... All All right, good morning, everyone. Welcome to day two of Cantor's Global Healthcare Conference. My name is Prakhar Agrawal. I'm a biotech analyst at Cantor, and starting today, we are very excited to host the team of Zealand Pharma, and representing Zealand, coming all the way from Europe, we have Adam Steensberg, CEO. Adam, thank you for joining us. Thanks a lot. Happy to be here. Obviously, a big year for Zealand, and big next 12 months for Zealand. So maybe why don't we just start off with, you know, an overview of where things are and some of the key priorities for the company? Absolutely. No, as you mentioned, it has been a very big year for us, as we are, you can say, pursuing our ambition of becoming one of the key players in the growing obesity market. Really, we kicked off the year with a fantastic collaboration agreement with Roche around our main asset, petrelintide, which I'm sure we get to talk more about. And since then, our focus for us has really been to make sure that we can accelerate that program together with Roche. And then, looking into the next period, we have key data readouts, not only for petrelintide in phase 2, but also with survodutide, which we have licensed to Boehringer in phase 3. So we really are excited about the upcoming period and the news flow that we have approaching rapidly. Yeah. And before we obviously go into the specifics, one dynamic that gets lost is you made a lot of senior hires this year, really building the company. So maybe just talk about more on why this was done, and why is not now the right time to build on the leadership as well? Right. So maybe just taking a step further back, a few years ago, we were kind of. We sat down with the board and said, "Well, where does this obesity market go?" And we were really bullish around when we looked at our pipeline opportunities, the contributions we could make into the obesity market, and we decided on a very ambitious journey towards becoming one of the key players in the market. So we have been building the organization, not only waiting for clinical data readouts, but also building the organization so we could lead in that journey. And then, as you mentioned, earlier this year, we hired a very strong Chief Development Officer, Stephen Johnson, to help us kind of lead our efforts as we progress petrelintide into phase 3 development for obesity and associated diseases, but also to, of course, build the clinical pipeline behind that. Then Utpal Singh, our new Chief Scientific Officer, who's really focused on generating the value that will come after petrelintide. We are in a situation right now where we can invest not only in our main asset, but also building the value that comes after. Got it. Maybe on the amylin space, what's your latest perspective on how amylin drugs will fit in the obesity landscape, and where do you see the biggest value for petrelintide? You know, we are actually super encouraged by how the market dynamics are playing out right now in the obesity space. I know there's a lot of disappointments, you may say, around that the volumes are not picking up faster with the GLP-1s, and maybe also some disappointments on the price pressure that we're seeing already. But when we look at that, we actually look at a fantastic opportunity for petrelintide because, as we have been saying all the time, GLP-1 therapies are very effective medicines, but they are also very difficult for many patients to be on, in particular, in the real world. One thing is how you are managed in a clinical study setting, which we still all tend to be excited about, but in the real world, we see people dropping off the GLP-1s. We think we have, with petrelintide, an alternative, a product that can give patients the weight loss they're looking for, but in a more pleasant weight loss experience. We really think that, you know, the dynamics we are looking at today will only be exaggerated further as we see alternatives coming out because then the conversations will change from, "Can you tolerate a therapy?" to, "Will you accept it?" If there is an alternative, what will patients accept? We at least speculate that even more patients will not accept being on a GLP-1 with all the side effects you often see with these molecules. Got it. And obviously, we've seen a lot of activity in the amylin space recently. Saw Novo's CagriSema data at ADA. Lilly presented some data for their amylin drug, which is with a caveat that it's a little bit early stage, but still as an amylin. So with all this competition coming in, which, you know, everyone probably predicted would happen, how do you sort of highlight some of petrelintide's differentiation in this increasingly competitive space? Yeah, it is really good to start to see more clinical data readouts in this space of the amylins. I would say with all the data that we have seen coming out this year, that confirms to us that we have what still looks to be the best-in-class opportunity. When you look at the totality of data, it is still important, when you look at these molecules, that you do not only focus on, let's