Ozempic -- oral Ozempic later this year, which will obviously also be exciting. In rare disease, I just want to call that out. I know it's a diabetes conference, but we expect to see regulatory approval of Mim8 in U.S. And obviously, we intend to do the regulatory submission of Etavopivat expecting a decision next year. Then obviously just advertising a little bit for what is immediately ahead of us in Q3, we expect to see the readout of the ZEUS trial. This is the first of the 3 cardiovascular outcomes trials that we do with Ziltivekimab. The ZEUS trial specifically is in patients with established cardiovascular disease, kidney disease and established inflammation, and the intent is basically to show improvement on 3-point MACE with the intervention. It is well established that increased IL-6 or increased inflammation is associated with increased risk of cardiovascular disease. We do know that more than 2 million patients live in U.S. with established cardiovascular disease and increased inflammation and therefore, huge unmet need because there is no treatment available. This is driving high levels of mortality, high levels of stroke myocardial infarction and so on. And therefore, if an intervention can improve that the potential is tremendous. What we've seen from Ziltivekimab is up to 90% lowering in CRP as a proxy for inflammation in such a population. We've also seen a safety and tolerability profile, which is important with anti-IL-6 treatment that is really attractive. So in Phase II, no increased risk of severe infections, no meaningful neutropenia, no meaningful impact on liver or dyslipidemia. So really, really a potentially attractive safety and tolerability profile but also a potential for really impacting outcomes for patients through reduction in cardiovascular events, MACE, that is myocardial infarction, stroke or cardiovascular death. So really exciting, really -- also, I had to call out high risk. This would be a first, and while we obviously await the data with high anticipation, it is a first-in-class, and that carries a risk that you have to take into consideration. But more to come in Q3. I think with that, we're going to Q&A.

Great. Thank you, Martin. Thank you, Mike. And as I said, we have around 25 minutes for Q&A, and Karsten is also joining us here on stage. Richard.

Richard Vosser, JPMorgan. Just we saw the CagriSema data in diabetes and you went through it slightly. But how are you thinking about that opportunity in diabetes? The REIMAGINE 1 data looked quite similar to the Reta data published just yesterday. So how are you thinking about it? How are the doctors thinking about amylin versus the use of glucagon in diabetes?

So I really don't want to talk either good or bad about my competitor, but I have to disagree with you that they look similar. So I think you're correct that retatrutide showed a 1.7 percentage point reduction in A1C, but the placebo arm showed 0.8% reduction. So when you placebo correct, which we have to do as a scientist, the reduction is around 1.1, 1.2 percentage points...

Just 1.1. Not 1.2.

Yes. All right. 1.1. Fair enough. And this is to be compared with what we've seen just with CagriSema, which is around 1.6 to 1.8 placebo-controlled. So I actually don't agree. I think the weight loss was comparable. But on glycemic control, I think CagriSema seems to stand out. And I would say the safety and tolerability profile with CagriSema also appears to be more attractive. Obviously, indirect comparisons, you know my caveats around that. But I don't think I fully buy into the premise of this is comparable between the 2. I actually think in type 2 diabetes CagriSema stands out, both on efficacy and safety and tolerability.

Great. Thank you, Martin. Martin Parkhoi.

Martin Parkhoi from SEB. Just a question on the 2 triagonist. Can you talk a little bit how you position them up against each other also on an indication level, which one is -- are they going in Phase III in all indications? Or are there some differences you will look at? And then just into that on UBT251, you mentioned the 2/3 in China and maybe we should try not to put up the expectations so much for the global readout in Phase II. So that being 30%. But can you talk a little about your expectations for that? And also what kind of dose levels you have used?

Yes, absolutely. So we're not going into too much detail when we talk about which indication we will pursue. I think your question is super relevant. So we'll not necessarily do what has been done for semaglutide, tirzepatide, retatrutide, CagriSema for that matter. I think we'll look at really targeting these opportunities to where the biology warrants it, maybe starting with higher baseline BMIs. As we've already seen, these biologies have really, really big weight loss potential. If you have a baseline BMI of 27 or 30 for that matter, you don't need a 25%, 30% weight loss. And therefore, we'll probably for both of them be looking at maybe even going towards higher BMIs. When it comes to comorbidities, we'll obviously look at the biologies. We know what GLP-1 does and has the potential to do. The triagonist containing glucagon or addressing the glucagon biology, it makes sense to go into, for example, MASH. We saw data today with another compound. I don't want to discuss their weight loss and their safety profile, but the data on the liver looked really, really interesting but you also saw a lot of discussions during this weekend on the amylin biology, for example, on bone preservation potentially on other benefits and taking a differentiated approach. So we're not necessarily -- or we are not going to pursue the 2 assets for the same indications. We can really, really think about what would be the right patient population to address with these biologies individually.

