諾和諾德 (NVO) 2021 Q4 法說會逐字稿

Hello, everyone, and welcome to the Q4 2021 Novo Nordisk A/S Earnings Presentation. (Operator Instructions)

Today, I'm pleased to present Lars Fruergaard Jorgensen. Please go ahead with your meeting.

Thank you very much. And let me start by thanking Bank of America and Sachin Jain for hosting us today. First slide is our forward-looking statements. So I remind you that we'll be talking about the future, and it might turn out to be different than what we preach.

Looking at the highlights for the full year of 2021. We are very pleased with how we have executed on all 4 quadrants of our strategic aspirations. We'll cover most of it today. But just on this slide, we mentioned that on ESG, we're very pleased in how we are living up to both our social and environmental responsibilities, making good progress there. And the other quadrants, you will hear about as we present.

So if you go to the next slide, this is an overview of our sales growth of 14% in 2021. Very strong growth. We see that both international operations and now also North America operations is a nice double-digit growth territory, both growing by 14%. And when you break it down to geographies, you see nice double-digit growth coming from all geographies.

The growth is supported by all therapy areas, obviously driven by strong momentum in the GLP-1-based franchises, diabetes and obesity, but also continued growth contribution from our Biopharm franchise.

If you go to the next slide, here's an overview of the Wegovy situation. You all know that we, unfortunately, late December had to announce a stop of supply from a contract manufacturer helping us with the filling of Wegovy. We do all API in-house, but we depend to a large degree on external filling, and this supplier had to take down manufacturing because of a GMP issue. We guided that we expected initially to be able to fulfill approximately 60% to 90% of, say, end of year business volume. We have improved that situation since then. And now we expect to be able to match what we were selling at the end of the year. And we're still on track to resuming full supply of the U.S. demand when we get to the second half year. So somewhat a better outlook for Wegovy supplies than we perhaps feared at the end of 2021.

With that, I'll hand over to Camilla for an update on commercial.

Yes. Thanks a lot, Lars. So in obesity, our sales grew by 55% last year, split with a 57% increase in North America and 52% increase in IO. We are now in the U.S. at 22,000 weekly scripts for Wegovy and more than 70% of those are coming from people who are new to the anti-obesity medication class. Despite the fact that we've now put our sales and marketing activities on hold until there is sufficient supply, then our commitment to obesity remains very strong and is unchanged.

On the next slide, you see the overall U.S. GLP-1 diabetes segment. And here you see our market growth around 30% driven by once weekly GLP-1. You also see our NBRx leadership now 63.9% and Ozempic remains the NBRx market share leader within the injectable GLP-1 segment. And overall, our market leadership is now above 50% market share.

And with that, we'll move on to Martin.

Yes, thanks very much, Camilla. As you know, we have initiated Phase III programs across all of our therapy areas. So while this slide is a little bit busy, it's actually only reflecting some of our R&D milestones, both obviously covering Q4 of '21 and going through '22.

In the diabetes space, obviously, we were super happy to receive both the Ozempic 2.0 milligram positive opinion from CHMP in Q4 '21 and the approval also in Europe in January of '22. And we're looking forward to a U.S. decision also on Ozempic 2.0 milligram later this year.

As you know, we are investigating the impact of icosema in type 2 diabetes, and we are expecting Phase II results of this, allowing us to make a Phase III stop-go (sic) [go, no-go] decision in second half of this year.

Also, I want to call out that we, in Q4 of last year, initiated the Phase III program for icosema, which is the combination of once weekly icodec and once weekly semaglutide allowing again for the true combination accruing the efficacy benefits and the downsizing of tolerability issues in that combination but also a convenience benefit in terms of this is an asset that can potentially replace basal bolus insulin therapy. And therefore, allowing patients going from 28 weekly injections to as little as 1 weekly injection. Obviously, a very attractive offering in that space.

Then '22 is going to be very, very exciting in that we have 6 icodec Phase III studies basically our entire Phase III program reading out during the course of '22 in both first and second half, allowing us to aim for a regulatory submission very early in '23.

