Zealand Pharma A/S

Good day and thank you for standing by. Welcome to the Zealand Pharma Results Full Year 2025 Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 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, Vice President, Investor Relations. Please go ahead.

Thank you, Operator, and thank you to everyone for joining us today to discuss Zeeland Pharma's results for the full year 2025. The related company announcement is available on our website at zeelandpharma.com. As outlined on slide two, I would like to remind listeners that during today's call, we will be making forward-looking statements that are subject to risks and uncertainties. Turning to slide three and today's agenda, I have with me on the call the following members of Xenon Pharma's management team. Adam Steensberg, President and Chief Executive Officer, Henriette Wendiger, Chief Financial Officer, and David Kendall, Chief Medical Officer. All speakers will be available for the Q&A session. Turning to slide four, I will now hand the call over to Adam Steinsberg, President and Chief Executive Officer.

Adam. Thank you, Adam, and welcome, everyone. 2025 was a breakthrough year for Seed&Pharma, especially considering the landmark partnership for betrayantide with rose. As we enter 2026, we are moving into the most defining and catalyst-risk year for Seed&Pharma's history, which includes phase 2 between-type data, and multiple key readouts from the phase 3 program in obesity with cerebral type. Moving to slide 5, obesity represents one of the greatest healthcare challenges of our time, not only because of its high and growing prevalence, but because of the long-term consequences of living with the disease. The longer people live with obesity, the greater the burden and the higher the risk of serious complications. Real world data clearly shows that treatment persistence with GLP-1 based therapies remains a major challenge. To date, up to 12% of Americans have been exposed to a GLP-1 based therapy, yet only a small fraction remains in treatment. Approximately half of patients who discontinued the other one therapies cite gastrointestinal adverse events as the primary reason. As a result, the key to unlocking the full value of this market is to develop therapies that deliver weight loss that patients desire, but with a better treatment experience that support long-term use in a real world. This leads me to slide six. In many other chronic diseases, physicians typically have access to a broad range of therapeutic options that can be tailored to the needs of the individual patients. In obesity, the treatment landscape remains comparatively narrow, where we today rely on a single therapeutic category. While the DLT1-based therapies clearly have advanced the field, they have not yet delivered what ultimately matters the most, long-term treatment persistence, durable weight maintenance, and sustained improvements in health outcomes. With Petrinatide, we see the potential to expand and strengthen the treatment paradigm for weight management. Moving to slide seven, the partnership we announced last year with Ross has delivered on everything we had hoped for. and our teams are currently moving full steam ahead and focused on finalizing the design of the phase three program that we expect to initiate later this year to position Petranitide as a future foundational and first choice therapy for people living with overweight and obesity. I want to emphasize that this is a true balanced partnership. This is reflected not only in the financial structure where we share profits in the US and Europe, but also at the strategic level with shared development and commercialization rights for the trinitide and the trinitide-based combinations. This structure allows us to retain significant long-term value of the franchise while preserving the strategic rights needed to support our ambition over the long term. Moving to slide eight, from one strong partner to another. Werner Ingenheim is positioned to lead the next wave of GLD1-based innovation with Cervarotide. And we are very excited about the potential of Cervarotide to emerge as the preferred therapy for a large population of people with obesity and MASH. Liver disease is one of the most prevalent comorbidities associated with obesity. As Boehringer highlighted at Obesity Week last year, when you see obesity, think liver. And as one of our external speakers and the principal investigator in Synchronized One noted at our Capital Markets Day, see obesity, think liver, treat the heart. This framing highlights the excitement for the upcoming phase 3 obesity data with Cervarutide, including data from the cardiovascular outcome trial. Switching gears to our research efforts on slide nine, our ambition extends beyond refining the near-term future of weight management. Over the coming period, we aim to build the most valuable metabolic health pipeline, supported by our competitive advantages with more than 25 years of expertise in peptide and metabolic health, proprietary know-how, and high-quality in-house data. Combined with rapid advancements in AI and machine learning, this strong foundation position us to remain at the forefront of innovation. While AI will improve efficiency across the industry, true differentiation comes from the quality and scale of proprietary data used to train these models. This is where we intend to focus our efforts. Our goal over the next five years is to advance more than 10 candidates into the clinic and set industry leading cycle times from idea to the clinic. In a field historically characterized by long and complex development cycles, the pace of innovation is accelerating and we intend to lead that. With that, I will turn it over to David.

