Zealand Pharma A/S

Good day and thank you for standing by. Welcome to the Zealand Pharma Results for Full Year 2024 Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1 and 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 and 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, Anna Kraskowska, Head of Investor Relations. Please go ahead.

Thank you, Alberta. Welcome, and thank you for joining us today to discuss Zealand Pharma's results for the full year 2024. You can also find the related company announcement and annual report on our website at zeelandpharma.com. As described on slide two, I caution listeners that we, during this call, will be making forward-looking statements that are subject to risks and uncertainties. Turning to slide three and today's agenda, with me are the following members of Zeeland Pharma's management team. Adam Steenspert, President and Chief Executive Officer, Himalaya Davinika, Chief Financial Officer, David Campbell, Chief Medical Officer. All speakers will be available for the Q&A session, along with Eric Cox, Chief Commercial Officer. Moving to slide four, I will turn the call over to Adam Steensberg, President and CEO. Adam?

Thank you, Anna. And thanks to everyone for joining today. 2024 was a transformational year for C-Land Pharma, with significant clinical advancement across our differentiated obesity pipeline. We were excited to share positive data and progress with Petrinitin-1-GLB2 receptor dual agonist and with Cervidotide, a potential best-in-class glucagon-GLB1 receptor dual agonist that is being developed by Boehringer Ingelheim. Turning to slide five, CLAM has an ambition to become a key player in the growing obesity market. And in 2025, we will expand our investments in and continue to focus on delivering on our differentiated mid to late stage obesity pipeline. Furthermore, we remain committed to advance our late stage rare disease programs in congenital hyperinsulinism and short bowel syndrome, where patients are in urgent need for better treatment options. And finally, we are progressing our early stage pipeline of next generation peptide therapeutics in the inflammation space. Moving to slide six, I would like to take a step back and remind everyone why we are so strongly focused on developing new treatment options for people living with overweight and obesity. The obesity pandemic has evolved in just 50 years. We have witnessed a substantial increase in the global prevalence of overweight and obesity rising from about 10% in the 70s to 40 to 50% today. More than 5 million deaths globally are today ascribed to overweight and obesity every single year. We are still in the very early stage of the evolution of the obesity market. And in the United States today, only 2% approximately of eligible patients get pharmacotherapy. The important point on obesity is not only whether you are obese or not, but for how long you have been living with obesity. For many, there is a limit to how long organs can compensate for the effects of obesity before they begin to fail. We know that more than 220 complications and comorbidities are associated with obesity. With the substantial increase in prevalence of overweight and obesity, also among children, I fear that in the coming decades we will see a significant increase in the prevalence of obesity-related comorbidities. The good news is that we now have the first tools available to help address this global healthcare challenge. But we do need many more and better treatment options for the very large and diverse population living with overweight and obesity. This leads me to slide seven. We have seen the approval and successful rollout of the first two once-weekly tier-one-based therapies to address the global healthcare challenges. In phase three clinical trials of longer duration, they have demonstrated potential for 15 to 21% mean weight loss in patients with overweight and obesity, and positive outcomes in several obesity-related comorbidities. On the flip side, tier-one-based therapies are often associated with a number of gastrointestinal adverse events, including nausea, vomiting, diarrhea, and constipation. And data suggest that up to 30% of patients with obesity on a GLP-1 treatment stop within one month before reaching their target dose, and that within one year, 60 to 70% of patients withdraw from treatment. Therefore, we believe there is a significant unmet medical need for therapies that can deliver the same degree of weight loss as the GLV-1 receptor agonist, but with improved tolerability and acceptability, including lower frequency and milder severity of gastrointestinal adverse events, so that patients have a more positive experience and can better achieve and, importantly, maintain a healthy weight loss. Based on clinical data to date, We are confident in the best-in-class potential of our long-acting amylin analog, Petrienside, that we are developing as an alternative to GLV-1-based therapies with the potential to represent a foundational therapy for weight management in the future. And with that, let's move to slide eight as I turn over the call to our chief medical officer, David Kendall, to discuss our R&D pipeline. David?

