Operator: Good day, and thank you for standing by. Welcome to the Zealand Pharma Interim Report Q3 2025 Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, [ Adam Langer ], Investor Relations of Zealand Pharma. Please go ahead.

Unknown Executive: Thank you, operator, and thank you to everyone for joining us today to discuss Zealand Pharma's results for the first 9 months of 2025. You can find the related company announcement on our website at zealandpharma.com. As described on Slide 2, we caution listeners that during this call, we will be making forward-looking statements that are subject to risks and uncertainties. Turning to Slide 3 and today's agenda. With me today are the following members of Zealand Pharma's management team; 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 subsequent Q&A session. Moving to Slide 4. I will now turn the call over to Adam Steensberg, President and CEO.

Adam Steensberg: Thank you, Adam, and welcome, everyone. The third quarter of 2025 has been a quarter of strong execution and continued momentum in our partnership with Roche. We achieved a key milestone in the petrelintide Phase II ZUPREME-1 trial in people with overweight and obesity, which put us well on track to report 42-week top line data in the first half of 2026. We are also rapidly approaching data from several Phase III trials with survodutide in obesity, starting with top line results from this 76-week SYNCHRONIZE-1 trial in the first half of 2026. Meanwhile, we are gearing up to outline our path towards becoming a generational biotech company at our Capital Markets Day next month. Moving to Slide 5. 2 years ago, we laid out our vision to become a key player in the management of obesity through innovation that address one of the greatest health care challenges of our time. Central to this vision was developing an alternative to GLP-1 therapies and to end the weight loss Olympics by focusing on the most important unmet medical need, a therapy that patients can and will accept to stay on. What excites me today is that Zealand and Roche has the potential to lead in the next class of drugs for weight management. We are very confident in the profile of the petrelintide as a potential best-in-class amylin analog, supported by the clinical data to date and the last robust Phase II program currently underway. We are rapidly approaching Phase II data with petrelintide and Phase III obesity data with survodutide alongside an impressive Phase III MASH program that is well underway. I look forward to this next catalyst-rich chapter and to sharing more from these programs at our upcoming Capital Markets Day, where we will also discuss our intensified early-stage efforts to build a generational biotech company. Let's turn to Slide 6. 6 months have passed since we kicked off our alliance with Roche. And I'm highly encouraged by the energy and commitment we have seen from both sides of the partnership. The agreement with Roche is more than just a deal. It's a shared commitment to redefine the future of weight management and to establish leadership in what could become the next foundational class of therapies. Last month, Zealand Pharma had the pleasure of welcoming Teresa Graham, CEO of Roche Pharmaceuticals to our offices for an engaging fireside chat about exactly this. I was also pleased to see Roche at their Pharma Day in September, conveyed to you their strong commitment to become a top 3 player in obesity. This is the reason why through a highly competitive partnership process, we identified Roche as the ideal partner for Zealand Pharma and petrelintide. Turning to Slide 7. Survodutide is licensed to Boehringer Ingelheim, a leading family-owned biopharmaceutical company with a strong legacy in cardiovascular, renal and metabolic diseases and a global presence across more than 130 markets. We're excited to see Boehringer Ingelheim potentially becoming the next major pharma company to enter the obesity market with a truly differentiated GLP-1-based therapy co-invented with Zealand Pharma. We were also highly encouraged by their strong presence at ObesityWeek in Atlanta last week. This leads me to Slide 8. The scale and complexity of obesity make it a distinct and complex disease area in which we identify different segments. In the prescriber-driven segment, a key motivation for prescription is focused on comorbidity risk reduction, improving health outcomes and relative weight loss. We believe survodutide has the potential to be uniquely positioned within this segment. The largest segment, however, is patient-driven. A significant focus here is personal weight loss goals and how individuals achieve them with potential to deliver the weight loss that the vast majority of people with overweight and obesity desire, combined with an acceptable tolerability profile and an excellent patient experience, we believe petrelintide is ideally positioned to lead in such a segment. I'm highly encouraged by the potential of both of our leading obesity programs, which holds potential to redefine the near-term future of weight management in key segments. And with that, let's move to Slide 9 as I turn over the call to our Chief Medical Officer, David Kendall, to discuss our R&D pipeline. David?

