Good morning and welcome to day three of the Jefferies London Healthcare Conference. My name is Lucy Codrington. I'm one of the European Pharma and Biotech Analysts based in London. It's my absolute pleasure to introduce Adam Steensberg. We'll be having a fireside chat, talking all things Zealand, all things obesity. Welcome, Adam. Thanks for joining us. I suspect there's a fair few in the room that already know the Zealand story. Let's focus in on petrelintide, your amylin asset, the main focus for the company, arguably in the near term. You had a partnership with Roche. What do you think attracted Roche to this asset? Where do you think this asset is best positioned in the future obesity treatment paradigm?
Yeah, I'm pleased to be here. There's no doubt in my mind that the partnership with Roche is actually more than a partnership. It's a shared commitment to go in and lead in this space of obesity treatments. I really think saying that, that is also back to what was so attractive about this opportunity, because with petrelintide, we have the opportunity to come in and lead in a new category and not just play into something that is already rather established. I think the opportunity to come in with a novel mechanism that can actually provide the weight loss that patients are looking for, and also in a more pleasant way.
I think for a very long time, and I think with a lot of companies who have not entered, the large pharma companies who have not entered the obesity space, they were a little bit concerned about that weight loss Olympics. How would you come in and win in a GLP-1 category where there were already established brands? Do patients really care about a few % more within an established category? We just came with a solution here with petrelintide. Those were the conversations we had with a lot of large pharma companies around coming in and leading in a new category. With Thomas and Theresa and the Roche team, we felt that commitment strongly. That is why we chose them in the end.
Great. Okay. You talked there about the more pleasant experience. In the past, you've talked about induction of satiety with amylin as being one of their key attributes. Could you talk us through why this is important? Is there any way of measuring that in clinical trials?
You know, the ultimate place to measure this is the experience of the patients. So that would be a personal experience, how you feel on a weight loss drug. And I think one of the key elements, and also why we have seen some disappointment in the market these days, is that patients fail to stay on therapies, on the GLP-1s. They're effective tools. They help people lose weight. But a lot of people stop taking them, so they do not get the support they need when they get into the weight maintenance. For petrelintide, what we hope to show and what we expect to see is a more pleasant experience and weight loss experience. And it actually goes beyond the GI tolerability issues that a lot of people discuss: nausea, vomiting, diarrhea, and constipation, where we also expect to see a more benign profile.
That way in which it helps people reduce the food intake, why would you take a medicine that makes you lose your appetite if you could take something that makes you feel full faster, meaning that you would turn up at your dinner party and actually have hunger but just eat smaller portions? That is why we are so committed and also excited about the opportunity to actually develop a medicine that can interact better or help, you can say, people actually live the lives they want to live and not just help them reduce the food intake.
Very clear. Okay. You also mentioned the benign tolerability profile potentially relative to GLP-1s. To what extent do those rates of GI adverse need to be lower in order for it to be considered differentiated from a GLP-1?
Yeah, but I would say with the early clinical trial experience we have today, what we have seen with petrelintide is an extremely benign tolerability profile when it comes to vomiting, diarrhea, constipation. And then we have seen very low rates of nausea, which may not even be nausea as we normally understand it, but just people feeling full. So the mode of action. So I would say with the data we've seen thus far, we know it's more tolerable than getting on a GLP-1 experience, at least short term. Remember, that's where you see most of the side effects. Of course, it will also have to be confirmed in later and larger studies that we see the same profile. Remember, it's been a consistent observation across three short-term trials.
For the GLP-1s, it's actually in that period of up to 16 weeks where we see the most side effects. We are very confident. Of course, it has to be shown. What gives us further confidence is if you look at the data that Novo Nordisk released last year with CagriSema from a 68-week phase III, thousands of patients overall in that program, you also see a very benign tolerability profile with their amylin analog. It really confirms this opportunity to come in and develop a class that will not only help people lose their weight, but also maintain the weight once they've achieved the weight loss.
Okay. You mentioned the Cagri data. We also had data from Lilly's eloralintide a couple of weeks back. The tolerability there perhaps was not as clean as maybe we were anticipating. We did see kind of 10%-20% discontinuation rates due to adverse events, not all GI. Do you still remain confident in that profile? Is there something potentially specific to that trial that may explain why the GI rates were maybe higher than we were expecting?