Thank you, Adam. I will begin with an overview of our pipeline shown on slide 10. Zeeland Pharma is in a unique position today with the potential to achieve five product launches over the next five years. We are also embarking upon a data-rich period ahead with important results from many of our clinical programs. All told, this represents an incredibly exciting and highly compelling path forward for our company. Let's turn to slide 11 in the Zupreme 1 trial with Petrelantide. We look forward to reporting top-line data from the Phase 2 Zupreme 1 trial this quarter. This trial is evaluating the efficacy and safety of petrolentide in participants with overweight or obesity without coexisting type 2 diabetes. Zupreme 1 is a dose-finding trial assessing five dose levels of petrolentide administered weekly versus placebo over 42 weeks of active treatment. The trial includes monthly dose escalation over a period of up to 16 weeks, followed by maintenance doses of up to 9 milligrams. The study's primary endpoint assesses change in body weight at week 28. However, top-line readout will also include important efficacy and safety measures at week 42. As previously shared, SUPREME 1 enrolled a population of 494 participants with a mean baseline BMI of approximately 37 kilograms per meter squared and includes a balanced distribution of females and males. This population differs meaningfully from those studied in our Phase I trials and also from populations enrolled in recent Phase II and Phase III clinical trials of other amylin analogs. Moving to slide 12 for a reminder of our ongoing plans for petrolentide. Together with our partner, Roche, we are looking forward to leveraging insights from the Zupreme 1 trial to inform the final design of a comprehensive and ambitious Phase 3 development program for petrolentide in weight management. We expect to initiate the Phase 3a registrational trials for petrolentide monotherapy later this year, which will be followed by a comprehensive Phase 3b program designed to further expand and unlock the full value of petrolentide. With Phase 2 data approaching, I would like to briefly revisit our target product profile for petrolentide. Our goal with petrolentide is to deliver the level of weight loss that the vast majority of people living with overweight and obesity are seeking, while also providing an improved patient experience to further enhance the use of petrolentide for long-term treatment. Accordingly, a successful outcome for us would be data that reinforces our confidence in Petrelentide's potential to achieve approximately 15% to 20% body weight reduction in longer-term Phase III trials, together with a safety and tolerability profile that represents a significantly better experience relative to incretin-based therapies, firmly establishing Petrelentide as a foundational therapy for the management of overweight and obesity. In parallel, we are excited about the opportunity to explore petrolentide as a backbone for future combination therapies. Petrolentide in combination with the dual GLP-1 GIP receptor agonist CT388 is the first combination being developed in our alliance with Roche. Zeeland Pharma and Roche remain on track to initiate the Phase II trial of the petrolentide CT388 combination in the first half of this year. Now turning to slide 13 and cervodotide, a glucagon GLP-1 receptor dual agonist that we believe has the potential to play an important role in the next phase of innovation in obesity and metabolic disease. In the first half of 2026, we look forward to the results from the 76-week synchronized one trial, which is evaluating the safety and efficacy of cervodotide in people with overweight or obesity without type 2 diabetes. In the prior 46-week Phase II obesity trial, cervodotide demonstrated very compelling and competitive weight loss of up to 19%. Beyond synchronized one, we expect additional readouts from the broader Phase III obesity program over the course of 2026. Together, these data are expected to support the first regulatory submissions for cervodotides. We are also excited and extremely encouraged by the ongoing phase three program evaluating servotetide in people with metabolic dysfunction associated to sciatohepatitis or MASH. This program includes two trials assessing safety and efficacy in patients with moderate to advanced fibrosis as well as in those with cirrhosis. Given the high unmet medical need and limited treatment options for this population, we believe cervodotide has the potential to become a key therapeutic option for people living with overweight or obesity and coexisting MASH. Let's now turn to slide 14 and our novel KB1.3 inhibitor. Yesterday, we announced positive top-line results from the first in-human randomized double-blind placebo-controlled Phase I trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of ZP9830 following a single administration to help email subjects. ZP9830 was very well tolerated with no serious or severe AEs or dose limiting safety findings at any of the dose levels tested. PK parameters increased in a dose proportional manner across the investigated dose range in line with predictions based on preclinical data. We are very pleased with the results of this trial that are very well aligned with our expectations, reinforcing our confidence in our KB1.3 channel blocker as a very promising drug candidate with the potential to target multiple autoimmune and inflammatory diseases. We look forward to reporting top-line results from the multiple ascending dose portion of this trial and progress in ZP9830 into Phase 1b2a development in the second half of 2026. With that, thank you very much for your attention. I would now like to turn the call over to our Chief Financial Officer, Henrietta Venike, who will review our financial results for 2025. Henrietta?

