Good day, and thank you for standing by. Welcome to the Zealand Pharma Interim Report Half-Year 2025 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 the session, you will need to press star one, one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one, one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Adam Lange, Vice President, Investor Relations. Please go ahead. Thank you, (Rhoda Rena), and thank you to everyone for joining us today to discuss Zealand Pharma's results for the first six months of 2025. You can find the related company announcement on our website at zealandpharma.com. As described on slide two, I caution listeners that during this call, we will be making forward-looking statements that are subject to risks and uncertainties. Turning to slide three 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 four, I will now turn the call over to Adam Steensberg, President and CEO. Thank you, Adam, and welcome everyone. Today, we stand in a unique position to realize our vision to become a key player in the management of obesity. We have a clearly differentiated mid-to-late stage obesity pipeline with two leading programs, petrelintide and survodutide, backed by strong partners in Roche and Boehringer Ingelheim. Both programs are rapidly approaching key clinical readouts with phase II data for petrelintide and phase III data for survodutide in our sights. Over the past two years, we have strengthened our organization and our internal capabilities, including recent appointments to our leadership team. Utpal Singh, as Chief Scientific Officer, will drive the next wave of innovation, and Steven Johnson, as Chief Development Officer, will lead our development and regulatory strategies. Finally, our robust financial position ensures the strongest possible foundation as we approach major upcoming catalysts for our leading obesity programs. With this momentum, Zealand Pharma is entering a pivotal new chapter, and I'm truly excited about what lies ahead. Turning to slide five, the Roche alliance for petrelintide has begun exceptionally well. With Roche, we are rapidly advancing the petrelintide monotherapy program. Once the 28-week data from the ZUPREME-1 phase II trial are in hand, which is expected by the end of this year, the underlying teams can move forward with the end of phase II meeting with the U.S. FDA. We expect to report the 42-week data in the first half year of 2026 and initiate the phase III program with petrelintide monotherapy in the second half of 2026. Meanwhile, we expect to initiate phase II for the first petrelintide-based combination product under the collaboration: petrelintide combined with Roche's leading incretin asset CT-388, a potential best-in-class GLP-1 dual receptor agonist, in the first half of 2026. It is full steam ahead with the Roche collaboration on the petrelintide clinical development program. Under the collaboration, Roche is responsible for all investments into commercial manufacturing and supply for petrelintide and the petrelintide-based fixed dose combination. With regards to manufacturing readiness, we are truly impressed with the decisiveness and firmness with which Roche moves forward. The early commitments and planning around manufacturing were a big reason why we chose them as our partner. They are already building out capacity at scale, including a state-of-the-art, high-volume, high-throughput fill-finish manufacturing facility in the U.S. These early and meaningful investments will significantly contribute to unlocking the full value potential of petrelintide and our shared ambition to establish the leading amylin-based franchise. At the Roche Pharma Day on September 22nd, we expect that they will provide further insights into their obesity strategy. At our Capital Markets Day in December, where our obesity strategy will take center stage, we look forward to sharing updates on the programs and on our efforts to become a key player in the management of obesity. Let's move to slide six. It is without a doubt that new and better treatment options are needed to tackle one of the greatest healthcare challenges of our time. With only a small fraction of eligible patients receiving pharmacotherapy today, we are clearly at the very early stage in the evolution of this market, which will require many therapeutic options with a range of different mechanisms to adequately address this chronic disease. Real-world treatment persistence with the GLP-1-based therapies remains a challenge, highlighting a clear need for more tolerable, simple, and patient-friendly options. As an industry, we have to move away from focusing on speed and magnitude of weight loss. This is not consistent with what the vast majority of people with overweight and obesity desire. We believe that a product with the best potential to become the preferred therapy for a broad population with overweight and obesity should deliver weight loss in the range of 10% - 20%, which the vast majority desire through a mechanism that offers a more positive patient experience with improved tolerability, including fewer and milder gastrointestinal events, so that patients can better achieve and, importantly, maintain a healthy reduction in their body weight. This is why we are so excited about the potential for petrelintide to become a foundational therapy for weight management. With that, let's move to slide seven as I turn over the call to our Chief Medical Officer, David Kendall, to discuss our R&D pipeline. David? Thank you, Adam. Today, I would like to focus my remarks on the continued advancement of our leading programs in obesity and obesity-related comorbidities. Let's move to slide eight. Together with our partner, Roche, we are exceedingly well positioned to establish the leading amylin-based franchise for weight management and rapidly expand into obesity-related comorbidities. As Adam just mentioned, petrelintide holds the potential as an effective and well-tolerated standalone therapy to address the needs of the majority of people with overweight and obesity. The broad scope of the collaboration set forth in the Zealand Pharma Roche Alliance enables us to fully explore and unlock the potential of petrelintide. The first combination product under the alliance will target the segment of people who need and desire greater weight loss and/or improved glycemic control while still leveraging the better tolerability of higher dose petrelintide and adding optimized doses of the incretin-based therapy CT-388. Turning to slide nine. In recent months, research and development activity in amylin-based treatments for weight management has increased significantly. Two years ago, we faced some skepticism about our approach to amylin as an effective and appealing standalone therapy and as an important alternative to GLP-1-based therapies. Today, however, amylin is emerging as the next major class of potential therapies for weight management. In June, we saw the first detailed phase III data for a long-acting amylin analog, cagrilintide. The long-term data showed no unexpected safety signals and a gastrointestinal tolerability profile that demonstrated considerably fewer and less severe GI adverse events than observed with GLP-1-based therapies. These data represent a major de-risking event for the petrelintide program as petrelintide shares both a very similar receptor profile and a structure based on the human amylin backbone like cagrilintide. That said, there are several key molecule-specific differences