Thank you, Adam, and once again, welcome, everyone. Today, I would like to focus my remarks on the continued advancement of our obesity programs and provide a brief update on other development and regulatory activities. Beginning with petrolentide, let's move to slide 9. As shown on this slide and as previously reported, consistently demonstrated best-in-class potential based on results from early clinical trials completed to date. These data have shown consistent and compelling data with respect to both efficacy and safety, as well as tolerability, and have provided the evidence necessary to rapidly advance the development of petrolentide as a potential standalone therapy for overweight and obesity. Turning to slide 10. In late 2024, we initiated a large and comprehensive Phase IIb trial with petrolentide in people with overweight or obesity, marking an important milestone for both the petrolentide program and for Zeeland Pharma. Zupreme 1 is a randomized, double-blind, placebo-controlled dose-finding trial comparing multiple doses of petrolentide or placebo over 42 weeks of treatment with five active dosing arms, the highest being 9 milligrams. As a reminder, the primary endpoint of percentage change in body weight from baseline will be assessed after 28 weeks of treatment, while the trial will continue for a total treatment duration of 42 weeks. To maintain trial integrity, we will continue to execute the trial in a blinded fashion throughout the entire treatment period. The separate team will be unblinded to the primary endpoint at 28 weeks solely for the purposes of advancing regulatory interactions with the goal of reducing the time between Phase 2 completion and the initiation of Phase 3. Full unblinding and disclosure of data will only be after completion of the full trial. We are very encouraged by both the rate of study initiation and participant enrollment into Supreme 1. December 2024 we announced the enrollment of the first participant enrollment has been significantly faster than initially anticipated and we project the completion of enrollment by the end of this quarter. let's move now to slide 11. In the first half of this year, we are continuing in our execution of the development program for patrol and tied with the plan the initiation of a second comprehensive phase to be trial. Zupreme-2 is a randomized, double-blind, placebo-controlled Phase IIb trial of petrolatide in people with overweight or obesity and coexisting type 2 diabetes. In this population, data suggests that amylin agonism may potentially deliver weight loss comparable with that observed in the non-diabetes population, another potentially important differentiation opportunity with amylin agonists as compared to GLP-1-based therapies. Zupreme 2 will enroll more than 200 adults and will compare three doses of petrolentide with placebo over an estimated 28 weeks of treatment, consistent with other clinical trials in people with overweight and obesity. The primary endpoint will be percent change in body weight from baseline, while key secondary endpoints will include change from baseline in hemoglobin A1c and change in fasting lipids. Now turning our attention to slide 12 and dapiglutide, our dual GLP-1, GLP-2 receptor agonist. Dapiglutide is designed as a potent GLP-1 receptor agonist targeting significant weight reduction and offers the potential to also leverage GLP-2 pharmacology and improve gut barrier function as well as targeting the low-grade inflammation associated with metabolic disease. In 2024, we reported top line results from Part 1 of the Phase 1B dose titration trial with dapiglutide, investigating the pharmacokinetic and pharmacodynamic effects of dapiglutide treatment with doses up to 13 milligrams given once weekly over a treatment duration of 13 weeks. We are both excited and encouraged by these data, and we look forward to presenting detailed results at a future scientific congress. In the first half of 2025, we look forward to reporting top-line results from Part 2 of the Phase 1b trial, designed to investigate doses of up to 26 milligrams over a treatment duration of 28 weeks. We also plan to initiate a large Phase 2b trial with dapaglutide in people with overweight or obesity in the first half of this year. And with that, let's turn to slide 13. An illustrative overview of the proposed Phase IIb trial design is shown here. This trial is planned to enroll more than 400 adults with overweight or obesity and will compare multiple doses of dapaglutide or placebo with up to five active treatment arms over a treatment duration of 48 weeks. Consistent with other trials of incretin-based therapies in people with overweight and obesity, trial participants will follow a dose schedule with monthly dose escalation steps. The primary endpoint will be percent change in body weight from baseline to week 36, and the trial will include a number of key secondary and exploratory endpoints, including an assessment of biomarkers for inflammation, markers of cardiovascular risk, and body composition. In this trial, we look very much forward to further evaluating the weight loss potential and tolerability of dapaglutide while also gaining more insights into the potential of dapiglutide to reduce inflammation with the opportunity to target specific high-risk populations. Turning to slide 14 and cervodutide. As reported in late 2024, Beringer-Ingelheim advanced cervodutide, a dual glucagon GLP-1 receptor agonist, into two large registrational Phase III trials in people with metabolic dysfunction associated steatohepatitis or MASH. These two trials, liverage in people with moderate or advanced fibrosis and liverage cirrhosis in people with compensated cirrhosis, are investigating the impact of this novel dual agonist on one of the most prevalent and serious obesity-related comorbidities. And we are very pleased with the development progress of servodutide, a product candidate we believe holds potential as a best-in-class therapy for both obesity and MASH. We are also excited that in 2024, Beringer Ingelheim has completed participant enrollment for synchronized 1 and 2, the registrational phase 3 clinical trials of servodutide in people with overweight and obesity with and without type 2 diabetes. If successful, servodutide could be the third to market incretin-based therapy and the first dual glucagon GLP-1 receptor agonist introduced in this exciting era of novel weight loss therapies. Moving now to slide 15 and a brief update on our rare disease programs. For dosiglucagon and congenital hyperinsulinism, we are prepared to resubmit part one of our original NDA for up to three weeks of dosiglucagon party manufacturing facility have been resolved in the form of a classification upgrade. Subsequent submission of part two of the NDA for chronic treatment of CHI is planned thereafter. As previously communicated, in late 2024, we received a complete response letter from the US FDA for the new drug application of glopaglutide for the treatment of short bowel syndrome with intestinal failure. We are working with the Agency to align on the design and execution of an additional Phase III clinical trial, which will enable U.S. regulatory approval. We expect to initiate the additional placebo-controlled Phase III trial with glopaglutide, the EASE-5 trial, in the second half of 2025. The EASE-5 trial was already in planning for support of additional global regulatory submissions outside the U.S. and Europe. but will now be based on alignment with the U.S. FDA and designed to support our subsequent U.S. regulatory submission. Simultaneously, we anticipate submitting a marketing authorization application in the second half of 2025 to support approval of glopaglutide in the EU. We remain deeply committed to doing everything we can to bring both of these treatments to patients living with these devastating rare diseases as soon as possible. And turning now to slide 16 on our early stage pipeline. I'm very pleased that we, in late 2024, progressed our first inflammation asset into the clinic. ZP9830 is a potent and selective KV1.3 inhibitor with potential to treat a broad range of cell-mediated autoimmune diseases. The first in-human clinical trial of ZP9830 is now underway, and we expect to complete the study by the end of 2025. This study is a phase one single ascending dose trial investigating the safety and tolerability of ZP9830 in healthy male study participants. The study will also investigate the pharmacokinetics and pharmacodynamics of ZP9830 as compared to placebo. While 2024 was a year of significant progress in our development pipeline, particularly for our obesity assets, we also made significant advancements in our research pipeline as well, partly evident by the progress of ZP9830. In 2024, we also increased the number of research projects advancing to discovery and lead identification phase by approximately 50%, which I believe is strong testament to our focus on continuously working to innovate and develop the next generation of peptide therapeutics. In 2025, we will continue to enhance our early-stage research effort with a particular focus on our Obesity Plus research pipeline of novel peptides targeting obesity and its distinct comorbidities. And with that, I would now like to turn the call over to our Chief Financial Officer, Henrietta Venneke, to review our financial results for 2024. Henrietta?

