Hi, everyone. Thanks for joining us for the next session. I'm pleased that we have Adam Steensberg, who's CEO of Zealand Pharma, with us today. Adam, thanks for joining us and making the trip over in person. Maybe just kind of to kick it off, if you wanted to kind of make some high-level introductory comments about Zealand, about the pipeline, about therapeutic focus, for some of the people that may be less familiar with the company.
Absolutely, and thank you for the invitation. Great to be here. Yeah, so Zealand Pharma is a Danish-based biotech company focused on peptide drug discovery and development. We have a very strong pipeline within obesity, both assets in Phase 1 through Phase 3, and together with our partner, Boehringer, one of them. And then we have opportunities in rare diseases and chronic inflammation, so basically leveraging our peptide drug discovery and development skills, which we have been refining, I would say, over 25 years. We have a few products that we have invented that are already on the market today. So a mature peptide drug discovery development engine with a very strong pipeline in obesity.
Perfect. So you mentioned obesity, which is obviously a key topic that everybody's been focused on through 2023 and likely into 2024 as well. Could you just kind of give us your view on where you, you think we are and where the kind of the sector is in terms of developments made in obesity, where we are, what's left?
Yeah. So of course, it has been on many people's minds and all over media for a few years, the obesity opportunity, if you will. I would rather call it the obesity challenge that we are seeing as a global entity. We, at Zealand Pharma, have been working with obesity-related products for more than 10 years, so it's not new to us. It's, I would say... But when it comes to products on the market, it's a rather new thing. We, having only seen the first product being launched a few years back. So I would say from a treatment perspective, it's really the early days still of obesity, of management of obesity. We see it as probably the biggest healthcare challenge that we have faced in modern time, the comorbidities that we see with the coming with obesity.
Today, we have two products that are approved to address this challenge. Just to put that a little bit into perspective, then if you take another area like hypertension, we have 10 different modalities on the market, 120 different medicines to treat hypertension, and we see obesity as a much, much bigger challenge. So it's the very early days. We expect a lot of, you can say, new opportunities to rise in the future.
Okay. And you mentioned that there's kind of two dominant players right now in the space, and there is this kind of opportunity for new entrants. Where do you see that?
Yeah. You know, this is, of course, always the thing that is difficult to predict about the future. But I think if you look back at history, what you have seen from most categories and most areas of treatment, and you have seen some of the first-generation molecules being taken over by newer generations, and I would actually guess that many people had not foreseen which would be the winner in the future. So I think what we're looking at right now are the first-generation opportunities to address obesity. And really where we have new opportunities in the future is molecules that are better suited towards targeting some specific comorbidities associated with obesity. It's actually more the diseases that are associated with obesity we are treating, rather than the weight loss per se. That's one area.
I also believe that we will see more and more shift towards medicines that are perhaps more suited for weight maintenance, because just with any other chronic disease management, I do not think that it's just a matter of losing weight. It's actually, the more important factor will be how you help patients maintain that weight loss.
Okay. And if you think about kind of the assets that you have in development, how do you think about those fitting in? I mean, one of the questions that we always get from investors, so you have semaglutide, which is in Phase 3. People ask us, "Well, why does this product need to exist in a world where we have semaglutide and tirzepatide?" So how would you answer that question?
Yeah, but I think first of all, we have to look into different classes. And really, the way we look at this at Zealand Pharma is there is the first class of medicines that are on the market today, they are built on GLP-1 as a backbone, meaning that that is what drives most of the weight loss, and then you can add additional pharmacology to that backbone to better target specific comorbidities or perhaps achieve a little bit more weight loss than what you can achieve with a mono-acting GLP-1. So what I see as the major unmet medical need going forward, if you have GLP-1 as a backbone, that is to truly, you can say, differentiate on some of the comorbidities associated with obesity to a larger extent than what the current medicines can do.
Of course, there will also be somewhat of a, you can say, a drive towards molecules that gives you a little bit more weight loss. But reality is that for most patients, the weight loss that we see with the current medicines in this 15%-25% is probably what they're looking for. So it will be a fraction of patients who will need significantly higher weight losses. So the key thing, if you have GLP-1 as a backbone, that will be how well you address comorbidities to obesity. And then I think for the next set of molecules, those that are in earlier stages of development or perhaps even still in preclinical development, that has to focus on novel modalities, because I do agree, we do not need, like, 100 GLP-1 molecules out there.
Yeah. Okay. And what about tolerability? Because that's always kind of a question, and it's something that still kind of remains to be seen as to how that plays out. So how do you think about that impacting that maintenance therapy?
Yeah. So if you take the product that we have developed, co-developed with Boehringer, and they are now responsible for the development, in the way we see the data today is that they have released the Phase 2 data set, where they had around 19% weight loss, which, if you make the projections towards longer-term studies, Phase 3 studies, you should get into the, to, I mean, 20%-25%, probably closer to 25% weight loss. And of course, it comes at a cost when you have a GLP-1 backbone, backbone, that is nausea and vomiting, especially in the titration phase, and also, as we have seen with other GLP-1s, constipation and other issues when you are in the maintenance phase. You can, to a large extent, to some extent at least, handle this by careful titration.
What we have seen with survodutide in Phase 2, we at least believe is similar degrees of nausea and vomiting as we've seen in the Phase 2 trials of the competing products. It's something we do believe that Boehringer can handle in the longer Phase 3 studies with more careful titration, use of antiemetic medication. And I think it's also a strong testament to this molecule that Boehringer is actually pursuing even higher doses in Phase 3 than what they utilized in Phase 2.
