Zealand Pharma A/S

Good day and thank you for standing by. Welcome to the Zealand Pharma results for Q1 2026 conference call. At this time, all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1, 1 again. 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 Zeeland Pharma's results for the first quarter of 2026. This is Eric Rojas, and I recently joined Zeeland 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 zeelandpharma.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, Henrietta Venica, 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 has been marked by defining milestones for Zeeland 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 Petronitide, we reported positive top-line results from the Phase 2 Supreme 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 GLB1-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 three registrational trials, which are planned for initiation in the second half of this year. This is a major step forward for the program, for C-Line Pharma, and for our collaboration with ROS. On Cervolutide, Berger-Ingenheim reported positive phase 3 results from the synchronized ONE trial, delivering competitive weight loss and meaningful metabolic improvements, supporting the potential of cervalutide as a differentiated therapy for people living with overweight and obesity. In our early pipeline, phase 1 data with our KB1.G channel blocker, showed its potential as a very promising product candidate with potential to address multiple 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 Xenon Pharma. Finally, marked by our strong balance sheet, are now initiating a share buyback program as we continue to fund our strategic priorities and long-term growth initiatives to build seed and pharma into a leader in obesity and metabolic health. Our collaboration with Ross continues to deliver. Just last week, I visited our genetic partners in San Francisco for a great and productive workshop. Both teams are now focused on the execution of the upcoming phase 3 trials for Petrilentide monotherapy and the phase 2 trial for the Petrilentide-Enicepatide combination product. Sealand and Ross will co-develop and co-commercialize Petrilentide and Petrilentide-based combination products. This means that we capture the long-term value by sharing profits with Ross on a 50-50 basis in the US and Europe. on both monotherapy and potential combination products. CLAN will receive $250 million at the first two 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 petronatide 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 two main focus areas. The first is redefining the near-term future of weight management, guided by our two late-stage candidates in Petroniatide and Cervalutide, both supported by world-class partners in Ross and Boehrner 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 three 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 2 data for betrinitide, followed by a formal endorsement of Phase 3 advancement and the first Phase 3 results with Cervalutide. 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 five product launches by 2030, Zeeland Pharma stands at a remarkable inflection point. Today, I would like to focus my remarks on the continued advancement of our two leading programs in obesity, Petrelentide and Cervetetide. We were very pleased to report positive results from the Zupreme 1 trial earlier this year, reaffirming the potential of petrolentide 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, petrolentide 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 participant treated with petrolentide 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 petrolentide. Taken together, the data demonstrate the potential of petrolentide 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 Petrelentide into Phase 3 trials with that initiation plan for the second half of this year. Switching gears to Cervitotide, 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 Beringer Ingelheim from the 76-week Phase III Synchronize-1 trial evaluating the safety and efficacy of cervidotide 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. Cervidutide delivered a competitive weight reduction of up to 16.6% from baseline after 76 weeks of treatment, while also demonstrating meaningful metabolic improvements. Servodutide also delivered a significant and clinically meaningful reduction in waist 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 servodutide 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 cervidotide to broadly improve metabolic health by providing meaningful benefits beyond weight reduction alone. We look very much forward to the American Diabetes Association's scientific sessions in June, where Beringer 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, Beringer-Ingelheim will also present full results from the Phase III Synchronized MASLD trial, which is investigating the efficacy and safety of cervidotide in people with overweight or obesity and confirmed or presumed metabolic dysfunction associated steatohepatitis or MASH. Additionally, the Phase III Synchronized Program with Cervidotide in Obesity includes four other clinical trials. We expect additional readouts from the broader Phase III obesity program throughout 2026, including from the synchronized cardiovascular outcomes trial. Together, these data are expected to support the first regulatory submissions for cervagitide for the treatment of overweight and obesity. If successful, Bering-Gergenheim 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 three liverage program, evaluating cervidutide in people with established MASH. This program includes two 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 cervidutide in MASH, we believe cervidutide has 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, Henrietta Venike. who will review our financial results for the first three months of 2026. Henrietta?

Thanks, David.