David Kendall: Thank you, Adam. Today, I'll focus my remarks on the continued advancement of our 2 leading programs, petrelintide and survodutide. Before doing so, I would like to begin by providing a brief update on our 2 late-stage rare disease programs and dapiglutide, our GLP-1/GLP-2 receptor dual agonist program. For dasiglucagon in congenital hyperinsulinism, our third-party manufacturers facility has not yet received the anticipated classification upgrade. And as shared previously, we have implemented a supply contingency plan, including the qualification of an alternative supplier to ensure we can bring this important therapy to patients in need as quickly as possible. For glepaglutide, our GLP-2 receptor agonist in development for the treatment of short bowel syndrome and intestinal failure, the Phase III EASE-5 trial remains on track to initiate before the end of the year with the purpose of supporting regulatory submission in the U.S. We remain encouraged and excited by the clinical profile of glepaglutide as a potential best-in-class long-acting treatment for patients living with short bowel syndrome and intestinal failure and look forward to confirming the positive findings of the previously completed EASE-1 trial. We have made the decision to pause the current development of dapiglutide. This decision is a result of a disciplined portfolio review and prioritization, seeking to focus our obesity portfolio investment on programs with the greatest potential for clinical differentiation and those offering the greatest potential for long-term impact for patients living with overweight, obesity and related comorbidities. Although dapiglutide has demonstrated the potential for a competitive weight loss profile based on the results of clinical trials completed to date, the GLP-1-based therapeutic space has become increasingly crowded, requiring even greater and clinically meaningful differentiation for assets which would be launched in the 2030s and beyond. While there is compelling scientific rationale for GLP-1/GLP-2 dual agonism to modulate low-grade inflammation more effectively than GLP-1 alone, the clinical requirements needed to demonstrate this differentiation in a dedicated obesity-related comorbidity would be long, complex and expensive. We have significant opportunities in both the amylin and incretin-based therapeutic space with our leading programs, including petrelintide, the fixed-dose combination of petrelintide and Roche's GLP-1/GIP dual agonist, CT-388 and survodutide as well as an early stage pipeline that includes novel mechanisms targeting obesity and inflammation with the ultimate goal of restoring and maintaining metabolic health. Please turn to Slide 10 and beginning with petrelintide. Our strong confidence in petrelintide is grounded in its overall efficacy, safety and tolerability profile. While amylin-based therapeutics can deliver clinically meaningful weight loss, we are not seeking to deliver the highest possible weight loss with petrelintide, but rather seek to target the weight loss that the vast majority of people with overweight and obesity desire and to do so with an excellent patient experience. We remain fully confident in the potential of petrelintide to deliver 15% to 20% weight loss in Phase III clinical trial and also remain highly confident in petrelintide's consistent clinical efficacy, safety and tolerability, underscoring its unique value proposition and the potential to become the leading amylin-based treatment and a foundational therapy for weight management. I'm extremely pleased with the strong execution in advancing the petrelintide clinical program at full speed. In late September, we reached a key milestone in the large Phase II ZUPREME-1 trial, which evaluates the efficacy and safety of petrelintide in people with overweight or obesity without type 2 diabetes, with the last randomized participant having now completed the 28-week primary endpoint visit. Additionally, earlier in the month, we completed participant enrollment in the Phase II ZUPREME-2 trial, which evaluates the efficacy and safety of petrelintide in people with overweight or obesity and coexisting type 2 diabetes. These achievements put us well on track to report 42-week top line results in the first half of 2026, report top line results from the ZUPREME-2 trial in the second half of 2026 and to initiate the Phase III program with petrelintide monotherapy also in the second half of 2026, together with our partner, Roche. Let's move to Slide 11. We also look forward to exploring the potential of petrelintide as a backbone for future combination therapies, unlocking its full value potential. Petrelintide/CT-388 is the first combination product under our alliance with Roche. This program will target individuals who seek even greater weight loss and/or improved glycemic control while optimizing the dose of each component. We anticipate that use of higher doses of petrelintide and optimized doses of the incretin-based therapy CT-388, a potential best-in-class GLP-1/GIP receptor dual agonist, can provide both robust efficacy while maintaining excellent tolerability. Zealand and Roche remain on track to initiate the Phase II trial with petrelintide/CT-388 combination in the first half of 2026. Now turning to Slide 12 and survodutide, a potential best-in-class glucagon/GLP-1 receptor dual agonist in late-stage development for the treatment of obesity and MASH. The Phase III SYNCHRONIZE program of survodutide in obesity consists of 6 clinical trials, all of which are expected to complete in 2026. In the Phase II obesity trial, survodutide demonstrated the potential to deliver highly competitive weight loss with doses of up to 4.8 milligrams. Notably, the Phase III trials are evaluating a higher maximum maintenance dose of 6 milligrams. This leads me to Slide 13. Following the last participant's last visit in the 76-week SYNCHRONIZE-1 trial, which evaluates the efficacy and safety of survodutide in people with overweight or obesity but without type 2 diabetes, we are rapidly approaching top line results from this trial in the first half of 2026. At the Obesity Society Annual Meeting in Atlanta last week, Dr. Carel Le Roux presented the baseline characteristics of participants in this trial, which are also shown on this slide. We are very pleased that Dr. Le Roux has agreed to join us at our upcoming Capital Markets Day next month, where he will share more insights on the potential of survodutide to represent the next frontier in the management of obesity and MASH. Now turning to Slide 14. We remain exceedingly optimistic and are very excited about the ongoing Phase III program with survodutide in people with metabolic dysfunction associated steatohepatitis or MASH, a serious obesity-related comorbidity with significant unmet medical need. Shown in this slide is an indirect cross-trial assessment of the registrational clinical trials for the 2 approved therapies in the U.S. for MASH today. The thyroid hormone receptor beta agonist, resmetirom and the GLP-1 receptor agonist, semaglutide. In the Phase II trial with survodutide in people with MASH and liver fibrosis, 38.6% of adults with moderate to advanced [ scarring ] achieved a placebo-adjusted biopsy-confirmed improvement in fibrosis without worsening of MASH after 48 weeks of treatment. We believe this represents the most compelling and strongest clinical data set to date on the critical endpoint of improvement in liver fibrosis. With these groundbreaking Phase II data and a comprehensive ambitious Phase III program now underway, the so-called LIVERAGE program, which includes 2 large trials, 1 in people with moderate to advanced fibrosis, F2 and F3 and 1 in people with cirrhosis, F4. We believe survodutide has the potential to become the therapy of choice in this large and growing market segment, offering a much-needed treatment option for people living with MASH and obesity. 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 9 months of 2025. Henriette?

