Zealand Pharma A/S

Good day and thank you for standing by. Welcome to the Zealand Pharma Interim Report Q3 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 1, 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1, 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Adam Lange, Investor Relations of Zeeland Pharma. Please go ahead.

Thank you, Operator, and thank you to everyone for joining us today to discuss Zeeland Pharma's results for the first nine months of 2025. You can find the related company announcement on our website at silanpharma.com. As described on slide two, we 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 Silan Pharma's management team. Adam Steensberg, President and Chief Executive Officer, Henriette Vennecke, 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. 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 Petunia-type Phase II Supreme I 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 cervical type in obesity, starting with top-line results from this 76-week synchronize one 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 market base next month. Moving to slide five. Two years ago, we laid out our vision to become a key player in the management of obesity through innovation that addressed one of the greatest healthcare challenges of our time, Central to this vision was developing an alternative to GD1-based 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 Celan and Ross have the potential to lead in the next class of drugs for weight management. We are very confident in the profile of Petrientide 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 Petrientide and Phase III obesity data with Cervidotide alongside an impressive Phase III MASH program that is well underway. I look forward to this next Catalyst with chapter and to sharing more from these programs at our upcoming capital market day where we will also discuss our intensified early stage efforts to build a generational biotech company. Let's turn to slide six. Six 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, Sealand Pharma had the pleasure of welcoming Theresa 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, convey to you their strong commitment to become a top three player in obesity. This is the reason why, through a highly competitive partnership process, we identified Roche as the ideal partner for C-Land Pharma and PetrinaSide. Turning to slide seven. Cervidotide 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 GF1-based therapy co-invented with Ceylon Pharma. We were also highly encouraged by their strong presence at Obesity Week in Atlanta last week. This leads me to slide eight. The scale and complexity of obesity make it a distinct and complex disease area in which we identified 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 Cervalutide has the potential to be uniquely positioned within this segment. The larger segment, however, is patient-driven. A significant focus here is personal weight loss goals and how individuals achieve them. The potential to deliver the weight loss that the vast majority of people with overweight and obesity desire, combined with an acceptable tolerability profile and and excellent patient experience, we believe that Trinitide 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 nine as I turn over the call to our Chief Medical Officer, David Kendall, to discuss our R&D pipeline.

Thank you, Adam. Today, I will focus my remarks on the continued advancement of our two leading programs, petrolentide and cervodetide. Before doing so, I would like to begin by providing a brief update on our two late-stage rare disease programs and dapiglutide, our GLP-1, GLP-2 receptor dual agonist program. For daziglucagon and congenital hyperinsulinism, our third-party manufacturer's 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 glopaglutide, 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 glupaglutide as a potential best-in-class, long-acting treatment for patients living with short-vowel 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 Petrelentide, the fixed-dose combination of Petrelentide and Roche's GLP-1 GIP dual agonist CT388, and Cervidotide, 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 petrolatide. Our strong confidence in petrolatide 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 Petrelentide, 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 Petrelentide to deliver 15% to 20% weight loss in Phase III clinical trials, and also remain highly confident in Petrelentide'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 and advancing the Petrelentide clinical program at full speed. In late September, we reached a key milestone in the large Phase II Zupreme I trial, which evaluates the efficacy and safety of Petrelentide 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 2 Zupreme 2 trial, which evaluates the efficacy and safety of petrolentide 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 3 program with petrolentide 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 petrolentide as a backbone for future combination therapies, unlocking its full value potential. Petrelentide CT388 is the first combination product under our alliance with Roche. This program will target individuals who seek even greater weight loss and or improve glycemic control while optimizing the dose of each component. We anticipate that use of higher doses of Petrelentide and optimized doses of the incretin-based therapy CT388, a potential best-in-class GLP-1-GIP receptor dual agonist, can provide both robust efficacy while maintaining excellent tolerability. Zeland and Roche remain on track to initiate the Phase II trial with Petrelentide CT388 combination in the first half of 2026. Now turning to slide 12 and Cervodotide, 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 synchronized program with cervodotide in obesity consists of six clinical trials, all of which are expected to complete in 2026. In the Phase II obesity trial, cervodotide 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 cervodotide 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. Carl LaRue presented the baseline characteristics of participants in this trial, which are also shown on this slide. We are very pleased that Dr. LaRue has agreed to join us at our upcoming Capital Markets Day next month, where he will share more insights on the potential of cervodotide 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 cervodotide in people with metabolic dysfunction associated steatohepatitis, or MASH. a serious obesity-related comorbidity with significant unmet medical needs. Shown in this slide is an indirect cross-trial assessment of the registrational clinical trials for the two approved therapies in the U.S. for MASH today, the thyroid hormone receptor beta agonist, resmeteram, and the GLP-1 receptor agonist, semaglutide. In the Phase II trial with cervodotide 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 two data and a comprehensive, ambitious phase three program now underway, the so-called liverage program, which includes two large trials, one in people with moderate to advanced fibrosis, F2 and F3, and one in people with cirrhosis, F4. We believe cervodotide 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, Henrietta Benecke, who will review our financial results for the first nine months of 2025. Henrietta?

