Zealand Pharma A/S ($ZEAL)

Good day, and thank you for standing by. Welcome to the Zealand Pharma Results for Q1 2026 Conference Call. [Operator Instructions] Please be advised that this conference is being recorded. I would now like to hand the conference over to your speaker today, Eric Rojas, Vice President and Head of Investor Relations. Please go ahead.

Thank you, operator, and thank you to everyone for joining us today to discuss Zealand Pharma's results for the first quarter of 2026. This is Eric Rojas, and I recently joined Zealand Pharma as Vice President and Head of Investor Relations. I'm pleased to be with the team today in Denmark to get the conference call started and look forward to working with all of you. The related company announcement for Q1 2026 is available on our website at zealandpharma.com. As outlined on the slide, I would like to remind listeners that during today's call, we will be making forward-looking statements that are subject to risks and uncertainties. Turning to today's agenda. Joining me on this call is Adam Steensberg, President and Chief Executive Officer; Henriette Wennicke, Chief Financial Officer; and David Kendall, Chief Medical Officer. All speakers will be available for the Q&A session. I will now hand the call over to Adam.

Thank you, Eric, and welcome, everyone. 2026 so far have been marked by a defining milestones for Zealand Pharma. At our Capital Markets Day in December, we announced our ambition to become a leader in obesity and metabolic health and made several commitments with the launch of our strategy, Metabolic Frontier 2030. I'm super pleased to say that we are on track and executing against our strategy. And what a start to 2026, it has been. Beginning with petrelintide, we reported positive top line results from the Phase II ZUPREME-1 trial that reinforced our conviction in its potential as a first choice treatment option for chronic weight management. The data showed a clear alternative to GLP-1-based therapies for weight reduction and long-term maintenance, setting a new standard for what to expect from a weight management journey. Building on these compelling results, we have now also confirmed advancement into Phase III registrational trials, which are planned for initiation in the second half of this year. This is a major step forward for the program for Zealand Pharma and for our collaboration with Roche. On survodutide, Boehringer Ingelheim reported positive Phase III results from the SYNCHRONIZE-1 trial, delivering competitive weight loss and meaningful metabolic improvements, supporting the potential of survodutide as a differentiated therapy for people living with overweight and obesity. In our early pipeline, Phase I data with our Kv1.3 Channel Blocker showed its potential as a very promising product candidate with potential to address multiple [ Audio Gap ] an agreement with the Danish Center for AI Innovation to access one of the world's leading AI supercomputers. These are investments in our ability to move faster and smarter as we build the next chapter for Zealand Pharma. Finally, marked by our strong balance sheet, we are now initiating a share buyback program as we continue to fund our strategic priorities and long-term growth initiatives to build Zealand Pharma into a leader in obesity and metabolic health. Our collaboration with Roche continues to deliver. Just last week, I visited our Genentech partners in San Francisco for a great and productive workshop. Both teams are now focused on the execution of the upcoming Phase III trials for petrelintide monotherapy and the Phase II trial for the petrelintide/enicepatide combination product. Zealand and Roche will co-develop and co-commercialize petrelintide and petrelintide-based combination products. This means that we capture the long-term value by sharing profits with Roche on a 50-50 basis in the U.S. and Europe on both monotherapy and potential combination products. Zealand will receive $250 million at the first 2 anniversaries of the collaboration. These are not contingent on any specific milestones other than time, meaning that we will receive the first $125 million here in the second quarter of 2026. In terms of the total development milestones of $1.2 billion, $575 million are linked to the initiation of the Phase IIIa trials with petrelintide monotherapy, which we expect to start in the second half of this year, as I mentioned before. We are steadily on track to execute our strategy to establish leadership in obesity and metabolic health. Our Metabolic Frontier 2030 strategy has 2 main focus areas. The first is redefining the near-term future of weight management, guided by our 2 late-stage candidates in petrelintide and survodutide, both supported by world-class partners in Roche and Boehringer Ingelheim. The second is focused on expanding our capabilities to build a leading pipeline beyond these near-term opportunities. We are leveraging our deep expertise in metabolic health, enhancing our capabilities through our new Cambridge Research Hub and complementing this with external innovation via partnerships such as those with OTR Therapeutics around small molecules and the Danish Center for AI Innovation. These are strategic investments to advance our ability to discover and develop the next generation of leading metabolic medicines, all aimed at delivering sustained leadership in metabolic health and achieving the 3 goals outlined in our Metabolic Frontier 2030 strategy. If you look at what we have accomplished in just the first few months of '26, it tells a clear story, a new research hub, AI partnerships, strong Phase II data for petrelintide, followed by a formal endorsement of Phase III advancement and the first Phase III results with survodutide. And in addition to these meaningful and defining milestones, we have a number of important catalysts still ahead of us in 2026 and remain firmly on track to deliver on all of them. And with that, I will now turn over the call to our Chief Medical Officer, David Kendall, to discuss our R&D pipeline. David?

