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Operator: Good day, and thank you for standing by. Welcome to the Zealand Pharma Results Full Year 2025 Conference Call. [Operator Instructions] Please be advised that, today's conference is being recorded. I would now like to hand the conference over to your speaker today, Adam Lange, Vice President, Investor Relations. Please go ahead.
Adam Lange: Thank you, operator, and thank you to everyone for joining us today to discuss Zealand Pharma's results for the full year 2025. The related company announcement is available on our website at zealandpharma.com. As outlined on Slide 2, 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 3 and today's agenda. I have with me on the call the following members of Zealand Pharma's management team: Adam Steensberg, President and Chief Executive Officer; Henriette Wennicke, Chief Financial Officer; and David Kendall, Chief Medical Officer. All speakers will be available for the Q&A session. Turning to Slide 4. I will now hand the call over to Adam Steensberg, President and Chief Executive Officer. Adam?
Adam Steensberg: Thank you, Adam, and welcome, everyone. 2025 was a breakthrough year for Zealand Pharma, especially considering the landmark partnership petrelintide with Roche. As we enter 2026, we are moving into the most defining and catalyst risk year for Zealand Pharma's history, which includes Phase II petrelintide data and multiple key readouts from the Phase III program in obesity with survodutide. Moving to Slide 5. Obesity represents one of the greatest health care 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 discontinue GLP-1 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 6. 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 GLP-1-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 petrelintide, we see the potential to expand and strengthen the treatment paradigm for weight management. Moving to Slide 7. The partnership we announced last year with us 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 III program that we expect to initiate later this year to position petrelintide 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 U.S. and Europe, but also at the strategic level with shared development and commercialization rights for petrelintide and petrelintide-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 8 from one strong partner to another. Boehringer Ingelheim is positioned to lead the next wave of GLP-1-based innovation with survodutide, and we are very excited about the potential of survodutide 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 SYNCHRONIZE-1 noted at our Capital Markets Day, see obesity, think liver, treat the heart. This framing highlights the excitement for the upcoming Phase III obesity data with survodutide, including data from the cardiovascular outcome trial. Switching gears to our research efforts on Slide 9. 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 advantage with more than 25 years of expertise in peptides 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 5 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 over to David.
David Kendall: Thank you, Adam. I will begin with an overview of our pipeline shown on Slide 10. Zealand Pharma is in a unique position today with the potential to achieve 5 product launches over the next 5 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 and the ZUPREME-1 trial with petrelintide. We look forward to reporting top line data from the Phase II ZUPREME-1 trial this quarter. This trial is evaluating the efficacy and safety of petrelintide in participants with overweight or obesity without coexisting type 2 diabetes. ZUPREME-1 is a dose-finding trial assessing 5 dose levels of petrelintide 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, ZUPREME-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 petrelintide. 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 III development program for petrelintide in weight management. We expect to initiate the Phase IIIa registrational trials for petrelintide monotherapy later this year, which will be followed by a comprehensive Phase IIIb program designed to further expand and unlock the full value of petrelintide. With Phase II data approaching, I would like to briefly revisit our target product profile for petrelintide. Our goal with petrelintide 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 petrelintide for long-term treatment. Accordingly, a successful outcome for us would be data that reinforces our confidence in petrelintide'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 petrelintide as a foundational therapy for the management of overweight and obesity. In parallel, we are excited about the opportunity to explore petrelintide as a backbone for future combination therapies. Petrelintide in combination with the dual GLP-1 GIP receptor agonist, CT-388, is the first combination being developed in our alliance with Roche. Zealand Pharma and Roche remain on track to initiate the Phase II trial of the petrelintideCT-388 combination in the first half of this year. Now turning to Slide 13 and survodutide, 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 SYNCHRONIZE-1 trial, which is evaluating the safety and efficacy of survodutide in people with overweight or obesity without type 2 diabetes. In the prior 46-week Phase II obesity trial, survodutide demonstrated very compelling and competitive weight loss of up to 19%. Beyond SYNCHRONIZE-1, 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 survodutide. We are also excited and extremely encouraged by the ongoing Phase III program evaluating survodutide in people with metabolic dysfunction-associated steatohepatitis or MASH. This program includes 2 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 survodutide 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 Kv1.3 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 healthy male 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 Kv1.3 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 ZP9830 into Phase Ib/IIa 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, Henriette Wennicke, who will review our financial results for 2025. Henriette?