Thanks, David, and hello, everyone. Let's turn to slide 15 and the income statement. Very new for the first nine months of 2025 was 9.1 billion DKK, produced primarily by the initial upfront payments received under our collaboration and licensing agreement with Roche. Of the 9.2 billion DKK in upfront payments received in the second quarter, 124 million DKK was deferred as of September 30, as it relates to the progression and completion of the phase 2 trials with paternity. Net operating expenses total 1.5 billion BKK for the first nine months of 2025. It's 73% of that amount dedicated to research and development. And the expenses are mainly driven by the ongoing development of petroleum time, including the last phase two trials and preparations for phase three. Net financial items amount to negative 62 million BKK for the period. primarily reflecting exchange rate adjustments related to the U.S. dollar deposit and currency evaluation. 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 16.2 billion DKK. a significant increase from the 9 billion BKK at the beginning of the year. This increase was, of course, driven by the initial upfront payment of the 9.2 billion BKK from Roche, partly offset by the operating expansion during that period, and the purchase of treasury shares to support Gital 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 $250 million in amortization payments over the next two years under the Roche collaboration, as well as potential development milestones of up to $1.2 billion. As I said 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 procurement time. while at the same time accelerating investment 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 2 and 2.3 billion BKK, excluding other operating items. The financial guidance has been narrowed from the 2 to 2.5 billion BKK, reflecting the decision to pause the development of daily glutides previously planned to advance into Phase 2B 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.

Thank you, Henriette. We are now at the cross of the most catalyst-rich period in seed and farmer's history. In just the first half of 2026, we expect to see Phase III enabling data for the green type, Phase III data for the root type, and Phase I data for what could become one pillar in the next wave of innovation from C-Land Pharma, our highly potent and specific KB1.3 iron channel blogger. Moving to slide 19, I can only encourage you to join us at our Capital Markets Day on December 11th, 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 C-Land 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 Rook, a pioneer in amylin leptin biology, as well as Karel Leroux and Louis Aron, 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.

Thank you. As a reminder, to ask a question, you would need to press star 1, 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1, 1 again. will take our first question and the question comes from the line of Kirsty Ross-Stewart from BNP Paribas please go ahead your line is open.

Hi there good afternoon thanks for taking my questions so two on Petrel and Tide please so with the Laurel and Tide trial now published I think interested to hear your thoughts on kind of the differences in the setup of the two trials in terms of baseline characteristics, titration, doses being explored, and how you would encourage us to look at your own data set 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 know, you're not targeting the highest possible weight loss with petrolentide, which seems quite in contrast to what Lilly have tried to do with their aloralintide trials. 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? Thanks very much.

Thanks for the question. And then maybe I can start and then hand over to David. We were extremely encouraged to see the Ivermectin-type data last week, which we really see building on what we already saw with Pagrillion-type last year. Remember, NOVO demonstrated that Pagrillion-type 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 amylin we have the potential to actually develop a new class of medicines that will provide patients with likely a 15 to 20 percent weight loss and does a true alternative to the guilty ones 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 ambiening class in the sense of filling food faster versus having lost their appetite. So we are extremely pleased, and you can say it actually increases our excitement around the upcoming phase two data with the training site and our efforts to prepare for the phase three trial contact, 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 trial design specifics there.

Yeah. Thanks, Kirstie. And trial design specifics, I'll reiterate what Adam said. I think 15 to 20 percent weight loss when we came forth with Petrel and Tide'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 demonstrates 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 petrolantide up to nine milligrams once weekly can certainly hit that sweet spot. You also mentioned, what does the market One simply needs to do some math. If somebody weighs 150 kilos, a 30-kilogram weight loss or 65 pounds of weight reduction is substantial. And I think five years ago, the world would have thought, you know, that's unachievable with what we've seen to date, including with loraglitide. So both in speaking with clinicians and in speaking with the vast majority of patients who seek weight management therapy, that 10 to 20% weight loss figure comes up repeatedly. They may not say 10 to 20%, but they will give you 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 patients seeking this. And finally, to your question about the baseline characteristics, just recall that with petrolentide Phase 1b, predominantly male participants, predominantly are 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 1b. We will have a much more balanced gender distribution in Phase 2, much higher baseline BMI as we reported in last quarter's call. And the likely contribution of a 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 1b 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.