In obesity, as you know, we received a positive opinion on Wegovy. You've also heard us announce that for allowing ourselves to prioritize Wegovy supply in the U.S., we will now initiate icosema Phase III for obesity in second half of this year.

Biopharma has been very, very exciting, both in the last quarter of '21, but also it is going to be -- continue to be exciting in '22. We've seen the very positive and very robust Phase III data coming out of Sogroya, our once weekly growth hormone therapy. We've seen the initial cohorts reading out on Mim8, our very aspirational hemophilia asset. These data allowed us to initiate Phase III already in Q4 of last year, initiate in the sense that we are running patients in and observing them, and we intend to initiate Phase III treatment with Mim8 in second half of this year following the readout of the full data set of Phase I and II.

And finally, and also very exciting, we'll see the Phase III concizumab results also in hemophilia and aiming for a U.S. and Japan submission during second half of this year.

And with that, over to you, Karsten.

Thank you, Martin. Looking at our P&L for 2021. The results really marked a step up in growth compared to what we've seen in the last few years. So delivering on our accelerated sales aspirations. So underlying double-digit growth at 14% in a historic context, 14% is the strongest growth rate we've seen for the company since 2006. And in absolute terms, the step-up is between -- from 2022 in absolute DKK is to the tune of 2x compared to the biggest step-up we've seen historically.

That, of course, is enabled through continued investments in our commercial franchise. So we have sales and distribution costs increasing by 15% at constant exchange rates. And furthermore, we're continuing to invest in our future growth platforms and technologies as Martin was just covering before, and our R&D costs increasing by 16%. We continue to drive efficiencies in our back office cost and hence, a lower growth rate there.

Net-net, operating profit increase of 13% at constant exchange rates. Then some financial items related to hedging and a tax rate of 19.2%, impacted by some one-offs related to our BD/M&A transactions that we entertained during 2020 and 2021. And as a consequence, a net profit increase of 13% and diluted earnings per share up by 15% to DKK 20.74.

And in terms of allocation to our shareholders, then the DKK 20.74 per share we basically used to deploy a dividend for the 26th consecutive year. So the proposal at the AGM will be a full year dividend of DKK 6.90 on top of the DKK 3.50 we issued in August. So in total, DKK 10 for the year of 2021. And on top of that, the Board is proposing -- or have decided on a new share buyback program of DKK 22 billion, up from DKK 20 billion in 2021.

Talking about 2022 outlook is a continuation of the solid growth we saw in '21. We do have a negative impact from VBP in China and having 340B benefits in the U.S. in our base. And as a consequence, we are guiding for a sales growth of 6% to 10% at constant exchange rates for the year.

Operating profit growth of 4% to 8% being impacted by the Dicerna acquisition, which closed on December 28 of last year. Currencies are very favorable in '22, mainly linked to the U.S. dollar, which at the time we issued our guidance. We used a U.S. dollar rate of DKK 6 -- [DKK 6, DKK 7 and up] per U.S. dollar compared to an average in '21 of DKK 6.29. So that drives the positive currency impact of 5 percentage points on sales growth and 7% on operating profit growth. So basically, the U.S. dollar, Canadian dollar and CNY, the Chinese currency, are the main drivers of the positive currency impacts you're seeing here.

Then we have 12 months on the U.S. dollar. And as a consequence, we have our hedging losses accounted on net financial items. And as a consequence, a loss to the tune of DKK 2.8 billion expected at the DKK 6.67 exchange rate kroner to U.S. dollar.

Tax rate 2022, as in previous years, and the continuation of our discipline in converting our earnings to cash flow and the guidance, excluding any major BD activities, free cash flow guidance of between DKK 50 billion and DKK 55 billion.

With that, back to you, Lars.

Thank you, Karsten. So we're excited about the momentum in our business coming out of 2021 and feel we are well on track to achieve our aspirations for 2025, looking at the build of our pipeline and also the coming readout for 2022. And we hope to see many of you at our Capital Markets Day on March 3 here in Copenhagen.

With that, I would like to close our presentation and open up for Q&A.

(Operator Instructions) Our first question comes from Sachin Jain with Bank of America.