Henriette Wennicke: Thanks, David, and hello, everyone. Let's turn to Slide 15 and the income statement. Revenue for the full year of 2025 was DKK 9.2 billion, driven by the initial upfront payment received under the collaboration and license agreement with Roche. The net operating expenses, excluding other operating items, totaled DKK 2.1 billion in 2025 and was within the guidance range of DKK 2 billion to DKK 2.3 billion. 76% of the net operating expenses in 2025 were dedicated to research and development, mainly driven by the clinical advancement of the petrelintide program, including the 2 Phase II trials and the preparation for Phase III. The S&M expenses are driven by the pre-commercial activities associated with mainly petrelintide, while G&A expenses reflect a strengthening of organizational capabilities, investments in IT infrastructure and legal expenses related to the patent portfolio. This resulted in a net positive result of DKK 6.5 billion for the year. Let's move to Slide 16 and the financial position. We ended the year of 2025 with a strong cash position of DKK 15.1 billion. Our cash position was strengthened during the year by the initial upfront payment of DKK 9.2 billion from Roche, partly offset by the operating expenses during the period. Our strong capital preparedness enabled us to meet all obligations under the collaboration with Roche for petrelintide, including the comprehensive Phase III 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 DKK 2.7 billion to DKK 3.3 billion, mainly driven by research and development activities. On the development side, key cost drivers include the expected initiation of a Phase IIIa program with petrelintide monotherapy and the initiation of a Phase II trial, the petrelintide CT-388 combination. In addition, strengthening our research engine is critical to realizing our vision of building a leading metabolic pipeline and the guidance, therefore, also reflects a step-up in research costs. Overall, the anticipated OpEx spend reflects the momentum we have built into 2026 and position Zealand 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 Roche of USD 700 million in 2026. This includes an anniversary payment of USD 125 million and a potential development milestone payment of USD 575 million, which is subject to initiation of a Phase IIIa program with petrelintide 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 ensure advance our pipeline and ultimately serve patients rest on our people. We are extremely proud that while we increased our headcount by 41% in 2025, we maintained a very high engagement -- employee engagement score of 8.9 on a 10-point scale. And at the same time, we maintained 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 setup 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 the science-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 partner to mitigate climate change. And with that, I will move to Slide 19 and turn the call back to Adam for closing remarks.
Adam Steensberg: Thank you, Henriette. Building on the momentum we created in 2025, we have entered the most catalyst-rich year in Zealand Pharma's history with defining data readouts expected for both of our leading obesity programs, petrelintide and survodutide. 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.
Operator: [Operator Instructions] We will take our first question, and the question comes from the line of Hakon Hemme from Danske Bank.
Hakon Hemme Jørgensen: In regards to the upcoming Phase II readout on petrelintide Phase II, the ZUPREME-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 petrelintide's tolerability profile in the announcement?
Adam Steensberg: Thank you, Hakon, for that question. So 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 data 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.
Operator: We will take our next question. Your next question comes from the line of Rajan Sharma from Goldman Sachs.
Rajan Sharma: 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 or Wegovy? And then maybe just to add on that, where do you expect net price to be in obesity by the time petrelintide launches?
Adam Steensberg: Thank you for your question, Rajan. And I think it's -- we have not -- our minds around the oral 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 all GLP-1s that are launching right now do not address the biggest -- what we consider the biggest issues with the GLP-1s, which is tolerability. As we discussed in the prepared remarks, we have 50% of the patients who stop taking these medicines is due to adverse events related to the gastrointestinal tract. So while we do expect the all options to expand the GLP-1 market, we do not think it will -- it's actually addressing the main issue around the current therapies that are around. And that's why we are 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 are 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 on therapy. The key to unlock the value of the obesity 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 petrelintide and the amylin category has the potential to unlock the market 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 obesity 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 GLP-1 dynamics will affect entrant 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. So -- but it's too early to provide any specifics on the net pricing when we launch petrelintide.
Operator: We will take our next question. The next question comes from the line of Kirsty Rosergewart from BNP Paribas. Kirsty Ross-Stewart from BNP Paribas.
Kirsty Ross-Stewart: Kirsty Ross-Stewart from BNP Paribas. So regarding the Phase IIIb development for petrelintide, can you just expand a little bit on the types of opportunities you're hoping to unlock with the broader clinical trial program? 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 are you 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 Roche regarding the future Phase IIIb development?
Adam Steensberg: Thank you for your question. I'll just start with a few remarks and then hand over to David. So as -- as you know, our -- the focus for the team right now is to accelerate time lines to a potential launch of petrelintide and in parallel, invest deeply in making sure that petrelintide will become a foundational and first choice therapy and thus also having the data foundation to support that positioning. And we will have -- we'll 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 CT-388 is also carrying investments as we progress these programs. And we will hope to see more combinations really utilizing petrelintide's potentially as a foundational therapy. But perhaps, David, you can comment a little bit more on the Phase III considerations and why we have strong believe that it can become a foundational therapy.