say, efficacy, and then disregard safety at the same. So you need to balance always what is the efficacy you are looking for, and what is the safety profile that is, or tolerability profile, that comes along that efficacy? When we look at the totality of that experience, we still think that petrelintide, by far, looks to have the strongest profile among these clinical assets. If you take cagrilintide, which is, of course, the one that is furthest developed, where Novo's main focus so far has been CagriSema- That's a combination product. That's not an alternative. Then, but what we were excited about, considering that data set from their phase 3 program, was actually the arm where they also tested monotherapy of cagrilintide, where they actually showed 12% weight loss with almost placebo-like side effects. And we think we have a product that will give more weight loss due to the specific features of our molecules that really reconfirm our belief that petrelintide has the potential to really lead in this new category, and also that the category can actually become the largest category within weight management. Okay, and maybe can you help us understand the specific differentiation versus cagrilintide? Is it the half-life potency or something else that you can do with petrelintide? Yeah, so a lot of these, there is, of course, a lot of, you can say, scientific rigor behind choosing these molecules. And if you think about cagrilintide by Novo Nordisk and then petrelintide by us, the way it interact with the amylin receptors and the calcitonin receptors, we believe are quite similar. And that's why it's really reassuring, not only the efficacy signal from cagrilintide, but also the safety signal from cagrilintide. So we have a very balanced approach, and we use also human amylin as the backbone. Other companies have chosen different paths, and I think we are starting to see now that maybe some of those decisions will then carry some side effects and maybe even some quite significant safety signals, which so far it looks like we have avoided with the decisions we have made. Compared to cagrilintide, we have a significant upside in the fact that our molecule is stable in neutral pH. What we believe that translate into is that we don't see the same degree of injection site reactions as has been seen with cagrilintide. We have not seen the same degree of immunogenicity, and then we have a much higher bioavailability, so we get more drug to the receptor when we inject. Okay, got it, and you announced a deal with Roche earlier in the year. I thought it was great economics, but maybe strategically, why did you feel Roche was the right partner to maximize the value of petrelintide? Yeah, so after we got our phase 1b data last summer, last year, we started a very kind of structured process to identify the right pharma partner for us to realize our vision of becoming a key player in obesity, which was extremely important for us, and this was a very competitive process. I had dinner with quite a few large cap CEOs to ultimately choose us. What was extremely important for us was the strong commitment they have made to actually become a leader in this space. We didn't just wanna team up with somebody who just thought it would be hard to have an obesity asset. We actually... It's a big effort to go in and lead in this space, and that was with us. We found a company who convinced us that they wanna lead in this. We were impressed with how they presented their manufacturing plans, because ultimately, you cannot just tap into existing manufacturing capacity. Yes, you can do that, but then you will not get the most efficient. And they convinced us that the plans they have by building new, fit-for-purpose manufacturing capacity would be a huge edge for us as we launch these molecules together. And then, of course, lastly, we actually managed to get 50%, shared economics on also the combination products with their CT-388, which is a GLP-1 GIP molecule. So of course, that added to the value opportunity. So yes, we are now sharing the profit fifty-fifty with us, but we actually also got a new value opportunity in, and at the same time, a lot of good economics. Yeah. So those were probably the three main reasons. Yeah, and on the manufacturing investment, we saw some announcements from Roche as well. I think $700 million investment in the North Carolina plant. Like, how much of that capacity is going to be focused on petrelintide? If you can speak about that. Yeah, I cannot share the specifics, but just I can share that we feel very confident that Roche is making the right investments in this, investments needed to support the launch without any, you can say, shortage, and it's perhaps also an aspect of this agreement which has been overlooked a little bit, like that while we will share all development costs and also the future profit, we certainly do not have to finance any manufacturing investments. That would be Roche, that is responsible for financing all these investments, which is, of course, also a lot of dollars. Right Short-term, at least for us, that we save. Got