Thanks, David, and hello, everyone. Let's start with the income statement. Revenue in the first three months of 2026 was 34 million DKK, driven by the collaborations and license agreement with Roche. Net operating expenses totaled 573 million DKK, 82% of that was dedicated to research and development, mainly driven by the Phase 2 Supreme Program with paternity, preparation for Phase 3, and also investment into the research portfolio. The SIM expenses are driven by pre-commercial activities associated with mainly paternity, while G&A expenses of 82 million DKK reflect continued organization scaling, IT infrastructure, and facility investments. Net financial items in the first three months of 2026 of 145 million DKK 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 14.5 billion DKK, which is expected to be further enhanced by 4.5 billion DKK milestone payments from Roche in 2026. Our strong capital preparedness enabled us to execute on all our key strategic priorities, maximize the value of petroleum type, intensify our efforts in our early stage research pipeline, and leverage external innovations 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 Market Day. At the same time, following the recent positive development in our leading obesity programs, we are leveraging flexibility in our solid financial position and strengthening outlook to return capital back to our shareholders. As announced this morning, we have initiated a share buyback program of 200 million US dollar, corresponding to 1.3 billion DKK. I am extremely pleased that a company of our nature is able to distribute capital back to shareholders without scaling back on 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 2.7 to 3.3 billion DKK, mainly driven by research and development activities. In addition, we are providing collaboration revenue guidance of 4.5 billion DKK for the full year following the confirmation of phase 3a progression for betrunenside monotherapy. We will receive from Roche a 125 million US dollar anniversary payment in Q2 and a 575 million USD development milestone in the second half of 2026 when phase 3a is initiated. The collaboration revenue amounting to 4.5 billion DKK was booked into our account 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 synchronized program with servutotide and clinical advancement of petrinatide including both the monotherapy and the combination with inizepatide. I will now turn over the call to the operator and we'll be happy to address your questions.

Thank you. If you wish to ask a question, you will need to press star one, one on your telephone and wait for your name to be announced. To withdraw your question, please press star one, one again. We will take our first question The question comes from the line of Kirsty Ross-Stewart from BNP Paribas. Please go ahead. Your line is open.

Hi, good afternoon. Thanks for taking my questions. So maybe first one, just on the upcoming Phase 3 Petrelenside trial. I think the FDA guidance requires one year of treatment on maximal dose in a Phase 3 trial. So given you're expecting to reach the maximal dose in three steps, Are you planning on running a 60 week trial and being able to kind of narrow the gap versus Lily 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 timeline? 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 up to Al can comment on kind of the priorities for the pipeline efforts, how far up the list is developing an oral and what, if anything, is above that on the priority list. Thanks very much.

Thank you, Kirsten. I will 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 3 program. David may provide a few more insights, but 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 Petrinitide, and so so we have a lot of efforts on that one when it comes to the oral therapies as we also announced announced at our capital markets day we are now collaborating with 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 about that opportunity into the future. So it's, of course, something we are investing in. We are also excited to see how the oil GF1s are taking off now. And of course, we need a few more months to see 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 the petroleum side. David, do you want to put a little bit more flavor on the petroleum side phase three program?

Happy to, Kirstie. Happy to, Kirstie, and thank you for the comments. As to duration, you're right about the regulatory requirements for one year of exposure at the to-be-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 three 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 three program. To add to Adam's comment, Kirstie, 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 what is achieved with the peptide therapies, noting that if, for example, an oral amylin is achieved, we would expect comparable efficacy and continued or even greater safety and tolerability profile. So, work underway on all fronts for potential oral assets as well.

Thank you. Thanks very much.

We will take our next question. Your next question comes from the line of Rajan Sharma from Goldman Sachs. Please go ahead. Your line is open.

Hi. Thanks for taking my question. I've got one on servodutide and one on petrolintide. Maybe just starting with petrolintide. So you haven't previously committed to higher doses in the phase three 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 3, and if not, why not? And then secondly, on cervidutide, what are you looking for in the synchronized massal data presentation at ADA, which might give you incremental confidence in cervidutide's profile both in MASH and obesity? And what do you think will be an acceptable discontinuation rate? Thank you.