Henriette Wennicke: Thanks, David, and hello, everyone. Let's turn to Slide 15 and the income statement. Revenue for the first 9 months of 2025 was DKK 9.1 billion, driven primarily by the initial upfront payment received under our collaboration and license agreement with Roche. Of the DKK 9.2 billion in upfront payment received in the second quarter, DKK 124 million was deferred as of September 30 as it relates to the progression and completion of the Phase II trial with petrelintide. Net operating expenses totaled DKK 1.5 billion for the first 9 months of 2025, with 73% of that amount dedicated to research and development. R&D expenses were mainly driven by the ongoing development of petrelintide, including the large Phase II trials and preparation for Phase III. Net financial items amounted to negative DKK 62 million for the period, primarily reflecting exchange rate adjustments related to the U.S. dollar deposits and currency devaluation. This was partly offset by interest income from investments in marketable securities. Moving to Slide 16 and the financial position. As of September 30, 2025, our cash position totaled DKK 16.2 billion, a significant increase from the DKK 9 billion at the beginning of the year. This increase was, of course, driven by the initial upfront payment of DKK 9.2 billion from Roche, partly offset by operating expenses during the period and the purchase of treasury shares to support Zealand Pharma's long-term incentive programs. I would like to remind everyone that in addition to this very solid financial position, we are entitled to receive a total of USD 250 million in anniversary payments over the next 2 years under the Roche collaboration as well as potential development milestones of up to USD 1.2 billion. As I stated in our last quarterly earnings call, I am very pleased with our capital preparedness. We are fully able to honor all obligations under the comprehensive Roche collaboration for petrelintide, while at the same time, accelerating investments in our early-stage pipeline to build the next wave of innovation. Finally, let's turn to Slide 17 and the outlook for the year. Net operating expenses for the year are now expected to be between DKK 2 billion and DKK 2.3 billion, excluding other operating items. The financial guidance has been narrowed from the DKK 2 billion to DKK 2.5 billion, reflecting the decision to pause the development of dapiglutide, previously planned to advance into Phase IIb development in 2025. This decision, as David also mentioned, reflects our active portfolio management and our sharp focus on investing in assets with the highest potential for clinical differentiation, commercial impact and long-term value creation. And with that, I will move to Slide 18 and turn the call back to Adam for concluding remarks.

Adam Steensberg: Thank you, Henriette. We are now at the cusp of the most catalyst-rich period in Zealand Pharma's history. In just the first half of 2026, we expect to see Phase III enabling data for petrelintide, Phase III data for survodutide and Phase I data for what could become one pillar in the next wave of innovation from Zealand Pharma, our highly potent and specific Kv1.3 ion channel blocker. Moving to Slide 19. I can only encourage you to join us at our Capital Markets Day on December 11, where we will set the stage for the rapidly approaching data readouts. We will also share more about our ambitious research strategy, which builds on Zealand Pharma's unique expertise in peptide R&D and our strong foundation to lead the next wave of innovation in obesity and related diseases and to continue our journey towards becoming a generational biotech company. I'm excited that we will be joined by Jonathan Roth, a pioneer in amylin-leptin biology as well as Carel Le Roux and Louis Aronne, recognized thought leaders in the field of obesity. They will join us on stage to share their valuable insights. I will now turn over the call to the operator, and we'll be happy to address your questions.

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

Kirsty Ross-Stewart: So 2 on petrelintide, please. So with the eloralintide trial now published, I think interested to hear your thoughts on kind of the differences in the setup of the 2 trials in terms of baseline characteristics, titration, doses being explored and how your -- or how you would encourage us to look at your own dataset in the context of Lilly's data to kind of make a fair comparison there? And then also, David, you highlighted in your opening remarks that you're not targeting the highest possible weight loss with petrelintide, which seem quite in contrast to what Lilly have tried to do with their eloralintide trial. I think there are some people that have sympathy with that message, but maybe you could argue as well that there's still some way to go to convince the market of the validity or the strength of that message. So I guess my question is, can you provide some feedback from your discussions with regulators or takeaways from market research with physicians and patients that may help to convince this move away from, as you call it, the weight loss Olympics.

