Good day, and thank you for standing by. Welcome to the Novo Nordisk conference call. [Operator Instructions] Please be advised that today’s conference is being recorded.

I would now like to turn the conference over to your first speaker today, Michael Novod, Head of Investor Relations. Please go ahead.

Thank you, operator. Good day, and welcome to this Novo Nordisk call regarding the top line results of the REDEFINE 4 Phase III trial. My name is Michael Novod, I’m the Head of Investor Relations at Novo Nordisk. With me today, I have CEO of Novo Nordisk, Mike Doustdar; and EVP, Research and Development and Chief Scientific Officer, Martin Holst Lange. All the speakers will be available for the Q&A session. Please note that this call and Q&A will be related to the top line redefined fall data announced today, and no further details will be discussed. Today’s call is being webcasted live, and a recording will be made available on our website. The call is scheduled to last around 30 minutes.

Next slide, please. As usual, we need to advise you that this call will contain forward-looking statements. These are subject to risks and uncertainty that could cause actual results to differ materially from expectations. For further information on the risk factors, please see the company announcement for the full year 2025 and the slides prepared for this presentation.

With that, I will turn it over to Martin.

Thank you, Michael. Next slide, please. REDEFINE 4 was an open-label trial, investigating the efficacy set of CagriSema 2.4 milligram compared to Tirzepatide 15 milligram. The trial was mainly conducted in the U.S.

After incorporating some of the learnings from REDEFINE 1, the study was extended to 84 weeks of treatment, while all other parameters were left unchanged. The primary endpoint for REDEFINE 4 was to confirm non-inferiority of CagriSema 2.4-milligram versus Tirzepatide 15 milligram. The trial included around 800 people with obesity with 1 or more comorbidities. Both treatments were administered once weekly with subcutaneous dosing with the same dosing regimen as in the REDEFINE 1 and REDEFINE 2 Phase III trials.

As Tirzepatide 15-milligram treatment was only commercially available in a pen format, REDEFINE 4 employed an open-label design, in which all investigators and participants were informed of the specific drug administered during the trial. In this trial, CagriSema did not achieve the primary endpoint of non-inferiority of percentage change in body weight relative to Tirzepatide.

Beginning from a mean baseline weight of 140.2 kilograms. If all people adhere to treatment, CagriSema 2.4 milligram achieved a 23% reduction in body weight after 84 weeks. In comparison, Tirzepatide 15 milligrams resulted in a 25.5% weight loss over the same period.

There are many factors that could contribute to the REDEFINE 4 outcome. First, CagriSema performed in line with REDEFINE 1. Surprisingly, the comparator performed unusually well on efficacy compared to what has typically been reported in most previous trials of similar nature. We’ve noted earlier that not all learnings from REDEFINE 1 to achieve the optimal clinical benefits of CagriSema were implemented into the REDEFINE 4 protocol.

In addition, as I mentioned, REDEFINE 4 was an open-label trial, which has the potential to introduce buyers in favor of a well-established, well-known product when it is compared to an investigational therapy. The safety and tolerability profile of CagriSema was consistent with data from previous REDEFINE clinical trials.

The most commonly reported adverse event in the trial for both CagriSema and Tirzepatide were gastrointestinal-related and were generally mild to moderate in severity. These data further support the added benefit of Cagrilintide offering clinical meaningful effects to what we have shown with Semaglutide biology alone. CagriSema 2.4 milligram was submitted to the FDA for obesity in December 2025 based on the REDEFINE 1 and 2 trials, and we look forward to a decision later this year.

The REDEFINE program for CagriSema continues as we aim to explore the full weight loss potential of these complementary biologies. The REDEFINE 11 trial reached out and is expected during the first half of ’27, and we plan to initiate the Phase III trial of a high-dose CagriSema in the second half of 2026.

With that, I will hand it over to you, Mike.

Thank you, Martin. Please turn to the next slide. CagriSema and obesity will allow us to further build upon the Wegovy brand, where we aim to provide patients with multiple treatment options to fit their weight loss and lifestyle needs. Not only does CagriSema provide patients the efficacy, safety and health benefits clinically proven by Semaglutide, including established evidence-based risk reductions across certain cardiovascular, renal and liver diseases but it also improves weight loss with the added benefits of Amylin.

As Martin mentioned, we continue to push the innovation bar with the ongoing and planned Phase III trials for CagriSema and CagriSema High Dose. CagriSema, importantly, built upon our current offerings within the Semaglutide family now with more choices for patients seeking weight loss therapy.