Thanks, David, and hello, everyone. Let's turn to site 15 and the income statement. Revenue for the full year of 2025 was 9.2 billion BKK, driven by the initial upfront payment received under the collaboration and license agreement with Roche. The net operating expenses, excluding other operating items, totaled 2.1 billion DKK in 2025 and were within the guidance range of 2 to 2.3 billion DKK. 76% of the net operating expenses in 2025 were dedicated to research and development, mainly driven by the clinical advancement of the paternity program, including the two Phase II trials and the preparation for phase 3. The SOM expenses are driven by the pre-commercial activities associated with mainly procurement time, while G&A expenses reflect a strengthening of organizational capability, investments in IT infrastructure, and legal expenses related to the patent portfolio. This resulted in a net positive result of 6.5 billion BKK per year. Let's move to slide 16 and the financial position. We ended the year of 2025 with a strong cash position of 15.1 billion DKK. Our cash position was strengthened during the year by the initial upfront payment of 9.2 billion DKK from Roche, partly offset by the operating expenses during the period. Our strong capital preparedness enable us to meet all obligations under the collaboration with Roche Computer Science, including the comprehensive phase three program. It will also allow us to intensify our efforts in building a leading metabolic health pipeline and deliver on our metabolic frontier 2030 strategy. Let's turn to slide 17 and the outlook for the year. For 2026, we guide for net operating expenses to be in the range of 2.7 to 3.3 billion DKK, mainly driven by research and development activities. On the development side, key cost drivers include the expected initiation of a Phase IIIa program with paternity monotherapy and the initiation of a Phase II trial with paternity TT388 combination. In addition, Strengthening our research engine is critical to realizing our vision of building a leading metabolic health pipeline, and the guidance therefore also reflects a step up in research costs. Overall, the anticipated OPEC spend reflects the momentum we have built into 2026 and positions Ceylon Pharma to leverage the future growth opportunities. And even though we only provide guidance on operating expenses, I would like to take the opportunity to remind you that Zealand Pharma is eligible for potential milestone payments for a rush of 700 million US dollars in 2026. This includes an anniversary payment of 125 million US dollars and a potential development milestone payment of 575 million US dollars, which is subject to initiation of a phase 3a program with the German site Monotherapy. Finally, let's move to slide 18 and our sustainability efforts. As a biotech company, we place the health and well-being of patients at the center of everything we do. And our ability to advance our pipelines and ultimately serve patients' risks on our people. We are extremely proud that while we increased our headcounts by 41% in 2025, we maintained a very high employee engagement score of 8.9 on a 10-point scale. And at the same time, we maintain our employee turnover rate at just 7.8%. We believe this is a testament to our unique company culture and our continued dedication to fostering an engaging and enriching workplace. This makes us confident that we have built a sustainable organization set up capable of supporting our long-term aspirations. We are also committed to taking responsibility for the environmental impact of our operations. In 2025, we committed to design-based targets initiative and joined the UN Global Compact. In 2026, we will continue our work to transition our company and collaborate closely with our business partners to mitigate climate change. And with that, I will move to slide 19 and turn the call back to Adam for closing remarks.

Thank you, Henriette. Building on the momentum we created in 2025, we have entered the most catalyst-rich year in Zealand farmers' history, with defining data readouts expected for both of our leading obesity programs, the train type and cervical type. As we execute on our metabolic frontier 2030 strategy, we are also highly energized to open our new research site in Boston this year, and to pursue additional partnerships that further strengthen and expand our pipeline. I will now turn over the call to the operator and we will be happy to address your questions.

Thank you. As a reminder, to ask a question you will need to press star 1 1 on your telephone and wait for your name to be announced. We ask participants to ask one question only To withdraw your question, please press star 1, 1 again. Please stand by while we compile the Q&A roster. We will take our first question, and the question comes from the line of Hakon Hem from Dankske Bank. Please go ahead. Your line is open.

Great. Thank you for taking my question. In regards to the upcoming Phase 2 readout on pretalentide, Phase 2, the Supreme 1, what level of details are you able to share with us on the day of the announcement? Apart from the weight loss, will you include data on pretalentide's tolerability profile in the announcement?

Thank you, Håkan, for that question. We can confirm that the data are anticipated this quarter, which of course means also in the coming weeks, and we are highly anticipating being able to share the data broadly. We will, as we always do when we share top line results, provide a balanced presentation of the data while also reserving that can be presented at scientific conferences later in the year. So you should expect a balanced view which will discuss both top line efficacy and safety tolerability. Thank you. Great.

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

Hi. Thanks for taking my question. I just wanted to get your latest perspectives on competitive dynamics in the obesity market following the first oral launch. I know you've always been clear in the view that injectables will be the largest segment of the market. Has anything changed given the launch trajectory of all Wegovy? And then maybe just to add on that, where do you expect net price to be in obesity by the time Petrolintide launches? Thank you.