So one on pipeline and then one on 483, if I may. So for Martin on pipeline, sema cagri Phase II data in diabetes is due second half of the year. Wondering if you can just provide a bit of background on target profile and what you've seen that gives you some confidence there. I'm specifically referring to any HbA1c blood glucose metrics you saw in the obesity data, which is a normal glycemic patients that gives you confidence. The reason for the question is I think there's always been greater excitement in obesity than diabetes. Just wondering whether that's shifting as we approach the Phase II data.

And then secondly, just on the FDA supply issue with Wegovy. Just a follow-up to my question on the call. So Henrik mentioned that supply should start at the CMO in the second quarter. I just wondered if you could clarify what steps remain between now and that supply restarting. I wonder if you could talk us through that. And I guess, I just wanted to get visibility, if you can, on one of the variables you've listed in December in time lines for sourcing of spare parts, and I guess potentially the [hepa filters]. So just wondering whether that's done and you're sort of getting close to completing production runs and sending validation data to the FDA.

Right. Thank you, Sachin. Martin, first, on icosema in diabetes.

Yes. Thanks a lot, Sachin. So first of all, I think it's important to call out that we've not seen any data on glycemic control with cagrilintide. As you obviously -- and you pointed that out yourself, we have data from obesity and obese patients. These are all normal glycemic and nondiabetic, and while we may see a hint towards impact on blood glucose, nothing that would substantiate us going into certainly Phase III.

That being said, as you obviously also know, an amylin analog is already on the market for the treatment of diabetes, pramlintide. While this is a short-acting analog, we do know that amylin has impact on gastric emptying. It does obviously had impact on body weight. It has impact on glucagon secretion. And therefore, we do believe that we need to investigate the potential impact of not cagrilintide in monotherapy but in combination with semaglutide to investigate that given that we don't have any clinical data Phase II, it seems to be the obvious place of doing that, allowing ourselves to initiate Phase III more or less at the same time as we aim to initiate the obesity trials, if that should pan out positive.

I can't speak to the entire product profile, but from a glycemic control perspective, it goes without saying from a regulatory perspective, we need to show more and better glycemic control than in semaglutide monotherapy.

Thank you, Martin. And on the 483 and the contract manufacturing organization for Wegovy, that's right, we expect to be able to supply the U.S. market in the second half, which implies that manufacturing will be up running in Q2 for us to fill up the supply chain before we get back and promote in the market. And to be able to resume manufacturing in Q2, there are 2 category of activities that needs to be completed. One is -- and that's built on the observations you can read about in the 483. One is in the camp of, say, procedural aspects, updates to the quality management system, training of employees, et cetera, that's not on a critical path. And then there are activities linked to maintenance in the facility, and you mentioned changing some fillers yourself. Those fillers are available now, which is an achievement in itself in a market where supply chains are stressed. But the fillers are in place.

And what is, say, the critical remaining aspect is the media fill. Whenever you have taken down manufacturing set up, you have to requalify it and you have to run a media fill proving under stressful conditions that the line is operating with integrity and producing sterile products. So that's an important step. It's a standard thing. All manufacturers operating with sterile manufacturing are used to doing that. We do it on our own lines on a regular basis. There's always a risk because you do this under stressful conditions.

So if there's a failed media fill, you have to do it again. But this is something you can do in a matter of weeks, not months. So we feel that there's good progress, that there's a competent contract manufacturing organization handling this. They know what they have to do, and we believe they can do it. There is, of course, always risk, but we think this is manageable. And we feel we have good confidence in our ability to resupply in the second half of the year.

Our next question comes from Michael Leuchten with UBS.

Michael Leuchten from UBS. Two questions for Martin, please. Firstly, Martin, can you just confirm that you have all the Mim8 data now for the Phase III. You were saying you're going to start recruiting patients into the Mim8 in the second half, but it wasn't entirely clear whether there's still some data outstanding that you need from the Phase I, Phase II trial or whether you have everything that you need.

And the second question on icosema. I was wondering if you could talk to what you learned from Xultophy and the lack of success for that product as you try to apply the same concept. I think there were some challenges with the lack of [separate] titration. I was wondering if you're aiming to address that in the clinical trial program or if that's our program as it looks for now what was the -- what effectively you did with Xultophy.

