Good afternoon, everyone. Thank you for joining us for another session at our 44th Annual TD Cowen Healthcare Conference. I'm Joyce Zhou, one of the biotech research associates. It's my pleasure today to introduce Adam Steensberg, who is the CEO of Zealand, and will be giving us a presentation this afternoon. Time permitting, we'll open up to the audience for Q&A at the end. With that, I will turn it over to you.
Thank you, and thanks for the invitation to present. We've really been looking forward to be here today, had some great meetings throughout the day. So, Zealand Pharma, we are a peptide-focused drug discovery and development company. Been around for 25 years, and, you can now say, even though that obesity is a theme that I guess has only started to be on your mind, in the last few years, it's actually an area, metabolic diseases and peptides, in particular, of how utilizing peptides to address metabolic diseases is something we have worked with for many, many years. So it's not new to us. We are just, grateful that people are starting to, you can say, pay more attention to, to the fact that we need, novel treatments, getting out here. I will be making forward-looking statements.
I guess you all expect that, but I will also have to make these disclaimers on that. So we are an international biotech company, but headquartered out of Denmark, around 260 employees. We have employees in the U.S., as well, including our Chief Medical Officer and Head of R&D, who lives in the U.S. So we are internationally focused a company. We are focused on peptide drug discovery and development. We used to have actually commercial infrastructure, and in the US, until a few years back, where we decided to refocus our strategy on peptide R&D, really allowing us to invest our efforts and also our money into the programs that I'm going to talk mostly about today, namely our opportunities in obesity. I still think it's important for you guys to know that we have had commercial operations.
We have actually been taking products all the way to the market. Today, we have licensed these out to big pharma players, but it gives us the expertise and the know-how and the experience to actually deeply engage in the programs that we are developing right now. To develop a peptide proof of concept drug is not a big problem, but to develop or design a peptide that can truly make it all the way to the patients, including all the features that you need to have a product that is easy to inject and take for the patients, that's a very, very deep skill that you have to develop over years, and we have done that repeatedly. We have had products approved and on the market today.
We have two products, one with Sanofi and one with Novo Nordisk, which we developed. Then we have a market cap of around $6 billion and a cash position of around $600 million to support our ambitions. So this is the pipeline of the company as it looks today, and as you will see, we are very well positioned within the obesity space, both with the three proprietary assets, where we have all the rights ourselves: dapiglutide, petrelintide, the amylin analog. And then we have survodutide, which we have licensed to Boehringer Ingelheim, and they're responsible for driving all development efforts for this program, and we just received royalties into the program. I will discuss these programs in more details as later in my presentation.
If you just look a few years back, most of the value and then most of the equity story around Zealand was really relating to the two rare disease assets that you see in the middle, dasiglucagon for congenital hyperinsulinism, and then glepaglutide for short bowel syndrome. So these are two products that targets rare diseases with a high unmet medical need, in particular, congenital hyperinsulinism. There are no approved treatments for this indication, and for glepaglutide for short bowel syndrome. There is already a GLP-2 on the market, sold and marketed by Takeda GATTEX, but we have a product which can be injected twice a week instead of the daily injections you have to do with the current product.
So both of these products, we expect to see regulatory decisions later in the year, and we are pursuing partnerships, commercial partnerships for those, so that, that will allow us to even further focus in on our obesity portfolio. Then, as I said, we have been 25 years in the making. We actually celebrated our 25th anniversary last year, and, so we actually have a very broad and deep research pipeline as well, and a lot of activities in the early pipeline. And two of the assets I just want to mention here, that we are public around are one, which is a Kv1.3 inhibitor, which is a broad anti-inflammatory target, and the other one is a complement C3 inhibitor. Both of those, we expect to enter the clinic later this year in the second half.
Historically, we have also been quite active in the type 1 diabetes space and will continue to develop in these efforts, but they are less in focus right now compared to some of the other opportunities. If we look into the news flow that we expect for this year, it is very rich, and it's really focused around our opportunities in obesity. If we start with petrelintide, that is our amylin analog, and that is the molecule which I would describe as the crown jewel in the pipeline.
It is also the molecule I will discuss more throughout my presentation today, because I think it's a unique opportunity to develop a non-incretin class of weight loss medications, so a weight loss medication that is not based on GLP-1 as a backbone as an alternative for those patients who cannot tolerate the GLP-1s, but we'll come back to that. Dapiglutide is one of the very few differentiated, truly differentiated, GLP-1 containing molecules in development. If you look across the quite rich pipeline within obesity right now, you will see a lot of molecules that have similar mode of actions as either a GLP-1 or a GLP-1, GIP. But we are the only ones that are pursuing this GLP-1, GLP-2 concept. So it's really to leverage the known benefits of the GLP-1, but then add GLP-2, which in theory should provide additional anti-inflammatory efforts.