Thank you, Adam. As always, I will begin with an overview of our pipeline. With the potential for 5 product launches by 2030, Zealand Pharma stands at a remarkable inflection point. Today, I would like to focus my remarks on the continued advancement of our 2 leading programs in obesity, petrelintide and survodutide. We were very pleased to report positive results from the ZUPREME-1 trial earlier this year, reaffirming the potential of petrelintide in chronic weight management and as a first choice therapy for millions of people living with overweight and obesity. As reported in the top line results from ZUPREME-1, petrelintide delivered double-digit weight reduction after 42 weeks of treatment with a pristine and exceptional safety and tolerability profile. In this study, rates of gastrointestinal adverse events were generally at or below those reported with placebo treatment. Importantly, no participants treated in -- with petrelintide in dose Group 3, the maximally effective dose, discontinued the trial due to gastrointestinal adverse events and approximately 70% of participants reported no gastrointestinal adverse events during the course of the trial, further highlighting the exceptional tolerability profile of petrelintide. Taken together, the data demonstrate the potential of petrelintide to address significant unmet needs in chronic weight management by providing a highly tolerable treatment option that supports long-term treatment adherence and achieves double-digit weight loss, obtaining weight reduction consistent with what the majority of those seeking weight management desire. We look forward to sharing additional data from the ZUPREME-1 trial at the upcoming American Diabetes Association Scientific Sessions in June, and we'll be advancing petrelintide into Phase III trials with that initiation planned for the second half of this year. Switching gears to survodutide, a potential best-in-class glucagon GLP-1 receptor dual agonist with the potential to play an important role in the treatment of obesity and metabolic disease, in particular, metabolic dysfunction associated liver disease. We were very encouraged by the recent positive top line results reported by Boehringer Ingelheim from the 76-week Phase III SYNCHRONIZE-1 trial evaluating the safety and efficacy of survodutide in people with overweight or obesity without type 2 diabetes. SYNCHRONIZE-1 enrolled a population of 725 participants with 59% females with a mean baseline BMI of 38 kilograms per meter squared and a mean body weight of 109 kilograms. The trial met both of the co-primary endpoints. Survodutide delivered a competitive weight reduction of up to 16.6% from baseline after 76 weeks of treatment while also demonstrating meaningful metabolic improvements. Survodutide also delivered a significant and clinically meaningful reduction in weight circumference, which is a clinical marker closely linked to reductions in visceral fat and cardiometabolic risk. Additionally, initial analyses indicate that body weight reduction with survodutide was predominantly driven by loss of fat tissue with lean mass contributing only a small proportion of total weight loss. We are extremely excited with these findings, which taken together demonstrate the potential of survodutide to broadly improve metabolic health by providing meaningful benefits beyond weight reduction alone. We look very much forward to the American Diabetes Association Scientific Sessions in June, where Boehringer Ingelheim will present the full data from the SYNCHRONIZE-1 trial. Beyond the SYNCHRONIZE-1 data to be presented at the American Diabetes Association Scientific Sessions, Boehringer Ingelheim will also present full results from the Phase III SYNCHRONIZE MASLD trial, which is investigating the efficacy and safety of survodutide in people with overweight or obesity and confirmed or presumed metabolic dysfunction-associated steatohepatitis, or MASH. Additionally, the Phase III SYNCHRONIZE program with survodutide in obesity includes 4 other clinical trials. We expect additional readouts from the broader Phase III obesity program throughout 2026, including from the SYNCHRONIZE cardiovascular outcomes trial. Together, these data are expected to support the first regulatory submissions for survodutide for the treatment of overweight and obesity. If successful, Boehringer Ingelheim would be the third company to market in the U.S. and Europe in this new era of incretin-based therapies for chronic weight management. We are also very excited by the ongoing execution of the Phase III LIVERAGE program evaluating survodutide in people with established MASH. This program includes 2 trials assessing safety and efficacy in patients with moderate to advanced fibrosis as well as in those with established cirrhosis. Given the high unmet medical need and limited treatment options for this population, supported by the groundbreaking Phase II data for survodutide in MASH, we believe survodutide have the potential to become a leading therapy for people living with overweight or obesity and coexisting MASH. With that, thank you very much for your attention. I would now like to turn the call over to our Chief Financial Officer, Henriette Wennicke, who will review our financial results for the first 3 months of 2026. Henriette?