Seamus.

Seamus Fernandez, Guggenheim. Just 2 quick questions. Martin, I'm just struggling a little bit with the math on the 34% of patients dropping out because they achieved 20% weight loss and then seeing only at the high dose of 14% weight loss as a relative driver from 36%. So just -- I'm trying to figure out what I'm missing there on...

I wasn't giving numbers. I was giving examples on some patients actually felt that they had lost enough weight. It was very clear that A lot of them, obviously withdrew due to adverse events. We had not optimized the titration that we'll do in Phase III. But quite a high number also decided to leave for other reasons, including that they had reached a weight loss that was sufficient for them. Don't try to match the number because I was not giving numbers.

Perfect. And then just in terms of 2 factors, and maybe this is a little bit more of a question for Mike. But in terms of the supply opportunity and the scale at which you'll be able to launch CagriSema, I think folks are definitely interested given the dual chamber pen and some of the perceived complexity there.

So it will be a global launch. I think at 1 point or the other, we had said that maybe we will launch the dual chamber for U.S. and do a co-formulation for the rest of the world. That strategy has changed. We will basically without the co-formulations with the dual chamber be able to launch this globally. So that's what we're pursuing.

Pete.

Pete Verdult, BNP. One for Martin. Just given all the news, all of the competing data sets we've seen and issues with fixed versus flexible dosing, placebo dropout, patients taking prohibitive drugs. And just the number of trials we're seeing, just in terms of clinical trial execution for cardio Phase III programs, Lilly and Novo are known to be good trial executed in the space. But are we being -- are we not asleep at the wheel, but how much more challenging now as Head of R&D of Novo is it to conduct these trials with all those facts to consider?

I would say, not necessarily more challenging, but you have to be more mindful of what you do. For us, these dynamics are not different than when we had the same dialogue in type 2 diabetes 10 years ago, 15 years ago. You saw improvements coming in. And you also saw drop in of other therapies in our cardiovascular outcome studies, we, Five years ago, 3 years ago, had dialogue on dropping on SGLT2s and impacting potentially the CV benefit of semaglutide. If you design and conduct the studies correct, then you will be able to take care of that. You've not seen -- I mean, we're doing studies all the time. You've not seen the impact of drop-in in our studies, yet it's obviously something that we monitor. It's also something that we dialogue with the investigators and they, in their turn, dialogue with patients on so that we can handle it. Some of it you can potentially also cover from a statistical perspective. I think when it comes to flexible dosing, we have to acknowledge, we took our learnings with CagriSema. Flexible dosing has to be employed. You've also seen some data today where false titration were used and leading to massive dropouts. That's not what you can do specifically from a regulatory perspective. But you have to employ flexible dosing in the right way. So again, we took learnings from CagriSema. We've taken those learnings into the REDEFINE 11. I think you heard me talk about at the quarterly meeting, that we already see the impact of that. And we're taking all of those learnings further into amycretin and we'll do that again when we go to the triagonist. So I think from a trial conduct perspective, if you do the right planning and you have the right approach, but there is an art to it, it's not more cumbersome, but you have to be mindful of what to do.

James.

James Gordon from Barclays. A question on UBT. So I saw the phase -- the earlier Chinese data, but there wasn't a lot of detail on the tolerability. So can you elaborate a little bit? Is it that you think this could be better on efficacy and/or tolerability or more like it's going to be quite similar to Reta? And like was there anything in terms of people having like skin sensitivity or cardiac issues? And then maybe just sticking with GGG, just so we saw the Reta data. In obesity, how are you thinking that might impact your injectable franchise next year? And how -- what the picture will be particularly like lower dose Reta say, versus CagriSema, please?

So I think the last question is for Mike or Karsten.

Karsten will take it.

All right. Your first question, sorry.

Additional details on tolerability.