that potentially make petrelintide superior, which are worth reiterating. These differences include petrelintide's chemical and physical stability, particularly around a neutral pH, the ability to administer higher milligram doses, a longer half-life, and greater bioavailability. We have also seen additional early-stage data from other amylin-based programs, including analogs derived from different backbones, such as salmon calcitonin, or analogs with different receptor binding and activation profiles. While these analogs contribute to the growing body of data available for amylin-based therapies, we remain highly confident in petrelintide's consistent clinical response, the very favorable tolerability and safety profile, and the peptide construct itself, underscoring petrelintide's unique value proposition and potential to become the leading amylin-based treatment and a foundational therapy for weight management. Our confidence is grounded in the totality of data we have generated to date. Petrelintide has demonstrated the potential to deliver the weight loss that the vast majority of people with overweight and obesity desire, even in studies that were conducted in a predominantly male population with a relatively lower baseline BMI, all factors that likely muted the overall weight reduction observed. To support this, we were pleased to present on slide 10 the additional data on individual responses of participants in our 16-week phase I-B trial with petrelintide at this year's ADA 82nd Scientific Sessions held in June. Of note, every individual participant treated with petrelintide in this trial lost weight during the study. Importantly, while only 21% of the trial participants were females, a greater treatment response was observed in females across all three petrelintide dose groups. This leads me to slide 11 for a brief status update on the petrelintide phase II ZUPREME-1 program. We have previously shared the trial designs for ZUPREME-1 and ZUPREME-2, so I will not go into further detail here. Back in March, we announced the completion of enrollment of more than 480 participants in ZUPREME-1, and today we are sharing the preliminary baseline characteristics of the participants in this trial. ZUPREME-1 has a population with a mean BMI of approximately 37 kg per meter squared at baseline and includes a balanced gender distribution with 53% of the participants being female, notably different than the population studied in our phase I trials. We look forward to reporting top-line results from ZUPREME-1 in the first half of 2026. Turning now to slide 12 for a brief update on dapiglutide, our first-in-class GLP-1, GLP-2 receptor dual agonist. We were very encouraged by the top-line results from part two of the phase I-B trial with higher doses of dapiglutide announced in June. These data showed a weight loss that is highly competitive compared to the currently available GLP-1-based therapies for weight management at similar time points, despite dapiglutide being studied in a predominantly male population again with a relatively lower baseline BMI. That said, we recognize that differentiation is absolutely essential, and our strategy is to leverage the dual mechanism of dapiglutide, which includes GLP-2 activity, and move into a dedicated phase II obesity-related comorbidity trial in the second half of 2025. Now turning to slide 13 in survodutide, a potential best-in-class glucagon/GLP-1 receptor dual agonist in late-stage development for the treatment of obesity and NASH. We are rapidly approaching top-line data from the SYNCHRONIZE- 1 and SYNCHRONIZE- 2 phase III trials, which are evaluating the efficacy and safety of survodutide in people with overweight or obesity, both with and without type 2 diabetes, respectively. The design of the SYNCHRONIZE phase III program builds on key learnings from the phase II obesity trial, where trial participants achieved mean weight loss of up to 18.7% after 46 weeks. Notably, these phase III trials will assess even higher maximum doses of up to 6 mg. We remain extremely excited about the potential of survodutide and novel dual agonist therapy for weight management and look forward to top-line results from SYNCHRONIZE- 1 and SYNCHRONIZE- 2, likely to be reported in the beginning of 2026. We are also very excited on slide 14 about the ongoing survodutide phase III program in people with Metabolic Dysfunction-Associated Steatohepatitis or MASH, a serious obesity-related comorbidity with significant unmet medical needs. Shown on this slide is an indirect cross-trial assessment of clinical trials with incretin-based therapies and MASH compared with the only approved therapy today, thyroid hormone receptor beta agonist. In the phase II trial with survodutide in people with (NASH) and liver fibrosis, 38.6% of adults with moderate to advanced scarring achieved a placebo-adjusted, biopsy-confirmed improvement in fibrosis without worsening of NASH after 48 weeks of treatment. We believe this represents the most compelling and strongest clinical data set to date on the important endpoint of liver fibrosis improvement. The LIVERAGE program initiated in 2024 is the largest ever phase III (NASH) program with an incretin-based therapy and the only program to also include patients with compensated cirrhosis. With the best-in-class NASH phase II data and the robust, ambitious phase III program underway, we believe survodutide has the potential to become the therapy of choice in a large and growing market, offering a much-needed treatment option for people living with. Excuse me, Mr. Kendall, apologies for interrupting you. Unfortunately, your sound is breaking up and dipping in and out, so we're finding it difficult to hear you. Can you try to say something again, David? Yes, can you hear me now, operator? I can hear you now, yes. I don't know the problem, but thank you, and I'll continue. Thank you. Turning now to slide 15, and apologies for the difficulties with the sound. Survodutide is licensed to Boehringer Ingelheim, as mentioned by Adam, and Boehringer Ingelheim is a family-owned leading biopharmaceutical company with a strong legacy in cardiovascular, renal, and metabolic diseases and a global presence across 130 markets. Boehringer Ingelheim holds sole responsibility for the global development and commercialization of survodutide. Zealand Pharma has no financial obligations to either development or commercialization under this agreement but is entitled to percentage royalties on global sales ranging from high single-digit to low double-digit. In addition, we are eligible for up to EUR 350 million in remaining outstanding milestone payments. Notably, Boehringer Ingelheim is an established leader in the CVRM and diabetes space, having developed and launched the leading SGLT-2 inhibitor, empagliflozin. The company has been instrumental in demonstrating empagliflozin's benefits in reducing cardiovascular risk, slowing the progression of chronic kidney disease, and alleviating the burden of heart failure. Moving to slide 16 for a brief update on our rare disease programs. For dasiglucagon and congenital hyperinsulinism, our third-party manufacturing facility has not yet received a classification upgrade. In the meantime, we have implemented a supply contingency plan that includes the qualification of an alternative supplier to ensure we can bring this product to patients in need as quickly as possible. For glepaglutide, for the treatment of short bowel syndrome with intestinal