it. And, when you were running the process and, like, what is, what was attractive about petrelintide to Roche, what were some of the two or three attributes that was really interesting? Was it the differentiated mechanism? Was it on the safety tolerability side? If you can just lay out the reasons that, you know, Roche thought, "All right, we have to be involved in the amylin space. Yeah. I think they will, of course, have to speak for themselves why they ultimately were so excited, as I would say, most of their peers in the industry was as well. Sure. For me, it's a logical consequence of looking in at the current market dynamics. With the GLP-1s, where we have two established brands, of course, it's gonna be hugely difficult to come in with another GLP-1 and start to lead if you already have very established brands. You're gonna have high rebate walls. You're gonna have a lot of prescribing experience with existing molecules, and you're also gonna fight against 10-20 years of data. Yeah. So, but coming in with a new modality, coming in with an alternative, then suddenly you have an opportunity to lead in a new category, instead of trying to eat your way into something that is very established. That is a much more attractive value proposition. Also, if you think about the launch years, it's a much more compelling opportunity to launch with a new category because you will be, you can say, the first alternative. Right For people who do not know where else to go. If you launch and with a similar mode of action, then you will have to convince somebody why you should take that molecule rather than a new and a very existing and well-known molecular entity. So this opportunity to lead in a new category, I think, is what was appealing to many of the companies we spoke to. Got it. Makes sense. Maybe onto some of the clinical data. You have the ongoing phase 2b that will read out. The forty-two weeks will read out next year. Just lay out what are you hoping to see, maybe starting with efficacy? Yeah. So what we hope to see is a molecule that can provide patients with a GLP-1-like weight loss, and that is in the mid-teens, so 15%-20%. Yeah W hat we, what we have seen, and then with a much more benign tolerability profile. We are already very confident in the tolerability profile because we have 16-week data. We have also data from the ORNOICE, which shows that it's almost placebo-like experience that you have when you get petrelintide as compared to when you get the GLP-1s. So, and on the efficacy side, we achieved 8.6% weight loss over 16 weeks, and those models would suggest that we can easily achieve the weight loss we are looking for. What I think is super important as we continue to mature our view on the future obesity market, is to maybe then go a little bit of that, what is the number? This is about a profile of a drug. Most patients, if you ask them, are looking for a 10%-20% weight loss, and thus, we have to get away from this weight loss Olympics. We need to get into talking about what is the profile of the drug, which drugs can give patients that weight loss they're looking for, but in a more pleasant experience. And then importantly, which is the big, big miss in of the current therapies, is: how do we manage to get patients to stay on therapy? Yep. The reason that we have so low volumes of patients on treatment is because they stop taking the GLP-1s far, far too early- Right To day, and we think we can change that with amylin. Yeah, and I think that's an important point because I think people underappreciate the duration of therapy for amylin drugs. So like, what are you, based on your research, what's the sort of stay time for GLP-1s, and how much further can you improve with an amylin therapy, as even as a monotherapy option? Yeah, but I think it has actually not changed a lot, the stay time on a GLP-1. And we know, I mean, from the launch years, I mean, that already within one month, we have 30% who drops off, and probably within a year, it's less than 50% who are still on therapy. And by those who leaves, and the majority are actually people who say, "It's because I cannot tolerate the drug." Of course, there are other reasons as well- Right B ut the majority is because they cannot tolerate it, and there's actually a big dilemma here, because if you only achieve a weight loss and you don't manage to maintain it, you could actually be worse off, so it is so important we start to think about how do we get people to stay on therapy, and we all know that an obese person is very motivated to lose weight. Once you have achieved the weight loss, you become less motivated, and that also means that you will accept less side effects. That's where we think amylin will come in and be something you can actually have, that you can also enjoy being on when you have achieved your weight loss, because it has this feature of making people feel full faster, rather than losing your appetite. It's actually also beyond the classical tolerability issues we discuss today. Yeah. And on the safety tolerability side, obviously, we have been comparing it