One of those new choices for patients is our Wegovy pill. As you know, we have launched the Wegovy pill in the U.S. as the first and the best-in-class oral GLP-1 with a weight loss close to 17%. And we have shared with all of you how great that launch has been so far.

Another option for patients is the Wegovy High Dose, where we will further maximize the weight loss of Semaglutide all the way up to 21%. Wegovy High Dose is now approved in EU and U.K. and a U.S. decision is expected by the end of Q1. At the same time, Novo Nordisk continues to drive next-generation obesity innovation in our pipeline.

Charging ahead on the next-generation GLP-1 Amylin, Zenagamtide, where we saw up to 24% weight loss after just 36 weeks in Phase II. This product will be available to patients both in forms of injection as well as oral offering.

You should also note that we will leverage all the learnings from the REDEFINE program in the Zenagamtide Phase III AMAZE program, which we just initiated.

Furthermore, we will offer our patients Cagrilintide monotherapy as a potential option for flexible coadministration and a fewer side effects.

And last but not least, we also have 2 exciting triple agonist advancing through the clinics, which have the potential to offer even higher weight loss. We will share more of that in due course.

Now back to you, Michael.

Thank you, Mike. Next slide, please. With that, we are now ready for the Q&A, where I kindly ask all participants to limit her or himself to 1 question, including sub questions. Operator, we’re now ready to take the first question.

[Operator Instructions] And your first question today comes from the line of Mike Nedelcovych from TD Cowen.

My question is about your overarching hypothesis about CagriSema. You’ve reiterated that REDEFINE 11 could reveal CagriSema’s full weight loss potential, so I’m assuming there were data points from REDEFINE 4, similar to those from REDEFINE 1, suggesting that efficacy may have been left on the table. Did you once again observe a dichotomy between rapid responders and slow responders, just as an example? And can you confirm whether there was a discrepancy between the arms in REDEFINE 4 in the proportion of patients that reach the target dose?

Thanks, Mike. That’s a question for Martin around learnings going into REDEFINE 11.

Yes. Thank you very much, Mike, for that question. We’re not going into further detail on the data. But I think it’s fair to say that what we’ve seen in REDEFINE 4 very much resembles what we see in REDEFINE 1, a robust around 23% weight loss and a good safety and tolerability profile.

As we also discussed with REDEFINE 1, and as you pointed out, not all patients reached the full dose potential of CagriSema and therefore potentially not the full weight loss benefit. That is also something that we see in REDEFINE 4. And therefore, we are strongly assuming that there is a further weight loss potential to be had when taking all of these learnings into account. We’ve done that in REDEFINE 11. And therefore, as we also previously discussed, we couldn’t do that, take those learnings into REDEFINE 4. We could do that for REDEFINE 11, and therefore, we had to really guide that the full weight loss potential will be derived from REDEFINE 11.

Great. Next question, please.

Your next question comes from the line of Michael Leuchten from Jefferies.

I’ll stick to 1 question. Can you just talk about the non-inferiority margin you applied and how it was derived in REDEFINE 4?

Thank you. And that’s a question for Martin as well.

Yes. So again, we’re not really going into the data. Of course, we applied the non-inferiority margin. We did not fully achieve that. And therefore, we’ve seen the data that we have. I think it’s important to point out that we see a consistent and robust 23% weight loss with CagriSema, but we also are a little bit surprised about the 25% weight loss that we see with the comparator drug.

Right. Next question, please.

Your next question comes from the line of James Quigley from Goldman Sachs.

Martin, could you speculate on why is that bound data actually look better than they did in the Lilly trials, as you said? What was the flexible protocol not applied to that? And again, following up on the first question, was it 100% of patients just on the 15-milligram dose throughout the trial? And again, the flexible dosing was not applied in this case, is that bound — what happen there?

Thank you very much, James, for that question. Obviously, we are still investigating the data, but what we can see already now is that — yes, just to step back, both treatment arms received the same flexible dosing. And while not disclosing the data at this point, it is very clear that more patients reached the 15-milligram dose at some point during the trial for Tirzepatide as compared to CagriSema.

We do believe that, that is largely derived from the open-label nature of this study. We do know, and we’ve seen that numerous times before that open-label storages drive buyers. In this case, more than 40% of the investigators are previous investigators on the comparator drug. They know the drug well. They have probably prescribed the drug and they feel confident in the drug. We know that drives the buyers, and that’s maybe why we have seen these surprisingly good data for the comparator drug.