Thanks, David, and hello, everyone. Turning to slide 17 and the income statement. Revenue for the full year of 2024 was 63 million DKK, mainly driven by the license and development agreement with no notice for Sigalov. Net operating expenses in 2024 of 1.33 billion DKK were within the guidance of 1.25 and 1.35 billion DKK. Net operating expenses are driven by R&D expenses of 920 million DKK, representing 69% of the company's operating expenses. The increase in R&D expenses compared to 2023 is mainly due to clinical advancement of the wholly owned BCT assets, paternaline and debut types, including preparation for large, comprehensive Phase IIb trials and activities supporting the regulatory review by the US FDA for the rare disease assets. Selling and marketing expenses of $88 million DKK in 2024 were mainly driven by pre-commercial activities associated with launch preparations for the rare disease assets. And the increase in general and admin expenses is a result of additional legal expenses related to our patent portfolio and strengthening of organizational capabilities in our IT infrastructure. Net financial items shows a net gain of 189 million DKK in 2024 compared to a net loss of 137 million DKK in 2023. This significant improvement mainly is driven by the interest income from the excess liquidity invested in marketable securities. Let's move on to slide 18 and the cash position. As of December 31, 2024, cash, cash equivalents and marketable securities were 9 billion DKK. I'm very pleased with the fact that we ended 2024 with a cash position that was 7.4 billion DKK higher than when we started the year. We truly believe we have an R&D pipeline of promising and differentiated obesity assets, and our strong cash position enabled us to significantly scale up investment in development of these programs. And this leads me to slide 19 and the financial guidance. For 2025, we anticipate operating expenses to be in the range of 2.0 and 2.5 billion DKK, which is a significant increase compared to 2024. This is mainly to support our mid-stage obesity pipeline and enhance our early-stage research efforts. As mentioned by David just now, by the end of 2025, we expect to have three large Phase IIb trials actively underway with our wholly owned obesity assets. One last phase 2B trial with paternal ties was initiated in late 2024, and in the coming months, we expect to initiate another phase 2B trial with paternal ties. We also expect to initiate a last phase 2B trial with David Glutine in the coming months. In addition to the clinical costs associated with conducting these mid-stage obesity trials, the 2025 OPEX guidance also includes TMT activity mainly related to API and drug product, but also activities to prepare for phase three. Simultaneously, we are building the next wave of innovation peptide therapeutics. As mentioned by David, we significantly increased our research effort in 2024. And in 2025, we will continue increasing investment in our peptide research, including our early stage portfolio on novel peptides tied into obesity and inflammation. Lastly, moving to slide 20, I would like to discuss our work with sustainability. While 2024 was a transformational year for Seymour & Farmer, it was also a defining year when it comes to our work with sustainability. We launched our first dedicated sustainability strategy, significantly increased our efforts to operate responsibly and build a sustainable organization while pushing for positive development of society. As a biotech company whose mission is to transform lives through peptide innovation, we place the health and well-being of patients at the center of everything we do. We remain firmly dedicated to advancing our R&D pipeline with focus of developing new and better medicine to serve patients. And our ability to advance our pipeline and ultimately serve patients rests on our people. Growing the number of headcounts by 30% as Zealand has in 2024 can be a challenge for any company. We are extremely proud and humble that we maintained a very high engagement score of 8.8 on a 10 point scale. And at the same time, we decreased our employee turnover rate to just 7.3% in 2024. We believe this is a testament to our unique company culture and our continued dedication to foster an engaging and enriching workplace. We are confident that we have built a sustainable organization set up and we look forward to continue the growth in 2025. We are also committed to taking responsibility for the environmental impact of our operation and lowering our green gas emissions. This year we calculated our GSG emissions for both 2023 and 2024. As expected, our missions lie in our value change activity, with over 99% of our mission coming from scope three. In 2024, we developed a climate change transition plan and are establishing reduction targets to ensure that our activities are in line with the goals of the Paris Agreement. We remain dedicated to transitioning our company and working together with our business partners to mitigate climate change And in 2025, we will formally commit to the Science-Based Target Initiative. And with that, I will move to slide 21 and turn the call back to Adam for concluding remarks.

Thank you, Henriette. I'm extremely pleased and proud of our achievements in 2024. From the very solid organizational and financial foundation that we have built, we expect to accelerate momentum in 2025 with important clinical advancement of our differentiated obesity programs and significant progress in our early stage research pipeline. We have created a very strong platform for accelerated growth and our pursuit of our ambition to become a key player in the growing obesity space and thus play our part in addressing what we believe is the biggest healthcare challenge of our time. We look forward to initiating the second planned Phase 2b trial with Petrinatide in the first half of the year. In the same timeframe, we also look forward to initiating a Phase 2b study in obesity with our potential first-in-class GLP-1, GLP-2 dual agonist Dapaglutide and announce top-line results from Part 2 of the Phase 1b trial, evaluating even higher doses of Dapaglutide with longer duration. These are just some of the many activities that we look forward to in what we see to be a very busy and exciting year for sealant farming. Thank you all, and with that, I will now turn over the call to our operator for questions.