Thanks, David, and hello, everyone. Let's start with the income statement. Revenue in the first 3 months of 2026 was DKK 34 million, driven by the collaborations and license agreement with Roche. Net operating expenses totaled DKK 573 million. 82% of that was dedicated to research and development, mainly driven by the Phase II ZUPREME program with petrelintide, preparation for Phase III and also investment into the research portfolio. The S&M expenses are driven by pre-commercial activities associated with mainly petrelintide, while G&A expenses of DKK 82 million reflect continued organization scaling, IT infrastructure and facility investments. Net financial items in the first 3 months of 2026 of DKK 145 million are mainly driven by interest income from excess liquidity invested in marketable securities and cash equivalents and exchange rate adjustments. We ended the first quarter of 2026 with a solid cash position of DKK 14.5 billion, which is expected to be further enhanced by DKK 4.5 billion milestone payments from Roche in 2026. Our strong capital preparedness enabled us to execute on all our key strategic priorities, maximize the value of petrelintide, intensify our efforts in our early-stage research pipeline and leverage external innovation to enhance our R&D capabilities. We are well on track to execute and deliver on our Metabolic Frontier 2030 strategy, which we presented late last year at our Capital Markets Day. At the same time, following the recent positive developments in our leading obesity programs, we are leveraging flexibility in our solid financial position and strengthened outlook to return capital back to our shareholders. As announced this morning, we have initiated a share buyback program of USD 200 million, corresponding to DKK 1.3 billion. I am extremely pleased that a company of our nature is able to distribute capital back to shareholders without scaling back what Zealand does best, research and development within metabolic health and with a continued appetite for organic and inorganic investments. And now to the outlook for the year. The financial guidance for net operating expenses in 2026 is unchanged and is expected to be in the range of DKK 2.7 billion to DKK 3.3 billion, mainly driven by research and development activities. In addition, we are providing collaboration revenue guidance of DKK 4.5 billion for the full year following the confirmation of Phase IIIa progression for petrelintide monotherapy. We will receive from Roche a USD 125 million anniversary payment in Q2 and a USD 575 million development milestone in the second half of 2026 when Phase IIIa is initiated. The collaboration revenue amounting to DKK 4.5 billion was booked into our accounts in early May. And with that, I will turn the call back to Adam for concluding remarks.

Thank you, Henriette. Leveraging our momentum, we have a number of important catalysts potentially shaping long-term value creation still ahead of us in 2026. These include data from all the key trials in the SYNCHRONIZE program with survodutide and clinical advancement of petrelintide, including both the monotherapy and the combination with enicepatide. I will now turn over the call to the operator, and we'll be happy to address your questions.

[Operator Instructions] We will take our first question -- the question comes from the line of Kirsty Ross-Stewart from BNP Paribas.

So maybe first one, just on the upcoming Phase III petrelintide trial. I think the FDA guidance requires 1 year of treatment on maximal dose in a Phase III trial. So given you're expecting to reach the maximal dose in 3 steps, are you planning on running a 60-week trial and being able to kind of narrow the gap versus Lilly who's got an additional titration step versus you? And are there any other trial acceleration efforts that you're looking at using to kind of bring up that launch time line? And then maybe secondly, on the more broad obesity market. I mean, I think it's fair to say that the orals are exceeding initial market share expectations. I think it's nearly 15% of kind of U.S. script volumes already going to the orals. So just interested on your view on the importance of developing an oral asset and perhaps maybe Utpal can comment on kind of the priorities for the pipeline efforts, how far the list is developing in oral and what, if anything, is above that on the priority list?

Thank you, Kirsty. I'll just provide a few comments and maybe hand over to David for a few other comments. It's, of course, too early for us to comment on the specifics of the Phase III program. David may provide a few more insights, but what I can reassure you that we are doing a lot of things to accelerate the program together with our partner, Roche, as we are very aware of the importance of speed to market. When you are building a new category as we aim to do with petrelintide and so we have a lot of efforts on that one. When it comes to the oral therapies, as we also announced at our Capital Markets Day, we are now collaborating with external parties on small molecules, and we have efforts to also explore the opportunities, broadly speaking, for all therapies when it comes to Amylin. As a company, we're actually more excited about that opportunity into the future. So it's, of course, something we are investing in. We are also excited to see how the oral GLP-1s are taking off now. And of course, we need a few more months to see how they -- if they are and how they're going to shape the market going forward. But it's an important thing to remember that most patients after a certain time will be off treatment with the GLP-1-based therapy. So if anything, it will actually just, you can say, expand the number of patients who have been exposed to a GLP-1 and also live through some of the difficulties on a GLP-1 and thus expand the market opportunity for a novel category as we are developing with petrelintide. David, do you want to put a little bit more flavor on the petrelintide Phase III program?