Thank you for your question, Rajan. And I think it's – we have not – our minds around the oil versus injectables have not changed due to the recent launches. It's very important, and we remain, you can say, focused on the fact that the oil GSD ones that are launching right now do not address the biggest – what we consider the biggest issues with the GSD ones, which is solubility. As we discussed in the prepared remarks, we have 50% of the patients who stopped taking these medicines due to adverse events related to the gastrointestinal tract. So while we do expect all options to expand the GLP-1 market, we do not think it's actually addressing the main issue around the current therapies that are around. And that's why we're so excited about being able to lead in a novel category, which we think have the potential to provide patients, as David discussed, the weight loss they're looking for, but a more pleasant weight loss experience. And it's really back to the thing which we have also advocated for for a long time. Instead of having such a keen focus on prices, as an industry, we need to move the focus into how we help patients stay in therapy. The key to unlock the value of the beauty market is to make sure that obesity medications are used as chronic therapies rather than event-based weight loss agents. And that's where we think the training type and the amylin category has the potential to unlock the market's value for obesity. When it comes to prices, and which of course has a lot of focus right now in the current competitive environment, also with having had compounders around, it's again Some dynamics that we have talked about for a long time and the uniqueness about the BT market is we have the more classical market where we have payers and insurance companies and then we have the self-paid market and you need to address both. Of course, when you launch with a new category which may provide a much more pleasant weight loss experience, there will be novel dynamics also with regard to pricing. So while the DRT1 dynamics will affect entrance into that market, we do anticipate that novel themes will play out when you launch novel categories, just as we have seen in other therapeutic areas. But it's too early to provide any specifics on the net pricing when we launch Katrina type. Thank you.

Thank you.

Thank you. We will take our next question. The next question comes from the line of Kirsty Ross-Stewart from BNP Paribas. Please go ahead. Your line is open.

Hi. Yes, Kirsty Ross-Stewart from BNP Paribas. Thanks for taking my question. So regarding the phase 3b development for betrelentide, can you just expand a little bit on the types of opportunities you're hoping to unlock with the broader clinical trial programme and how much of the total opportunity do you believe is represented by the monotherapy Is that kind of the majority part? Is that what we should be thinking as the main part? Or just, you know, you're seeing this as a small portion and just the tip of the iceberg. And just related to that, can you remind us on the financial obligations from you and Rosh regarding the future phase 3B development? Thank you.

Thank you for your question. I'll just start with a few remarks and then hand over to David. So as you know, the focus for the team right now is to accelerate timelines to a potential launch of the training type. And in parallel, invest deeply in making sure that Petronatide will become a foundational and first-choice therapy and thus also having the data foundation to support that positioning. And we will share all costs with our partner, us, in those efforts. It's clearly the monotherapy that have our key focus right now, but as David also discussed, the combinations now starting with CD388 is also carrying investments as we progress these programs, and we would hope to see more combinations really utilizing the training types potentially as the foundational therapy. But perhaps, David, you can comment a little bit more on the Phase III considerations and why we have strong belief that it can become a foundational therapy.

Yeah, thanks, Adam, and thanks, Kirstie. As noted, the Phase IIIb program, beyond rapid acceleration of the Phase IIIa program to ensure the earliest possible submission and potential approval. You can imagine that it is obviously the outcomes that matter most to patients and their providers that will be the focus not only of the weight loss studies in Phase IIIa, but focusing on those complications which we know are readily tied to weight reduction, such as obstructive sleep apnea, osteoarthritis, and osteoarthritis pain, noting that amylin agonists may have the unique potential to favorably alter bone metabolism and impact pain markers. as has already been shown for the GLP-1 agonist, reduced weight has its benefits and going beyond that. But beyond those, I think attention to preserving muscle mass, maintaining functional status, focusing on the population that seeks weight-reducing therapies the most, specifically women and women's health implications. And finally, a very important impact of those coexistence comorbid conditions, cardiovascular outcomes being primary, looking at the impact on liver disease and other metabolic dysfunction associated comorbidities. As Adam noted, the focus initially is on monotherapy. establishing amylin-based therapies and petrolatide in particular as a foundational therapy, but understanding that in complex metabolic diseases such as lipid disorders, hypertension, type 2 diabetes, we have learned that the complexity of these diseases often requires multifaceted approaches to therapy. So combinations with incretin-based therapies and other modalities as being investigated by us and others, we believe will become the cornerstone of the optimal treatment for obesity and its related conditions. To reemphasize what Adam stated, of petrolentide as monotherapy, which we firmly believe can be foundational, but also substantially improve the patient experience will be the focus of Phase 3A with the extension in Phase 3B to unlock the full potential of this asset.

And just maybe a comment from me, Kirsten, as well on the financial obligations. So, yes, we will share costs both on Phase 3A, but also Phase 3B, 50-50 with Roche. As I mentioned in my remarks, we will receive $575 million in connection with the Phase 3 initiation, And we will also receive 575 million US dollars in connection with Phase 3B initiation from Washington.