Absolutely. Thanks very much, Michael. So first of all, on Mim8, as you know, we run sort of a combined Phase I/II study with a number of single ascending doses and then a number of multiple ascending doses. During the course of Q4 of last year, we started to see the readout of some of the earlier multiple ascending doses. They actually called for us to sort of, at that dose level, see a safe and tolerable profile as well as a pharmacokinetic profile that allows us to at-risk actually initiate recruitment into Phase III already in Q4 of last year. So we have started recruiting patients. They are what we call in a run-in period where we observe them on their current medication and we aim to initiate actual treatment in second half of this year.

This approach obviously allows us to cut time. So at the time point where we have the full readout of the Phase I/II trial and have interacted with the regulatory authorities, most patients will be recruited. And therefore, we can go directly into the dosing part in the second half. That actually allows us to almost cut the full development part of Mim8 R&D sort of time in half. So instead of the normal 7 to 8 years development time in the clinical phase, we actually aim to have 4 years from first human dose to a final dose in Phase III for Mim8. So this is an at-risk approach, but we are actually already now recruiting patients into the study.

On icosema, I think that's sort of a combined question to myself and Camilla. Obviously, on the clinical profile, what we saw on Xultophy was very, very attractive. And it was actually easy to try to create and physicians who have initiated patients on Xultophy do not find any issues in not -- in having sort of the fixed-dose combination because when combining a GLP-1 analog and an insulin, you actually mitigate the tolerability issues that you see with the mono components. So that combination leaves for less gastrointestinal side effects from the GLP-1 component and less risk of hypoglycemia from the insulin component.

That makes it an attractive clinical offering. And obviously, we need to be even better in the icosema Phase III to secure a very clear but also a very simple titration, reaching the good efficacy and the good safety profile but then, obviously, also, again, calling out the convenience aspect. And normally, I wouldn't call out convenience, but in the case of icosema that has the ability to go in and sort of compete with insulin basal bolus treatment, we are talking about moving from 28 weekly injections to 1 weekly injection. I think even for me who wants to normally focus only on efficacy and safety, that is a convenience play that is quite substantial and will have an impact on patients and actually also treating physicians.

Maybe Camilla also wants to talk a little bit on how we intend to go with icosema vis-a-vis Xultophy.

Yes. I just wanted to say that there is, of course, an increased demand for these types of combinations, especially now in China, we just had Xultophy approved in October 2021, and we will be focusing significantly on that also in China. But also in Region Japan, we see a very steep increase in the usage of Xultophy, same in other parts of Latin America, but also in East Asia. So there is a very good and underlying demand for Xultophy at the moment. And of course, that also gives us good hope for icodec and icosema.

Thank you, Martin. Thank you, Camilla, and thank you, Michael, for the questions.

Our next question comes from Rajan Sharma with Deutsche Bank.

It's Rajan Sharma at Deutsche Bank. First one just on icodec. Could you just kind of think about the commercial opportunity there? So basal insulin was obviously flat globally in 2021. And so how are you thinking about the icodec opportunity? And the potential to return the franchise to growth, obviously, once we get through VBP.

And then the second was just a clarification on the Wegovy supply. Could you just confirm that you don't need a -- or the plant doesn't need a reinspection?

Thank you, Raj. And Camilla first on the commercial aspects on icodec.

Yes, icodec. We're looking forward to bringing icodec to the market, obviously, because it has a number of significant advantages for patients, in particular, that we can reduce the number of injections from 7 to 1 a week, obviously. Having said that, we also are looking at potentially, of course, increasing our share in the basal segment, which we traditionally have not had the same market share as in the other insulin segment.

And in addition to that, we also hope that the ease of use with icodec and the efficacy of it can help expand the market further. So lots of benefits for us in bringing icodec to the market, and we look forward to that a few years down the road.

Thank you, Camilla. And on Wegovy reinspection, yes, it is our understanding that it's not required to conduct a reinspection and the U.S. FDA would have a look at the facility at the next regular inspection, whenever that will take place.