Happy to, Kirsty, and thank you for the comments. As to duration, you're right about the regulatory requirements for 1 year of exposure at the IIb marketed treatment dose. And obviously, there, it's a balance between achieving that as rapidly as possible. One thing that helps you expedite execution of Phase III is fewer dose escalation steps. On the other hand, you want adequate duration to ensure that you've reached the maximal weight lowering effects. And as we've seen more broadly in the weight management space, trials beyond 60 weeks out to 78 weeks are the common practice. But to your second comment about triggers for speed, obviously, the sooner you can get to maintenance or the -- to be marketed treatment dose, the more rapidly you get last patient last visit. But that will be balanced not solely by the regulatory requirements, but also looking to achieve the final nadir in weight reduction that's possible. And again, those time intervals I quoted are the ones that are under consideration for our Phase III program. To add to Adam's comment, Kirsty, on orals, obviously, one of these efforts is our announced partnership with OTR on which we're working with a number of potential oral assets. Given the uptake, certainly, we see the opportunity. It is also our mind, however, that having efficacy and tolerability that mimic as closely as possible to what is achieved with the peptide therapies, noting that if, for example, an oral amylin is achieved, we would expect a comparable efficacy and continued or even greater safety and tolerability profile. So work underway on all fronts for potential oral assets as well.

Your next question comes from the line of Rajan Sharma from Goldman Sachs.

I've got one on survodutide and one on petrelintide. Maybe just starting with petrelintide. So you haven't previously committed to higher doses in the Phase III despite the good tolerability that we've seen. So could you just provide your latest thoughts around this now that you've had time to reflect on that ZUPREME-1 data set? Is it reasonable to assume that you will go to higher doses in Phase III? And if not, why not? And then secondly, on survodutide, what are you looking for in the SYNCHRONIZE-MASLD data presentation at ADA, which might give you incremental confidence in survodutide's profile, both in MASH and obesity? And what do you think will be an acceptable discontinuation rate?

Thank you, Rajan. Maybe just to start with survodutide. I think we, of course, look very much forward to see the presentation of the full data on the specifics on losing fat versus muscle that was highlighted in a qualitative statement in the Boehringer Ingelheim release. I think you cannot underestimate the value, not only from the prescriber perspective and the health, you can say, that you can generate by mostly losing liver and visceral fat and then preserving muscles. But I think it's also something that will speak directly to the patients if you have a product that can actually target the weight loss to the abdominal visceral and liver fat and protect the muscles to some degree. So that is, of course, a very important data set also hopefully supported by the readout from the MASLD study. So it is a very important part of the presentation at ADA, I would view also from a patient perspective. But David, over to you.

And one additional comment, Rajan, on the survodutide data. I think this is very simply a clinical assessment without biopsy to determine the suspected presence of liver disease, something that will obviously be quite common in clinic as a former practitioner, seeing a significant number of patients with diabetes coexisting overweight and obesity and abnormal liver function studies. This will be the first glimpse, if you will, into the potential without pursuing liver biopsy, which is required in the LIVERAGE program and is the endpoint for indication seeking in that LIVERAGE program, but I think will be a great bellwether of the potential of the LIVERAGE program to deliver and provide clinicians the confidence that should they see patients who meet those clinical criteria, survodutide can and likely will be a preferred alternative. To the petrelintide question and higher dose, I think as you well know, Phase II clinical trials are dose-ranging trials where we were able to see significant reductions in body weight at each of the top 3 doses in exposure, dose Group 3, 4 and 5. It is unusual that one reaches a therapeutic efficacy plateau without limitations from tolerability. So in contrast to many of the incretin-based therapies where dose-limiting may occur due to either tolerability issues or in the case of GLP-1-based therapies, increase in heart rate, we were able to achieve max efficacy at dose Group 3 as was shown in the top line results. But the other 2 higher doses showed no greater abnormalities in either tolerability or new safety signals, which gives us great confidence in the safety margin with what was the maximally effective dose falling at that midrange or dose Group 3. So you could anticipate that if that is the maximally effective dose, that's the dose that will be taken into Phase III. We now also have nearly 150 or more individuals who are exposed to even higher doses with comparable safety and tolerability gives us great confidence in the safety margins of what is likely to be the maximally effective dose. So expect that and details, obviously, on the full data set will be available during the presentations at the American Diabetes Associations Scientific sessions.

We will take our next question, and the question comes from the line of Andy Hsieh from William Blair.