Thank you. As a reminder, to ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. We will take our first question. The first question comes from the line of James Gordon from JPMorgan. Please go ahead. Your line is open.

Hello, James Gordon, JPMorgan. Thanks for taking the questions. Firstly, a petri partnership and the rate-limiting factors for getting that done. So can you just confirm, do you think any more data might be needed, either for your product or for competitor amyloid molecules? Might a potential partner want to see Cagri-Sema data presented? Or if you think all the necessary data is now available, Why wouldn't a partnership, say, potentially happen in the coming months versus later in the year or even into 2026? Second question on partnership, just how important is it that you retain co-promotion rights in the US and or Europe versus who the partner is and what they can do for the product? And a final question, so Glepper, you mentioned the EASE-5 study, which you need probably to get into the US. When do you think that will read out?

Thank you, James. For your questions, I will start by addressing the first one and then, yeah, I can actually also address the last one. But if we start with the Petronaside partnering, as you know, we started the process in the second half of last year and it has been incredibly important for us to make sure that we have run a very structured process, reached out to as many large pharma companies as possible, making sure that Everyone who were interested heard our vision for the program and then starting a dialogue with as many as possible. So we have had a very structured process. And what we also have been saying and what I feel very comfortable saying today also is that we are exactly where we want to be in that process. It's not my sense that we are waiting for additional data readouts or what have you. But for us, of course, if you are to engage in a long-term partnership, it's really important that you get it right. So the three parameters that we have set out for ourselves in the start remains the same. The partner has to be a large pharma company who have a vision of winning in this space in the 30s and not just be part of it. Then we have to share the vision for Trinitide about becoming a foundational, ultimately with the potential of a foundational therapy for weight management And then, of course, it's extremely important also with the cultural fit, given that it's a long-term partnership. And that's kind of taking me back to one of the other questions you had, what is important for us in that partnership when it comes to the more structural elements? And we do think it's important that it becomes a co-development and co-commercialization partnership with profit share. That is what we have pursued. That does not mean that we would have similar operational involvement or we would try to retain as much strategic flexibility as possible. But it is important that it's a true collaboration and not one which is just a licensing agreement. And I feel very comfortable that we can achieve that based on the dialogues we have. And I can also say that where we are right now, it's not about engaging more parties. It's probably more about narrowing the field down. We are where we want to be. We do not guide on when we expect it. I think that is not in anybody's interest, but we are where we want to be on these discussions, and we feel that it's a very competitive situation. On EAST-5, again, we plan to start the study here in the second half. We will have an interaction with FDA on the exact details on some of the designs, and we will only communicate on when we expect results at a later time point. Thank you.

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

Charlie Hayward, Bank of America. Thank you for taking my questions. I have two, please. So the first is on your target, Petri, 15 to 20% weight loss. Given Cagri saw 12% weight loss, what's your confidence in still being able to achieve the top end of that range? So the 20% weight loss and what drives that confidence? And secondly, can you remind us of your plan and timelines for your Petri Phase 3 trial discussion with regulators or the FDA? How do you expect to start those? And I think as you're likely to be discussing fairly broad Phase 3 plans, including a CV trial with them, from partner discussions you've had to date, do you think that's a conversation that a potential partner is likely to want to be involved in? Thank you.

Thanks. I'll just start and then I'll hand over to David. Of course, you can say where we are in the program, as David also mentioned on the phase two enrollment, which is going incredibly fast, we need to start to think about phase three planning sooner rather than later. And of course, it is relevant for any party to be part of that. So we see that and share that observation. But again, we do feel we are set up to So, also to deliver on those designs, but it is, of course, something that would be relevant to consider in these discussions. David, will you address our considerations about the 15 to 20 percent, given also the data earlier this year and perhaps some of the other elements?

Yes. More than happy to, Adam, and thanks, Charlie. Yeah, I think, you know, while the CAGRI summer data left some with questions unanswered around both the CAGRI dose and the impact of amylin agonists. I think that trial and those results to us gave us additional confidence in the potential of putrelentide. As you know, and as we've shared previously, Both cagrelentide and petrolentide are these balanced calcitonin amylin receptor agonists, which we believe is a critically important feature to achieve the greatest effects on body weight. In addition, petrolentide, we believe, can be dosed at significantly higher milligram doses, which may support additional efficacy. Similarly, both the bioavailability and the activation, at least at the receptor level, is as good or, in this case of bioavailability, significantly higher than CAGRI. So, while Phase II and 28 weeks of exposure may not take us to this target, 15 to 20 percent, which we would expect after a year or more of treatment, All of those features, the physical, chemical, and pharmacokinetic, pharmacodynamic features of petrolatide give me and I hope others great confidence in achieving that 15% to 20%. And I think as a reminder, people should review labels of the existing GLP-1-based therapy for obesity, the data with semaglutide, where after... more extended treatment. They achieved 14.9 to 16% weight reduction in their phase three clinical trials. So we are often distracted or, if you will, recall things based on recency, which is the dual agonists and the other assets, which have achieved 20% or more In terms of phase three startup, premature to speculate, but obviously with completion of the phase two B studies and end of phase two interactions with the agency, which we would anticipate would happen. both near the end of this year and into next year. Phase III startup we hope will be enabled as quickly as possible in the coming year. And then finally on your question on CBOT, obviously this is a significant investment. We will want to see both Phase IIb data effects on markers of CV risk before that design. is finalized, although I can say we have initiated the early parts of that process already. And to your point, pending the partner discussions would obviously welcome a partner into these discussions when it occurs.