Thank you, Rosanne. Maybe just to start with Cervarotide. 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 Bernheim 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 visual 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 MASL study. So it is a very important part of the presentation at ADA. I would leave also from a patient perspective. But David, over to you.

And one additional comment, Rajan, on the cervidotide data. I think this is... you know, 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 a liver biopsy, which is required in the liverage program. And as 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, cervidotide can and likely will be a preferred alternative. To the petrolatide question and higher dose, I think, as you well know, phase two clinical trials are dose-ranging trials where we were able to see significant reductions in body weight at each of the top three doses in exposure, dose group three, four, and five. 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 three, as was shown in the top line results, but the other two 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 mid-range or dose group three. So you could anticipate that if that is the maximally effective dose, that's the dose that will be taken into phase three. We now also have nearly 150 or more individuals who are exposed to even higher doses with comparable safety and tolerability rates. 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 Association's scientific sessions.

Okay. Thank you very much.

Thank you. We will take our next question. And the question comes from the line of Andy Sheefer and William Blair. Please go ahead. Your line is open.

Hi, this is Kelsey Lusser and on for Andy Shea. Thanks so much for taking our question. So we've seen companies in the field conducting studies to better position for the maintenance market done through independent phase three 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 three program for Petrolentide, what's your strategy to generate maintenance data to maximize the asset's value? Thank you.

Thank you for your questions. And I agree that it's, of course, extremely important, in particular when you're developing a category like Petrolentide and amylin that you focus in on maintenance, because this is the big dilemma in the current market that most patients face. 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 Petrinatide, 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 Petrinatide as a first choice medicine. If you consider a patient who think about going on a weight loss journey and an interaction with a healthcare 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 Petrinatide 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 in 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 this trial top running.

Thank you. Thank you. We will take our next question. Your next question comes from the line of Benjamin Jackson from Jefferies. Please go ahead. Your line is open.

Great. Thanks, team, for the question. Just a couple from 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 an 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 Servo 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 three would be super useful. Thank you.

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 their statements around both the opportunity to treat patients with overweight and obesity and patients living with muscle. 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 Berger 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?

Yeah, happy Benjamin did comment on Supreme 2. A couple of specifics to your question. Certainly, the effect on body weight is the primary endpoint for Zupreem 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. Pramlentide, 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 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 is 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 significantly 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 three 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 three 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 estimand 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 three that are learnings from Zupreme 1. The other thing that many have noticed is phase two 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.

Amazing. Thank you so much.

Thank you. We will take our next question. And the question comes from the line of Alexandra Hammond from Wolf Research. Please go ahead. Your line is open.

Thanks for taking the question. I guess as you think about the Phase II readout for petrolentide and CT38 combo, is there a specific efficacy threshold that that combo needs to clear to justify it 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 petrolyne ties, we'll see like tolerability profile. Thank you.

Thank you for your question. And thank you for bringing up also the combination where we will start the phase two study in this quarter. And we are highly excited about the opportunity to not only develop the petrolyne tie as a monotherapy, as a first choice therapy for the many who we're looking for that double-digit weight loss and a very benign surrogacy profile. With the combination product, I think 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 candidates for biotic surgery, for instance. There's also people living at obesity and type 2 diabetes at the same time as David just alluded to, a combination of a GLD1 and amylin could actually be a very interesting opportunity for such patients. So I would say the phase two design 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 the truantide, look for the profile of the drug and match that to a 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.

Thank you. Thank you.

We will take our next question. Your next question comes from the line of Nasrat Hussain from UBS. Please go ahead. Your line is open.

Nasrat, on behalf of Xi'an from UBS, I have two questions, if I may. First, with Phase III mass-solved data for silver detide 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 mass-solved and MASH trials? How much read-across do you expect for Masold to mash? And are there any biomarkers, subgroup analysis, or secondary endpoints for Masold 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 Petri and other earlier stage programs progress. So could you comment on your current view of the survey to the royalty stream? Have we now seen the full obesity tolerability data set? And if so, does the recent Servo data change your expectations for that royalty stream? And then lastly, did confidence in future Servo-driven cash flows play a role in the decision to initiate the buyback at this point? Thank you.