David Kendall: Yes. Thanks, Adam, and thanks, Kirsty. As noted, the Phase IIIb program beyond a 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 with 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 coexistent 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 petrelintide 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, petrelintide as monotherapy, which we firmly believe can be foundational, but also substantially improve the patient experience will be the focus of Phase IIIa with the extension in Phase IIIb to unlock the full potential of this asset.
Henriette Wennicke: And just maybe a comment from me, Kirsty, as well on the financial obligation. So yes, we will share costs both on Phase IIIa but also Phase III 50-50 with Roche. As I mentioned in my remarks, we will receive USD 575 million in connection with the Phase III initiation, and we will also receive USD 575 million in connection with Phase IIIb initiation from us.
Operator: We will take our next question. Your next question comes from the line of Andy Hsieh from William Blair.
Tsan-Yu Hsieh: Congratulations on a 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 ZUPREME-1, semaglutide and tirzepatide showed an additional 2% and 3% weight loss from 42 weeks to study end. So objectively, should we subtract that 2% to 3% 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 as a biologic. So if they're successful, do you think that, that might set a precedent for all the peptides out there, including petrelintide?
Adam Steensberg: Thank you for your question, Andy. And I would say when you -- and of course, everybody compares across studies. When we have designed our ZUPREME-1 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 III. 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 in order to have the most robust data set for Phase III 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 -- we would expect in that study under these study conditions that translate into a 15% to 20% weight loss in a Phase III study setup. 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 would 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 Olympic 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 call 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 3 to 6 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 the weight loss Olympic, 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 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 that -- those efforts as key focus.
Operator: We will take our next question. Your next question comes from the line of Yihan Li from Barclays.
Yihan Li: Yihan from Barclays. So I guess I wanted to switch gear a little bit to survodutide and also MASH. So for MASH, based on our recent KOL checks, I believe the off-label use of including MASH appears increasingly common. So for example, our physicians would still use tirzepatide in MASH, 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 survodutide will be launched in 2027, and we understood you might be more offense on this partnership, but also wondering anything you could share regarding its commercial strategy across obesity and MASH?
Adam Steensberg: Thank you for your question. And it's important to note that it is Boehringer Ingelheim, who is solely responsible for the development and the commercialization of survodutide. We will just get milestones and then high single to low double-digit royalties. The profile that we have seen thus far from the clinical data released by Boehringer for survodutide gives us a lot of confidence in the molecule, both with regards 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 GLP-1s on the market today. We look forward to seeing the Phase III data. When it comes to the MASH data, the Phase II MASH data that we have seen and is also expressed by Boehringer at the time when the data was released, we see them as breakthrough data. These are unprecedented levels of improvements. And I think that's also reflected in the fact that Boehringer have decided to invest in the largest ever Phase III program for MASH, 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 MASH, but also with the scope of the program could provide very early indications of clinical and not just biomarker improvements. With regard to what you mentioned as off-label use, if I heard you right, of the GLP-1s, I would say please remember that the majority of MASH 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 survodutide. So we have 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 in obesity.
Operator: We will take our next question. The question comes from Xian Deng from UBS.
Xian Deng: Xian from UBS. So 2, please. The first one is on ZUPREME-1. So really appreciate you emphasized -- reiterated the importance of tolerability. So just wondering, looking into ZUPREME-1, just wondering what sort of profile do you -- 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 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 tirzepatide and Taltz in psoriasis, which actually showed better skin clearance than Taltz alone. Of course, that's in psoriasis 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 autoimmune players on something similar as well?
Adam Steensberg: 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 you also saw that yesterday, we also announced a Phase I data readout with our Kv1.3 ion channel drug, 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 Kv1.3 data and the opportunity to perhaps link metabolism and inflammation in the future. But David, maybe you want to elaborate.
David Kendall: Yes. 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 I 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 ZUPREME-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 petrelintide, 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.
Operator: We will take our next question. The question comes from the line of Jen Jia from Cantor Fitzgerald.
Jennifer Jia: This is Jennifer Jia on behalf of Prakhar Agrawal from Cantor Fitzgerald. So I was wondering for the upcoming Phase IIb obesity readout for petrelintide, in what way can it differentiate on safety, tolerability versus Lilly's amylin eloralintide, and also for the combo with petrelintide with CT-388. Could you give more context on dosing across the 2 products, titration schedule as well as how you want to mitigate the GI tox previously seen with CT-388?