Adam Steensberg: Thanks for your question. And then maybe I can start and then hand over to David. We were extremely encouraged to see the eloralintide data last week, which we really see building on what we already saw with petrelintide last year. Remember, Novo demonstrated that petrelintide can deliver 12% weight loss and we consider with a 2.4-milligram dose, which we consider a very low dose. And it really, you can say, underscores the potential that we have been communicating all the time around the amylin class that with amylins, we have the potential to actually develop a new class of medicines that will provide patients with likely a 15% to 20% weight loss and thus a true alternative to the GLP-1s. And very importantly, we expect this weight loss to be a more pleasant weight loss experience with significant less side effects, but also the nature in which the patients would reduce their food intake, we think would be superior in the amylin class in the sense of feeling full faster versus having loss of appetite. So we are extremely pleased, and you can say it actually increases our excitement around the upcoming Phase II data with petrelintide and our efforts to prepare for the Phase III trial conduct, really underscoring what we have been moving towards for a very long time. And David, maybe you want to touch a little bit upon important trials and design specifics there.

David Kendall: Yes. Thanks, Kirsty. And trial design specifics, I'll reiterate what Adam said. I think 15% to 20% weight loss when we came forth with petrelintide's potential to achieve this. I think at first, there were actually some skeptics that looked at this and said that can't be possibly achieved. We've seen early [ Cagri ] data. But I think the data we saw recently from another compound in this class clearly demonstrate that GLP-1-like weight loss percentages are achievable. And we think, as Adam referred to, that higher milligram dose exposure, higher bioavailability and the excellent tolerability profile we've seen to date with petrelintide up to 9 milligrams once weekly can certainly hit that sweet spot. You also mentioned what does the market seek. One simply needs to do some math. If somebody weighs 150 kilos, a 30-kilogram weight loss for 65 pounds of weight reduction is substantial. And I think 5 years ago, the world would have thought that's unachievable with what we've seen to date, including with [ liraglutide ]. So both in speaking with clinicians and in speaking with the vast majority of patients who seek weight management therapy, that's 10% to 20% weight loss figure comes up repeatedly. They may not say 10% to 20%, but they will give you a number -- a desired number of pounds or an end target weight that generally reflects that. I think some of the data from GGG high-dose GLP-1-based therapies, which we believe suffer from challenges with tolerability can get you to the 20-plus percent range, but that serves a vast minority of the patient seeking this. And finally, to your question about the baseline characteristics, just recall that with petrelintide Phase Ib predominantly male participants, predominantly or a leaner mean population with a BMI just under 30 kilograms per meter squared. Both of those factors, we believe, could have significantly muted the response we saw in Phase Ib. We will have a much more balanced gender distribution in Phase II, a much higher baseline BMI as we reported in last quarter's call. And the likely contribution of predominantly female, very high BMI population, I think, is well worth considering it may amplify the observed results rather than mute as a predominantly male and leaner population. I think it's also important to read the details of both diet and exercise instruction in the trial. We achieved our results in Phase Ib with limited to no other intervention. So I encourage you and others to look at the full construct of all of these trials before jumping to just top line numbers. So I'll stop there.

Operator: We will take our next question. Your next question comes from the line of Hakon Hemme Jørgensen from Danske Bank.

Hakon Hemme Jørgensen: Hakon Hemme, Danske Bank. Also a question regarding petrelintide study design. The [ eloralintide ] data from last week demonstrated that patients did not experience weight loss -- a weight loss plateau like we see with the GLP-1 treatments, likely due to the restoration of leptin sensitivity by amylin. So how does this influence your consideration on the trial duration for petrelintide in Phase III? And how do you see the trade-off between potentially achieving greater weight loss with a longer study compared to bringing petrelintide to the market sooner?

Adam Steensberg: Thanks for that question. We're going -- I'll let David answer.

David Kendall: Thank you, Hakon. I think 2 very important observations. The absence of plateau, which I think was readily evident both in our short Phase Ib studies with petrelintide, but certainly offers that potential where longer exposure, some of it required for regulatory review and approval out to beyond 68 to 72 weeks will allow us to assess whether this is a continued effect. And I think importantly, speaking back to the mechanisms that Adam discussed a satiety or fullness where one feels full faster and stops prospective food intake as opposed to a food aversive signal that hit suddenly and may be consistent at least in theory, could contribute to a continued gradual weight loss over longer periods of time. So in both our own visual extrapolations and I think now looking at the elora high-dose data, noting that the higher doses were perhaps less well tolerated than the 3-milligram dose, you see not only progressive weight loss, but GLP-1-like effects, something we've been talking about for most of the past 2 or 3 years. So I think it will be important to observe what we pull out of our 42-week Phase I trial. And then the design for the longer Phase III trials will directly answer your question, but would expect the potential for progressive weight loss out beyond 1 year of treatment.

Operator: We will take our next question. Your next question comes from the line of Lucy Codrington from Jefferies.

Lucy-Emma Codrington-Bartlett: Sorry, sticking with the elora data from last week. So in light of that data, do you have any updated thoughts on the importance of the receptor activity that has previously been discussed? And you mentioned that you're confident it will still be best-in-class. I just wanted to know what drives that confidence given the data we've seen so far for elora. Then secondly, just following up on the trial design. Just to confirm, this trial will have no lifestyle interventions, is that correct? And then secondly, related to the trial, did you specify to have a balanced sex ratio in the trial? Or is that just happenstance? And then on dapiglutide and the decision there, I just wonder, you're obviously not short of cash. So kind of what was the thought process in terms of stopping this study? Was there any discussion with Roche about this? I appreciate you're not partnered, but did you discuss it with Roche? And also, any thoughts on potential combination with petrelintide down the line? And what studies would be need to be done in order to enable that?