Thank you. We will take our next question. Your next question comes from the line of Hakon Hembrough-Jorgensen from Danske Bank. Please go ahead. Your line is open.

Great, Håkan Hemme, Danske Bank. Also a question regarding Pritalentide study design. The illalentide 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 Pritalentide in phase three? And how do you see the trade-off between potentially achieving greater weight loss with a longer study compared to bringing pretzel inside to the market sooner.

Thanks for that question, Håkan. I'll let David answer.

Thank you, Håkan. I think two very important observations. The absence of plateau, which I think was readily evident both in our short Phase Ib studies with petrolentide, 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 sense of satiety or fullness where one feels full faster and stops prospective food intake as opposed to a food-aversive signal that hits 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 ALORA high-dose data, noting that the higher doses were perhaps less well tolerated than the three 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 two or three years. So I think it will be important to observe what we pull out of our 42-week phase one trial, and then the design for the longer phase three trials will directly answer your question, but would expect the potential for progressive weight loss out beyond one year of treatment.

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

Hi. Thank you for taking my questions. 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 dapaglutide 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, you know, a potential combination with petrolintide down the line and, you know, what studies would be needed to be done in order to enable that? Thank you.

Thank you for the question. I'll start with the first one on the polls on BAPI. You know, it's I think it's very evident, and it will be even more so at the capital market day, that we have what we believe is really a leading opportunity in the tier-one space with the cervical type, which we have aligned to Berner, which do not only have a huge potential for weight loss, but actually also addressing liver health, and in particular, mass, and potentially other organ damages by activating lipolysis. So it actually has a strong profile towards managing comorbidities to obesity. And now with the Rose partnership, we also, as you know, got shared economics on the combination product with CB388, that is, we want the IP, meaning that's going to be the combination opportunity we are going to focus on, and thus that became less relevant for combinations with amitin. 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 GLG-1 marketplace in five, six 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 the one market was not worth the effort, 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. We basically believe we can apply our capital better in those early programs. So I would say it's a very 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 the training type, we remain and we are even more confident in the potential to deliver these 15% to 20% weight loss, which we know will address by far the vast majority of the weight loss that patients are are desired. And as I said before, the data that came out last week underscores the potential that we also saw with the chagrin type last year. Remember, chagrin type was only 2.4 mg, which is a very low dose compared to where we take the chagrin type 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 readouts, 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 case two study that we will report Supreme 1, we have applied diet and exercise 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 genders to make the best possible decisions for your phase three 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 screw it too much in phase two.

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. ALORA, 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, 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 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 Luce made, which is all of this receptor biology work and knockout activity in animals really requires confirmation and clinical testing. And to our end, with a predominantly female population, higher BMI population treated with high doses. There was no substantial difference, I think, based on the authors' 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. Thanks, Lucy.

Thank you very much. Thank you. We will take our next question. The next question comes from the line of Andy Shee from William Blair. Please go ahead. Your line is open.

Thanks for taking our question. So it's about the patient experience that you comment frequently about. So in the context of co-formulation with CT388, I'm curious about your take on how important it is to harmonize the number of step ups between, let's say, paternitide and CT388 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 two 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 patronetized clinical trial experience.

Thank you. Thanks for the questions. Maybe I can just start and also you again, David. I think, as we have always 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 data sets. If you go two addresses with very potent biology, as we have today, especially in this data, 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 entities, you don't want to push this too much in this data. could that be driving some of the fatigue that we're seeing? Maybe if you have a, let's say, 4% weight loss over one week, that's probably not fat that could be 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, the signs of fatigue. But again, let's see. We, as you know, apply actually titration throughout our entire phase, all cohorts in our phase two study, something that has not always been done with other programs. 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 amylins actually deliver weight loss even at the initial doses. And it's, of course, clear that ultimately when we titrate together with the GLB-1, it will be the GLB-1 that determines how to titrate because those are the ones that really need titration from a TR to the BDC approach. David, next.