This is Kelsey Lucerne on for Andy Hsieh. So we've seen companies in the field conducting studies to better position for the maintenance market done through independent Phase III trials like the ATTAIN-MAINTAIN or MARITIME-Switch study or incorporating maintenance regimens into an open-label extension portion. So as you prepare to launch the Phase III program for petrelintide, what's your strategy to generate maintenance data to maximize the asset value?

Thank you for your questions. And I agree that it's, of course, extremely important, particularly when you're developing a category like petrelintide and amylin that you're focusing on maintenance because this is the big dilemma in the current market that most patients fail to stay on the GLP-1s and thus never will get to explore the health benefits of the weight loss and the benefits of getting to these therapies. So we have a keen focus, of course, with petrelintide an opportunity now to develop a medicine that can be used not only as a weight loss agent, but actually a chronic therapy as they should be used in this category. It's too early for us to comment on the specific trial elements of our studies in more details. But rest assured, once they get up and running, you will all get the insights into the program. It's a very ambitious program, and it's, again, if the intent we have with this molecule is to, as David and I also shared in our prepared remarks, is to develop petrelintide as a first choice medicine. If you consider a patient who think about going on a weight loss journey and an interaction with a health care prescriber, if you look into other chronic therapy areas, most patients will always be exposed to the most tolerable approach that has a good chance of getting the patient to go. And that is our ambition with petrelintide to make it a first choice therapy that can help most patients getting to the goal they're looking for. And then, of course, as important, we need to make sure that patients also stay on therapy so they don't lose the benefits of that weight loss. So we will focus on both parameters in our program and look forward to provide further updates as we get these trials up running.

Your next question comes from the line of Benjamin Jackson from Jefferies.

Just a couple for me. The first on ZUPREME-2 in the second half of this year, is there anything you're watching for there that perhaps could surprise you and change the way that you think about the development program at all? Obviously, historically, GLP-1s have shown 35% or so less weight loss in the overlapping cohort of type 2 diabetics and obese. Do you expect to see the same thing here with amylin? Or is there a chance that it's a little bit different? Then secondly, on ZUPREME-1, is there anything in the trial design now that you've had time to reflect on it that perhaps would suggest that something within the trial design itself limited that efficacy and caused that plateau at the top doses rather than the actual kinetics of the molecule itself? And then if I can squeeze in a third, I think I know the answer, but I'll try it anyway. Do you have any sense whether your partner, Boehringer, intends to provide more indications around their commercial strategy for survo at ADA or when we could perhaps get a little bit more clarity on that? Obviously, less of incentive to talk to the market about that. But any thoughts around those 3 would be super useful.

Thanks for the question. And just to address your last question first, we cannot comment further on Boehringer's plans, but we, of course, notice significant excitement in the releases and the statements around both the opportunity to treat the patients with overweight and obesity and patients living with MASLD. But it is up for Boehringer to comment more specifically on the plans and when they expect to be on the market. But we are at least extremely excited and look forward to the symposium at ADA that Boehringer will host and share more data from the program. So more on that. I'm sorry, we cannot provide more clarity to that at this moment. David?

Yes. Happy, Benjamin, to comment on ZUPREME-2. A couple of specifics to your question. Certainly, the effect on body weight is the primary endpoint for ZUPREME-2 in these individuals with overweight and obesity with coexisting type 2 diabetes. While we expect an effect on hemoglobin A1c reductions in glucose, it is well known that amylin agonists are generally less potent in terms of overall glucose lowering, but do have a significant glucose lowering effect. Petrelintide, in fact, the only approved amylin was approved only as an adjunct to insulin therapy for glucose lowering. But the unique mechanism of action of amylin being a non-insulin stimulatory signal, only exerting much of its effect on blood sugar through postprandial glucose control in part by effects on gastric emptying with short-acting agents and a clear effect on suppressing glucagon, we would -- we will look closely on whether there is greater preservation of the weight-reducing effect in the type 2 diabetes population that is close to or comparable to that seen in the non-diabetes population. To your point, GLP-1s with their potent insulin stimulatory signal, insulin as a storage hormone, abrogates some, in fact, a significant portion of the weight lowering effect of GLP-1-based therapies in those with type 2 diabetes. So a preservation of that effect or at least a smaller loss of any of the effectiveness in the type 2 diabetes population. Why is that important? Clinically, if an individual with well-controlled diabetes is truly on a weight-reducing journey or a weight loss journey, then having a therapy that can achieve comparable effects, whether there is or is not abnormalities in glucose tolerance will be an important insight. Obviously, because of the regulatory requirements to include diabetes patients in your Phase III programs, understanding that a similar dose response and dose effect can be observed is similarly important. So preservation of that weight effect would be the primary one we will be looking closely at and obviously, it would be confirmed then in the Phase III trials. In terms of ZUPREME-1, as we've alluded to in previous discussions following the release of those top line data, there are a number of trial constructs, which will be put in place, which in great part, are done to achieve a study population that most closely reflects the future potential clinical population, which is a preponderance of females, up to 75% females and females seek weight-reducing therapies much more commonly. The other things that are learned in this and any trial is site selection and persistence on therapy, meaning the true treatment est demand in terms of overall result, and that will be working on not just recruitment, but recruitment, retention and then persistence on therapy. So those will be some of the key things we focus on in Phase III that are learnings from ZUPREME-1. The other thing that many have noticed is Phase II trials where doses are escalated more rapidly tend to give you a deeper initial weight loss curve but sacrifice tolerability significantly regardless of the therapy. So we are not in a position where we're going to push the speed of dose escalation because the very clean tolerability profile is something we wish to preserve, still expecting a clear double-digit weight loss with the appropriate population studied.