failure, the phase III EASE-5 trial remains on track for initiation in the second half of 2025 to further support regulatory submission in the U.S. In June, we were pleased to announce the submission of a marketing authorization application to the European Medicines Association seeking approval of glepaglutide in the E.U. We remain incredibly excited and encouraged by the clinical profile of glepaglutide as a potential best-in-class long-acting treatment for the management of short bowel syndrome with intestinal failure. With that, thank you very much for your attention, and I would like to now turn the call over to our Chief Financial Officer, Henriette Wennicke, to review our financial results for the first half of 2025. Henriette? Thanks, David, and hello, everyone. Let's turn to slide 17 on the income statement. Revenue in the first six months of 2025 was DKK 9.1 billion, driven by the initial upfront payment under the collaboration and license agreement with Roche. Of the DKK 9.2 billion in upfront payment received in June, DKK 9.0 billion was recognized as revenue in connection with the closing of the agreement in May 2025. The remaining DKK 262 million of the initial upfront payment is associated with the progression and completion of the phase II trials with petrelintide, of which DKK 167 million was deferred as of June 30, 2025. Net operating expenses totaled DKK 968 million for the first half of 2025, of which 78% was spent on research and development. The R&D expenses are mainly driven by the development of petrelintide, including the last phase II trials and preparation for phase III. R&D expenses also reflect preparation for phase II with dapiglutide, increased investments in the Kv1.3 ion channel blocker, as well as development and regulatory activities related to the rare disease programs. Net financial items amounted to - DKK 157 million. This is driven by exchange rate adjustments, which primarily relate to USD deposits and currency revaluations on account receivables and cash equivalents. This was partly offset by interest income from the investment in Michaelh old Securities. Let's move to slide 18 on the cash position. As of June 30, 2025, our cash position totals DKK 16.6 billion, a significant increase compared to the DKK 9 billion at the beginning of the year. This is, of course, driven by the initial upfront payment of DKK 9.2 billion from Roche, partly offset by operating expenses for the period and the purchase of treasury shares to support Zealand Pharma's long-term intensive programs. I would like to use the opportunity to remind everyone that on top of this very solid financial position, we are entitled to receive a total of $250 million in anniversary payments over the next two years under the Roche collaboration, as well as potential development milestones of up to $1.2 billion. The vast majority of these development milestones are tied to the initiation of phase III trials with petrelintide monotherapy. As I stated on our last quarterly earnings call, I'm pleased with our strong financial position. We can fully honor our obligation under the comprehensive Roche collaboration for petrelintide and at the same time accelerate investment in the early-stage pipeline to build the next wave of innovation. Let's turn to slide 19 on the financial guidance. I will keep this short as there are no changes to the outlook for the year. We confirmed the financial guidance on net operating expenses, which are expected to be between DKK 2 billion and DKK 2.5 billion, excluding transaction-related costs associated with the Roche agreement. With that, I will move to slide 20 and turn the call back to Adam for concluding remarks. Thank you, Henriette. Two years ago, at our Obesity R&D event in London, we laid out a bold vision to become a key player in the management of obesity through innovations that address one of the greatest healthcare challenges of our time. Today, I can say with confidence that we are exactly where we want to be, towards realizing that vision. We have the survodutide phase III obesity data and petrelintide phase II data in our sights, and we have significantly strengthened our capabilities to execute and our financial position to both advance our clinical portfolio and invest in the next wave of innovation. Please save the date for our Capital Markets Day on December 11th, where we will share further insights and updates and discuss why we are so excited about the prospects for Zealand Pharma. I will now turn over the call to the operator, and we'll be happy to address questions. Thank you. As a reminder 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, and the question comes from the line of Rajan Sharma from Goldman Sachs. Please go ahead, your line is open. Hi, thanks for taking my questions. I've got a couple on petrelintide. Firstly, Adam, David, it would be good to get your perspectives on the alorilintide data that we saw at ADA in June. I'd just be interested in your thoughts on how petrelintide compares and any learnings on what this means for the ongoing debate between amylin selectivity versus DACRA. Secondly, just on body composition, which I know is a secondary endpoint in ZUPREME-1, at ADA again, we saw that data from Novo 's REDEFINED trial suggests that there was no benefit on body composition from the amylin component of CagriSema relative to the GLP-1. Just wondering if there's any reason why petrelintide may be different or should we expect any benefit here to be sort of an upside to your base case assumption. Thank you. Thank you, Rajan. Maybe, David, you would take a first go on answering these questions. Can you hear us, David? Happy to. I'm on mute and hopefully clear on the microphone. Rajan, thanks for your question. I'm happy to provide perspective. I think the Alora data, which are obviously early phase data in a relatively small population, as we alluded to in the prepared remarks, show us that one of the other key players in the space, Eli Lilly, has a great interest in amylin-based therapies. I think there was some excitement over both the dosing regimen and the clinical response. I would say from our perspective, two very important key points. One, you alluded to data that colleagues from Novo Nordisk reported in a separate session, separate from the Alora poster presentation, suggested that Alora, like other balanced amylin agonists, does result in an acute lowering of serum calcium in animal models, which suggests that Alora, despite what is reported and what has been in some hands, an amylin-specific receptor profile, is very likely a more balanced or pan-receptor activator across the calcitonin, amylin-1, and amylin-3 receptors. That said, the clinical response in our mind, particularly at the two, I'll call them, middle to high doses, is quite consistent with other drugs in this class, despite the exuberant response in their highest dose group and the dosing interval. I think, given the small data set, there are also a lot of unknowns about this asset, in particular, the reports of several neuropsychiatric adverse events, which is distinctly different than what has been reported both with cagrilintide and with petrelintide, as well as headache, which has been reported with other amylin agonists and indeed with pramlintide back in the day. Provocative tests to initiate or trigger headache were enhanced with another amylin agonist, amylin receptor agonist. I'd say, you know, certainly encouraged that there is attention to this space. We do not