Adam Steensberg: Thank you for the questions. I will start with the first one on the pause on dapi. I think it's very evident and it will be even more so at the Capital Markets Day that we have what we believe really a leading opportunity in the GLP-1 space with survodutide, which [indiscernible], which do not only have a huge potential for weight loss, but actually also addressing liver health and in particular, MASH and potentially other organ damages by activating lipolysis. So it actually has a strong profile towards managing comorbidities of obesity. And now with the Roche partnership, we also, as you know, got shared economics on the combination product with CT-388, their GLP-1/GIP, meaning that's going to be the combination opportunity we are going to focus on. And thus, that became less relevant for combinations with amylin. What we have been exploring over the summer was addressing segments of the obese patients, which were suffering from specific comorbidities. And in doing those in-depth evaluations, it's very clear that it will require, as David also said, very large investments and long commitments before getting to understand the full potential for differentiation. And if you then consider the GLP-1 marketplace in 5, 6 years from now, you will see that it's a very crowded place. And we came to the conclusion that the level of clinical differentiation we would have to show by coming that late into a GLP-1 market was not worth the efforts, in particular not because we have such a rich early pipeline and fantastic ideas, which you will hear more about that we want to invest in and apply our capital. So we basically believe we can apply our capital better in those early programs. So I would say it's a very, you can say, considered decision and one which allows us to invest even more in our early-stage pipeline as we mature the company towards a generational biotech. When thinking about the upcoming data for petrelintide, we remain and we are even more confident in the potential to deliver the 15% to 20% weight loss, which we know will address by far the vast majority of the weight loss that patients are desired. And as I said before, the data that came out last week underscores the potential that we also saw with cagrilintide last year. Remember, cagrilintide was only 2.4 milligram, which is a very low dose compared to where we take petrelintide today. And so the confidence in the best-in-class potential comes from -- when we look at the consistency of the data we have seen across our early-stage clinical trial readout, the balance between efficacy and tolerability has been outstanding in our minds and then the potential to dose high and continue into the longer-term study that we are soon to report gives us that confidence in the Phase II study that we will report ZUPREME-1. We have applied diet and exercise, and we do have a gender balance of around 50-50 as opposed to the 80% females that were reported in the study last week. But again, that has been done from a very firm development perspective that you want to have exposures in those gender to make the best possible decisions for your Phase III design. You actually introduce a lot of risk by having very few of one gender because you don't get to learn about your molecule in those genders if you skew too much in Phase II.

David Kendall: And Lucy, I'll take the question about the receptor biology and receptor differentiation. I think [ Thomas Lutz ] said it quite well in his introductory talk saying there's still quite a bit to understand elora based on data reported by Lilly has about a 12-fold higher affinity for the amylin receptors than calcitonin. But I think it's important to note that the proposed or the hypothesized improvement in tolerability was clearly not demonstrated. There was significant nausea, I think, up to 64% in one of the treatment groups at relatively moderate doses. Similarly, if one looks in the appendix, there's not just a transient, but a small decrease in serum calcium, which is also indicative of some calcitonin effect. So our own conclusions are that with balanced agonism as we have seen with petrelintide, we have seen one of the best, if not the best, tolerability and safety profile and that it does not sacrifice tolerability, particularly around GI side effects. I think the other comments that Thomas Lutz made, which is all of this receptor biology work and knockout activity in animal really requires confirmation in clinical testing. And to our end with a predominantly female, higher BMI population treated with high doses, there was no substantial difference, I think, based on the author's conclusions in tolerability versus historic GLP-1 programs. And we would at least posit that some of the changes, including the drop in serum calcium indicates some and perhaps significant calcitonin receptor activity in clinical treatment. So we will continue to explore how these may differ. But I think as Thomas Lutz concluded, the answers will come from the clinical trials.

Operator: We will take our next question. The next question comes from the line of Andy Hsieh from William Blair.

Tsan-Yu Hsieh: So it's about the patient experience that you comment frequently about. So in the context of co-formulation with CT-388, I'm curious about your take on how important it is to harmonize the number of step-ups between, let's say, petrelintide and CT-388 in the titration step, especially given the tolerability profile, incretins will likely need a more prolonged titration period. So that's question number one. Question number 2 has to do with another adverse event profile that was raised during the conference, which is fatigue. Based on our KOL discussions, I think this is probably one of the overlooked adverse events affecting patients' quality of life. That number appeared to be numerically higher than what we've seen. So I'm just curious about your take on this and also what you've seen with petrelintide clinical trial experience.