And then lastly, we have survodutide, which is being developed by our partner, Boehringer Ingelheim. They just reported fantastic data in NASH, top-line data in NASH earlier this week, demonstrating for the first time a molecule that is based on GLP-1 anti-fibrotic effects in NASH. And they will, later in the year, as you can see here, present the full data set at a scientific conference here in the first half, which will be quite interesting. Last year, they revealed great weight loss potential for the molecule as well. And then we have our rare disease programs, where we expect regulatory decisions later in the year, and also, as I mentioned before, initiation of new clinical studies, human studies.
Before we dig into the programs, I really want to spend a few minutes sharing our view on the medical needs and also a little bit on how we see the direction going forward into obesity. For a long time, we have, as an industry, been pursuing this goal of more and more and more weight loss, trying to put the goalpost as the level of weight loss you can achieve with bariatric surgery. That has, you can say, been driven by the fact that early days, several years back, we saw some weight loss medications in the market that only gave you 5%-6% or maybe up to 10% weight loss, and that didn't meet the needs of the patients. So we've been pushing this narrative of more and more weight loss.
I would argue that a lot of the experience we have now from these products, once they get into the market, that most people are not looking for more and more weight loss. They are looking for the right amount of weight loss for them, and we have to understand that humans actually have a lot of pressure in taking in energy. That is why we become obese in this environment. So if you really want to push it towards 30% or more weight loss, that will actually mean that you have to reduce your energy intake to a significant degree. And I'm not so sure that everyone is going to be ready to reduce it to that degree.
What many people will say, "If I achieve a 15%-20% weight loss, that's probably good enough for me." And the good news is, with the data that we have seen for some of the first products that were approved in this indication, that actually leads to very significant health benefits, like we saw with the SELECT study with semaglutide. So I would argue that the sweet spot for new medications is going to be in the weight loss of 15%-25%. And then where you can truly differentiate in the future is how well you address the comorbidities to obesity, because after all, it is not the weight we are treating. It is we are treating obese individuals to prevent the comorbidities, the other diseases that are following with being obese for a long time.
The other thing that I truly believe that people have overlooked for some time because we have been so excited around how the GLP-1 molecules are being taken up into this space is, just look into any other chronic therapy area. We need, we need different modalities. We don't need more of the same. We don't need a hundred beta blockers. We need. If you don't respond well to one beta blocker, probably you will also not have the best experience on the next one. You will need a different modality. So what the world need for a complex situation, a disease like obesity, is not only more GLP-1 containing molecules, it is also different modalities for those who don't have a good response to a GLP-1, those who cannot tolerate a GLP-1. And that's where our amylin comes in, and I'll come back to that.
An alternative for those patients who tried a GLP-1 but decided, "That is not for me." I think another point, which I will not touch too much upon today, is but as a general observation, we are perhaps too much locked into the general notion that we only tap into the healthcare payer systems today and in the way we think about how these products will reach patients in the future. And I just truly believe that we underestimate people and patients' desire to have these medications to promote health benefits, and therefore healthier lives, and therefore also the opportunity that patients are actually going to a large extent, a lot of patients are going to pay out of pocket themselves in the future for these medicines.
And that is a very different pocket of money we're looking into than just looking into the healthcare budgets today. So as I mentioned, if you look across the different pipelines in development right now, you will find a lot of GLP-1 containing molecules, but they are all, to a large extent, based on the same principles. And in my view, the world do not need more of the same. The world need choices, it need different opportunities for specific patients that either are very good at addressing specific comorbidities such as diabetes and heart disease, which many people associate with obesity, but I would see, say, even more so, addressing diseases that are less well known for many people, like fatty liver disease or Alzheimer.
So I do truly believe that in the future, we need to focus on medicines that can target, you can say, that can be addressing complications to obesity, that the first molecules do not do that well. We also need different modalities, and that's where amylin comes in as one of our crown jewels, because it is, well, probably that category of amylin-containing molecules is probably one of the most promising alternatives to the GLP-1. So starting with petrelintide, which is our amylin analog, it's a, it's a product that is to be administered once weekly as an injection. It has a half-life of 10 days. It can be formulated at neutral pH and is a very potent molecule.
As you can see here, these are data we released last year from a six-week study, where we demonstrated that either the 0.6 mg or the 1.2 mg dose resulted in a 5% weight loss in overweight but otherwise healthy individuals. That is a quite remarkable finding. This is actually similar to what you can see from a GLP-1, suggesting amylin as a monotherapy could potentially be as effective as a GLP-1 for introducing weight loss. Later in the year, in the second quarter, we will have a data readout from a 16-week study, where we also test even higher doses. Then, you know, the question I get the most at this conference or any other conference: What should the weight loss be?