with semaglutide, but don't you think the market is moving now more closer to tirzepatide, which has really good safety tolerability as well? So how would you compare amlins versus, let's say, dual agonist, like a GLP-GLP agonist, which has good safety? Yeah, but I politely probably have to disagree with your statement there. In my book, I think the safety and tolerability profiles between Wegovy and Zepbound are quite similar. You may... the data at least suggest that you can get a higher weight loss on Zepbound. But again, as we discussed before, if you balance things net-net, you still have all the side effects with the GLP-1 tirzepatide class that we have also seen with the GLP-1 class. I think another kind of fact underscoring this is that while the clinical data we always discuss for these molecules are data generated with the highest doses, so what was the weight loss you achieved with, let's say, 15 milligrams of Zepbound? then the real-world evidence suggests that very, very few patients ever get to these doses. They end at much lower doses. I actually believe that the average dose being used real-world for Zepbound is around seven and a half milligram, which is a very low dose, so they don't actually experience the weight loss that the clinical data suggests they can do. And then you might ask yourself, why is that? Why do they not get to those numbers? And we think a lot of that has to do with the tolerability profile. We used to talk a lot about just not vomiting and nausea, but I think we need to discuss diarrhea in particular, because these are side effects that tend to stick and not be able to titrate yourself out, especially when we start to think about the new classes of oral GLP-1s, where, in my book, at least, looks to be even worse. Got it. And you disclosed some pooled baselines during the last earnings call. But maybe just a broader question on obesity trials. We are seeing a lot of discontinuations in the obesity trials, especially on the placebo arm as well. We saw this with Lilly's orforglipron data. Viking had an overall readout that had a lot of discontinuations as well. What are you doing to mitigate this risk? Because this is a forty-two-week trial as well. Yeah, right. I mean, we of course don't have the data yet, but but I also hear other companies who have not seen the same issues. So I don't know. Before we see the actual data, it's actually difficult to say what the real reasons are behind those discontinuations. Of course, there is this observation that if people don't achieve a weight loss in a placebo group, they could be less motivated to stay in the study. That could also, again, coming back to orforglipron, be why you had more discontinuations than average on even an active drug, because people did not achieve the weight loss they were looking for. So I think we need to see the individual data before we can start to draw conclusions. Okay. Anything you can comment on the pooled discontinuation rates in the ongoing trial? No. I mean, again, we try to keep a high level of data integrity on our clinical studies and not be too, you can say, to introduce any risk. So we like to keep things blinded until we have the data. Okay. And once you have the 42 weeks, I know there will be an interim readout this year to start the regulatory discussions around the phase 3 plan. But what could a phase 3 development plan look like? And a follow-up to that, like, does Roche plan to run a CV outcomes trial for amylin analogs? Y eah, but even when we engaged in the partnership, we had, of course, a clinical development plan agreed, and, you know, it is to be communicated by us together, the exact, you can say, design of those phase III studies, but I think you can anticipate that it's gonna be a quite classical obesity program. We will also have to focus on demonstrating cardiovascular outcome data, because otherwise we would not be able to pursue our vision of making petrelintide a foundational therapy. So ultimately, we will also provide CV outcome data in this setting to underscore the potential for, of course, much more than just weight loss. All the risk markers that are normal risk markers for cardiovascular disease actually are coming down with the amylin class as well, so we have high expectations to the risk reduction as well. I think it's really important also when you launch a new class in a market that is as undeveloped as the obesity market. You don't need to think about switching from existing therapies or how are you gonna do X, Y, and Z. For us, it's enough to show that we can deliver the weight loss that patients are looking for and underscoring that it's a more pleasant weight loss experience. We don't have to go out and capture GLP-1 users, because anyway, most will have stopped taking therapy, so they will be restarters or naive, and it doesn't really matter for us who we get on our drug. Yeah. And so I guess on that point, investors think that the biggest opportunity for Amylin drugs could be post-GLP-1s or even tirzepatide for patients who don't tolerate these drugs or don't stay on these therapies