In part, we probably also had to ascribe this to biology. These data had never been shown before as far as I’ve seen in previous audits. So obviously, this is the one-off. Obviously, we don’t fully appreciate that it happens in our study, but that is what it is.

Thank you, Martin. And the next question, please?

Your next question comes from the line of Peter Verdult from BNP Paribas.

Peter Verdult, BNP. Mike, just 1 for you. Just a simple one, but important. At launch later this year, how are you going to look to actually differentiate CagriSema given the data you have right now? And just kind of squeeze on a very quick one, yes or no question. Any appetite to redo REDEFINE 4 at either a higher dose or with a more forced titration schedule?

Yes. So thanks very much. A couple of things. First of all, you have to go back to how products are sold and they’re sold according to their label. So the label that we have is, of course, based on — not this trial, but the previous 1 and the label that our competitor has also is below basically the CagriSema’s similar label. So I think we need to just be aware that there is an abnormality with this trial and how the comparator product has done and that abnormality and the 25% or so that we’re talking about is neither in their label nor has it been really seen in their own trials, any other trials, you could even argue that in the real-world evidence. So that I think the market figures that out as we go forward. The clinical experience of the physician and the label trumps anything and everything else when it comes to commercialization. We strongly believe that CagriSema has right now the best weight efficacy than any product currently in the market. So that is a very strong belief.

Now going forward, of course, as I mentioned, we will very quickly and soon release the data from REDEFINE 11 when they’re available early next year. Not long after the product is going to be in the market, that will help. But we also have made no secret and I think Martin just alluded to it, that we are designing the CagriSema with the higher dosages of it. So — and you have seen what happens to Semaglutide when it goes from 2.4 mg to 7.2 mg, and you could do your own modeling what that means. So I’m still incredibly optimistic about CagriSema.

And then when you put it in the context of the Semaglutide molecule where you have basically now current somewhere in the market at some 15%, 16% high dose of sema, which is coming up at 21% and now, of course, sema with Amylin, call it, at least minimum 23% we have shown 2x. That shows the projection. Next to it, of course, is the oral offering at 17%. So I think the brand recognition here and the increased percentages as we’re getting more and more is how we’re going to treat this product when it comes to the market.

And Martin the consideration.

Appetite — yes, sorry. Thanks, Mike.

Sorry?

Appetite for doing additional trials like REDEFINE 4.

So obviously, we have to look at the data and understand the data as both Mike and I alluded to, we did believe that we now understand the priority and the optimal way of using this biology in clinical trials. That basically means that we expect to see a potentially higher weight loss with REDEFINE 11, but we’re also investigating higher doses. When we see the outcomes of those data, I will not rule out that we would do additional head-to-head studies.

Operator, next question please.

Your next question comes from the line of Harry Sephton from UBS.

Do you have any comments on the relative tolerability profile of the 2 products in the study? And maybe just to touch on CagriSema again, not getting to the high dose as much as Tirzepatide. Could that just be simply a tolerability issue? And in this instance, you have a less well-tolerated product with lower weight loss?

Great question for Martin regarding tolerability.

Yes. Thank you very much. So the tolerability that we see in this trial, both for CagriSema, but also Tirzepatide is in line with what we’ve seen in previous duties. Obviously, we don’t have fully insight into the comparator drug, but very much in line.

That also makes us believe because when I say that more patients at some point reach the highest dose of the comparator drug, doesn’t necessarily mean that they stayed on that dose, but they then achieve the weight loss potential with that dose. We do believe that the potential difference in dose levels is more derived from the open-label nature of this trial and the fact that a great number of the investigators were very familiar with the comparator drug rather than any difference in safety and tolerability.

Great. Next question please.

Your next question comes from the line of Emmanuel Papadakis from Deutsche Bank.

Congratulations on the results. I mean maybe a question around longer-term dynamics. CagriSema looks somewhat obsolete now as a competitive upgrade Semaglutide, especially with the 7.2 mg available, as you mentioned, or is there a competitive alternative to Tirzepatide? So what can you do to accelerate Zenagamtide — excuse me, the new name for Amycretin. And where are your confidence levels that will look a more convincing solution relative to CagriSema?

Thank you, Emmanuel. Question for Mike regarding how we want to optimize and also look at the commercial potential for next generations.