Adam Steensberg: Thanks for the question. Maybe I can just start and hand over to you again, David. I think as we have also said all the time, it is about time to move beyond the weight loss Olympics, not only because it's not what patients are looking for, but it's also a clear observation on our end at least. And I would also say maybe you see that in some of these dataset, if you go too aggressive with very potent biology as we have today, especially in the start, you might actually introduce situations you're not looking for. And our observation, and you will also see that in earlier study data from several [ amylin ], you don't want to push this too much in the start. Could that be driving some of the fatigue that you're seeing? Maybe if you have a, let's say, 4% weight loss over 1 week, that's probably not that, that could be a fluid that you lose and how would that make the patients behave. So recognizing that we work with extremely potent biology, as David also mentioned before, who would have thought that you could achieve a 20% weight loss with a pharmacological intervention just a few years back. And here we are, but you have to be careful and otherwise, you may see things you don't like. So that is a key observation. When we look at our studies, we have not seen it in our programs thus far, signs of fatigue. So -- but again, let's see, we, as you know, apply actually titration throughout our entire phase of all cohorts in our Phase II study, something that was -- has not always been done with other programs. So -- and so far, we have not seen it. On the titration steps, before handing over to you, David, I also just want to mention, I mean, what we have seen thus far is that amylin actually deliver weight loss even at the initial doses. And it's, of course, clear that ultimately, when we titrate together with the GLP-1, it will be the GLP-1 that determines how to titrate because those are the ones that really need titration from a GI tolerability approach. David?

David Kendall: Yes, I'll reemphasize that, Andy, and harmonizing those, I think, gives us the opportunity, as I said, to find what is the most applicable dose escalation scheme for petrelintide to get to what we hope is maximal dose with very good tolerability. As Adam said, we've seen less fatigue than in our placebo-treated subjects in the Phase I trial and very limited GI tolerability issues, that would allow you to either simplify the addition of very low dose incretin-based therapy. So it would further slowdown to get to not a maximal dose as is often done in Phase III trials or Phase III to see the maximum weight loss. But an optimized dose, let's say, dose 3 of the 388 compound and dose 5 of the petrelintide compound is what the alignment looks like. We would base that on the petrelintide dose escalation scheme monthly as what we're testing in Phase II and Phase III. So the question is then how do you formulate a fixed-dose combo to get to the optimize, not maximal dose of 388. So this is not simple math. I think we have our manufacturing team on edge for the types of combinations that are possible. But this work is well underway, and I think will allow us to do exactly what we set out to do, which is to find a very effective therapy that optimizes tolerability while still leveraging the efficacy of both components.

Operator: We will take our next question. Your next question comes from the line of Kerry Holford from Berenberg.

Kerry Holford: Mine is more bigger picture with regard to the market and your expectations here. So clearly, since the last update, we've had Lilly Trump deal. We now have clarity on pricing in the U.S. [indiscernible] cash pay in the Medicare channel. So I would just be interested to hear how that deal and the details that we have so far may be impacting yours and Roche's forecast and the opportunity for your next-gen obesity pipeline assets? Will it essentially now be more difficult for you to unlock the value and deliver strong returns in this market? Just your thoughts from that big picture perspective.

Adam Steensberg: Thank you for that question. And we will -- actually at our Capital Markets Day in December 11, address our considerations about the current market dynamics in more detail. But maybe just to share a few considerations. I think it's a very dynamic market right now. We have already seen that a very large part of the uptake has been in the direct-to-consumer space where prices have been lower than the list prices. And we've also seen rebating in this space when it comes to the commercial channel. So it's actually a blessing to be where we are right now where we can learn from these dynamics and then design our programs and go-to-market strategy together with Roche according to those dynamics and how we think they will play out in the future. That allows us to actually define the future instead of just trying to tap into something that work. On the value opportunity, I think the key single most important parameter to unlock the value in this market and actually truly address the obesity pandemic, that is to develop therapies that patients will stay on and thus increase the volume of patients who get to these therapies. It's a huge problem that in today's market, many patients would use the GLP-1-based offerings as a little bit of an [ event-based ] therapy with the majority of patients being off therapy within a year. And a lot of that has to do with side effects we know from IQVIA data. So we focus to unlock the value of this market and to change -- to get excitement into this space again, I truly believe is by making sure you develop therapies that people can stay on and thus, you will see the volumes go up. And then the pricing part that people like to discuss so much is less of an issue as long as people stay on therapy. It's only an issue if you only stay on therapy for 1 to 3 months, and then you need to go out and find a new patient to capture that value you lose by the patient stop taking it. So we actually like the clarity that we see more and more clarity. We understand that it's still a very dynamic market. We would expect to see a significant number of changes in the coming years. And together with Roche, we would build our go-to-market models accordingly.

Operator: We will take our next question, and the question comes from the line of Prakhar Agrawal from Cantor Fitzgerald.

Prakhar Agrawal: Congrats on the quarter. So I had a few. Maybe firstly, going back to receptor biology. [indiscernible] is having elora as a more selective amylin, especially on amylin 1 receptor and seems to be balanced on amylin 3 and calcitonin. So maybe if you could talk about whether potently targeting amylin 1 versus amylin 3 receptor has any clinical implications in obesity and beyond. And if you can remind us about petrelintide's activity on amylin 1 versus 3 receptors? And secondly, on the trial for Phase IIb ZUPREME-1, if can you talk about how the discontinuation rates are trending as it has been an issue with some of the recent trials? And when you disclose the data next year, whether you will disclose both efficacy and treatment regimen demand when the data disclosed?