longer. Like, do you agree with that sort of perspective? And what are your thoughts on what will it take for Amylin drugs to move to the front line? Yeah, but I think you really have to change it around because already today, I don't care if it's a naive patient or if it's somebody who have been already exposed to a GLP-1, a restarter. But in my mind, Amylin should become a first-line therapy, because if it can give your patients the weight loss they're looking for, and importantly, help patients maintain that weight loss, why would you have to go through another modality that carries more side effects and tolerability issues? And if you look into today's market, where I guess in U.S., there's, what, 3% of obese individuals on treatment, but is it more, north of 10% who have been exposed? I mean, those other 7%, they would be considered restarters, and they... Yeah. Okay, got it. Makes sense. And on the 50-50 share of your co-commercialization with Roche, can you walk us how you're thinking about it longer term? Do you intend to take part in commercialization in key markets like the U.S., or could you look at monetizing that part of the share as well? No, but it was extremely important for us when we engaged in this partnership, number one, that it was a true partnership with an equal say in the partnership. It should be profit share in the U.S. and Europe. Then we also, as you say, wanted to have the opportunity to contribute with up to 50% of the commercial rollout, and this is to be discussed with us in the partnership, how much we will, you can say, tap into that opportunity. But we do think we have a very important role in continuing to lead in this, and we also have an ambition for the company to become a key player in the obesity market, and that means the most likely scenario is, of course, that we will play a role. We need to discuss with us and also see how things develop, how big of a role we'll play in the first rollout. Then we may do a bigger stake in the next rollout. Remember, it's a partnership that also could include combination therapies and so on, but we have maximum flexibility in how to run that, so that is something we'll have to communicate on in the coming years. Got it. I did want to touch on the combination as well, because we've talked about monotherapy, but that's something that you got with the Roche deal as well. So maybe talk about your product strategy there and CT-388, which is Roche's GLP-1 GIP agonist. There is a perception out there that the tolerability data was not good with that drug compared to the other dual agonists, so why do you think that this combination could have a good, especially the safety side? Yeah, I think you're right, that we have also heard that perception that the tolerability profile was not good. I think if people took the time to actually sit down and evaluate the data, they would come to a different conclusion, and our conclusion is actually that CT-388 looks to be among the strongest GLP-1/GIPs out there. Of course, it's gonna be quite similar. That would be our expectation, at least to Zepbound, but I actually think it looks very strong as a GLP-1/GIP. So we are super excited about the opportunity for combinations, and we will have to start the phase 2 studies first half next year to evaluate what is the right balance between petrelintide and CT-388, because I'm not sure that Novo got the right balance with their CagriSema. And why would you not take the most tolerable molecule and max out on that, and then just add a teaspoon of the less tolerable would be the GLP-1 component? So we will explore different combinations and then ultimately make decisions before we move into phase III. It's a product opportunity, these combinations, for those who are most morbidly obese, who really need to lose the highest amount of weight, or perhaps patients living with type II diabetes and obesity. So there could be a pocket of patients who would really benefit from combination therapies. Having said that, we truly believe that the monotherapy carries the biggest potential because it, we think it can deliver the weight loss that the majority of obese individuals are looking for in a very pleasant way. Got it. Maybe on some of the other pipeline assets, and I did want to touch upon survodutide, which I believe is one of the most under-the-radar phase 3 readouts in obesity early next year. So talk about your perspective on what the street is missing on this, asset and the readout. Yeah, but I think you're right. Boehringer being a private company, it doesn't have a lot of attention by investors. But if you look into the history of Boehringer as a large pharma company, they have launched some of the most successful drugs in the cardiometabolic space. And we think with survodutide, they have probably one of the most differentiated, strongest GLP-1 assets in development right now. It's a combination of a GLP-1 and a glucagon. And at least the phase 2 data, the way we read them, suggest that you can get a weight loss that is quite similar to what you see with the GLP-1/GIP class and similar