Thank you for your question. And maybe I'll just address the Servo 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 350 million euros. 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 muscle data We also know, and I think that's been clear for a very long time, that they are extremely committed into the MASL program with Liberage 1 and 2, where they are enrolling close to 3,500 patients, both F2 and F4. So it's two programs, one in obesity and one in MASL, 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 two data for the training side and the decision to move into phase three, which provides clarity on the near-term milestones from that program. But as important, the phase three readout from server side has created a lot of clarity on our future revenue streams and de-risked, 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 Buy Back program, and as Adam alluded to, we've just had two major de-risking events for our leading obesity programs. This, of course, gives 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 resource investments. So we have in the past coming that we will increase our resource efforts fivefold in the next coming five years compared to the last five years. And then we 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 as our confidence has increased over the last period and our financial flexibility have also increased.

Thank you.

We will take our next question. Your next question comes from the line of Suzanne Van Vultrassen from Van Lanshop, Kempen. Please go ahead. Your line is open.

Hi, team. This is Romy on for Susanna. I have two questions. The first, knowing now the progress of petrolentide to start phase three in the second half of the year, I was just wondering where ultimately you see petrolentide 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 Petri for the phase three study? Yeah, that's my question. Thank you.

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 health care 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 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 the train site is what we have called the sweet spot that you can deliver double-digit weight loss with a tolerability profile, which in phase two with the maximum effective dose was similar to placebo when we look into the GI effects. The other thing which we think 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 DLT1s by making people feel full faster. It doesn't affect your appetite to the extent that a DLT1 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 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 two or three months. This is a journey that should be solved over a longer period. But still, it's a natural place to start with a product profile like Petrinatide. If you then need more, that's where you turn to a combination product, as we're doing with CD388 and Petrinatide. 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 between-site to be even better tolerated than what we had seen in the phase one studies in a large cohort of patients, also having exposed patients to higher doses, which will not be carried forward into phase three, but with a lot of safety around it. So, when we move into phase three, 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 two study. So, we are very confident that we get a profile of a drug that addresses exactly what patients are looking for. When you do market research, you will also hear that one out of five patients are looking for a weight loss of less than 10% and four out of five patients are looking for a weight loss of less than 20%. The average weight loss that patients experience on tazepitide 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. Thank you.

Thank you. We will take our next question. Your next question comes from the line of Charlie Hayward from Bank of America. Please go ahead. Your line is open.

Hi, Charlie Howard, Bank of America. Thanks for taking the questions. First one is just on the petri 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, will there be any debate on how we should think about the potential plateau after the 42-week period? And then on the prior comment to dose ranging, obviously the higher three doses showing very similar weight loss. Is there any meaningful difference in the weight loss curves between those three and the time it took to reach that 10% to 11% weight loss? And the final question, just at a higher level on obesity and potential petri pricing as a monotherapy. I think the market's 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 material acceleration in volumes. How are you thinking of pricing evolution going forward from here? And do you still see Petri potential premium pricing as an option in a consumer-driven market? Thank you.

Thank you. And it is, 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, I 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 Petrinatide so far suggests that it's a good 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 Petronitine 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 your 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 the two and the different doses, 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 three, and you will probably understand some of these features better at ADA. Thank you, Tim. Thank you.

Thank you. Once again, if you wish to ask a question, please press star 1, 1 on your telephone. We will take our next question, and the question comes from the line of Mohit Patel from Wells Fargo Securities. Please go ahead. Your line is open.

Hi, this is Susan Andra Mohit. Thanks for taking our questions. As pairs 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.

Thank you for that question. And of course, as we launch the Petrinatide in the future, it will be incredibly important to collect real world evidence for state 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 amylins as you do with the TZ1. It's more about escalating And if you look at the early days that we released, even the lower doses patients can expect quite significant weight loss. So it's a major difference here between the DLT1s and the amylins, at least with Petrinatide, 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 DLT1s today. David, do you want to add further?

Yeah, 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 three, 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 primatide and exenatide were switching did occur, because these are two 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 allude to in the real world, will all be part of our consideration for a robust Phase 3B 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.