see these data as clearly differentiating from other amylin-based therapies, including petrelintide. As I alluded to, we are quite pleased with the consistent and now comprehensive data sets we have pulled together from all the phase I trials, and obviously, phase II will tell us much more about that treatment response. To your question about body composition, Adam, I'm happy to turn it back to you or make comments myself. Please comment, David. Yeah. I think the Novo data, in a relatively small subset, using a less precise but a broader and more applicable approach, which is DEXA, did not provide clear evidence of changes or preservation of muscle mass. However, as you well know, Rajan, there is now broad evidence from non-clinical models, and I emphasize non-clinical models, that amylin analogs are associated with significant preservation of lean mass, particularly in these high-fat fed animals who are gaining weight. That is very different than older adults or those in clinical trials who are usually at a high weight but stable, who then enroll in clinical trials. We still remain quite confident that amylin analog-based therapies, including petrelintide, particularly using the MR-based measurements we are using in the subset of patients in ZUPREME-1, can and will be both the approach and the studies that will demonstrate as clearly as possible what happens to lean mass. Importantly, while lean mass preservation to us is important, there's really a value add on top of what Adam and I alluded to, and that's significant weight loss, particularly in the range of 10% - 20% that the vast majority of patients desire, and the tolerability profile, effects on other biomarkers, effects on lean mass, we think are significant value adds but not key to the success of these molecules. Thank you. Thank you. Thank you. We will take our next question. Your next question comes from the line of Kirsty Ross-Stewart from BNP Paribas. Please go ahead, your line is open. Hi there, yeah, this is Kirsty Ross-Stewart from BNP Paribas. Two questions from me. Firstly, on the kind of safety and tolerability profile of sublingual petrelintide, you've kind of spoken about the target weight loss between 15% and 20% annually before, but I was wondering if you could give some more color on what you believe would be clinically meaningful in terms of side effect profile. I noticed your slide indicating that kind of over half of patients are not willing to accept any GIAE. In light of that, what do you believe would represent a sufficient improvement over GLP-1s to induce a kind of meaningful uptake in intolerant patients? Maybe one also on dapiglutide and any read across that you see from the upcoming evoke data from Novo. Maybe you could talk to the potential to dapiglutide to address diseases such as Alzheimer's, where microglial inflammation plays a role, and what you'd like to see maybe in your own exploratory data or Novo 's upcoming data to give you the confidence to go here beyond the program that you're starting later this year. That would be great, thank you. Thank you, Kirs. Maybe I'll start and then see if David has additional insights to add. The ratio between efficacy and safety and tolerability, I think it is, as we also alluded to in the prepared remarks, a super important question. If you look out today, most patients actually have the tools available that can provide them with the weight loss they're looking for. The problem is most patients don't ever get to the highest doses, and we think a large part of those are because of side effects. If you do market research, you will learn that if you ask individual patients, overall, most of these patients would come back and tell you that they're looking for a 10%- 20% weight loss. It's also clear that the biggest challenge is to not actually achieve the weight loss today, but actually maintain that. If you don't stay on therapy, then most patients will regain the weight. When we talk about a tolerable profile, and how we are designing our program with petrelintide, it is actually with that in mind to make sure we target not only the maximum weight loss, but the optimal ratio between weight loss and side effects. What we've seen from our program thus far, as David also alluded to, is a very robust set of data suggesting that ultimately with the dosing that we are pursuing, we would expect to get into a mean weight loss of between 15% and 20%. If you look into the GI, in particular side effects, but also other side effects, we have seen minimum to no GI side effects in these cohorts when dosed at the levels and with the titration regimes we use. It is actually important to note also, as we saw from the cagrilintide phase III data, that it's of course not just about nausea or vomiting or other GI defects. It's also the severity of these. Are they mild, moderate, or severe? We at least saw with interest that even with cagrilintide at the doses where they deliver just around 12% weight loss, it was almost an entirely mild event, which was in contrast to what you see with GLP-1-based therapies. It's not only the event rate, but also the severity of these side effects that we think we can reduce significantly with our approach to amylin. On dapiglutide, I think the evoke study will be super important. Remember, it's rather low doses of a GLP-1 that is applied into that study, but we have also recognized that the profile of a GLP-1 and a GLP-2 could be interesting in a disease like Alzheimer's. It could also be interesting in a more GI-driven inflammatory condition such as IBD. David, do you want to add further insights? Yeah, just one thing to add then, Kirsty, thanks to Adam's comment about, you know, we clearly believe with amylin analogs, less common, less severe, but I would also add that different character of those GI side effects. While that's difficult to tease out in clinical trials in the clinic, and in particular experience back with pramlintide, this sense of fullness, satiety, that sense of feeling full more quickly, feeling full faster, is very different than the food aversion signal and the nausea. We think similarly we'll have a different character. To Adam's point, in our phase I program to date, only a single patient who discontinued treatment with petrelintide out of all those exposed. In particular, when we started at lower doses in the multiple ascending dose and titrated up in a scheme, even though it was every other week, that tolerability profile demonstrated, I'll say, substantially fewer events and less severe. What we believe will be different characters or characteristics of that adverse event profile. The other comment I would make is what I emphasize, which is a distinct difference between tolerability, particularly in a clinical trial which is designed to keep people on therapy. Yes, if the only therapy available to me is an incretin-based therapy, I may tolerate it, but when options become available, is it the most acceptable therapy? We will obviously strive to look more carefully at not just tolerability, the reported effects, but how acceptable is this to those who take an amylin-based therapy versus any experience with an incretin-based therapy? Thank you. Thank you. We will take our next question. The next question comes from the line of Michael Novod from Nordea. Please go ahead, your line is open. Thank you very much. Michael from Nordia, a couple of questions. First, maybe can you discuss sort of around the commitment priorities, et cetera, with