And I'd also like to add that we are also bringing in line more sites as part of the production expansion strategy. So more sites will come in line over the next year or so. So we believe we have a robust and future-proof supply setup for Wegovy.

Our next question comes from Wimal Kapadia with Bernstein.

So just one for Martin. There's a lot of competitive data this year. But in particular, I wanted to ask about the BI-Zealand dual agonist and the Lilly triagonist. Now these targets that Novo have looked at in the past and did not pursue. You kind of said the same with GIP, but now obviously, you've restarted that program. So just curious, particularly about these 2 programs, the GLP-1 and glucagon combo and the triagonist, why you have conviction that they were not worth the investment at the time and is this something you would reconsider depending on what happens with the competition data?

And then my second question is maybe for Camilla. It's one I've kind of asked before, but now we're getting close to the time, so maybe you have a different view. But just on pricing for Ozempic high dose that we're getting potentially the approval in March. But the net pricing of Ozempic is still around $18, according to my math. And Saxenda -- and Wegovy, assuming similar to Saxenda, will be over $30 net price. So should we just be thinking about splitting the difference when we're thinking about Ozempic high dose or would you take a slightly different strategy? And I am asking because from a time line perspective, you may be on the market with a high dose before tirzepatide is launched in diabetes.

Thank you, Wimal. So first, Martin, on the competitive front with dual and triagonist.

Yes. Thanks very much, Wimal. So when we make our portfolio decisions, obviously, we look at our overall strategy but we also look at our clinical profiles. And as you alluded to yourself, we've had both dual and triagonist in our pipeline. And we have to say that on balance, looking at efficacy, looking at safety profiles, we found that this is obviously also what you see in our portfolio right now. The combination of an amylin agonist together with a GLP-1 agonist to be substantially more attractive than what a dual, triagonist in the GIP glucagon space could offer.

I think it's reasonable to say they will be effective. But what we've seen is also that, that efficacy comes with a safety cost. So on balance, there was a decision that made a lot of sense or it makes a lot of sense to us. Obviously, we also have to safeguard, there's always attrition in what we do. And therefore, we also put a bet in on a GLP-1/GIP agonist and aiming to have the best GLP-1 agonist and the best GIP agonist, obviously, that could also be an attractive offering.

Thank you, Martin. Camilla, on pricing Ozempic high dose versus Wegovy.

Wimal, we are, of course, looking forward to getting the approval also in the U.S. of Ozempic 2.0. Have to say, of course, Ozempic is a great product. You saw how good the penetration we had last year. And there is 80% of people getting good control with Ozempic 1.0. There might be a remaining group of people that could benefit from intensifying to 2.0. So that's why we look forward to bringing that to the market.

In terms of pricing and net pricing and differences between diabetes and obesity, this is not something I can get into the details of at this point in time. But clearly, to say that for now, we have Wegovy on the market in the U.S. in obesity recognized for that indication. And then we have Ozempic for people with diabetes in the U.S. at 2 different price points for 2 different indications and 2 different groups of people. So more to come on that when we have the approval of Ozempic 2.0.

And you might have to ask for a third time, Wimal, sometime in the future.

Our next question comes from Keyur Parekh with Goldman Sachs.

A few, if I may. The first one is just following up on a couple of the previous questions. One, as you think about the headline data we see from tirzepatide, what is your base case expectation for kind of the amount of weight loss we see with that agent? What do you think would be an upside and a downside surprise to your base case?

Secondly, as you think about positioning icosema, both kind of from a regulatory perspective and from a commercial perspective, I'm kind of surprised you're not running a head-to-head versus Xultophy. So I would be keen to understand why you're not doing that.

And from a regulatory perspective, are you still expecting this molecule to be used post kind of failure with GLP-1 and basal insulin? Or do you think this can be moved earlier in the treatment paradigm?

And then lastly, Camilla, for you, 55% kind of obesity growth in 2021. As we look at 2022, is it fair to assume that your growth rate will be higher than that for the full year?

Thank you, Keyur. And let me try to give a bit perspective from my side on tirzepatide and then perhaps, Martin, you can add -- or I don't know, Camilla, if you can add on commercial.