Yes. Sorry. So the poster that was shown today was not ours. It was basically shown by the investigators that worked on the study together with United, and they decided just to look at the dropout rates. When we look at the data, we can only do modeling, transferring the data from Phase II in Chinese subjects to Phase II first in a Caucasian population and then into Phase III. There we see -- we never plan to see superiority over, for example, retatrutide, it's the same biology. But we see the potential for parity on weight loss plus/minus. And then we see a tolerability profile that at least in this study and the other data that we have looks maybe more attractive than what we've seen for another triagonist. I mean you saw the dropout data. Obviously, it's a small study, and we have to take that into account. Nevertheless, if you look at the actual data, and I've been privileged to those data, it looks quite attractive. Not in the small studies, I mean sample size is not to really make those observations.

Yes. And James, thanks for your question on the competitor 4-milligram. I think the important notion is that if you look at our portfolio today, then with our injectable sema franchise, most recently launched sema high dose, 7.2 in the U.S. market. we have a highly competitive portfolio in terms of efficacy, proven brands, go-to-markets and acknowledgment around all the comorbidities of that brand. And on top of that, then, as you know, we launched with the Wegovy pill. So we heard some hints around convenience of competitor play. And there, I think that the Wegovy pill has proven with the uptake Mike showed earlier that if you want convenience, then a daily pill like the Wegovy pill is hard to beat. So we welcome competition and look to expand the market. And with our portfolio, we are ready for that combined with CagriSema, which will be approved at that point also.

Maybe I can a little bit add to that also, James, that from what we hear from the patients thereafter the magnitude of the weight loss and tolerability and the speed of the weight loss. So from the data is from our competitor, yes, with 1 titration, you can get to 19% weight loss, but you need to wait 80 weeks to get there. That's very different than, of course, if the situation was after 4 months -- 4 weeks, you titrate and then you get to the 19%. So I think patients don't care so much about 1 or 2 or 3 dose changes, but how fast do they get to that percentage weight loss. And then as Karsten touched upon, if you look at the products available right now in the market, ours or even our competitors, in a fewer weeks, you get to that level weight loss basically at very similar, if not better tolerability. So that's how I look at it from a patient's angle.

James.

James Quigley from Goldman Sachs. I've got 2 amylin-related questions. So firstly, on Zenagamtide, how are you thinking about the doses and the titration scheme for the Phase III. You mentioned that the Phase III will be a new titration scheme. So how did your modeling give you confidence on that? And are there any other measures as well that you could take to help attenuate the safety profile, the tolerability profile in the Phase III. And second, we've heard a lot on amylin biology at the meeting and as more data emerges in the class. How do you think about differentiation between the assets that we've seen data for? So does DACRA versus SARA matter? Do you believe these are molecule-specific, dose specific? Anything on Cagri versus Zenagamtide versus Petre versus Eloralintide. Any views there would be great. Yes.

Absolutely. So on dosing, I mean, we have to go back to what we saw with CagriSema. There are a group of people who can titrate these biologies, GLP-1 plus amylin biologies every 4 weeks as we basically intended, and they had in REDEFINE 1, a better, i.e., lower side effects profile as compared to Wegovy dose 57%. Then there's a group of people who actually got the bigger weight loss more than 25%. But who also started to go down in dose basically because they either lost weight too fast or because they saw side effects. That group of people, you should not recommend to titrate every 4 weeks, you have to acknowledge that they are super responders, so they should titrate with lower frequency. And we basically, for convenience, decided every 8 weeks. So we now have employed that in REDEFINE 11. As we already discussed, we can see that works that improves how many patients actually get to the higher doses and stay on those doses with a good safety and tolerability profile. Again, I'm looking at blinded data, I can't see weight loss but I can see how many patients go to the recommended dose. And we are doing that in REDEFINE -- sorry, in the AMAZE program as well. What we are also doing is actually adding an extra dose step, acknowledging that the dose steps chosen in Phase I and II were maybe slightly too ambitious. And again, that makes us quite confident that we will see the weight loss potential that we've already discussed in type 2 diabetes also the glycemic control, but with a tolerability profile comparable to that of CagriSema. And then on amylin biology, I mean, jury is still out. You've heard me talk a lot about, in particular, when it comes to cardiovascular outcomes. I do not think -- actually, I think I know that a GLP-1 is not just a GLP-1 semaglutide for example, it stands out on CV benefit as compared to other incretin-based therapies. I have to assume it must be the same for amylin-biology. We've seen one asset with a weight loss comparable to cagrilintide but with low dose response on the higher doses, whereas we can actually see that if we increase the dose of cagrilintide, we can get to higher weight losses. There's another competitor that have seen a very high weight loss, but where we are a little bit in doubt of what the tolerability profile will look like because at some doses, they saw a really good tolerability profile. At others they looked at tolerability profiles that resembled GLP-1s. And you don't want a 19% weight loss if you get the same tolerability profile as the GLP-1 because then it's just for patient, another GLP-1. The promise has to be that you get to your desired weight loss with a better tolerability profile. And that is where we see cagrilintide right now stand a little bit out.