People say, "It has to get up in the teens, it has to be very high." I just really want to remind everyone, it doesn't have to get up there. What we are doing, we are not trying to beat the GLP-1s, we are trying to develop an alternative to the GLP-1s for those who cannot tolerate it. If you look into data readouts at week 16 for a product like semaglutide, that was 8% weight loss. So we don't need to get up to the very high degrees of weight loss. If we get 8%, for instance, or 7% in a 16-week trial, in a large phase III study that lasts for, for more than a year, we would get north of 15%, which is, to my opinion, what many people would want.
It's also back to this observation, today, we talk about weight loss. In the future, it will be as much about weight maintenance. And there, you know, you need therapies which people can tolerate. And one of the hallmarks about amylin or petrelintide is it looks to be more tolerable than the GLP-1s. There's less nausea and vomiting reported, at least in our observations, compared to the GLP-1s. And importantly, if you look into a GLP-1, the way it reduce your energy intake, your calorie intake, is by making you lose your appetite. So you turn up at the buffet, and you look at the buffet and say, "Not for me, I'll pass. I'll get out of here." That can be socially disturbing because we have a lot of social interactions around food.
Amylin works on satiety, so that is the feeling you have when you have eaten, and it may basically make you turn up at the buffet, you start to eat, and then you just stop earlier. So we speculate that it will be a much more pleasant experience to reduce your calorie intake on an amylin than a GLP-1, but further data will be needed for that. We are in the full planning of a large phase II-B study that we plan to initiate in the second half of the year. Dapiglutide is, to my opinion, one of the very few truly differentiated GLP-1 containing molecules in development, and it's really trying to leverage all the known benefits of GLP-1 and then adding additional anti-inflammatory properties by the GLP-2 component. And, we have reported this four-week study where we saw 4% weight loss.
Later in the first half, we will report a phase II-A study. It's a smaller study, where we will look into specific biomarkers and also intestinal integrity and so on with this molecule. Later in the second half, we will report a phase I-B study, where we test even higher doses. Both of those studies should allow us then to start a phase II-B study with dapiglutide in obesity next year. The whole, you can say, focus for this program is not to get more and more weight loss. Our ambition is to get good enough weight loss, and with this molecule, we believe it could be 20%-25% weight loss, but then be even better at addressing comorbidities where you have inflammation associated, which could be NASH, and it could also be Alzheimer.
I would really speculate now, but my guess is in a few years from now, a lot of people, a lot of the focus when we talk management or treatment of obesity will be, could we develop medicines that are could also address Alzheimer's-associated obesity? You know, some people have for some time, or actually for quite a long time, described Alzheimer's as type 3 diabetes. So there is a lot of scientific data connecting the obesity pandemic to also development of Alzheimer's. And we think neuroinflammation, and in general, organ inflammation, plays a big part of the damage that organs are experiencing when people are obese. Then there's this program that Boehringer is developing.
Last year, you can see this to the left, they reported weight loss data from a phase II study, suggesting demonstrating around 19% weight loss over 46 weeks. They are now in phase III and a last phase III study in obese individuals with and without diabetes. They have a cardiovascular outcome study. They're testing this in different geographies as well. And our expectation is with this amount of weight loss at week 46, they should get into tirzepatide-like weight loss in the phase III trials. But the true differentiation for this molecule is really the data that Boehringer reported on Monday this week, where they demonstrated for the first time that a GLP-1 containing molecule can actually also address fibrosis in patients with MASH.
And that is the first time we have had MASH results from two other GLP-1 containing molecules, which did not meet the fibrosis endpoint. So we are truly excited about this opportunity. There's a huge underrecognition of MASH in obesity. Most people, if you ask them, and even you will see some analysts, they will call obesity for diabesity, which is, in my mind, a little bit strange because there's only 20% of obese individuals who have diabetes. There's actually 35% of obese individuals who have MASH. So it is misleading to call things diabesity. You forget about all the other comorbidities associated with obesity. O besity, and the reason that people do this is because the GLP-1 grew out of a diabetes experience into the obesity space.
But there's actually diseases associated with obesity that are much more in need for novel treatments, such as NASH, Alzheimer's, than in diabetes. So Boehringer is responsible for this program. We are receiving high-single to low double-digit royalties from a potential future sale. Then we have our two rare disease programs, which used to be a lot of Zealand's equity story. We are extremely committed to get these products to patients, but the way we wanna do that is through partnerships. So we have them in the regulatory approval phase, I expect to have decisions later this year for this one, and the next one I will share with you. And for both these programs, we expect to establish commercial partnerships to have somebody else to take the lead and make sure these programs get to the patients.