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

Thanks for taking our questions and congratulations on this stellar 2025. Adam, I appreciate that you're moving the field away from the weight loss Olympics, as you coined the phrase. Just to gauge expectations for Supreme 1, semaglutide and terseptide showed an additional 2 and 3 percent weight loss from 42 weeks to study in. So, objectively, should we subtract that 2 to 3 percent from your TPP goal, just to account for the timing difference and gender mix for the imminent readout? And also, if you don't mind, maybe a macro question on what Lilly has done recently. We wanted to recategorize retachetide as a biologic. So if they're successful, do you think that that might set a precedent for all the peptides out there, including petrenatide? Thank you so much.

Thank you for your question, Indian. And I would say when you, and of course, everybody compares across the studies. When we have designed our Supreme One study, we have had one key focus, and that is to generate the most robust data set to allow us for the most robust decision making to move into phase three. So we have not enhanced the study with a disproportional high amount of women or high BMI, and we've also decided to look at the data point of week 42 instead of week 48, as others would do, and also have the most robust data set for phase three decisions. So when we then As David also shared in his prepared remarks, think about what are the weight loss that we anticipate to see and that we would expect in that study, under these study conditions, that translate into a 15 to 20 percent weight loss in a phase three study set up. That's how we will look at the data. And I would say, historically, when you look into male to female ratio, if you take a study that is enriched with only females versus males, you could probably expect what 5% more weight loss in the female-only cohort. If you then also enhance the BMI and the study duration, then you will see even higher differences. So we are looking for a data set that when we do our internal modeling will allow us to get this 15% to 20% weight loss. And the reason that we have called to end the weight loss Olympics is just the plain fact that patients are not interested Most patients are not interested in a weight loss above 20%. So why is it that we as an industry and a community keeps talking about those numbers as if they were so important? You can do these surveys among patients and you will get the same answer across any survey that we have seen thus far. And that's why I called for the end. As I also said, And as we discussed also in one of the prior questions, the key to unlock the value in this market is to develop therapies that provides patients with the weight loss they're looking for. And as importantly, therapies that they can stay on instead of therapies where they only take them for three to six months and then stop taking them. The big dilemma we have with people don't stay on therapy is that most will likely regain the weight and thus never get to the health benefits. So both from a patient, a society perspective, but also from a company value perspective, the focus has to be on treatments that deliver the weight loss that the most patients are looking for, 15 to 20%, and then importantly, medicines they can stay on. And that's why I'm calling to end the Weight Loss Olympics. Focus on medicines that deliver what the patients want, and you will unlock the value in this market. On your other question, With regard to milis efforts to move from a small molecule designation to a biologic, I'm sure that industry is looking into different ways to enhance, you can say, the positioning of their drugs. And I will not share our specific efforts to protect the value of our programs, but rest assured that we also have those efforts as key focus. Thank you. 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.

Hey, Yihan from Barclays. Thanks for taking our question. So I guess I wanted to switch gears a little bit to Servo the Tide and also Mesh. So for Mesh, based on our recent KOL checks, actually the off-label use of incretin in mesh appears increasingly common. So for example, our physicians would still use triseptide in mesh if possible, even though we know it is not formally approved by regulators. So I'm just curious from your market research, are you observing something similar in terms of this physician behavior? And also more broadly, like assuming Cervodotide will be launched in 2027, and we understood we might be more offhand on this partnership, but also wondering, you know, anything you could share regarding its commercial strategy across obesity and NASH. Thank you so much.

Thank you for your question. And, you know, it's important to note that it is Brian Engelheim who is solely responsible for the development and the commercialization of Cervodotide. We will just get and then high single to low double-digit royalties. The profile that we have seen thus far from the clinical data released by Boehringer Preservatotype gives us a lot of confidence in the molecule, both with regard to weight loss, but also in MASH. On the weight loss parameters, as we have discussed before, We think the weight loss levels and the weight loss experience is going to be quite comparable to what we have seen with some of the market leading field, the ones on the market today. We look forward to seeing the phase three data. When it comes to the mass data, the phase two mass data that we have seen, and it's also expressed by Boehringer at the time when the data was released, we see them as breakthrough data. These are unprecedented levels of improvement. And I think that's also reflected in the fact that Boehringer have decided to invest in the largest ever phase three program for MASS, not only addressing F2 and F3, but also F4 patients, which gives unique opportunities to broaden the potential label if approved beyond into the most severe cases of MASS, but also with the scope of the program could provide very early indications of clinical and not not just biomarker improvements with regard to what you mentioned as all flavor use if i heard you right of the other ones i would say please remember that the majority of mass patients are obese in the first place and thus of course it's a logical choice to use the existing medicines to help patients achieve some weight loss as many MASH patients suffer from both obesity and other complications than MASH. So that is only a natural consequence. What we believe is that once you have a product that can make a significant larger effect on the disease status, we should expect to see a very attractive take-up, also exemplified by the enrollment into the Phase III program and Phase II program for cervidotide. a high confidence in the program. We have a high confidence in Boehringer's ability to execute. They are one of the strongest large pharma players in the cardiovascular metabolic space, and we look forward to see the data coming out this year, including the cardiovascular outcome data and obesity.