Yeah, I'll reemphasize that, Carly, Andy, and harmonizing those, I think, gives us the opportunity, as I said, to find what is the most applicable dose escalation scheme for petrolentide to get to, you know, 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 one 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 slow down to get to not a maximal dose, as is often done in phase two trials or phase three to see the maximal weight loss, but an optimized dose. You know, let's say dose three of the 388 compound and dose five of the is what the alignment looks like, we would base that on the Trelentide dose escalation scheme monthly is what we're testing in phase two and phase three. So the question is then how do you formulate a fixed dose combo to get to the optimized, 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.

Thank you so much.

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

Oh, thank you for taking my question. Mine is more bigger pitch with regard to the market and your expectations here. So clearly since the last update, we've had the Novo-Lily-Trump deal. We now have clarity on pricing in the U.S. They've used the market at least by the cash pay and the Medicare channel. So I would just be interested to hear how that works and the details that we have so far may be impacting yours and Bush's forecast for 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 bigger picture perspective. Thank you.

Thank you for that question. We will actually, at our Capital Market Day in December 11th, 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. 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 growth 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 works. 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 volumes of patients who get to these therapies. It's a huge problem that in today's market, many patients would use the Gilded One-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 IQ data. So we just 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 we will see the volumes go up and then you know The pricing part that people like to discuss so much is less of an issue as long as people stay in therapy. It's only an issue if you only stay in therapy for one to three 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 you 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 those, we would build our go-to-market models accordingly. Thank you.

Thank you. We will take our next question. And the question comes from the line of Prakhar Agwar from Cantor Fitzgerald. Please go ahead. Your line is open.

Hi, thank you for taking my questions and congrats on the quarter. So I had a few, maybe firstly going back to receptor biology. Lily says having Elora is a more selective amylin, especially on amylin-1 receptor and seems to be balanced on amylin-3 and calcitonin. Maybe if you could talk about whether polently targeting amylin-1 versus amylin-3 receptor has any clinical implications in obesity and beyond. And if you can remind us about better than diets activity on amylin-1 versus 3 receptors. And secondly, on the trial for phase 2b, zoprene-1, if you can talk about how the discrimination 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 estimate when the data is disclosed. Thank you.

I will start and hand over to you, David. We do expect to disclose the top line efficacy data from both estimates, I would expect, including the relevant safety observations. On the receptor profile, if you look into preclinical data, I remind you that both we and NOVA have had a firm effort for many, many years and came up 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 trees. We have one which is quite similar, we believe, to the one that kakurintide has. Ultimately, we need, as David also said, to see clinical data. When we look at the early clinical exposure for which we actually have among the different amine molecules, that is where we get a lot of confidence in our approach if you start to compare, let's say, the single ascendant 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 are probably some of the more honest data sets here where there's this 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 data set, which suggests that we have a profile of the drug that has found the right balance between efficacy and safety to the DDCs. So, and we will review more of this at our Capital and Markets Day, which will answer probably in more detail some of these questions. And David, I don't know if you have more to add to this.

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. As Adam said, Kegri and Petralentide are clearly balanced receptor agonists activate all three receptors in our hands with equal potency. The Gubra now Abdi asset is similar in our hands, slightly greater predilection for the amylin than the calcitonin receptor. And the Lilly molecule, aloralintide, 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 line up using the ELORA data as an example? There were, in the early phase trials, an increase in the number of headaches, whereas with petrolentide, we've seen less headache than with placebo. The newly reported adverse effect of bradycardia Bradyarrhythmia and syncope reported in the ALORA 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, the balanced agonism of both cagrelentide now through Phase III and our Phase Ib data and beyond for patrelentide give us great confidence that that is not only an acceptable receptor profile, it is an incredibly effective and well-tolerated profile.

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 Li from Barclays. Thank you so much for taking our question. So we have to So the first one is the petroline type phase three timing. So it seems like you have already completed the end of phase two meeting with the FDA. So just curious if you could walk us through, you know, what remains before initiating the phase three monotherapy trial, which is now planned in the second half of next year, especially given your competitor. Eli Lilly, actually, they moved up very fast. We thought that phase three will start by year end. Yeah, thank you. And the second question, actually, is on the alloying type lean mass data. So again, they showed 60% to 70% of the mass reduction from metals and also the other 30% from the lean mass. However, an interesting thing is that it doesn't seem to have a continued decline in the lean mass from the week 24 to week 48. So suggesting, you know, the lean mass loss could potentially stabilize after 24 weeks. I'm just, like, curious. Does this suggest maybe amylin-based therapy could inherently preserve lean mass better over time? Like, any thoughts will be appreciated because I'm just thinking could be used as a post-GRP1. So just curious what your thoughts there. Thank you very much.