And that, of course, will to that degree could to a very significant degree support our efforts in obesity, making sure we have the funding to go all in on our obesity efforts. Dasiglucagon for CHI, it's actually a small pump where we infuse dasiglucagon to these small patients who are born with a genetic defect, where they produce too much insulin, meaning that they end up with low blood sugar all the time, and a lot of these children will have to have their pancreas removed early after birth.
By giving them glucagon, which works opposite to insulin, we can balance this, and then with time, as these small children, they grow up, they will actually grow out of the disease to some extent, so we hopefully can save the pancreas and have and they can get more normal lives as they grow up. So, if approved, it will be the first product approved for this indication, and I would say, addressing one of the at least biggest unmet medical needs I've ever worked on throughout my career in biotech and pharma. The other product, this is glepaglutide for short bowel syndrome, which has been developed in this auto-injector, where you just take off the cap, and then you inject yourself twice a week.
So this is a long-acting GLP-2 analog, where we, a few years back, reported fantastic phase III data, demonstrated that we could reduce the parenteral support needs by 45% in these patients. So we're demonstrating an effective and long-acting GLP-2 analog developed in an auto-injector. Already today, there is a GLP-2 on the market that's a short-acting, shorter-acting GLP-2 that you need to inject daily, and plus, you need to mix it, so it's only stable as a powder. So you need to inject, mix it before you inject it, and you have to account for weight and other things. So a much more complicated injection procedure.
So we think we have, if approved, it could be a better solution for patients, and again, we have passed day 60, so we would expect to get a PDUFA date very soon by FDA, and then you would expect that to be sometime in December this year. For this, we are also entertaining partnership discussions to reach the patients and to commercialize the product. Net-net, if you look into the year for Zealand Pharma, it's really a year where there will be a huge amount of focus on obesity. We spent a lot of efforts last year starting new studies and preparing for this. There will be a number of important data readouts, both in the first half, but also in the second half.
Then when we get into the second half, that's where we expect regulatory decisions on our two rare disease assets. We expect to start new clinical studies in the chronic inflammation area truly utilizing our broad peptide platform. And probably one of the busiest years, but also a year where we truly invest in preparing for phase III. And this is back to our experience with developing products all the way to market. With where we are right now with our obesity drugs, we need to prepare, make the preparatory steps to be ready for phase III, and that, of course, includes investing in making sure that we can get the process for API production up to what would be a commercial scale production in the future.
So we do all these processes in investments, and that I think is something you would normally not experience for a smaller biotech like us, but we are actually trying to do things right here and invest in things beyond just clinical data in order to make sure we can move as fast as possible and as far as possible to the next phases. We would expect, before we start phase III in obesity, to have commercial partnerships with some large pharma companies who, like us, have an ambition of winning in the obesity space and not just being a player there in the future. So with that, I think it would be time for questions and, hopefully, some answers. Yeah?
Thanks so much for the great presentation. I was wondering on NASH, you mentioned that there was no worsening of fibrosis, but as you know, the approval is resolution with no worsening of fibrosis or one-stage improvement of fibrosis, with no worsening of NASH. Did you meet that endpoint of resolution of NASH, or are you just saying an improvement without getting specific?
So this was pretty much studied, but it was actually, you know, they, they did meet the improvement in NASH scores, but on top of that, they also had improvements in fibrosis. So that was what I tried to at least say, that it's the first GLP-1 containing molecule, which has also reported improvements in fibrosis, which is, of course, a very important outcome. And I would say now we expect that they would move into phase III, where they need to, as you mentioned, achieve both endpoints.
One or the other.
Yeah.
But one stage improvement in fibrosis, or you don't know?
No, but that was, that was what they reported. They had a one-stage. They had a statistical significance in the one-stage improvement in fibrosis, the first GLP-1 containing molecule. There's a little thing that I will share with you guys. Remember that FDA has indicated that they will approve a NASH drugs based on biomarkers. These are conditional approvals, which have to then turn into full approvals later when companies can show that these improvements in biopsies also relates to clinical benefits. And at least my own prediction is that based on the GLP-1 class of medications, including tirzepatide, if we meet the imaging endpoint, there's a very likely, high likelihood we can also reach the clinical outcome endpoints because we've already now seen the many organ benefits that GLP-1s can actually provide. But that is just my, me speculating. Yes, there was Lee, John, one question there first.