Very helpful. Thank you.

Thank you.

Thank you. We will take our next question. The question comes from Zion Deng from UBS. Please go ahead. Your line is open.

Hi, it's Kim from UBS. Thank you for taking my question. So two, please. The first one is on Supreme One. So really appreciate you emphasized, reiterated the importance of tolerability. So just wondering, looking to Supreme One, just wondering what sort of profile would you actually consider as really your target profile in terms of tolerability? Would you say let's say, do you think it's actually possible to achieve, let's say, placebo level, you know, similar to placebo level of vomiting and constipation? So, any color on that, that would be great. So, the second one is sort of a general question. So, a few days ago, so Eli Lilly showed some quite interesting data combining tazepatide and TALS in psoriasis, which actually showed better skin clearance than TALS alone. Of course, that can arise with patients that are also obese, but just wondering if you have any thoughts on that and would you consider, for example, in the future collaborating with some other LTE immune players on something similar as well? Thank you.

Thank you for your question. I'll just start by putting some thoughts on your second question and then hand over to David to follow up and also address your first question. I think maybe also, Saul, that Yesterday, we also announced a phase one data readout with our KB1.3 ion channel dropper, which is a broad autoimmune anti-inflammatory target, which has potential across a number of inflammatory conditions. And thus, we see that as a potential pipeline in a product. And there's another notion out there that in relation to the obesity pandemic, you actually see quite significant increases in the prevalence of some chronic autoimmune and inflammatory conditions which had otherwise been seen as being rather stable. So we see a strong link between the obesity pandemic and the rising prevalence of some of these conditions. And it's clear that if you name things like psoriasis or even IBD, there are some strong links with the obesity pandemic. So we are highly energized by our own K1.3 data and the opportunity to perhaps link metabolism and inflammation in the future. But David, maybe you want to elaborate.

Yeah, and again, thanks for your questions. On the issue of tolerability, noting that tolerability is really a collection of factors, we focus obviously a great deal on the GI adverse events that have been made so central, particularly to incretin-based therapies. And while our phase one data to date have suggested the potential for significantly lower rates of nausea, vomiting, and certainly lower rates of the more chronic GI adverse events associated with GLP-1-based therapies, namely diarrhea and constipation, in Supreme 1 and subsequent trials, tolerability and acceptability of the entire experience will be the focus of our evaluation so looking obviously at GI adverse events but in combination with the injection experience the experience around dosing and dose escalation and back to the question that was posed to Adam on orals versus injectables If one thinks about the currently available therapies and the target product profile for petrolentide, we anticipate that the weekly injection will consume about 10 to 20 seconds of an individual patient's time, which clearly can be associated with the acceptability of a treatment, assuming that injection experience is without reactions, pain, discomfort, which we have seen in our Phase I trials to date. So I encourage you and others, as we will be doing, to look at tolerability and acceptability as a collection of these factors, GI adverse events and more. And to Adam's ultimate point, if that experience is highly acceptable to patients, that will further encourage long-term persistence on therapies, and particularly therapies that give patients the weight loss they desire.

Thank you. Thank you.

We will take our next question. The question comes from the line of Jen Gia from Cantor Fitzgerald. Please go ahead. Your line is open.

Hi, this is Jennifer Gia on behalf of Pekar Agarwal from Cantor Fitzgerald. Thank you for taking my question. So I was wondering, for the upcoming Phase 2b obesity retail for Prichal and Tai, in what way can it differentiate on safety, tolerability versus lilies, amline, and loralentide, and also for the combo with pertralentide with CT-388. Could you give more context on dosing across the two products, titration schedule, as well as how you want to mitigate the GI tox previously seen with CT-388? Thank you.