Adam Steensberg: Thank you for that question. It's 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 category -- 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 petrelintide, 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 with what we have seen in the Phase I and thus, that we are fully on the path to deliver on our target product profile. And thereby, as we have also communicated several times, we think petrelintide and amylin in general has the potential to be a larger category for weight management than the GLP-1s because if you allow patients to stay on therapy and you don't have to go out and capture new patients all the time, you would rapidly see the volumes of such a category outgrow the volumes of a category where people stop 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 petrelintide has the potential to be the best-in-class amylin of those that are in the clinic today. The combination product, of course, is also a unique opportunity. And with CT-388, when we did the diligence and the partnership with us, our conclusion was that CT-388 look to be potentially also a best-in-class GLP-1/GIP molecule. And we look very much forward to seeing further data from that program. But the combination -- when we think about the combination with that molecule, our gut feeling, if you will, would be to max out on the potential of petrelintide and then add a teaspoon of the GLP-1 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.
Operator: We will take our next question. The next question comes from the line of Kerry Holford from Berenberg.
Kerry Holford: A question from me is just on the planned Phase IIIa study design. I wonder if you can share any more detail on that. It's clear the message here is to expect you to accelerate launch and deal with the CVOT data later. But can you discuss the endpoint, the study time period that you're looking at for the Phase IIIa study? I mean, for example, could we see a scenario where 6 months weight loss is sufficient to get a first approval for petrelintide?
Adam Steensberg: Thank you for your question. I think what we can reassure you is that we, together with us, we are doing everything possible to accelerate, and we have some -- 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 time lines 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 a launch. What is also important here to note and one of the main reasons that we decided to partner this program at the time we did was, of course, investments into manufacturing capacity -- and we have been extremely pleased to see the announcements that have come out with, with regard to investments into high-volume, high-throughput manufacturing capacity, which, of course, is needed if you want to secure a successful launch 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 Zealand today is that we are -- as I conveyed at our Capital Markets Day, and we continue to operate as a biotech company, but we -- and that's the -- 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 petrelintide. 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 of course, the profit share we have in this partnership is unique and it's 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 time lines as we move the program into Phase III, but it's just perhaps one quarterly call too early.
Operator: We will take our next question. The question comes from the line of Suzanne van Voorthuizen from VLK.
Suzanne van Voorthuizen: This is Suzanne from Kempen. Looking beyond the Phase IIb readout that we're all eagerly awaiting and I believe how petrelintide 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 petrelintide to be positioned within the amylin class? What would you expect in terms of differentiation versus the other amylin 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?
Adam Steensberg: Thank you, Suzanne. 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 and tolerability and safety findings also when we compare across the different modalities, 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 in until today. Another key aspect, which I think is important to note as well is as we enter this market, this will be the #1, 2 and 3 focus for Zealand and to build petrelintide into a leading molecule within the amylin 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 will build complementary skills, including focus on high throughput research labs machines that are built -- labs 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 OTR, 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 few years.
Operator: [Operator Instructions] We will take our next question. The question comes from Rajan Sharma from Goldman Sachs.
Rajan Sharma: 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 CT-388, which is a GLP-1/GIP co-agonist?
Adam Steensberg: Thank you, Rajan. I'll hand it over to David.
David Kendall: Yes. 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 GIP pharmacology, while it is still in its infancy, both with the development of tirzepatide 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 analogs, 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 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.
Operator: We will take our next question. The question comes from the line of [ Susan Shaw ] from Wells Fargo.
Unknown Analyst: This is Susan on for Mohit. Just a quick question on ZUPREME-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, where do you expect to see the most improvement on the side effects?
Adam Steensberg: Thank you for your question. The rationale was for the dose titration or you could even say that it is even a titration because you can expect, of course, to see weight loss even at the lower doses, but it's is the ability to get to the higher doses is a dosing escalation every 4 weeks is a practical way to do it. Our Phase Ib 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 GLP-1s, 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 GLP-1, but we have not seen that with the amylin. In all our titration step, 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.
Operator: We will take our final question. The final question comes from the line of Jen Jia from Cantor Fitzgerald.
Jennifer Jia: On 9830, the channel blocker, what indication would you consider pursuing? And what would be the rationale for that?
Adam Steensberg: Yes. So we have some very good ideas about where we want to take the molecule in next, and also -- but -- and what you should expect is that we will be pursuing several indications also in parallel, because if you look into the biology rationale, 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 I study. So we think we have something that could be a future jewel in our pipeline. So -- but the specific indications, we'll have to come back with later. 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.
Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.