But I think Camilla alluded a bit to the momentum we have right now with Ozempic. You have all seen what Wegovy did when it was launched in the U.S. So I feel we have a really, really good proposition in what we have at hand based on the semaglutide molecule. We have higher dose. We have a broad portfolio in obesity. So this is really about expanding the market.

And I think there's -- I hope there's room for both products, but I would know for sure that there's room for Ozempic and Wegovy because that's established already now. And the feedback we get from both physicians and patients in terms of what it does for them, both Ozempic and Wegovy, is amazing.

So I think we are building the go-to brands here that is not necessarily going to be easy to compete against. Having said that, I have a high respect for Eli Lilly as a competitor and I think they will give it their best shot. But we have a very solid ground and I feel comfortable about that. I don't know if, Martin, you want to speculate on their positioning.

I can only echo what you said. I don't think I should be speculating on their positioning. But I think it would be fair that -- to say that I look much forward to see what their label is going to look like. As you know, we all look at different estimates, treatment policy versus trial product estimate. And in a label, those data may look a little bit different and maybe less impressive than what we had seen so far. So I'm looking forward to see the label to see the actual difference on both glycemic control and also weight.

And then obviously, weighing that up against the safety profile, we know that semaglutide, to Lars' point, it's on the market. It's super well perceived. And that is in part because of an attractive safety profile.

We've seen quite a high withdrawal rate from some of the tirzepatide studies, even in the face of low withdrawal rates of semaglutide in the same study. So I think on balance, semaglutide will hold its ground on the combination of attractive efficacy getting 75% to 80% to target and then obviously on a very attractive safety profile. And then obviously, with a fast follow-on from our side in the shape of Cagrisema.

Thank you, Martin. Camilla, there was a second question on obesity growth, where we see growth now, a bit north of 50%. While we don't guide specifically on growth rates per category, what are your perspectives on that?

Yes. So the perspectives are that the first year of COVID-19, we did see a dip in the obesity growth because people were not going to see the doctor. However, in the meantime, there has been an increased understanding that it is important to treat obesity. We even saw studies where it was proven that the risk of death for people living with obesity getting COVID-19 was significantly higher. So the understanding from payers, health care authorities and providers that it is important to treat obesity because of the risk of long-term complications such as cardiovascular disease and diabetes and some types of cancer is extremely important.

And I think also in our numbers as of last year, you see that, that understanding also turns into more prescriptions. And especially with Wegovy even so also a patient-driven demand for a weight-loss product in the range of 17% to 18% like Wegovy. So the underlying dynamics in obesity is positive when it comes to treatment getting to patients. And of course, that general momentum, I think, is important to rely on. And without giving any indications of growth rates for this year because that obviously also depends a lot on exactly the time of which we will be back with the full supply for the U.S. and so on.

Good. Thank you, Camilla. Thank you, Keyur.

Lars, sorry, can I -- sorry, I thought there was another question on the positioning for icosema, regulatory and commercial. Sorry.

Yes. So basically, for icosema, we aim at a simple and convenient once-weekly treatment and it basically means that we hope to be able to be an alternative to base bolus insulin at a similar HbA1c. And of course, just with fewer injections and also a good weight profile, a good [hypo] profile and an efficient HbA1c profile. So that's how we see icosema being used. And in particular, in the regions of Europe, of Asia and also the Middle East, and I already talked to earlier, Japan and China being very important for fixed-dose combinations of insulin and GLP-1.

Good. Thank you. I hope that satisfied you, Keyur.

Our next question comes from Simon Baker with Redburn.

Two, if I may, please. Firstly, for you, Camilla, just going back to your comments on Xultophy demand. You cited a number of regions and countries where you're seeing increased demand for the combination. Flipping that on its head, I wonder if you could give us your thoughts on why there isn't increased demand in other regions. What's holding back? Is it physician preference? Is it reimbursement? Some thoughts on that would be very helpful.