I think we have to remember that also with amylin, just as the GLP-1s, we're actually working with very potent biology. You do not want to overdo any of these modalities. We know that if you give just a very high dose of amylin without titration, you will also see more GI effects. You may also see other side effects you do not want to have in a chronic therapy. I think if you look at the Lilly data, there were a few cohorts where they did not apply titration. That is also where they reached the highest weight loss. I think that was also where we perhaps saw side effects which would not be supportive of the class as such. Once they got in the cohort where they applied titration, they reached a slightly lower weight loss, but also a much more benign tolerability profile.
It's always when we look at these data, you have to balance the effect versus the side effect profile. Playing with potent biology as we do, you don't want to overdo it. The good news is that the data we saw from Lilly, the data we saw from Novo Nordisk last year underscores what we have been saying now for two years, that petrelintide and amylin as such has the potential to deliver this 15%-20% weight loss in a very benign way.
Okay. Before we move on to the actual weight loss component, still sticking with the tolerability, there were some adverse events in the elora data, including fatigue, alopecia. Do you think these are related to perhaps the lack of titration or potentially a class effect? Have you seen these with petrelintide?
It remains to be seen. We have not seen it with petrelintide. Novo Nordisk have not seen it as far as we know. With CagriSema, it's something that Lilly have observed with their amylin analog. Of course, there's probably two potential reasons for that. Either it's because of lack of titration, or it's a molecule-specific event with the fatigue and alopecia that we will have to learn in larger studies. Remember, it was a somewhat smaller study. It's also a study which had 80% females. We do not even know where these adverse events were observed. It was with the male or the females, but they will have very few males to actually assess the safety aspect of their molecule in giving the balance to us women. We will have to learn a lot more about these molecules.
I would probably believe that either it's lack of titration or potentially molecular specific events.
Okay. And petrelintide is in its own phase II. We're expecting the data first half next year. You talked a lot about the target profile of 15%-20% in longer-term studies. We saw with Eli Lilly that they could achieve that in a shorter-term study. How would you frame expectations into your data? Is there any reason that we wouldn't potentially get that 15%-20% in this study? Do we need to wait for phase III?
Of course, that remains to be seen. The data will come out the first half next year from our 42-week study. What is important to highlight here is that we do apply titration for the same reasons we just discussed before. It's potent biology. Our understanding is at least if you want to reach the higher weight loss levels, you should apply titration. What does that mean? The other thing which may even be more important is that in that study, there were 80% females. In our study, we have 50% females. A very balanced cohort to best and foremost how to move into phase III. If you look back at the phase I data that we discussed last year, we had only 20% females.
It was also very clear from that one, and we had published those data, that females lose significantly more weight compared to males on these modalities. I would actually argue that in our internal modeling work would suggest that if you take a study and have only 100% males versus 100% females, you would probably get 5% more weight loss by having only females. Of course, that's something that means a lot. Again, if you want to do the most thorough development program in phase II, that's where you get to understand your molecule. That's where you want to understand your molecule in different genders. In phase III, that's where in our minds at least you can think about screwing the gender balance a little bit to inform the label.
Got it. Okay. You mentioned kind of two key differences there: the titration, the gender balance. The BMI baseline is also slightly different. Do you expect that to contribute much, or is it not too much?
Again, it remains to be seen because it is slightly a few points higher in the Lilly study compared to ours. Of course, historically, it has been shown the more overweight, the higher BMI, the more weight loss. That is also driving additional weight loss. Whether these few points in the upper end of the 30s matters, we need to still see. If you compare to our earlier study, we actually had a BMI of 29, which is low. Of course, there is a limit to how much weight you can lose if you have a BMI of average of 29. There could be a flaw, if you will. Whether it means something up here, we will have to see. At least it is, again, not biased towards us.
Okay. There's been a lot of debate about the importance of receptor balance when it comes to amylins. Now we've had the phase III data, the phase II data from some of the competitor assets. Has your thinking changed on what is the best balance to achieve when it comes to amylin and calcitonin?
Not really. We remain very confident in our approach where we stimulate all three receptors: amylin, 1, 3, and calcitonin. It's a similar profile to cagrilintide, where we have already seen a very low dose delivering 12% weight loss. Now we see eloralintide, which may have a little bit more potency on the amylin receptor compared to calcitonin. I would say there's still debate out there how it touches the different receptors. We have other modalities which look to be more towards calcitonin.
When I look at the phase I data, which has been published for most of the single ascending dose data, which has been published for most of the amylins in clinical development right now, I still have a lot of confidence in the receptor profile in the sense that if you look at the first dose that gives significant weight loss after eight days, a single dose, with our molecule is 0.7 mg, we can achieve a 2.6% weight loss after eight days with no vomiting. If you looked at eloralintide, they had to go up to 4 mg to achieve a 2.2% weight loss, so slightly lower with no vomiting. The first dose where they had vomiting was 12 mg. There they had 3.2% weight loss. The first dose where we had one patient with vomiting, that was 1.4 mg.