We will take our next question, and the question comes from the line of Alexandria Hammond from Wolfe Research.

I guess as you think about the Phase II readout for petrelintide and CT-388 combo, is there a specific efficacy threshold that, that combo needs to clear to justify moving into the Phase III? And how does tolerability kind of factor into that bar? Is there a scenario where a modest efficacy gain over a monotherapy is sufficient for that if it can kind of preserve petrelintide's placebo-like tolerability profile?

Thank you for your question. And thank you for bringing up also the combination where we will start the Phase II study in this quarter. And we are highly excited about the opportunity to not only develop petrelintide as a monotherapy as a first choice therapy for the many who are looking for that double-digit weight loss and a very benign safety profile with the combination product, I think we are -- we actually believe we have a number of opportunities to look into other segments of patients. Of course, there are still the patients who need the highest weight loss, those who would historically be candidate for biotic surgery, for instance, there's also people living in obesity and type 2 diabetes at the same time, as David just alluded to, a combination of GLP-1 and amylin could actually be a very interesting opportunity for such patients. So I would say the Phase II design that we -- and the study that we are initiating now has been designed so we can actually get several answers for what is the right profile of the drug and targeting those specific needs. I would say we don't have specific thresholds. We will, as we did with petrelintide, look for the profile of the drug and match that towards specific patient needs in that broader portfolio of opportunities that we are developing towards the patients who live with obesity and comorbidities at the same time.

Your next question comes from the line of Nusrath Hussain from UBS.

On behalf of Xian from UBS. I have 2 questions, if I may. First, with Phase III-MASLD data for survodutide coming at ADA and the ongoing Phase III-MASH trials across F2, F3 and F4, could you outline the major differences between patients that you enroll for MASLD and MASH trials? How much read across do you expect from MASLD to MASH? And are there any biomarkers, subgroup analysis or secondary endpoints for MASLD that could be informative for fibrosis improvement, especially in F4 MASH? And then secondly, you've announced a $200 million share buyback at a time where we would expect R&D and SG&A to increase as petre and other earlier-stage programs progress. So could you comment on your current view of the survodutide royalty stream? Have we now seen the full obesity tolerability data set? And if so, does the recent survo data change your expectations for that royalty stream? And then lastly, did confidence in future survo-driven cash flows play a role in the decision to initiate the buyback at this point?

Thank you for your question. And maybe I'll just address the survo program. Remember, it's Boehringer Ingelheim, who are running the program, and we are entitled to high single to low double-digit royalties and outstanding milestones of around EUR 350 million. And we cannot comment on the specifics for neither the data that Boehringer is going to present at ADA here in June, but we know that they do expect to present data from the obesity MASLD data. We also know, and I think that's been clear for a very long time that they are extremely committed into the MASLD program with LIVERAGE-1 and 2, where they are enrolling close to 3,500 patients, both F2 and F4. So it's 2 programs, one in obesity and one in MASLD that they are highly committed to. And as I also alluded to in my prepared remarks, with this coming out of this quarter where we have had Phase II data for petrelintide and the decision to move into Phase III, which provides clarity on the near-term milestones from that program. But as important, the Phase III readout from survodutide has created a lot of clarity on our future revenue streams and derisked, you can say, our operations and adding to a very strong financial position. Henriette, maybe you want to comment a little bit more on that situation?