Many thanks.

Yep. Thanks, Charlie.

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

Thank you very much, Michael Lovath from Nordea. A couple of questions. So starting with the piglutide, can you sort of try to detail what you were sort of hoping to see in terms of the 28-week data for 26 milligrams in order to say that this is a qualifying candidate to move further with and where there could also potentially be partnering interest for this asset in terms of weight loss or other biomarkers? And then secondly, on glipaglutide, is there any reason to believe that EMA would not take the same stance as the FDA because the CRL was clearly surprising? So maybe you can go into a bit of more details on why we should not expect the same risk on an EMA approval or non-approval. Thank you.

Thank you, Michael. I will just start with Debbie and then I will hand over to to David, but on DAPI with qualifying of the weight loss, I think it's really important for us to kind of state that with DAPI, it's not just about weight loss. We would look to weight loss that is similar to what we see from the currently available, the ones out there, like perhaps tazibutide-like weight loss in long-term studies. We already know for many patients that it's actually enough, and even in today's market, many patients don't take the top doses of the products that are available today. The key differentiator for DAVI is its potential on inflammation and low-grade inflammation. So we are looking for weight loss that you can take it in the range of what we have today with, let's say, a product like Tazibutide, and then, of course, ultimately, to have a differentiating opportunity when it comes to addressing low-grade inflammation. Do you want to add further to this and then also discuss Glipper, please?

Yeah, absolutely. Thanks, Adam. And Michael, with DAPI, those biomarkers will be equally important, I will say. And one point to add to Adam's is, in many cases, the incretin-based therapies in earlier studies have been tested only at lower doses. We see that with some aglutide looking at Higher milligram dose exposures, triseptide, as Adam referred to, pushing to the 15 milligram dose, did occur in the clinical program. It's in the label, but challenging for some to take. So for us, it is both to ensure we see the efficacy on weight loss and understand the tolerability at those top doses and across that dose range, understand the biomarkers. For glopaglutide, EMA certainly has a different set of requirements in terms of substantial evidence of efficacy, and we are obviously engaged with the European authorities and EMA on outlining our submission package. Given the differences in requirements and in RIs, what will be confirmatory evidence from these five, which will provide the FDA with the additional evidence they seek. We believe that the compelling evidence that was generated both for reductions in parenteral support and enteral autonomy with the single EASE-1 trial can, and in discussions with the EMA, will serve as the information necessary for approval of this rare disease asset. So I think a number of things give me quite reasonable confidence that the EMA will give this a full, thorough review with the existing data package.

Okay, thank you.

Thanks, Michael.

Thank you. We will take our next question. And the question comes from the line of Suzanne van Voothuizen from VLK. Please go ahead. Your line is open.

Hi, team. This is Suzanne from Kempten. Thanks for taking my questions. First, on the patrilentide phase 2b study that's ongoing, fully understood that it remains blinded until 42 weeks. But I'm just wondering if we could expect some sort of communication from the company around the 20-week time point. Not data, but... for example, having reached this point or updates on the regulatory interactions. And secondly, I was wondering if you can share your views with regards to NOVO also starting a phase three study with gigrelentide monotherapy. Obviously, petralentide seems like a better molecule, but since this is a change in NOVO's side to also develop as monotherapy, just wondering how you look at this. Thank you.

Thank you, Suzanne. And I will also start, and then maybe David have a few extra remarks. But we do not anticipate to share any data from the 28-week data point. It will be a blinded review. It will probably be obvious from clinicaltrials.gov and other places where we are in the process, but as that will be reported, but we will not share data or observations from that because it is a blinded study group that will look at it, so the rest of us will not have access We have also, of course, noticed that following NOVA's full year results that they have put calcurentide phase three planning on one of their pipeline sites. We think it's a good support for the story and the positioning that we have been pursuing for petrientide for a long time. As David has shared also with the data, we feel comfortable around the profile of petrientide. We do believe we can achieve higher doses and you can say, of course, we see this as, again, validation of the approach that we have taken for some time that amylin monotherapies looks to have a potential for becoming very significant contributors to weight management, pharmacotherapeutic weight management in the future. And we are So for us, it's really an exciting observation and one which underscores the potential we have with Petronasite, which we truly believe is a best-in-class molecule. David, do you want to add some more flavor to this?

Nothing further from me, Adam.

Okay.

Thank you, Suzanne.

Perfect. Thank you. Thank you. We will take our next question. And the question comes from the line of Prakhar Agrawal from Kanta. Please go ahead. Your line is open.