And then for Martin, going back to something that was touched on yesterday, the sema-GIP combo study, the Phase II that started in November. I see that, that study is due to report out in October or finishing October. That seems a little early. So I just wonder if you could give us any thoughts on that. And also on the dose selection of the GIP that you picked, in that it seems quite a broad range from, I think, 2.4 to 21.6 milligrams.

Thank you, Simon. So Camilla first on Xultophy demand and flipping it on the head, why not all regions.

Yes, why not all regions. So in the regions where we don't see a strong uptake of Xultophy, it's basically because there has been a traditional preference for loose combinations of products, especially in the U.S. So that's really the reason.

On the other hand, we see in other countries like China, there's been a long tradition for using combination insulin and mixed insulin. So it is down to preference to a large extent. And that's also why for our insulins for a number of years, we work with what we call the market fit approach to be able to supply the market with the type of insulin that is generally preferred from the doctors and the population.

Thank you, Camilla. Martin, on sema-GIP time line and also dose of GIP?

Yes, thanks very much. So as you rightly called out, this is a Phase II study. And therefore, time lines are designed to allow us to look at efficacy, safety, but actually also doing the dose finding. And that means, obviously, that we have made time lines as short as we can to allow us to have those readouts.

The sema-GIP offering is going to be a fixed dose combination, and that also means that we need to test different doses of GIP up against the backbone of semaglutide. And that basically means that we have to explore a range to secure that we obviously investigate the optimal efficacy, but also to secure proper safety and that does call for a quite wide range of dose testing in that setting.

Our next question comes from Peter Welford with Jefferies.

Just returning to Wegovy, a couple here. Firstly, just with regards to the CMO. Just so I can understand, is Novo going to do their inspection from your side working with Catalent before the facility comes back online? And I guess it'd be helpful if you could provide something as to what Novo has been doing during this process from your side to resolve this issue.

And then secondly, just on the PDS290 FlexTouch platform. Apologies if I missed this yesterday. Could you just explain again why that is an ex-U.S. platform and is not being pursued in the U.S. at this time? And equally, the additional sites that you say will come online in the next year or so. Are these sites going to be -- to provide drug to both the U.S. and Europe? Or will these sites be specifically to meet the future U.S. demand that there is?

And then could I just ask just on the copay card. I appreciate, obviously, understandably, they've been withdrawn at the moment. When the drug is brought back again in the second half and presumably there's going to be significant pent-up demand that's accumulated during the last 6 months. Should we assume then copay cards will come back in earnest? Or do you think, given you had 6 months also to improve payer coverage and access, we should assume that copay cards will perhaps be less material to an extent versus the original Wegovy launch back in last year?

All right. Thank you, Peter. Let me try to give your questions a shot here. So on the Wegovy contract manufacturer, we have a very good partnership with the company. Obviously, we were disappointed about the situation they ended up in after the inspection from the U.S. FDA. But we are very pleased with the professionalism whereby they are handling this. We work closely together with them. I cannot go into all the details of what that involves. But we are close to the situation, and we feel very comfortable in how they are handling it. And as such, this is a partnership, and we are not going to do a formal inspection of what they do because we're close to it.

On the PDS290 platform, we felt it would be a good idea for us to register 1 more, say, technology platform, so to say. The platform in the U.S. is based on a single shot device and a syringe inside that, that is filled by -- mainly speaking, by our contract manufacturing partners. We can do a bit in-house, but that's mainly outsourced.

The PDS290 platform is an in-house [no noise] platform. So that's something we fill and pack ourselves. So when we add new sites for Wegovy supply, that is for the single shot presentation, i.e., what we have in the U.S. market today. What platform will end up using in other markets remains to be seen, but we are adding strategic flexibility in having more platforms.

On the copay card, you're right. They were established at the time of launch, a large success in generating attention to Wegovy and interest in Wegovy. We have stopped it again, and they will eventually run out of time, so to say, we feel that there's good awareness about the products. So when we launch it again or when we start -- well, it is in the market still. But when we start promoting it again, we need less of that type of support to it without going into all the details about what our plans are. But we think that the awareness about Wegovy, the willingness to prescribe and seek care is high.

Our next question comes from Simon Mather with BNP Paribas.