Yes. Thank you, Adam, and thank you for the question. You're absolutely right. We launched the share buyback program. And as Adam alluded to, we've just had 2 major derisking events for our leading obesity programs. This, of course, give us increased flexibility in our outlook, but also confidence in our outlook for the years to come. And that has allowed us to launch the programs. We are not compromising on the development programs. We have all the research investments. So we have, in the past, commented that we will increase our research efforts fivefold in the next coming 5 years compared to the last 5 years. And that will continue. And that will both be with organic and inorganic investments across the board. So the deal we did before Christmas with OTR, you will likely see more deals coming up in the period to come. So I think you should see this in -- as our confidence has increased over the last period and our financial flexibility have also increased.

Your next question comes from the line of Suzanne van Voorthuizen from Van Lanschot Kempen.

This is [ Romy ] on for Suzanne. I have 2 questions. The first, knowing now the progress of petrelintide to start Phase III in the second half of the year. I was just wondering where ultimately you see petrelintide fitting into the general obesity market and more specifically within the amylin class based on the data we have to date? And secondly, I think you already mentioned this in the previous answer, but can you confirm your weight loss expectations for petre for the Phase III study? Yes, that's my question.

Thank you for your question. And I think when we at least look at the future obesity market and when we -- based on our market research, we do with patients and other stakeholders in the market, it's important to consider that obesity is a chronic disease. And for an individual patient, it's very often a journey when you start a weight loss program towards an objective of losing some weight. If you look into other chronic diseases where there are multiple choices of medicines in diabetes, in hypertension, in lipid-lowering space, most often patients will be started on the most tolerable approach. And then after a few months, they will have an interaction with the healthcare provider to discuss if they are on the right trajectory to achieve the goals that they have, have their goals changed or are they not moving with the speed that they are considering. And if they are not, then you can start to have a conversation should we add or change something. But that is -- and then you would often go to the more cumbersome, perhaps even slightly more effective tools, but you don't start patients with the most cumbersome tool just because it can provide a slightly more average weight loss. So this is why we are -- you can say the way we view this is that -- and why we keep saying this first choice, this is the logical first choice, the profile of petrelintide is what we have called the sweet spot that you can deliver double-digit weight loss with a tolerability profile, which in Phase II with the maximum effective dose was similar to placebo when we look into GI effects. The other thing which we think is you need to appreciate also as we get into a market with a new category, it's not just about effect and tolerability, it's also the experience that you have being on a drug. And as David has mentioned many times, amylin works in a very distinct way from the GLP-1s by making people feel full faster. It doesn't affect your appetite to the extent that the GLP-1 will do. It helps you feel full faster once you start eating. And we think it will add to the overall better experience of being on an amylin and thus, again, serve that need as a first choice. And I would -- to further build on this, if you are a patient who have spent, let's say, 30 years becoming morbidly obese or having a very high BMI, you don't need to solve that in 2 or 3 months. This is a journey that should be solved over a longer period. So -- but still, it's a natural place to start with a product profile like petrelintide. If you then need more, that's where you turn to a combination product as we are doing with CT-388 and petrelintide. And that's the logical approach to treating patients in a more mature market. And that's why we continue to say that we are super excited with the profile that we saw because we actually observed petrelintide to be even better tolerated than what we have seen in the Phase I studies in a large cohort of patients, also having exposed patients to higher doses, which will not be carried forward into Phase III, but with a lot of safety around it. So when we move into Phase III, we do expect to see, as David also alluded to earlier, higher weight loss numbers as we expect to enroll more female patients, run the study for longer and address a few of the other trial-specific elements of the Phase II study. So we are very confident that we get a profile of a drug that address exactly what patients are looking for. And when you do market research, you will also hear that 1 out of 5 patients are looking for a weight loss of less than 10% and 4 out of 5 patients are looking for a weight loss of less than 20%. The average weight loss that patients experience on tirzepatide today in the real world is around 12%. It's not the 22% or even higher numbers that people like to talk about. So we believe we have a product that speaks directly to what patient wants and the tolerability profile is of such a magnitude that it would be considered a first choice medicine if and when it gets to the market.

Your next question comes from the line of Charlie Haywood from Bank of America.

It's Charlie Haywood, Bank of America. First one is just on the petre weight loss curves that we're expecting to see at the upcoming conference. Any comments on the shape of that curve? And if once we've seen the data, there will be any debate on how we should think about sort of potential plateau after the 42-week period? And then on the prior comment to dose ranging, obviously, the higher 3 doses showing very similar weight loss. Is there any meaningful difference in the weight loss curves between those 3 and the time it took to reach that 10% to 11% weight loss? And the final question, just sort of higher level on obesity and potential petre pricing as a monotherapy. I think the market has obviously seen aggressive price cuts and is panning out to much more of a consumer-driven market. So given potentially price, i.e., $150 instead of oral could have been the driver of a material acceleration in volumes. How are you thinking of pricing evolution going forward from here? And do you still see petre potential premium pricing as an option in a consumer-driven market?