Hi, thank you so much for taking my questions. Maybe firstly a clarification, Adam. The press articles today morning are saying that you're guiding partnerships by end of 2025, early 2026, versus you're not commenting on timing here. So if you can clarify this, please. on the potential timing of partnership discussions and as a follow-up uh discussion around amlin monotherapy versus combinations how is that resonating with potential partners and is there interest from companies that are not involved in the obesity space as you are working through the partnerships thank you thanks for your questions and um

I would say on your first question around partnership, I think we have been extremely clear and repeatedly, including in all conversations we have had around this release, that we do not guide on timing. We raised a lot of capital last year to make sure that we can pursue all the development efforts needed. We also started a partnering process last year. We are exactly where we want to be in this one. several reasons we have decided not to guide on timing for this. When people ask me and ask for my personal perspective, I'm also happy to say that it's probably more likely to happen this year than next year. But that is also just based on an observation and some of these points we have discussed today that likely a partner would prefer to be part of phase three design and phase three discussions, and you basically need to partner up this year to do so. It's not our observation that anyone are looking for more data, but we are not going to guide on it, and we have not changed any guidance on this, also not in this call or today. On the mono and the combo therapy, I think there is a very big recognition of the monotherapy potential. It's a really attractive, you can say, consideration to enter a market with a potential new modality where you don't have to go in and fight for your share of an established market, but actually you can tap into a novel market addressing patients with a novel modality and not just trying to take market share from something that is already quite established. Obviously, the monotherapy that is creating the most excitement, having said that, of course, there is a recognition of the potential of combination therapies. I mean, Novo have already shown us, both from a weight loss perspective, what you can envision to achieve when you start to combine these. And we have a deep recognition also that there are, of course, segment of patients who need the higher weight loss. We are also just very firm that the majority of these individuals will not be looking for a weight loss that is approaching 30%. The majority of patients will be looking for one which is around 15% to 20% weight loss. But of course, there are patients who need higher weight losses. There's also patients who may need that extra support during the weight loss phase and then less during the weight maintenance where a monotherapy could then come in. So we recognize the potential of both. That's also why we plan to start a combination study later this year with a tier 1. But the Most excitement is and remain on the monotherapy, the opportunity to create and develop Petronitide as a novel foundational therapy for patients and then you can always add a little bit of GLT-1 on top of that if the patients need more or need more in the weight loss phase. Thank you.

Thank you. We will take our next 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 question. And just on the partnering point, sorry to ask another one on this, but could you just kind of remind us how you think about the optimal timing for this partnership? I guess the question that I'm trying to ask is beyond the additional capital that a larger partner may bring, at what point do they add value to Petrolin's development process beyond what Zeeland can do alone, given that you probably have as much experience as any company with the mechanism itself. And then secondly, sort of related to that, just on that combination trial with the JLP1, is that likely to come after a partnership has been announced? Just trying to think about what the identity of that JLP1 partner could be, or is there potential to initiate a combination with DAPI? Thank you.

I think you're going to get the goal for the most sneaky question because I just told you that we plan to start the GLP-1 campus study later this year. So that I cannot comment on if a partnership will be before or after we start the campus study with GLP-1. But nice try. I would say coming back to the partnering process, we have had a very good process. We are exactly where we want to be. we have the conversations we wanna have right now. It's not our feeling that we need more data. It is really, and then you talk about what is the optimal timing. One thing is of course phase three design. Another thing is at one point we also, a partner will have to consider manufacturing investments and so on. But again, we are not gonna comment on timing, but as you can imagine, we have a process and we have been following that process and we are exactly where we wanna be on it.

Okay, maybe just on the, maybe less sneaky then, the bit that I also asked on the DAPI combination, could that be a potential combination partner with petrolintide?

I think actually DAPI is also an interesting combination partner, but it's probably not what we would do first because you want to, you can say the first combination experiences, you probably want to work with a product where you have, you can say, better understanding of the 1 component before you start to combine. We don't want to use two molecules that are that early stage. But obviously, later in the process, they could be an interesting considerations for sure.

Thank you.

Thank you.

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

Great. Thank you for the question, team. So firstly, just a very short one on the DAPI Part 2 data. Is the hope here to present it alongside the 13-week data at the medical conference that is referenced this year? Is that the hope, or is it too early to think about because we haven't had the readout yet? And then the second question is more about the rationale of Zupreme 2 and the obese diabetics here. is the end goal to try and find a label for obese diabetics with this molecule, obviously noting the different impact on HbA1c that it has, or is it more of an exploratory study? And alongside that, what is building confidence of the potential difference of amylin when you look at the weight loss in obese individuals versus obese diabetic individuals? I think some data has pointed to that potentially there's a little bit more weight loss relative to GLP-1s in diabetic individuals. What builds confidence around that, and is there anything you can point to for us for this trial? Thank you.

Thanks. I will start, and then David can add. So the 26-week data plan is probably one which we will release when we have the result meeting, so we cannot time it around the 13-week data that is going to be presented at a scientific conference due to disclosure obligations. But it is set to read out this first half. So, of course, it could be close, but we cannot commit to that yet. And then on Supreme 2, it is really a study to assess, of course, the weight loss potential in obese individuals with type 2 diabetes, where, as you noted, we have quite compelling data to show that where we have seen that amylin analogs looks to be as effective from a weight loss perspective in patients with type 2 diabetes as non-diabetic patients living without diabetes, which is not the case for GF1. David, do you want to add a little bit more flavor to this, maybe?

Yeah, happy to, Benjamin. A really good question. Petralentide and amylin agonists, I think, have two and perhaps more distinct characteristics in their putative mechanism of action. One is in contrast to GLP-1s and incretins, remember are named incretins due to their capacity to stimulate additional insulin secretion, particularly in the post-meal period, but chronic elevation of insulin, remembering that insulin is an anabolic hormone. It's a storage hormone. So when you stimulate insulin secretion, particularly in those with diabetes who have or relatively poor glycemic control, you will take those circulating calories and store them. To your point, amylin agonists are not put forth to be as potent a glucose-lowering agent, given that its effects are mostly on gastric emptying and glucagon suppression, as well as food intake. But in addition, there is evidence that amylin agonism, way back to the pramlentide and other asset days, is also insulin sensitizing. So both insulin sparing and insulin sensitizing characteristics of amyloid agonist in those with diabetes would be expected to maintain the weight loss you see in the non-diabetes population. Obviously, to your point, if glycemic control is substantially poorer than is desired, are these likely to be the most potent glucose lowering agent? I think the Data with cagrelentide versus semaglutide show that for glucose-lowering GLP-1 agonists are likely to be the most effective. But for weight loss alone, we believe amyl and agonism can maintain the same degree of weight loss in the diabetes as non-diabetes population, probably due to those factors I mentioned and others that will be explored. Thank you so much. Thanks, Benjamin.