tolerability profile. Where it really stands out is in the potential management of MASH, because glucagon is known for actually getting nutrients out of the liver, so on top of what a GLP-1 can do. And the data Boehringer presented last year, early last year, as they put it themselves, was groundbreaking data. So we have high expectations compared to the benefits that we have seen with semaglutide thus far. I think the clinical phase 2 data are very promising on survodutide. And I think it's also a testament to the opportunity, if you look into the investments Boehringer is making into the phase 3 program in MASH, where they have 3,500 patients, not only F2 and F3 patients, but also cirrhotic patients. I think that shows you how much they believe that this product can actually be a groundbreaking therapy for patients living with MASH and obesity. Do you see this product as more of an obesity plus MASH or MASLD sort of a value proposition, or could it have a more broader plain obesity with a better, hopefully a better safety tolerability profile in phase 3? Yeah, but that, of course, again, it's up to Boehringer to communicate around that. But I see a huge opportunity for Boehringer to generate very, very significant clinical, meaningful, and significant data in the MASH space, which could help them maybe position survodutide a little bit outside the average GLP-1 experience, where we will see a race to the bottom on pricing. And, you know, you don't wanna launch a new modality into a category where you're seeing lower and lower prices all the time, as we discussed before. And I think Boehringer have a unique opportunity here from a value perspective to, if the data comes out the way we hope, to really place survodutide in a pocket by itself, because if it can truly deliver on MASH beyond the weight loss. We believe it will be incredibly difficult to launch another GLP-1 containing molecules, unless it has a true clinically meaningful differentiation compared to the existing molecules. How will you make that successful? And I think with survodutide, Boehringer have all chances to actually differentiate when it comes to people living with MASH. Got it. On dapiglutide, what are the next steps there for the program in obesity? Yes, so dapiglutide is another differentiated GLP-1 molecule that has also GLP-2 on board, which we believe will be able to control inflammation to a larger extent than the GLP-1s on their own. We will start a phase two study later this year, and within the coming months also communicate more specifically around the nature of that study. But a little bit aligned with what we just discussed with survodutide, for us, it's gonna be important to go beyond the weight loss. This world doesn't need more GLP-1s for weight loss. We have enough, and people struggle to stay on them. So we will focus on pockets of patients where we think inflammation is a major driver for some of the comorbidities to obesity, and then target development of this molecule towards such patients with obesity and a specific indication on top of that. Got it. Got it. And maybe you do have an R&D event later this year. Just help us understand, well, what should we expect? Yeah, but it's mid-December, December eleventh, I think it is. We have our R&D day coming up in London, and it's really, for us, an opportunity to set expectations for what is probably the most news flow-rich, catalyst-rich half year for any company in this space, as we're approaching phase three data readouts with survodutide, phase two data readouts with petrelintide. But also a unique opportunity to share our thoughts around the future innovation in this space. So we look forward to introduce Utpal, our new scientific officer, and let him talk about what we think could come beyond petrelintide and drive future success of Zealand. And, we talked about some of the senior hires that you have made. You're sitting in a very strong capital position. Longer term, what can we expect from the company internally or even externally to really build on this profile that you have in the metabolic disease space? Yeah, but we are extremely ambitious, and we think we have the right to be so because we have two of the strongest and most differentiated molecules in mid- to late-stage development right now. And as you said, we have the team. We have spent actually more than 25 years in this space, and we have been able to attract some key talents to also lead the next journey. We are extremely ambitious of where we wanna take the company as we grow in the coming years, and we are hyper-focused and also luckily in a capital situation which allows us to also invest in the next value drivers. This is not just about a single asset. This is about us now leveraging our twenty-five years of experience, our strong capital position, our leadership in the next generation, molecules for management of obesity to propel into a next, accelerated journey of the company. Unfortunately, that's all the time we have today, but thank you to the Zealand team for joining us, and thank you to the audience for listening in. Thank you.