Roche? Obviously, we've seen a lot of movement in the obesity market and also a lot of movement to obesity market sizing forecasts over time. Has there been sort of any big discussions in the collaboration? Has that also changed sort of what the bar is in terms of what an amylin can do in terms of monotherapy weight loss when we look into the phase II readout in the first half of 2026 for petrelintide? Secondly, maybe you can just try to discuss the sort of potential licensing or partnering strategy around dapiglutide. Will the phase II that you're doing with regards to comorbidities, will that lead to sort of conclusive results in order to start potential partnering discussions? How should we sort of evaluate the road ahead for dapiglutide following the phase II-B? Thank you, Michael, I will take a shot on these answers or these questions. If you think about the developments in the obesity market right now, we have been saying for quite some time that we think people are too focused on who gets the highest weight loss and who can deliver it the fastest, because market research with patients would actually suggest the opposite. Most patients are looking for a 10%- 20% weight loss, and actually some patients struggle. If it's too fast, they want a visible weight loss. They want to see that something happens, but it can also be too fast. I think that is the market condition we're looking at. That is what I would describe as GLP-1 launch fatigue and actually not obesity fatigue. For companies who have set out on a mission to address what we consider the biggest healthcare challenge of our time, for us, and I would include us in that kind of statement, that is an opportunity we are looking into at the moment. That is basically identifying the shortcomings of the current medicines out there and suggesting where we can actually play. We can be out there with a medicine that delivers the weight loss that are quite similar to what the products are doing today, but hopefully with a more tolerable profile and thus allow more patients to stay on therapy. A key part for why we chose to partner with us was that they already, a few years ago, took a big step into this space, and they have had a very strong commitment to wanting to get into this space and lead. We wanted somebody who has the same ambition as us, somebody who doesn't just want to get in because it was the talk of the town, but a company who really means it. This is what we try to allude to during the prepared remarks, that we are extremely impressed to see the firmness with which they move forward. We were, of course, extremely pleased to see also the investments into manufacturing capacity. I think sometimes it's overlooked that it's not just about a clinical data set and then a decision to move forward, because once you decide to move forward, if you want to be launch-ready, you need to make very substantial investments into manufacturing. Otherwise, you will face the issues that the two front-runners faced with supply constraints and what follows there. Our sense in our dialogue with Roche is that they are as committed, if not even more, as they have been for a long time to come into this market and become a leading company to address what both companies see as the biggest healthcare challenge of our time. If anything, I would say the bar for success is being lowered in my mind these days because more and more people realize that it's very few patients that are going for that 25%+ weight loss. Realistically, those patients who need the highest weight loss are more likely to benefit from combination therapies rather than single modalities. That is how you treat chronic diseases, by combining different modalities if you need more effect than what one modality can do. You very seldom see people maxing out on one modality because often you will see side effects and safety concerns following pushing things too much. It's much better to combine. I think we are just being confirmed in these months and years on the strategy, and I think Roche feels the same. On the dapiglutide phase II program, I think it's a very fair observation that our focus right now is to get the phase II study started to clearly identify the differentiation potential for dapiglutide in addressing inflammation to a larger extent than the other GLP-1s. Our hope, of course, will be that following those data, we will go out and discuss with potential partners on that program. We also recognize that we need those data in hand before we will have sufficient clinical excitement to progress partnership discussions on that. Okay, great. Thank you. Thank you. Thank you. We will go to our next question. Your next question comes from the line of Andy Hsieh from William Blair. Please go ahead, your line is open. Great, thanks for taking our question. Appreciate the additional color about the ZUPREME-1 baseline characteristics, potentially hinting at a better outcome than what we've seen before. Two questions for us. One has to do with Roche's manufacturing infrastructure that you announced in the press release and the synergy that can be derived from that project. I'm curious if both petrelintide and CT-388 are produced with the same means, i.e., synthetic or recombinant. I'm just curious if you can comment on that. The second one has to do with the titration strategy when it comes to the phase II combo study that is expected to start later this year with petrelintide and CT-388. Are you thinking about something that could be a little bit different from what we've seen in REDEFINED 1 and REDEFINED 2, you know, with the in-sync titration or maybe staggered titration, basically titrating one followed by the other the following week? Just curious about how you think about this titration strategy that could optimize tolerability profile. Thank you, Andy. I will answer your first question and then hand over to David. When we announced the manufacturing capacity expansions that have been announced in North Carolina by us, it's a high capacity, high volume filled finish capacity. That is drug product and filling lines. It's actually the critical path of getting products to patients to have the filling capacity up running for pre-filled pens. It is where we have seen supply constraints historically, and it's probably where we need the biggest investments. When it comes to API, a synthesis of the program, it's actually easier to handle, and it can be handled with suppliers and infrastructure that are more or less, I mean, we will need investments there as well, but it's actually the filled finish and drug product filling lines that are causing shortages. It's also where you can probably gain the biggest benefits by making sure you have high volume lines because it is the most costly part of your full product. On the synthesis part, we have, you can say, all things in place to support the amount of drug substance needed for launch. Those plans were actually already being built by us before we entered the partnership. So, David? Thank you, Adam and Andy. Thanks for the question. I think you already alluded to what for us is an opportunity to do things significantly differently than was executed in the redefined program where, as you know, both assets, the Cagri and Sema, doses were essentially tied together, meaning you escalated one, you escalated the other. Similarly, the goal in that program, while the studies were complex, was to push to higher doses and also to push to greater weight loss. Tough to answer in a