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

Hi, just one question from me, please. What are you hoping to show with your Phase 2b Supreme 1 data in the non-diabetic obese population? And what more do you think this will tell you around the clinical profile of Petri than we already know from your data last summer? And just finally, do you think you need this data to realise full value of any sort of partnership discussions? Thank you.

Thanks for the question. With regard to partnership discussions, it is not our, you can say, belief that further data are needed to continue these discussions. I think we have a very strong data package and good alignment on what the data shows, of course. So I would say it's not data readout from between two and three are not related to the discussions we have. On what we expect to see from that data set, what we have set high level is that it should just continue to confirm our target product profile of being able to achieve 15% to 20% weight loss in longer-term phase III studies. So, of course, ultimately, one thing is the number we will achieve after 48 weeks, but the other one is, of course, the slope of the curve and what have you. Because in general, with weight loss medications, you expect to see continuous weight loss over time, in particular with molecules, which patients can then stay on for sure. So we are not giving a specific guidance for what we expect from that number. That would be more complicated. But as long as we are confident we can achieve 15% to 20%, then we will be very happy in longer-term studies.

Great. Thank you.

Thank you.

Thank you. We will take our next question. The question comes from the line of Thomas Franken from KBC Securities. Please go ahead. Your line is open.

wanted to ask one question. Given that you view amylin as a potential backbone therapy in obesity, what is your strategy for this target beyond Petri? Do you plan to explore alternative or less frequent dosing regimens, for example, or monthly versus weekly dosing? Thanks.

Thank you for your question. I think, number one, we truly believe that once-weekly dosing is a very attractive administration form for patients. But having said that, of course, we also recognize that some patients could potentially prefer less frequent dosing or other modalities. And we are investing at, you can say, bench work into exploring different opportunities for also changing, making longer, you can say, formulations that allow for less frequent dosing and oral administration. But these are all lifecycle management activities that will only get into the clinic in a partner framework where we would, of course, you can say, hope to continue to build the franchise out around the train site. But the key focus is, of course, the ones weekly dosing, getting into phase three and obesity, and then rapidly also progressing into associated comorbidities to truly build, including CV outcomes studies, to truly build what we believe can be a foundational therapy. But there's plenty of opportunity to then expand around that franchise for sure. So thanks for that question.

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

Thank you very much. Couple of questions left to me, please. With regard to the phase three preparation investment for you, does that relate to both petrol and diet and WTI? And I wonder if you can just talk about exactly what you are looking to entail here. And in the context of thinking about phase three, is there any scenario under which you would consider pursuing that next stage of development on your own? for both or one of those two products. Then with regard to the SAFE2B program, Perpetual Insight, I wanted to check, are you measuring body composition, quality of weight loss in both Dupreme 1 and 2? I can see from your slides that Dupreme 1, but also second study. And then essentially, you talked at great length about the differentiation potential for petrolinthoid intolerability. So I'd just love to hear your expectations of whether the body composition angle could be a key point of differentiation for this drug. So thank you.

Thank you. I'll start and then hand over to David again. So the investments that you are looking at this year is, of course, number one, we have three large phase 2B studies that are going on. But we are also going all in and investing in all the activities needed to progress as shiftly as possible into phase three for both programs. And it's of course additional smaller clean farm studies. It's manufacturing of product. It's actually scaling up, you can say, to make sure we have the right batch sizes that can also be continued into commercial scale. It's device development to make sure we have the right device options when we move into phase three. It's all those things that we typically don't talk too much about, but I incredibly important to move in with confidence into phase three, especially when you are addressing a large disease like obesity. You need to have thought all these elements through and invested in them in good time. And that is what our investments are going into this year. For phase three initiation, it's not our ambition to get into phase three alone. But again, we are not guiding on when we will have the partnership, but we would definitely expect to move into Phase 3 with a partner, but that doesn't change the fact that once you start Phase 2b, you need to start the Phase 3 planning big time and make these investments into devices, API, drug product, and so on, which is what we're doing already now. David, maybe you want to talk a little bit about the Phase 2 design, body composition, solubility, and differentiation. Thank you.

Happy to, Adam. And as Adam said, Phase 3 Enabling work is fully underway. The body comp, as noted in Zupreme 1, will be a component of the outcomes as we are doing this by MR measurements, MRI. This is a dedicated sub-study because you need the technology and the centers that can execute the MR measurements. a bit more specific to lean mass, meaning muscle mass versus fat mass, than is DEXA. At present, the opportunity to measure body comp in Zupreme 2 is also present. The mechanism by which we'll do that remains under discussion, but we believe should body composition measurements in Zupreme 1 demonstrate that preservation of lean mass, as has been demonstrated in animal models, that doing so in a more generalized fashion, for example, using DEXA is possible. But MR, as I said, is perhaps the more specific. You also asked the question as to whether this can or would be differentiating if I refer to the more recent FDA guidance or draft guidance on obesity programs. The same questions exist at the agency as exist for all of us, and that is, can you preserve functional lean mass? Um, certainly losing muscle mass and then one who is sarcopenic or losing muscle mass, uh, inherently older adults, um, those who are less active, uh, those who may have complicating conditions, um, would be critically important. So getting functional measures at some point in phase three, whether that be grip strength, a six minute walk, other things, uh, will also in our mind be important, uh, alongside those specific measures of fat versus muscle and or lean mass so yes we will continue to pursue this and at least clinically I believe in selected circumstances this could be a very important differentiator thank you thank you we will take our next question

And the question comes from the line of Laura Hindley from Morgan Stanley. Please go ahead, your line is open.