Adam Steensberg: I'll start and hand over to you, David. And we do expect to disclose the top line efficacy data from both estimates, I would expect, including the relevant safety observations when we disclose the data. On the receptor profile, if you look into preclinical data, I remind you that both we and Novo had a firm effort for many, many years and came out with balanced profiles towards these receptors. And as David just alluded to, probably quite a few of the molecules we're looking at right now have some receptor activation on all 3. We have one which is quite similar, we believe, to the one that petrelintide has. Ultimately, we need, as David also said, to see clinical data. When we look at the early clinical exposure for which we have -- actually have among the different amylin molecules, that is where we see -- get a lot of confidence in our approach if you start to compare, let's say, the single ascending dose studies across the different molecules where we have data now available and published both from us, but also the competing programs. And if you then account for female to male, BMI and other aspects. But the single ascending dose data, probably some of the more honest datasets here where there's less bias, that gives us a lot of confidence and the robustness of our observations where we have not seen some side effects in one study and then others in another one, the first one disappearing, we have a very robust dataset, which suggests that we have a profile of a drug that has found the right balance between efficacy and safety tolerability. So -- and we will review more of this at our Capital Markets Day, which will answer probably in more detail some of these questions. And David, I don't know if you have more to...

David Kendall: Thanks, Prakhar. And I think as you and we are learning this receptor biology, when it's assessed in vitro, looking at receptor occupancy and activation doesn't necessarily provide the entire clinical picture. And as Adam said, cagri and petrelintide are clearly balanced receptor agonists activate all 3 receptors in our hands with equal potency. [ The Gubra now AbbVie ] asset is similar in our hands, slightly greater predilection for the amylin than the calcitonin receptor. And the Lilly molecule, eloralintide while touted to be amylin more specific, it clearly had GI tolerability issues associated with it, something that calcitonin receptor dialing back has been touted to improve, but hasn't been demonstrated clinically to demonstrate. I think the other point that Adam makes that's critically important is regardless of this, how does the clinical safety and tolerability and efficacy profile lineup using the elora data as an example. There were in the early phase trials, an increase in the number of headaches, whereas with petrelintide, we've seen less headache than with placebo. The newly reported adverse effect of bradycardia, bradyarrhythmia and syncope reported in the elora trial is unique amongst this class to my knowledge. I have no idea if that's related to receptor biology or other mechanisms. Again, the clean profile and the balanced agonism of both cagrilintide now through Phase III and our Phase Ib data and beyond for petrelintide give us great confidence that, that is not only an acceptable receptor profile, it is an incredibly effective and well-tolerated profile.

Operator: We will take our next question. Your next question comes from the line of Yihan Li from Barclays.

Yihan Li: Yihan Li from Barclays. So we have 2. So the first one is the petrelintide Phase III timing. So it seems like you have already completed the end of Phase II meeting with the FDA. So just curious if you could walk us through what remains before initiating the Phase III monotherapy trial, which is now planned in the second half of next year, especially given your competitor, Eli Lilly, actually, they moved very fast for the Phase III will start by year-end. And the second question actually is on eloralintide, the MASH data. So again, like they showed 60% to 70% of the MASH reduction from [indiscernible] and also the other 30% from the [indiscernible]. However, an interesting thing is that it doesn't seem to have a continued decline in the lean MASH from the week 24 to week 48. So suggesting the lean MASH loss could potentially stabilize after 24 weeks. I'm just like curious, does this suggest maybe amylin-based therapy could inherently preserve lean MASH better over time? Like any thoughts will be appreciated because I'm just thinking like amylin could be used as a post GLP-1. So just curious what your thoughts there.

Adam Steensberg: Thank you for that question. And I can reassure you that we are moving as fast as possible forward to Phase III initiation with petrelintide. Right now, our expectation would be second half of next year and as we have communicated today, we have reached the primary endpoint of the study. And we are, of course, also anticipating a meeting with FDA as fast as possible once these data has been analyzed and progressing as fast as possible. So -- and top line data will be available first half next year. So it's a shared commitment from Roche and us to accelerate as much as possible to get these treatments to patients ultimately and help achieve their health goals. So this is progressing with a high sense of urgency, but the Phase III start is set for second half next year. I think we need to actually wait for our Phase II data with petrelintide before we will comment more on the balance between muscle and fat preservation. Remember, we use MRI as an assessment of body composition, which is a much more precise mechanism than the [ DEXA ] scans that have been utilized by other companies. We, as everyone know, have seen extremely strong preclinical evidence for muscle preservation with the amylin class, and we need to now see human evidence before addressing this more, and we think we will get some, at least high-quality data from our Phase II study, which will be able to address this in more detail.

Operator: We will take our next question. Your next question comes from the line of Theodora Rowe Beadle from GS.

Theodora Beadle: Thank you very for taking my questions based on dapiglutide, if that's okay. So firstly, why did you take the decision now to pause the development of the dapiglutide rather than further exploring the potential anti-inflammatory benefits? Has there been some data generated internally, for example, that could drive that decision? And then secondly, could there be developments elsewhere in the space that change your thinking on dapiglutide? So specifically thinking about if Novo show a benefit in Alzheimer's in the evoke trial?