single study. With the fixed dose combination with petrelintide and CT-388, obviously, phase II data will provide us the necessary information to understand which doses can optimize the clinical response, but balancing what Adam and I have both referred to, which is the tolerability and acceptability profile of each asset. We are discussing multiple options, but instead of maximizing each, I would say our goal in phase II will be to optimize each. I mean, we would anticipate that that is higher dose amylin-based therapy, petrelintide, at the maximally effective doses. If it, in fact, remains as well tolerated as we've seen in the early phase trials, then adding what I'll call an optimized, but not necessarily maximal dose of the incretin-based therapy to provide additional weight loss, glycemic control for those with diabetes, potentially cardiovascular risk reduction. In discussions with our Roche partners, whether this will be, I'll call it a high petrelintide, low CT-388, high mid, or high high, I think we collectively in the alliance with Roche agree that if you go to high doses of both, you will achieve the greatest weight loss. Balancing that with an acceptability and tolerability profile where we think we can fully leverage the better tolerability of the amylin-based therapy while still adding adequate or optimized doses of CT-388. That is our current strategy pending all of us having line of sight to the phase II dosing data. Finally, creating as simplified a dose escalation scheme as possible so you don't have multiple doses or changes. Obviously, this is intended as a fixed dose co-formulated asset. Phase II will teach us a great deal. Great question and more to follow, Andy. Great, thank you so much. Thank you. We will take our next question. Your next question comes from the line of Prakhar Agrawal from Cantor. Please go ahead, your line is open. Hi, thank you so much for the invitation and congrats on the quarter. Maybe first, there's a massive disconnect between the stock price and the value of petrelintide ascribed by Roche during the deal. I'm sure you'll agree with that. You have so much cash in hand, and you'll have milestones from Roche next year with high probability of achievement. Why not consider something like a share buyback given the disconnect? If not share buyback, could you consider (BD) in the metabolic disease space as there are many opportunities out there, for example, in China? One clinical question. Coming out of ADA, the other question on the CagriSema data was the impact on CV and inflammation markers, which were more modest compared to GLP-1s, even for CagriSema and petrelintide. What are your thoughts on the CV inflammation data and implications for petrelintide when ZUPREME-1 reached out? Thank you. Thank you, Prakhar. I will take the first question and hand over to David for the second. Remember that the announcement we announced, the partnership with Roche in March and we closed in May, is a historic and transformative partnership in that it's a true co-development and co-commercialization partnership. It's not a licensing agreement. We will have, in order to realize the full potential of the 50% value and future profits of not only petrelintide, but also the combination product of petrelintide and CT-388, we both have to carry our share or cover our share of the development costs. It is incredibly important for us to be well-funded as a company to deliver on that opportunity to have 50% of future profit from this partnership. Of course, we don't have to invest into manufacturing, which Roche will carry all the manufacturing investments, but we will have to carry our share of the development cost and the pre-launch cost. For me, it is actually more important to make sure that we stay as well capitalized as possible so we can deliver on our commitments into this partnership. The last thing I want to do is to put Zealand in a position where we cannot honor our financial obligations into the partnership. While we are extremely well capitalized, we also believe it is super important for us to be in a position where we can continue to honor our obligations from a financial perspective. Also recognizing that we are a company, we are an innovation company, we are a biotech company who have delivered again and again great innovations. We do expect to continue to invest in the rest of the pipeline to deliver on our ambition to become a leading player in the obesity space and the associated diseases. We think we have a significant opportunity to leverage our 25 years of expertise and experience in peptide drug discovery and development and tap into these unique opportunities that are now coming true in obesity and all these related diseases. You should not expect a share buyback program from Zealand. On the next question, David, I will hand over to you. Yeah, thank you, Adam. Prakhar, a very important question, and we saw what you and others did in the Cagri data. I will simply state that while amylin analog therapies clearly are not GLP-1-based therapies, GLP-1s have demonstrated cardiovascular risk reduction in both diabetes and obesity, likely have pleiotropic effects due to receptors on multiple tissues. Both the magnitude and direction of CV risk markers for us in our early phase program with limited data in the broader CAGRI program, including their phase II readouts, still demonstrate directionally what we consider very positive evidence that blood pressure, potentially markers of inflammation, and body weight, all three very important determinants of CV risk. There is also non-clinical evidence of direct effects of amylin agonism on cardiac tissues, not through receptors, but likely through other mechanisms, either through vagal afference or through body weight reduction. In our mind, and as Adam alluded to, we are not looking to go toe-to-toe with GLP-1s. We are looking to develop a unique class with unique benefits. You and I discussed at a recent fireside chat that one sure way not to get cardioprotection from GLP-1-based therapy will be that you cannot take it or will not take it due to tolerability issues. We strive to leverage our data with petrelintide and the program looking at cardiovascular outcomes to determine if amylin-based agonists with these improvements in risk markers can and will, as we would hypothesize, reduce cardiovascular risk. Yes, lesser magnitude, but to us, both directionally and more broadly across clinical programs, evidence that cardiovascular risk markers all trend in the direction that will support cardioprotection from amylin analog therapies, including petrelintide. Thank you. Thank you. We will take our next question. Your next question comes from the line of Cerena Chen from Wells Fargo. Please go ahead, your line is open. Hi, thanks for taking my question. I wanted to ask what you think is the real addressable market opportunity for patients who cannot tolerate GLP-1, since we've heard anecdotally from doctors that discontinuation due to tolerability is fairly low and much less than that 60% discontinuation within one year that's commonly cited. I'm curious perhaps what your market research indicates is the real discontinuation rate from the more current GLP-1s, like semaglutide and tirzepatide. Thank you. Thank you for the question. I think, number one, we have clearly witnessed that once these molecules are utilized in a clinical setting with perhaps sometimes less experienced prescribers, discontinuation rates remain very high. I