Thank you for that question. As we have tried to convey on this call, the most important aspect for us when we review these data is to confirm that we have a product that lives up to the target product profile, which we have discussed a number of times, which is delivering a 15% to 20% weight loss and a more pleasant weight loss experience. If we have that, we will have a leading molecule within a new category. And I think it's really, really important To also look back at the data that have been generated thus far with the training type, which gives us the confidence when we look across the different amylin assets, we have what looks to be the best-in-class amylin analog in development. And that's why we move towards the Phase II data with a high level of confidence, both with regard to weight loss and tolerability data. But the most important part for us is to get confirmation in this Phase II data wrap data with what we have seen in the Phase I, and thus that we are fully on the path to deliver on our target profile. And thereby, as we have also communicated several times, we think the Trinitide and amylin in general has the potential to be a larger category for weight management than the GSV-1s, because if we allow patients to stay in therapy and you don't have to go out and capture new patients all the time, you would rapidly see the volume of such a category outgrow the volumes of a category where people stopped taking medicines early on. So this is the key focus for us when we look at the data. And we move forward based on the prior data experience, which I think we have released to the market. So we all have the opportunity to look at those data that Petrinatide has the potential to be the best in class amylin of those that are in the clinic today. But the combination product, of course, is also a unique opportunity. And with CD388, when we did the diligence and the partnership with us, our conclusion was that CD388 looked to be potentially also a best-in-class 1-DIP molecule. And we look very much forward to seeing further data from that program. But when we think about the combination with that molecule, our gut feeling, if you will, max out on the potential of the trinitide and then add a teaspoon of the GS1 component to enhance the weight loss experience for those patients who need the highest weight loss. And so we look forward to share more on the study designs and of course ultimately the data that comes out of the Phase IIb study for the combination that we will start later this year. Thank you, Jennifer.

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

Thank you. A question from me, please, just on the planned phase 3a study design. I wonder if you can share any more detail on that. It's clear the message there is to expect you to accelerate launch and deal with the CBOT data later, but can you discuss the end point, the study time period that you're looking at for the Phase 3a study? I mean, for example, could we see a scenario where six months weight loss is sufficient to get a first approval for petrolentide?

Thank you. Thank you for your question. I think what we can reassure you is that we, together with Ross, we're doing everything possible to accelerate, and we have identified some very good levers and have a lot of confidence that we can accelerate and push this program as fast as possible forward. We cannot share the details, also the exact details on submission timelines due to the fact that this is a partnership, so we need to agree on when to discuss these things. But we are all on in both organizations to make sure that things are being accelerated towards submission and ultimately announced. What is also important here to note, and one of the main reasons that we decided to partner this program at the time with it was, of course, investments into manufacturing capacity. And we have been extremely pleased to see the announcement that Ross has come out with with regard to investments into high-volume, high-throughput manufacturing capacity, which, of course, is needed if you want to secure successful loans when these products hit the market. And I think that's, again, coming back to the uniqueness of the partnership we have here and the uniqueness of CELAN today is that we are As I conveyed at our capital markets day, and we continue to operate as a biotech company, and we will bring in the best from that world. But in the collaboration with us, we will also leverage the strength of a pharma company as we approach the market with the train side. And I don't think you have seen many of these partnerships, but that is why we keep coming back to the strategic value and the And of course the profit share we have in this partnership is unique and is one which we are extremely pleased with to see also how it progresses. We will hopefully soon be able to share more on the exact timelines as we move the program into phase three, but it's just perhaps one quarterly call too early.

Thank you. Thank you. We will take our next question. The question comes from the line of Suzanne van Woutersen from VLK. Please ask your question.

Hi, team. This is Suzanne from Kempten. Thanks for taking my question. Looking beyond the Phase 2b readout that we're all eagerly awaiting and I believe how Petra could provide an alternative to incretins and the product profile you're targeting is very clear. But I wonder if you could elaborate for the longer run based on the knowledge today and the data sets that have been reported for the various amylin assets out there, how do you expect the tridentite to be positioned within the amylin class? What would you expect in terms of differentiation versus the other amylins later down the line? And maybe one clarification about the research site in Boston, what will this hub focus on and how would that complement the capabilities in Copenhagen? Thank you.

It is too early for us to share our thoughts about the ultimate differentiation between the different amylin analogs. We have been extremely pleased with the data that we have seen thus far when it comes to the balance between weight loss, tolerability, and safety findings. Also, when we compare across the different modalities, the different amylin analogs in the clinic today. So, and we see a clear opportunity to continue to develop that differentiation that we have already observed until today. Another key aspect, which I think is important to note as well, is as we enter this market, this will be the number one, two, and three focus for Zeeland to build Petronitide into a leading molecule within the aminine class. Others will have to spend more time thinking about existing franchises. and how to protect current molecules that are already on the market. And that's a strength and a force which I don't think people should underestimate. On the research side, in Boston, as Utpal shared a little bit on our Capital Markets Day, but it's really going to be a site that will complement what we do in Denmark. In Denmark, we are one of the strongest, if not the strongest research group within peptide chemistry and also having worked in metabolic diseases and health for more than 25 years have very unique expertise in those areas. In Boston, we'll build complementary skills, including focus on high-throughput research labs, machines that are built specifically to tap into the automatization that we are seeing in research these days. And on top of that, we are also going to broaden out to modalities beyond peptides. And part of that broadening out will be through partnerships. We just announced one in December with OCR, which has to do with small molecules. But we expect to announce more partnerships, but we will also build some in-house capabilities so we can become best partners to these opportunities. So it's broadening beyond peptide modalities, and it's also with a high focus on automatization and high throughput, really leading to our firm conviction that we can deliver industry-leading times from idea to the clinic as we build our infrastructure in the coming period. Thank you for that.