In our book, it looks like we are probably 5%-10% times more potent and having the same tolerability profile. I would say I would still go with my receptor profile.
Okay. Taking a step back from molecule specifics, drug pricing is in the headlines more than ever at the moment, and obesity medicines are at the center of that. In light of the more recent announcements, how are you feeling about the commercial opportunity of drugs that are going to be launching in three to five years' time? Should we be thinking about amylin as a premium product or a mass market product?
I think you should think about it both as a premium and a mass because, as we talked about before, it's about developing medicines that people can actually stay on. We need to treat obesity like a chronic disease and not an event-based weight loss experience because then you don't get the health outcomes. The reason that we are in this space is because we do truly believe that obesity represents the biggest healthcare challenge of our time. In order to address that healthcare challenge, we need to treat patients. We cannot just treat them event-based as many patients do today on a GLP-1. The key thing to actually unlock the value in this market is not to discuss prices, it is to discuss how do we manage to get patients to stay on therapy because then you get the volumes up.
Is it 3% of the US obese population who's on treatment today and much less globally? There's a huge need and opportunity to expand the volume. If we truly are to address this market, we need to have it turning into a chronic therapy market and not event-based. On drug pricing, of course, there will be competition within the GLP-1 space, which will further add to that. It's only natural that the first category of treatments that are introduced into a therapeutic area will at some point be cheaper. You launch novel innovation that gives different experiences and also the opportunity to stay on therapy and thus hopefully better outcomes in the real world if people stay on therapy. It's only natural that there will be different pricing dynamics in a new category.
Okay. And then actually going back to the molecule, toward the end of the year, we're expecting data for a monthly amylin analog. Based on what we know about this asset to date, what should we be bearing in mind when we're comparing this asset to Zealand's petrelintide? And what makes you confident that a weekly can still be differentiated versus a monthly?
When I look across the different amylins, which are in clinical development, I have not seen a monthly profile yet. I've seen products where people have expressed that it's a once-monthly product. When I look at the half-life of the amylin that is in clinical development right now, they've all been designed in my mind with a once-weekly profile. Some companies have decided, perhaps we don't know yet, to push it for a once-monthly dosing. In our minds, it's again playing a little bit with fire because we are working with very potent biology. If you push something that was meant for once-weekly to have the most steady exposure into a once-monthly dosing, you'll have very high peak to trough exposure. You might end up seeing some side effects based on that that you don't want to have.
What I would say, however, is if it turns out that it's okay to take a once-weekly product that has more of a once-weekly profile and make that once-monthly, we could do it as well. We just think it's a very bold move. Again, if it turns out that that's okay with amylin, we could choose to do so. The half-life of the molecules that we have seen in the clinic thus far, at least in our minds, suggests that they are once-weekly and should be used as once-weekly products.
Just to clarify there, you could do it with petrelintide, with a reformulation of petrelintide, or with some backup assets you might have?
If you look at the half-life, a half-life of 10 days, which is what we have with petrelintide versus one which is 11 or 12 days, that does not change your opportunity to go once-monthly. We could do it with petrelintide if we thought it would be the way forward. We just think it is coming back to what we discussed before. It is more important to have the most pleasant weight loss experience rather than to compromise on the side effects if you push dosing into every four weeks instead of once every week. If it turns out that with amylin you could do it, we could also do it with petrelintide.
Okay. All right. Taking a step back and thinking about the Roche deal, you secured probably a best-case deal in that situation, ticked all the boxes that you were looking for. With it, you got quite a significant amount of money in terms of upfront and then additional milestones to come. How should we be thinking about Zealand deploying that cash beyond the obvious spend on your amylin program?
Yeah. When we entered this partnership, of course, it was most important to us that we got a committed partner and then also a partnership where we could be truly equal partners, which will allow us to develop into a generational biotech, a biotech which will have a foot in all parts of the value chain. With the partnership we have here around petrelintide, we have the opportunity to play up to 50% of the commercial role. Now with the capital we have, of course, with that also comes we have also obligations, which means that we have to pay half of the development and commercialization expenses. The capital we have and the capital structure we have applied allows us to honor all these obligations until we start to be profitable, not only for petrelintide, but also the combination product.