Kind of following on from that in terms of Wegovy demand, you don't see the need for copay cards. Maybe you can help us just understand because numerous times, you said you expect to have unconstrained supply for the second half of the year in the U.S. if all things go to plan. Can you help us get a sense as to what you believe the actual underlying demand for the product is because one would assume with the copay card, availability is clearly a "no-brainer" for people to want the drug when you can get a 6-month supply for $150. And so just any kind of sense as to what you think an underlying demand curve for Wegovy would be in a normal non-GIP treatment option would be. That would be helpful.

And then maybe just -- sorry, maybe just on Cagrisema, if you could help us understand. The amylin has previously been shown to cause large hypoglycemic events. I'm just wondering if that's part of the go, no-go decision? And can you remind us the degree of hypoglycemia you may have seen in the obesity trials? Just trying to get a sense for your level of confidence.

So thank you, Simon. So on Wegovy underlying demand, you can say, we -- I want to mention is that we are building the market access. So we have brought support by the 3 big PBMs, but we still have to have employees opting in. So compared to when we launched mid-summer, obviously, we have been working hard in getting, say, effective access up. So that's obviously something that comes in as a benefit when we launch again.

So we expect that we would have, say, a 50-50 percent of people who have access and that's a much, much stronger position compared to when we launched. Hence, the need for having the, say, the copay support programs at the time of launch. So when we look at unaided awareness, if you look at social media activity, et cetera, we think that there is a very strong case for having a good uptick when we get back and promote it in the second half of this year.

And then the second question on Cagrisema and the amylin component. Martin?

Yes, so important to take into account that pramlintide is used primarily in type 1 diabetes, but also a little bit in type 2 diabetes, but both in combination with insulin. So events of hypoglycemia has sort of occurred on the backbone of insulin, which, in our case, does not apply neither in obesity, obviously, but certainly also not in -- when we take this into type 2 diabetes.

So I think as with everything else, when we combine both OADs, but also injectables with insulin, we have to take care and think about both reducing the insulin dose, but obviously also monitoring more frequently. But broadly speaking, this is not applicable for Cagrisema considerations.

Sorry, can I just add 1? So the go, no-go decision is primarily based on whether or not you get an incremental significant decline in HbA1c versus semaglutide, is that fair?

That would be fair. Obviously, we always look at safety, but we are doing the Phase II study specifically to see if we can observe an efficacy on glycemic control.

Thank you, Simon.

Next up, we have a follow-up question from Sachin Jain with Bank of America.

So just 2 more, if I may. So apologies, Lars, just back on the 483 given you gave a bit of color. Have you had any media fill runs yet? Or will you have data by the time of the CMD? Just to clarify there.

And then secondly, just a bigger picture question as you think about sema cagri with potential in diabetes and obesity. I wonder if you could just touch on the pros and cons of branding this combo in obesity, the same as diabetes. Obviously, for semaglutides, you did it differently with different pricing. But tirzepatide is potentially coming with similar branding and similar pricing with obesity pricing, therefore, potentially at a discount to Wegovy. Just wonder if you could just talk about how you're thinking about that as you approach the sema cagri Phase III program.

Okay. Thank you, Sachin. And of course, the benefit of transparency is, of course, it generates more questions. But when you ask about details like timing of media fill and stuff like that, it's too detailed for us to get into. So I'll just say, overall, we feel that we're making good progress. We buy into the plans our partners have. We feel they are quite confident in being able to execute that. So we cannot go into more details around that.

On Cagrisema and obesity, obviously, there's some time before we'll see competition in the obesity space. We have picked a pricing strategy that makes sense for us. What we see is that we're actually gaining strong reimbursement and market access based on the pricing strategy we have. How that will develop in the future based on our own success in clinical development and the success of our competitors is a bit premature for us to speculate on. Right now, we can see that there's a strong demand based on the price point we have. And I think that talks to the unmet need and the level of clinical differentiation that the products have that have been brought to the market by Novo Nordisk.

Thank you, Sachin Jain and Natalie, for hosting us today, and thank you all for your interest in Novo Nordisk. We look forward to see you hopefully at the Capital Markets Day, March 3.

Thank you very much. Goodbye.