Thank you. And it's, of course, too early for us to comment on the specifics around pricing, except that, of course, ultimately, it will be value-based pricing. And I just, again, want to highlight this thing that from a society point of view and from a health perspective, you actually don't get a lot of value if patients don't stay on therapy because, yes, you may experience a weight loss, but if you're regaining that weight loss and also with less muscle, you may even be worse off. So in order to get value out of these medicines, you need to make sure that patients can stay on therapy. And that's why we think it's incredibly important, the profile of petrelintide so far suggests that it's active product that people will be able to stay on to a larger extent than those where there are more side effects. So that is one important part when you look at this from a health perspective. We also have to realize, as you brought up, that a lot of these prescriptions are patients paying themselves. And again, just broadly speaking about value-based pricing, what is the value of having a better weight loss experience? That is something we need to understand better, but we thoroughly believe that petrelintide can deliver a better weight loss experience than when you lose weight on a GLP-1. So these are things that we'll continue to explore and discuss with our partners. But it gives us confidence, in particular, in this opportunity to actually address the maintenance setting and thus making sure that patients stay on therapy for longer. That is, of course, an important part to the overall value of the franchise. And it also speaks to the other comment about the volumes. If you manage to get patients to stay on therapy, of course, volumes will go up. On the specific weight loss curves and plateau and the different doses, we -- that's to be discussed at the ADA meeting, of course, and we'll present more data and a more full data set at ADA. I just again have to remind people, as we also have -- David had highlighted that there were a number -- the balance between men and females in this study was quite dramatic, and there was actually a 6% difference in weight loss between the males and the females larger than what we had anticipated, but not uncommon to see differences between males and females. These are things that will be addressed in Phase III, and you will probably understand some of these features better at ADA.

[Operator Instructions] We will take our next question, and the question comes from the line of Mohit Bansal from Wells Fargo Securities.

This is [ Susan ] on for Mohit. As payers increasingly focus on real-world adherence and durability, what evidence do you think you need to demonstrate that better tolerability translates into improved persistence independent of pricing and out-of-pocket cost sensitivity? And then a separate question on switching. What do we currently understand about switching patients between GLP-1s and amylin? Do you think that we need additional stuff to understand if additional titration or dose escalation is needed between switching between the different mechanisms of action?

Thank you for that question. And of course, as we launch petrelintide in the future, it will be incredibly important to collect real-world evidence for stay time for these medicines and use them as arguments for why you can actually provide additional value to society and demonstrating that patients actually stay on therapy for longer. So that will be, of course, an important argument in this. And as David has also shown also in the prepared remarks today, I think when we talk about the escalation phase, it was 98% of patients in this study who managed to get to the top dose. So it's not -- we actually don't consider that you need to titrate the amylin as you do with the GLP-1. It's more about escalating. And if you look at the early data we released, even the lower doses, patients can expect quite significant weight loss. So it's a major difference here between the GLP-1s and the amylin at least with petrelintide that it feels that we believe that patients will be able to follow the escalation steps without having to individualize the titration for every patient, which will simplify the prescription in the real world compared to what we see with the GLP-1s today. David, do you want to add further?

Yes. And I think Adam speaks to a very good point, Susan, and that's that the dose escalation and not titration to ensure that patients get to the most effective dose and stay on the most effective dose. We know with all of these centrally acting agents that, that dose escalation is an important part of the overall experience. Given that at dose Group 3, you would have a limited number of dose escalation steps, that means you get to the maximally effective dose not only in a high proportion of individuals, but at an earlier point in time. As regards to your comment on switching, little is known. There were studies done many now decades ago with petrelintide and exenatide where switching did occur because these are 2 unique receptor families, receptor systems and GLP-1 and amylin-based therapies act through these different systems, it would be anticipated that if one switches from one to the other, it would be clinically appropriate to have a dose escalation scheme that pays homage to the newest therapy being introduced. But obviously, that persistent studies, the things you alluded to in the real world will all be part of our consideration for a robust Phase IIIb program and beyond to better understand how can we make the experience for patients, those living with obesity, their providers, the pharmacists, all who are involved in this value chain to make this the best experience possible. And again, simplicity with tolerability is only part of that story.

Thank you. This concludes today's question-and-answer session. I'll now hand the call back to CEO, Adam Steensberg, for closing remarks.

Thank you all for attending and for your questions. We look forward to future announcements and updates and to connecting in the coming weeks and months.

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