Thank you. Once again, if you wish to ask a question, please press star 1 1 on your telephone. We will take our next question. And the question comes from Rajan Sharma from Goldman Sachs. Please go ahead. Your line is open.

Hi, thanks for taking the follow-up question. Could you just discuss the rationale for restarting development of a GIP analog? Firstly, just to clarify, is this the same asset which you previously deprioritized? And then just in terms of strategy here, do you expect to see monotherapy activity, or is this really a combination asset for the future? And how should we think about that in the context of CT388, which is a GLP-1 GIP co-agonist? Thank you.

Thank you, Rajan. I'll hand it over to David.

Thanks, Rajan. Yes, this is the asset that has been part of our pipeline all along. And as you have likely noted, I mean, the interest in leveraging GIT pharmacology, while it is still in its infancy, both with the development of triseptide and other GLP-1 GIP molecules, the recent announcement of Novo looking at combinations with an amylin analog. But our understanding, as we've stated all along, that combination therapies can ultimately be leveraged to target this complex metabolic set of disorders, obesity and beyond. And while GIP monotherapy, as has been reported by others, may not in and of itself have potent weight-reducing effects, the potential to further improve insulin action or insulin sensitivity, the ability to unlock even greater effect of other molecules, including amylin-analog other incretin hormones and other peptide signals is becoming clearer. And for us, this is yet another venture into the potential for combination approaches to targeting these complex metabolic diseases. And again, our commitment to improving metabolic health overall goes beyond, as Adam said, simply reducing body weight, simply targeting MASH to improving things like insulin action, targeting specific aspects of fat cell or adipocyte behavior, and using this pharmacology to really target multiple tissues, multiple organs, and further enhance the effect of other peptide and non-peptide signals. So starting with the first in human, to ensure understanding of the PK and safety and tolerability, and then we hope to rapidly advance into assessment of unique combinations with amylin assets and other signals.

Thank you.

Thank you. We will take our next question. The question comes from the line of Susan Chaw from Wells Fargo. Please go ahead. Your line is open.

Hi, this is Susan on for Mohit. Just a quick question on Supreme 1 dose titration cohorts. Can you speak a little bit more on the rationale behind the timing and the step-up doses that were chosen for the trial? And as a follow-up, you know, where do you expect to see the most improvement on the side effects?

Thank you for your question. The rationale for the dose titration, or you could even say is it even a titration because you could expect, of course, to see weight loss even at the lower doses, but it's the ability to get to the higher doses. A dosing escalation every four weeks is a practical way to do it, our phase one B data suggests that we could do more frequent dose escalation and not compromise the tolerability from a GI side effect profile. It was clean, as you remember, except for one dosing arm where they started at a higher dose than what we do here. So it's also about the practical timing for dose escalation. I don't think we have the same issues as you have with the TLC1s, where you need to titrate carefully. And remember, also, a lot of patients, you will have to down titrate when you have decided to titrate up, then you have to back off for some weeks and then back off. That is what becomes, that's why it becomes so complicated to get patients to the higher doses of the GERD1, but we have not seen that with the aminins. In all our titration steps, we have seen patients being able to tolerate the next dose with any significant new adverse events. So for us, it's more a practical decision rather than something that has to decide with how you have to do it, actually, from a side effect profile. Thank you.

Thank you. We will take our final question. The final question comes from the line of Jen Gere from Cantor Fitzgerald. Please go ahead. Your line is open.

Thanks so much for taking this follow-up question. On 9830, the channel blocker, what indications would you consider pursuing and what would be the rationales for that?

We have some very good ideas about where we want to take the molecule in next. And what you should expect is that we will be pursuing several indications also in parallel. Because if you look into the biology rational, we are looking at what could become a pipeline in a product. It's too early for us to share which indications we are going for, but you should expect us to pursue several indications in parallel. It is a target that industry has been pursuing for a very long time without success because of the difficult nature of addressing this target. And that's also why, as David shared before, we are extremely excited about the fact that we have not only seen PK, but also clear effects of target engagement from a PD perspective in the phase one study. So we think we have something that could be a future jewel in our pipeline. But the specific indications we'll have to come back with later.

Thank you.

All right. Okay. And with that, I would like to 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. Thank you for participating. You may now disconnect.