Hi, thanks for taking the question. So yeah, following on on the theme of phase three planning, can you remind us what your current cash position would support in terms of development progress for your wholly owned obesity pipeline assets? And then back on the theme of quality of weight loss, on your slide for DAPI glutide phase 2b design, you have a body composition endpoint. Is there any evidence that you would flag to suggest that GLP-2 would have a differentiated effect on quality of weight loss? And then finally, when you're having your negotiations for partnership around petrolintide, is there also any discussion around dapiglutides, or is it entirely focused on amylin for now? Thank you.

Thank you for your question. I'll start by answering the last question, and then Henrietta will provide some favors on the CASP position, and maybe David, you can discuss the last question. But we are very focused on Katrina Tide and these partnership discussions and try not to complicate it with DAPI. So that's the simple answer to that one. And I think that will be next once we have concluded Katrina Tide. Henrietta, do you want to discuss this?

Yes. Thanks for your question. As you know, on the run rate, we don't really guide on the run rate anymore. And of course, we have a step up in OPEX now in 2025 compared to But I think, as you also recognize, there are a lot of moving pieces when it comes to our runway. We have a very sufficient cash position, 9 billion Danish in the bank as we start the year. And of course, as we progress, we can easily fund phase two. And then we will, of course, also, when time comes, we will see revenue streams coming in from server due time. And then, of course, there will be potential partnerships, both on paternal time, but also around, as you said, that can add to that runway. So I think we are in a very good spot where we have the cash available to fund the activities we have at hand and also progress some of these initiation of phase three activities that would be required early on. We actually invest heavily in that as well. So we have the cash needed for now. I think that's it.

David?

I'm happy, Laura, to discuss your second question, the quality of weight loss in DAPI. I would say we're investigating this for two reasons. One is to understand, is this similar to or distinct from other GLP-1-based therapies, where obviously when you profoundly food restrict, the muscle mass loss can occur. There is not, to my knowledge, any direct effect of GLP-2 on preservation of lean mass or any specific signals on this is a growth factor in some ways so there is at least the theoretical potential the other a point of interest is if inflammation is substantially impacted which we believe it may be will that change if you will the metabolic environment of adipose tissue so adipose tissue in those with overweight and obesity is tends to be affected by an inflammatory microenvironment. If we can diminish that microenvironment, do we at least see the capacity to mobilize fat stores? So I would not go into this hypothesizing for you that we will see a difference, but I think important for us to understand, one, is it like other agents in the GLP-1-based therapeutic classes, and is there any other unique effect that may come from GLP-2 either directly or indirectly through its effects on inflammation?

Great, thank you. Thank you. We will take our next question, and the question comes from the line of Jesper Ilso from Carnegie. Please go ahead, your line is open.

Thanks so much. A question for Eric Cox. It's a bit more broader question, but you previously worked in Karmat, which were acquired by Ross. So perhaps you can share your sort of view on the general deals phase in the obesity market today versus back when you worked in Karmat, because I think a typical question we also get is, yes, we have very good BCI assets, more and more innovation, but we haven't yet seen the bigger deals, and we are starting to see some deals happening from China for smaller early-stage assets. So just interested in your view and sort of what is sort of the barriers to these bigger deals happening or holding a deck. Thank you.

Sure. So thanks for the question. I think it's difficult to predict to kind of what that future looks like, but I think we all know that in the last 12 months that we've seen quite a significant change in the marketplace. I think that we start to learn more about the GLP-1s and we start to see is where there's new opportunities. And I think as Adam has already articulated, I think we're starting to see is that the vast majority of the patients are still seeking between 15 to 20% weight loss and they're looking for new therapies. So, it's hard for me to predict is where we're going and what's going to what's going to do a deal but i think we know this market is constantly evolving and will continue to evolve to look for more improved medicines to give them a better overall patient experience thanks thank you we will take our next question your final question comes from the line of julian harrison from

BTIG. Please go ahead. Your line is open.

Hi, this is Rae on for Julian. Congrats on all the progress and thank you for taking our question. Just a couple from us on glupaglutide. First, is it abundantly clear that an additional study is necessary in the US or is there an opportunity to potentially refile based on the existing data? And then as a follow-up to that, what could the approximate timeline to refiling the NDA for glupaglutide in the U.S. look like? Thanks.

Thank you for that question. We are quite certain that we need to do these five, so that is definitely the plan right now and based on the feedback we have. As David has said, we feel comfortable around, you can say, the first phase three study and also agreeing on the effect and safety profile, but FDA has asked for more evidence. So we are quite confident we have to do another phase three study. We do not yet guide on when we expect to have data ready and thus be able to resubmit the But we plan to start the phase three study in the second half of this year, and then we will provide more clarity on timelines. Thank you.

Got it. Thank you. Very helpful.

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

With that, we would like to thank you all for attending and for your questions. We look very much forward to future announcements and updates and to connecting in the coming weeks and months. Thank you.

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