Remember, we've also got profit share on the combination of petrelintide and CT-388, the GLP-1/GIP, which Roche is now pushing into phase III. In addition to that, we also have the means to significantly increase our investments into the early research pipeline and early development. That is coming back to our aspiration to develop Zealand into a generational biotech where we will not just be a petrelintide story in three to five years from now. We want to be a petrelintide story that is changing the near-term opportunity in the obesity market for patients. We want to be the company who has the pipeline to also drive innovations in the years to come. We will discuss that much more at our Capital Markets Day coming up here in December. It is a very ambitious strategy to continue to lead in this space.
We think we are uniquely positioned as a company to actually enter a period of accelerated growth now based on our legacy and our strong presence.
Okay. And then if we think about Zealand historically, you have done the commercial route before and took a step back to focus on your core expertise of R&D. I guess what would trigger? Is it guaranteed that you will take that opt-in to commercialize petrelintide, or is it just a nice-to-have, but you still see your strengths as being an R&D-focused company?
There's no question that our current strength lies in our R&D capabilities. That's why I would argue that we are probably among the strongest companies when it comes to peptides, but also to actually drive innovation in the next era of metabolic diseases where we will share more on our aspirations. It's also a fact that as a company, we want to develop into a generational biotech, and we want to establish a commercial presence in the US. That is something that we anticipate that we will. What we have not decided yet is exactly how to do that alongside Roche. It's, of course, a conversation we will have with Roche as well. How do we best contribute also into the commercial rollout together with them? It's a completely different opportunity to do it alongside a large pharma company as compared to doing it alone.
That's not something I aspire to do.
Okay. Let's move on to survodutide, which is perhaps a forgotten part of the Zealand story. But given that we're expecting phase III data in the first half of 2026 as well, it's partnered with Boehringer Ingelheim. Under the existing partnership, given that they're private, how long can they sit on that data before they have to share it with you?
A very long time. We do know that they expect to share the data, broadly speaking, starting early next year. We actually believe that next year will be a big survodutide year. For those of you who attended Obesity Week last week or a few weeks back, you would also notice that they had a very strong presence at Obesity Week with sponsoring three symposia and a big commercial booth also saying, "See obesity, think liver." I think many of you guys next year, when you see obesity, you will actually think BI because they will be out there, we expect.
Okay. With that, you mentioned the liver aspect. They have quite a comprehensive MASH program. How do you think about survodutide when it comes to obesity? Should we be thinking about the weight loss component, or will their liver effect be able to compensate if the weight loss is not perhaps up to scratch?
Yeah. Here, of course, I cannot speak on their behalf because it's Boehringer who's responsible for developing this program and also commercializing. We just receive royalties, high single to low double digit royalties on the program. It is clear if you look at, just look at that tagline, "See obesity, think liver," see how they have communicated about it. The opportunity really is to have a product that gives patients the weight loss, a GLP-1-based product that gives patients the weight loss they're looking for. The clear differentiation is in the glucagon component, which helps burning fat in the liver and potentially also other organs. It could actually be a product that turns out to be extremely strong when it comes to organ protection. Right now, you can see the focus is on liver.
Boehringer presented some fantastic data last year in MASH, probably the best data that we have ever seen. They have the largest probe beyond the obesity program where they also have cardiovascular outcome and what have you. In MASH, they have the largest program, 3,500 patients, not only F2 and 3, also end stage F4 patients. It is a program that is not only focusing on biomarkers, which would allow you to get a conditional approval, but one which looks into outcomes as well. We do think that they would play on that potential for a significant differentiation when it comes into liver health. It is probably one of the most underserved consequences of living with long-standing obesity. Remember, if you become obese as a child, you will have, let's say, 40 years of obesity challenge on the liver.
That's where you might end up with end-stage liver disease. It's less of a problem for the liver if you become obese when you're 40 because something else will make you leave this world before your liver gives up.
Okay. Dapiglutide was your other obesity asset, GLP-1, GLP-2. You recently announced the decision to discontinue, well, pause development of that. How should we be thinking about Zealand's approach to building up its pipeline? And what drives confidence that you are best positioned to find the next innovation in cardiometabolic health?
Remember, we have actually more than 25 years' history, not only in peptides, but also working in metabolic diseases. We have an extremely strong management team now leading research and development and new Chief Scientific Officer and new development. We have an extremely experienced and competent organization. That combined with some of the changes and some of the opportunities we see in data science allows us to utilize all that experience and accelerate it into the future because AI is a funny word, but it only works if you have something unique that you can put into that opportunity. With the 25 years of data collecting in this space, Zealand is among the few companies in the world that has data that can actually help to utilize all these promises of modern technologies.
Okay. With that, we've run down the clock. I'd like to thank Adam for his time and to you, the audience, for attending.