Adam Steensberg: Thank you for that question. And as we have indicated today, we have decided to pause the program because we do recognize that it's a very attractive profile, both with the clinical profile we have seen thus far and also its potential to lower inflammation even further than the existing GLP-1s. We actually think it's probably the most differentiated GLP-1 containing mid-stage development candidate. The decision has been reached now partly, as I explained, due to the fact that we have CT-388 where we can -- as we will combine with amylin, also, of course, very much because we see now -- we see survodutide approaching, but then also just realizing that the investments needed to show the clinical differentiation and then the need for clinical -- the amount of clinical differentiation you would have to demonstrate if you launch a GLP-1-based therapy in the [ '30s ], it's a very, very high bar to pass due to the competitiveness within the GLP-1 class of medicines. And that's coming back to why we are so excited about the amylin class because it's an alternative. And if you think about how you manage chronic therapies, normally, if you cannot achieve your goal with one class, then you move on to the next. And if you need more, then you start to combine. So -- and if you then -- and we'll talk much more about that at our Capital Markets Day, consider the rich pipeline we have of early-stage assets, we have really taken a view that there's significant higher value creation opportunities by investing in these next opportunities for which we have some -- we consider at least very good ideas for how to drive the next wave of innovation and differentiation in this space. So for us, it was not, as you can imagine, an easy decision since the molecule actually looks very strong, but we also think we have so much exciting opportunities in our pipeline that the money are actually more wisely spent there.

Operator: We will take our next question. Your next question comes from the line of [indiscernible] from UBS.

Unknown Analyst: Just on survodutide. So you'll probably cover this more at your CMD, but in terms of the Phase III readout in the first half of next year, where do you expect tolerability will likely land considering that in the Phase II data we've seen so far, there's a pretty high level of GI toxicity?

Adam Steensberg: Thank you for that question. And we, of course, soon will have the data. And please also remember that the Phase II study design, if you compare the safety or tolerability profile with the Phase II studies of -- of some of the marketed products, you will actually see a quite similar profile of tolerability. So we, of course, what we expect with survodutide is a comparable tolerability profile to the existing molecules and also a comparable weight loss. The true opportunity for differentiation is the activation of lipolysis with glucagon and thus providing better liver health as we saw with the MASH program. Also remember that Boehringer is actually pursuing higher doses in the Phase II than what they -- in the Phase III than what they did in Phase II. And that gives us a lot of confidence that by using -- applying the right titration being flexible around how you titrate as you have to be with GLP-1 allows them to go much higher. They have already tested that higher dose in the MASH population in Phase II, which is applied in the Phase III program for obesity. So we have a lot of confidence that the profile will come across as a very strong and effective GLP-1-based therapy with a tolerability profile that is comparable to what's on the market today and a clear edge towards their health.

Operator: We will take our final question, and your final question comes from the line of Mohit Bansal from Wells Fargo.

Mohit Bansal: So a couple of questions from my side. First of all, so given that with CagriSema, we saw a little bit of tolerability when you combine GLP-1 with amylin. And I fully appreciate the sentiment that combining GLP-1 and amylin could be interesting. But at the same time, do you -- given that amylin does have some GI tolerability issues, and it could compound with the GLP-1. So do you think the better use of amylin could be more of an immunotherapy versus a combo therapy, maybe in post-GLP setting or maybe as a monotherapy in the frontline setting? So that's first question. And second question is, we saw with eloralintide that, I mean, Phase I was -- tolerability was better versus Phase II, we saw a little bit higher GI issues. So in that context, I mean, what do you expect with petrelintide in terms of tolerability in Phase II trial as you see data in more patients?

Adam Steensberg: Thank you for your question. And we definitely see amylins in particular, petrelintide having the potential to become a foundational and first-line therapy, a first choice therapy. I think what many have not really thought deeply about today is that, and we've -- yes, I think we all recognize that GLP-1 for many patients are difficult to tolerate. Many patients accept these therapies today because there's no alternative. What will the conversation be if there is a more tolerable approach to weight loss? Then you don't talk about will you tolerate it, then you will start to have a conversation, will you accept the tolerability profile of a GLP-1 if you can actually experience a more pleasant weight loss on a different modality. I think that's what we have to think about now. So that -- and that's what excites us and why we believe we have the potential to drive first choice and foundation therapy. So we definitely see, as we have said all the time, the biggest opportunity for monotherapy as an alternative and a first choice treatment for obese individuals who want to lose weight and importantly, maintain that weight loss because that is the key to unlock the value of this market is to make patients stay on therapy so they don't regain weight, and it's also the key then to achieve the health benefit. If people don't stay on therapy and they regain weight, they will not achieve the health benefit. There's also significant potential for combination therapy, but that would be for the most [indiscernible] patients living, for instance, with type 2 diabetes. As David also alluded to before, we have a different approach to the combination where we want to max out, if you will, on the amylin component, which we consider the more tolerable part of the combination and then just add a teaspoon of the GLP-1 component. And thus, we expect to have a more tolerable approach to that combination that maybe has been seen with other approaches to combination. So again, on the expectation for our Phase II study, we have -- as you can hear, we have a high level of excitement and high expectations for the profile that we will see with our upcoming 42-week data with petrelintide. Thank you.

Operator: This concludes today's question-and-answer session. I will now hand back for closing remarks.

Adam Steensberg: 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. Thank you.

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