Thank you for that question. And I can reassure you that we are moving as fast as possible forward to phase three initiation with the . Right now, our expectations would be the second half of next year. And as we have communicated today, we have the primary endpoint of the study. are of course also anticipating a meeting with FDA as fast as possible once these data have been analyzed and progressing as fast as possible. And top line data will be available first half next year. So it's a shared commitment from Rose and us to accelerate as much as possible to get these treatments to patients automatically and help achieve the health goals. So this is progressing with a high sense of urgency. But the phase three start is set for second half next year. I think we need to actually wait for our Phase II data with the training type 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 data scans that have been utilized by other companies. We, as everyone knows, 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'll get some at least high quality data from our phase two study which will be able to address this in more detail. Thank you.

Thank you. We will take our next question. Your next question comes from the line of Theodora Rowe-Beedle from GS. Please go ahead, your line is open.

Hi, thank you very much for taking my questions, both on dapiglutide, if that's okay. So firstly, why did you take the decision now to pause the development of 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 dapaglutide, so specifically thinking about if Novo show a benefit in Alzheimer's in the Evoque trial? Thank you.

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 for the clinical profile we have seen thus far and also its potential to lower inflammation even further than the existing GILD1s. We actually think it's probably the most differentiated GILD1 containing mixed-base development candidates. The decision has been reached now, partly, as I explained, due to the fact that we have CD388, where we can, as you will combine with amylin, also, of course, very much because we see now, we see server-side approaching, but then also just realizing that the Investments needed to show the clinical differentiation and then the amount of clinical differentiation you would have to demonstrate if you don't want to do the one-phase therapy in the 30s. It's a very, very high bar to pass due to the competitiveness within the tier 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 it's If you think about how you manage chronic therapies, normally if you cannot achieve, you go 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 to have 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 consider these very good ideas for how to drive the next wave of innovation and differentiation in this space. So 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 is actually more wisely spent there. Thank you.

Thank you. We will take our next question. Your next question comes from the line of Alec Ebling from UBS. Please go ahead. Your line is open.

Hi. Thanks for taking my question. Just on cervodotide, so you'll probably cover this more at your CMD, but in terms of the phase three readout in the first half of next year, where do you expect tolerability will likely land, considering that in the phase two data we've seen so far, there's a pretty high level of GI toxicity? Thank you.

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 solubility profile with the Phase II studies of some of the marketed products, you will actually see a quite similar profile of solubility. So we, of course, what we expect with 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 Neuagon and thus providing better liver health as we saw with the MAST program. Also remember that Beringer is actually pursuing higher doses in the phase two than what the in the phase three than what they did in phase two. 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 at phase one, allows them to go much higher. They've already tested that higher dose in the mass population in phase two, which is applied in the phase three program for BPP. So we have a lot of confidence that the profile will come across as a very strong and effective She has one-phase therapy with a solubility profile that is comparable to what's on the market today and a clear edge to where they will help.

We will take our final question. And your final question comes from the line of Mohit Bansal from Wells Fargo. Please go ahead. Your line is open.

Great. Thank you very much for squeezing me in, and this is my debut on this call. So a couple of questions from my side. First of all, given that with Cagri-Semma, we saw a little bit of tolerability when you combined GLP-1 with Amlin, and I fully appreciate the sentiment that combining GLP-1 and Amlin could be interesting. But at the same time, given that Amlin does have some GI tolerability issues, and it could compound with 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 the first question. And the second question is, we saw with Leralentide that, I mean, phase one was tolerability was better versus phase two, we saw a little bit higher GI issues. So in that context, I mean, what do you expect with petroenteritis in terms of tolerability in phase two trial as you see data in more patients? Thank you.

Thank you for your question, and I We definitely see amyloid in particular for Trinitide 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 I think we all recognize that these are the ones for many patients that it is difficult to tolerate. Many patients accept these therapies today because there's no alternatives. 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 TLD-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. 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 individuals who want to lose weight. And importantly, maintain that weight source because that is the key to unlock the value of this market is to make patients stay in therapy so they don't regain weight. And it's also the key then to achieve the health benefits. If people don't stay in therapy and they regain weight, they will not achieve the health benefits. That's also significant. potential for combination therapy, but that would be for the most morbid diabetes all 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 GF1 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 two 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 risk-experience time. Thank you.

Thank you. This concludes today's question and answer session. I will now hand back for closing remarks.

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

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