think David alluded to another extremely important question, and that is around acceptability. Remember, right now we are in a world where there's no alternatives. At least one opportunity or one situation we could be in is that people are actually ready to accept more side effects than if there was an alternative. Imagine a world where there would be an alternative which would provide the same degree of weight loss, but where you have less GI side effects, where you do not lose your appetite and your interest in food, but more feel full faster, and thus can enjoy social events around food. I think history has shown us that people, once they have choices, will actually go for those choices. If there are choices, people are ready to accept less than if there is only one solution. We are quite firm, not only considering the discontinuation rates we have seen today, but also anticipating that if there is a more tolerable approach, acceptability would actually drop even further for the current therapies in our ambition to position petrelintide as a future foundational therapy for those patients who want to potentially have a more pleasant weight loss experience if we can continue to deliver on the data that we have seen thus far with this molecule. Thank you. Thank you. We will take our next question. Your next question comes from the line of Yihan Li from Barclays. Please go ahead, your line is open. Hi, Yihan from Barclays. Thank you for taking all the questions. I have two. The first one is on petrelintide. Thanks for sharing the baseline data. Actually, based on our very quick calculation, according to what the petrelintide showed in phase I-B, it seems like based on the data shared today, petrelintide could potentially reach around 10% weight loss at week 16 in the ZOOM pre-amp trial after adjusting for male-female ratio, baseline BMI, and slowing the titration schedule. I think it's indicating very promising potential to reach weight goals we like around 13%- 15% weight loss at 42 weeks. Just curious, is this something you are looking for? Also, could you please remind us what kind of parameters you will share in the top line in the first half of next year? We should expect an investor call for the PR, right? The second one is kind of a follow-up. It's about the efficacy durability for the amylin class. We saw at ADA, the REDEFINE 1 trial from Novo, the cagrilintide had a relatively slow weight loss from around 44 weeks versus semaglutide or CagriSema actually showed a very clear continued weight loss post 44 weeks. There are some concerns or more of a question mark for me, like how the amylin class may produce strong early weight loss, but the efficacy may potentially wane faster than the GLP-1s over time. Just curious, how should we think about this weight loss durability of the amylin class? Thank you very much. Thank you for your question, and maybe I'll just answer quickly. We were actually quite impressed to see petrelintide at the dose of 2.4 mg delivering close to 12% weight loss in a 68-week study because we considered 2.4 mg of petrelintide to be a very low dose of amylin compared to the 9 mg we are testing now with much higher of our amylin analog with much higher bioavailability. At least as one comparison, I think if you consider utilizing a very low dose of a GLP-1, you would also at one point see that there would not continue to be weight loss. We are excited about the potential for us to test even higher doses as, of course, as you also alluded to, we would expect higher doses to provide more weight loss and thus also the ability to achieve longer-term continuous weight loss. We, of course, as David also alluded to in his prepared remarks, are very aware of the fact that in general, women or females lose more weight in these studies than males. We had only around 20% in our phase I studies. Now it would be just around 50% females in the upcoming phase II. Most often, people report from their phase III trials around 60%- 65%, up to 70% females. There is, of course, an opportunity here that just the trial design and the inclusion of the patients into these studies can help on the numbers. What we are firmly focused on is to achieve a weight loss that hits that bar of around 15%- 20% weight loss in the most pleasant way for a patient. We somehow refuse to be into a very tight numbers game as long as we are confident that based on our 28- 42 weeks data that we can achieve that 15%- 20% weight loss in a phase III study. With a very pleasant experience and less side effects, we will be extremely bullish for the opportunity for petrelintide. Thank you. Thank you so much. Thank you. We will take our next question. If I could also ask participants to limit yourselves to one question only for the interest of time. Your next question comes from the line of Sophia Graeff Buhl- Nielsen from JP Morgan. Please go ahead, your line is open. Good afternoon, thanks for taking my question. Could you provide any updated thoughts on how you see the opportunity in MASH, not only in light of the upcoming survey data, but also with the potential label expansion for Wegovy in the U.S. in the second half? Thank you for that question. I think it's highly relevant. As we have also tried to indicate in our call today, I think perhaps people do not ascribe significant and enough value, and also you can say opportunity around the survodutide franchise. I think we still need to realize, most people still need to realize that up to 35% of obese individuals have some degree of NASH. It is one of the most underserved consequences of living with NASH, and we only have one new FDA-approved treatment for these, which provided around 11% ease in fibrosis without worsening of MASH. If you look into the data that Boehringer Ingelheim have presented last year in MASH with survodutide, as they themselves described as groundbreaking, we will agree to that. It was approaching 40% reduction in fibrosis without worsening of MASH. I would say we are looking at something that can truly change the needle for those patients who live with that condition or are at risk for that. If you look into the phase III program that Boehringer Ingelheim are investing in in MASH, which is in at least to our knowledge, by far the largest program, not only targeting F2 and F3, but also cirrhotic patients, including very strong commitments to follow these patients on to clinical outcomes. That's a testament to also Boehringer Ingelheim's belief in their ability to differentiate survodutide into this and provide a treatment option for these patients that can make a meaningful clinical impact. 