Simon Baker.

Simon Baker from Rothschild & Co Redburn. Two, if I may, please. Just following up on a couple of earlier questions and starting with James's. Are there any differences you'd call out between the receptor affinity across the 3 amylin receptors in calcitonin between Cagrilintide and Zenagamtide. You answered -- I was going to ask the question about does this actually matter? Do we know? And then just picking back on something that Pete was talking about, particularly in light of some of the data we saw this afternoon on Survodutide. Going forward, is it practical or ethical to run placebo-controlled obesity studies going forward? It'd be good to get your perspectives on that.

Absolutely. So I think the jury is still out if it matters, the specificity for amylin versus calcitonin, they are all slightly different. There's also a difference between Cagrilintide and Zenagamtide, and that's where I've seen the most data close end. They appear to have the same weight loss potential, the same tolerability potential. Some are saying you want more calcitonin for bone preservation, maybe. Others are saying, you want more amylin for better weight loss and better tolerability. I'm not sure we've seen those differences pan out. So what we are doing is basically to ensure that we have a portfolio of Amylin biology that caters to basically both. Yes, really good question. I think as long as there's a regulatory requirements, we'll have to continue doing the placebo-controlled studies for better words, we had to do active comparator for CagriSema with the individual monotherapies. We don't mind doing that. Our aim is to take differentiated products to the market. So we've already now shown that CagriSema is a step-up vis-a-vis semaglutide like Cagrilintide in monotherapies.

[indiscernible] Martin, you're losing market share with Ozempic, why would you not file for CagriSema in obesity, just given that you have capacity for global a global launch.

So you mean CagriSema in diabetes. Basically because we need to have the REIMAGINE data -- sorry, REDEFINED free data before we can do the regulatory submission.

Michael?

Mike Nedelcovych, TD Cowen. One of your competitors showed some compelling, if early data for a once-monthly injectable at this conference. I'm curious if your approach to that effort has evolved at all? Do you think a once-monthly injectable could be a meaningful segment in the obesity market?

So I mean, obviously, we've been curious about once-monthly. You also saw that we were interested in that specific asset. That being said, I'm not sure that the data were as compelling as we had hoped for, in particular, on the tolerability side, but also a little bit on the efficacy side. I think the efficacy side is a matter of dosing. And maybe they will see a bigger weight loss in Phase III, but they really had to think about their titration because the once-monthly tolerability was not as attractive as I would have expected and to give patients something for -- in a once-monthly setting. The proposition has to be that it is a very attractive tolerability profile. So we are also pursuing less frequent dosing. Obviously, part of what we just discussed can be mitigated by even longer half-life. As you see us taking once modestly asset into Phase I this year. And we can -- if everything goes right, have those assets potentially in the market around the turn of the decade, to be able to compete in that space in a meaningful way. But again, the tolerability profile has to be better than what we've seen.

Ben.

Ben Jackson, Jefferies. One for you, Martin, on UBT, is this a scenario whereby you can get the SNAC technology involved again and go with the oral route. And perhaps when can we start to see that progressing? And then a really quick one for yourself, Mike, I think you made a couple of comments in an interview today talking about the potential for aesthetics and longevity. Is that through using the obesity and Type 2 diabetes portfolio as well? Or is there more interest to diversify beyond these core areas as well?

Yes. So we're got to realize not any peptide lends itself to the SNAC technology. That being said, we are obviously pursuing an oral version of UBT251. I just want to advertise, we're also doing oral Zenagamtide as we just discussed, an oral version of an amylin. And then we have actually a small molecule, which is the ACSL5 inhibitor that started Phase I a couple of months ago.

And I was basically making a reference that the biologies that we are playing around with and have expertise in can do multiple different things, and we will not shy away from pursuing and following the science in those biologies. So that was the reference.

All right. We have to cut here, but thanks a lot for joining this Novo Nordisk investor event at the ADA of 2026 in New Orleans. Thanks, Mike. Thanks, Martin, and thanks, Karsten. Thanks all for joining. And there's also be a couple of minutes afterwards to discuss with management.

Thank you very much.

Thank you very much.

Thank you.