Does amylin spare lean muscle mass? I mean, there's some preclinical data that suggests it does, speaking back to the differentiator versus GLP. So how do you, how do you see that?
We have high hopes. I mean, the animal models that where this has been tested, it's very, very clear that amylin preserve muscle mass, sorry, as compared to other weight loss regimes, including the GLP-1 class. So I think there's a lot of data to suggest this. We still need the human evidence to support it, but I think there's different hypothesis that scientific hypothesis that can support these observations. So I do think it will, to a larger extent than the GLP-1s, preserve muscle mass in the clinic as well. But it's, I think we have to be careful here because any weight loss program is, will be associated with some degree of muscle loss because you carry less weight, and that's okay.
The upside is, of course, if you can preserve muscle to a little bit larger extent, then you will also increase your resting energy metabolism. And that's a fantastic thing because you can eat a little bit more and still maintain your weight loss. So it really comes back to this thing that in my mind, if you look across the preclinical, but also even more so the clinical data with amylin, it really suggests that you can have a higher quality weight loss, and the patient experience of that weight loss will be superior to other molecules. Yes?
Related to that, what's the soonest we can get next data from that?
Yeah, so we don't have it in the next study. We thus plan, and then the study that reads out here in the second quarter, we do plan to have it included in our phase II-B study. So you'll have to wait a little bit for that. Yeah?
Can you just tell us anything that you hope to learn from the data?
Yeah, I mean, so the question was on amycretin, and I've also-- that's also a question I've gotten a lot today, and, you know, I know we are close to know, but we're not that close, so, I cannot help you. I would also say one thing, CagriSema and amycretin, these, both these opportunities include GLP-1. So if you have a great experience on semaglutide or another GLP-1, and you wanna get even more of that, then you, in my mind, then you get on amycretin, or you get on CagriSema. If you don't have a great experience, you don't get on amycretin or CagriSema because you just get more of the same. You get on a product like amylin because that's an alternative experience. So I don't see them as a, as a direct competitor to what we are pursuing right now.
I see it as super GLP-1s, if you will. Yeah. Yes?
Can you elaborate a little bit on the tolerability profile you mentioned? I think you're studying higher doses in six-week portion. What allowed you to up the dose?
Yes, so we have so far, we have single ascending dose experience up to 2.4 mg, and then in our six-week multiple ascending dose, we only did 0.6 mg, 1.2 mg. If we start with the latter study, we only had mild events of nausea, and I don't think we had any vomiting. And we have tested quite a lot of GLP-1s as well, and if you do such a study with a GLP-1, and you achieve 5% weight loss, that is not the profile you will see. So just based on that small data set, we can see that it's more tolerable, at least in our experience. The 2.4 mg we tested just as a single dose did carry some nausea, and I think perhaps also one milder event of vomiting.
Still, I would say significantly more tolerable than what our experience is with the GLP-1 class of medicines. So with the 16-week data, of course, we still expect to see some nausea intolerable. Our experience is it's less. I think for you guys, it's gonna be extremely important to not only look into the numbers but also look if it's mild, moderate, severe. What is the event rate? How many times do a patient experience this? Is it just one, once, and so on. So it's not just the number of patients who experience this, but it's also the duration. How many events would you have? So there's more to this, but I would say based on the experience we have so far, it's significantly more tolerable than what we ever seen with GLP-1s. Okay, but yeah.
Maybe I can just ask one more question as we kind of hear. As you think about positioning your amylin monotherapy as out of the bars, not to be equal to one, but to the bar for group one, in theory, is there a potential to combine muscle performance in the future?
Yeah. So the question was around utilizing amylin as a monotherapy, as a combination therapy. It's very clear that there's, of course, also an opportunity to combine our amylin with another GLP-1. Novo Nordisk have already shown that if you combine CagriSema with the amylin, you get really significant additional weight loss. There's additive effects here. So that is, of course, an opportunity. In our minds, that is really an opportunity that is most interesting for the most obese patients who really need the most weight loss. The amylin monotherapy is really our key focus, but we will, of course, pursue the combination therapies as well down the line to address the most patients who need that as a patient.
But one thing I really think that we should really all think about is already today, there's a lot of patients, I don't know if it's 20 or 30%, that decides that a GLP-1 is not for them after they have tried it. And remember, this is a world where there's no alternatives. If there was an alternative, at least my prediction is a number of more patients would actually say, "I would like to try that." And then if you look at the profile of amylin with the data that we've seen thus far, it's really suggestive that it could be a leading class for weight management in the future. So that's why we are so excited, and we actually think it's important to develop it first as a monotherapy because we think that that's where the biggest need is right now.
With that, thank you.
Thank you.