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. Sorry, thanks for the question. I'll keep it short. Adam, I mean specifically for you here, I guess we've seen recently the market in the GLP-1 sense develop to expand in a cash pay setting and a DTC setting. I think previously we've, you know, you've had questions about whether you think that the obesity market ever could get to a state where it could be OTC, and this is probably one of the closest steps you can get towards it. I'm wondering what you're thinking here in terms of amylin and how you could, whether you believe that is something you can position in a cash pay setting in the future or is very much your focus being on a long-term, long adherence population and market. Any thoughts or any changes in the way you envision the market developing, that would be great. Thank you. Thank you. That q uestion, and I think, as you alluded to, it is, of course, something that we have been following closely, and we have also been clear in our statements around this. In order to ultimately address the obesity pandemic and all the diseases that follow, we need novel ways to get these products to patients, and direct to consumer once you have enough safety and experience around them, is one way to go for sure. The cash market, I think we are already now seeing how important it is. Maybe people have been surprised how fast it has moved. I don't think anyone could honestly question if it would come because we know how interested patients are in getting on these treatments, and the willingness to pay for these treatments has also been clear for a long time. It's just a matter of how fast it comes, and it really opens unique opportunities for companies like us and Roche as we enter the market. Of course, it's something we have to discuss and plan for. If you look at a profile like the one we have for petrelintide, I would say that, of course, lends itself extremely well into that segment if it turns out that it is an easier prescription, it is an easier product to be on, and it will deliver the weight loss that patients are looking for. I don't see a disconnect between consumer payments and then long-term staying on treatment. I actually think a lot of patients would be willing to also pay for staying on treatment as long as their weight loss and weight maintenance experience is one which they will accept. Thank you for the question. Thank you. Thank you. We will take our next question. The question comes from the line of Julian Harrison from BTIG. Please go ahead. Your line is open. Hi. This is (Rian) for Julian. Thank you for taking our questions. You mentioned the value-add effects and the importance of weight loss quality. Is there a number you would like to see on body composition in ZUPREME-1, or is less lean mass loss relative to existing therapies enough to translate into preference in practice? Thank you for your question. We cannot provide a specific number. I would say, as David also alluded to, any weight loss program will be associated with some degree of muscle loss because you carry less weight. What we would be looking for in our program is, of course, that we don't have exaggerated muscle wasting, as we may have seen with some of the GLP-1s when you lose weight too fast and too dramatic, getting into a very negative energy balance and reducing, increasing your insulin levels, etc. It is probably too early to provide a number, but healthy weight loss for us is one which at least does not exaggerate the muscle wasting during the weight loss. Thank you. Great. Thank you. Thank you. We will take our next question. The question comes from the line of Jacob Mekhael from KBC Securities. Please go ahead. Your line is open. Hi there, and thanks for taking my question. I have a question on the case study trial for dapiglutide in an obesity-linked, you know, condition in the second half of this year. Can you share what that condition would be? Given that there are multiple obesity-linked diseases that you can pick from, could you walk us through the criteria that you use to select that indication? Thanks for your question. It's probably one quarter too early to share the specific indication, but we'll come back in not that distinct future. Clearly, for us, it's about differentiation. We don't want to be among those companies who develop undifferentiated weight loss agents that do not make a true difference for patients. Okay, thank you. Thank you. In the interest of time, we have one final question. The final question comes from the line of Carsten Lønborg Madsen from Danske Bank. Please go ahead. Your line is open. Thank you very much for taking my question here. I just had a question to slide 10 where I shared this gender data was quite impressive weight loss for the females in the trial. At the same time, isn't it also a little bit concerning to you that you see maybe no additional response or maybe even less response in the male part of the trial when doubling the dose from 4.8 mg- 9 mg? I was interested to hear your view on this. I mean, David, I don't know if you have further comments to this one, but number one, remember, it's a small data set. It could be, again, we don't know what doses are the right ones. That is what we explore in phase II. Even if you look at the mid-dose or the 4.5 mg dose, if you look at those numbers, you can say that could, of course, deliver the weight loss we are looking for also in a long-term study. That's why we are entering such a rich dose finding in phase II. When we looked into the early responses in the phase I study, there was a tendency for differences in how fast these people lost weight. We still would say believe that the higher doses could provide more regardless of the end number in this study suggested that the two higher doses were equally effective. David, any further comments? Yeah. I think two points, Adam. One, actually in this cohort, the 4.8 mg, we saw this group lose weight at similar doses more quickly. That may have actually overemphasized, as Adam said, in this small cohort, it's difficult to differentiate. You actually see in the two higher dose cohorts, particularly the 9 mg, there's significant individual variation in a small data set that can provide you a number of questions but doesn't provide the clarity. I think the 480+ participants in the full phase II-B will be a better way to address that. The other is to be aware that across weight loss approaches, and that's diet and exercise as well as medical therapies, women on average lose 3%- 5% more body weight over a year or more of exposure. I think those are the things we weigh our gender balance on. I think phase II will be a much more robust data set for us to address your question and the dose finding for us. Mm-hmm. Excellent. A small quick follow-up to that one, which is also part of my first question but completely unrelated. In terms of phase III trials, we have learned so much about the obesity space over the last 52 weeks that it's developing rapidly all the time. Should we expect that you're planning for a sort of a classic phase III setup with overweight, overweight diabetics, etc.? Are there room for some new phase III trials? I'm thinking maybe sort of a GLP-1 naive or GLP-1 failure, so where you could sort of differentiate petrelintide even more versus what's on the mic today. Thank you for your question, Carsten. These are super important considerations, which we are discussing with (Ross) right now. We will have to wait a little bit to provide updates. I would kind of also say that since we are developing an alternative, it's probably super important just to get out there. You don't need to, as long as you provide the first alternative with a more pleasant side effect profile. Most patients do not stay on therapy on the GLP-1s today. I don't need to go out and convince the patients to stop taking something and then get on your new treatment. Most patients who have been exposed to a GLP-1 will, at the time we launch it, not be on a GLP-1. This focus on shifting and so on from being on a GLP-1 to getting to another modality, I think it's less of an issue here because we know from market data that most patients do not stay on GLP-1 for a long time. Great. Thanks. Thank you. Thank you all for attending and for your questions today. We look very much 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.