3 Yes. I think Emmanuel to say it’s obsolete is quite belittling a fantastic drug in all honesty. Again, when CagriSema will make it to the market early next year as the first Amylin-based product, it will have the best weight loss label than any product marketed at that time. Let’s start with that. It will have the best weight loss label than any marketed product at that time.

Then, of course, we basically know that sema high dose has now 21%. Let’s take the latest results at CagriSema at 23%, but the CagriSema, the 23% is with the design trial that Martin has now alluded to, and we have multiple times mentioned to you that there is an upside to that when the design of the trial is less flexible, that’s the REFINE 11. We’ll see what the number is once that trial plans itself.

But we also have said inside CagriSema, what that you have seen in all of these trials, including the REDEFINE 11, there’s only 2.4 milligram of Semaglutide. We are starting a trial soon with 7.2 milligrams Semaglutide in that. And then basically, you will see that the life cycle management of CagriSema will pan itself as it is. So that’s all on the injectables. It has nothing to do with the pill. The pill is doing phenomenal. I think it’s the first and the best-in-class pill that you will see for a very, very long time to come. So that has its own. There is no other pill that has shown — can get anywhere close to the 17% weight loss, and we have explained that also. It’s the only pill that’s a peptide. All the other stuff is small molecules. So they have the small molecule efficacy. So that, I think is — but that’s a whole different topic on its own.

Then you’re speaking to Zenagamtide, Amycretin, which is the whole next generation of the products were coming after CagriSema, and that will also show its benefits, and we are taking all the learnings, as I mentioned, from these REDEFINE studies into the AMAZE trial studies and then you’ll see the benefits of that as well.

And then last but not least, stand still for the results of the triple agonist that we will basically announce in due course. So we have 2 triple agonists, and we are incredibly excited about that as well.

Thank you very much, Mike. And our next question?

Your next question comes from the line of Carsten Lonborg Madsen from Danske Bank.

Yes. So the CagriSema high dose that you will be initiating 2.4 mg, 7.2 mg. What does your internal modeling say about adding 7.2 milligrams similar to Cagrilintide, and why don’t you also increase the Cagrilintide dose in that trial?

Thank you very much, Carsten. And the question for Martin on higher dose CagriSema.

Thank you very much, Carsten. I’ll not guide exactly what our model says on the weight loss potential. But let’s say that it’s more than what we’ve seen with the CagriSema 2.4 milligram plus 2.4 milligram and with a comparable safety and tolerability profile. So clearly, an upside on the efficacy potentially without having to compromise on safety and tolerability. And from that perspective, that is a very attractive offer [ open-label nature ]. We have tested higher doses of Cagrilintide in combination with Semaglutide without seeing added benefits on weight loss. So therefore, based on everything that we know also from the step-up trial, it makes sense to increase the dose of Semaglutide but not necessarily Amycretin — sorry, Cagrilintide.

SP119072186 Great. Thank you very much, Martin. Operator, the next question, and we have 1 question left.

Your next question comes from the line of Martin Parkhoi from SEB.

Yes. Thank very much. Just on the same type, of course. Last year, you also announced that you drop your duels, your going — you had Tirzepatide as an actual comparator. Now we see these results today. And I note that if we look at the trials that you so far have on your 19, you use Semaglutide as an action comparator in AMAZE 8. You use Semaglutide as an active comparator. Have you just realized that you cannot eat a Tirzepatide and you’re using Semaglutide as the active comparator going forward?

And then just to follow up on the 419, can we talk a little bit about what your goals are with this with respect to are you going for a best-in-class side effect? Or is the weight loss that you’re going for in that one?

Thank you, Martin, and 1, 1.5 question to Martin.

Yes. So we obviously will do comparator studies when there is that opportunity. I think clearly, you’ve heard both me and Mike talk about the open-label nature of REDEFINE 4 and the potential for substantial buyers that is introduced both on the efficacy potentially also on safety and tolerability when reporting on that. So an ability to do head-to-head comparisons with a competitor drug would require the ability to blind. And that, obviously, we are working on as we speak.

Great. Thank you very much, Martin. And with that — I’m sorry, and this concludes the Q&A session. Thank you for participating, and please feel free to contact Investor Relations regarding any follow-up questions you might have.

Over to you, operator. Thank you.

Thank you. This concludes today’s conference call. Thank you for participating. You may now disconnect.