Okay, perfect. And then I guess kind of mechanistically with survodutide, it's a GLP-1 glucagon co-agonist. Just could you remind us what you think is kind of the differentiation of the glucagon co-agonist there?
So we have already seen with semaglutide from Novo Nordisk what a GLP-1 can achieve. When you add glucagon to that or a little bit of glucagon, not too much, at least in our minds, you should be careful not to have too much glucagon on board. Then you, at least, at least in theory, can increase your energy expenditure slightly more because that is what glucagon is known to do, and that should, in theory, drive additional weight loss. Perhaps more importantly, glucagon is also known to specifically target the liver and get nutrients out of the liver. So you know, any weight loss would also result in decreased fat in the liver.
With this molecule, we do hope to see even increased levels of decreased levels of fat in the liver, and thereby, hopefully, this molecule could contribute more to targeting the NASH or NASH component of obesity.
Okay. And then on survodutide, I guess it's kind of a couple of years away from the Phase 3 readout, but just thinking ahead slightly, what does kind of the perfect product profile for that drug look like to you?
It is what I would describe as good enough weight loss for a GLP-1 backbone molecule, which would be in that range of 20%-25% weight loss. But then the key differentiator would be, and let's see that we have data coming out here in this first half of the year, if we also generate strong data in NASH.
Okay. And I guess on that NASH component, we have the readout coming this year. At your R&D day back in December, I think some of the physicians on the panel there mentioned that they could potentially see a potential for a fibrosis benefit. Could you maybe just put into context what you're expecting from the readout and your views on whether there could be a fibrosis benefit with survodutide?
Yeah, I mean, I think they built that observation on prior observations from bariatric surgery, where you have seen effects on fibrosis following bariatric surgery and weight loss associated with that in longer term studies. So of course, there is a chance that we can pick that up also in a study like this. But I just, again, have to remind people to be a little bit careful because there's only a one-year duration in this study, and when you are addressing NASH from a metabolic component, it could take a little bit longer before you would have see the impact on fibrosis. But so I would say a best case scenario for me is not to have fibrosis, but of course, a blue sky scenario is if they also meet that already in a one-year trial.
Okay. And then maybe just moving to kind of the other assets that you have in development for obesity. So at the R&D event last month, you kind of highlighted the GLP-1, GLP-2, and your amylin analog. Could you just kind of put into context those assets and again, what you're looking for in terms of product profile?
Yeah. So if we start with dapiglutide, our GLP-1, GLP-2 dual agonist, then it's so important to remember, as I said in the beginning, that we are not just treating weight loss, we're actually treating diseases associated with obesity. And beyond the metabolic challenge that many organ will experience in obese individuals, there's also an inflammatory component that has been known for many, many years that is not just metabolic challenges, but also inflammatory drivers that will cause the organ damage that you see to the liver, the heart, the kidney, the brain. And I think with dapiglutide, we have really good preclinical evidence to suggest that by having both GLP-1 and GLP-2, we will be able to control inflammation to a larger degree than just having a GLP-1 on board.
So it's really a molecule which we expect will be differentiated in the sense that it could address not only NASH, which is known to have a last inflammatory component, but also neuroinflammation, for instance, obesity or Alzheimer, for instance, is associated with obesity. That's one of the comorbidities to obesity. So could dapiglutide be a very strong opportunity to address Alzheimer, which is also a big challenge to society? So that's really controlling that inflammatory component. When it comes to amylin, it's a different opportunity in the sense it's a completely different modality compared to the GLP-1 class. The way an amylin introduce weight loss is different from how GLP-1s do it. GLP-1s will decrease your appetite, and an amylin will increase your satiety. So that is the feeling you have after you have eaten.
So it's two very different ways that they work. amylin also, you can say, in contrast to GLP-1s, actually decrease insulin whereas then GLP-1 will increase insulin. In theory, that should be helpful when it comes to preserving muscle mass in your muscle, when you lose your weight, because you don't build up fat as you do when you increase insulin. And we have preclinical data suggesting that amylin could actually increase the quality of the weight loss, meaning you lose less muscle when you lose your weight. And then I would say the very important other aspect is, and these are early clinical data that we have seen, but also from some competing programs, it looks to be a more tolerable way of losing your weight, meaning you don't see the same degree of nausea and vomiting, as you do with a GLP-1.
We are extremely excited about amylin as a next generation, different modality that could complement our GLP-1 and opportunities for patients who would like to try something else than a GLP-1-based medicine.
Okay. We have 16-week Phase 1 data this year. I guess, what are you looking for from that data set to validate your excitement in your amylin?
So we have seen two data sets so far from petrelintide, our amylin analog, and one was the once, you can say, one single ascending dose, Phase1 study, and then we had a six-week data set where we saw 5% weight loss after six weeks treatment. Now we have a 16-week study, and I would say if we can get weight loss data that puts us on par with the first generation GLP-1s, like, semaglutide, for weight loss, for weight management, then I would be hugely excited. And, you know, this is actually 7%-8% weight loss after 16 weeks, that would probably take you to the weight loss that you see, 17% in longer term Phase 3 studies.
Then, of course, looking at the tolerability profile to, if that's confirmed from what we saw in the earlier clinical experiences, then in my book, we have something that looks extremely interesting.
And then on the kind of lean muscle mass piece, do you think that the 16-week data set that we will get this year will have any kind of informative data to kind of support that?
No, not to a large extent. That will be covered in later studies with the where we'll look specifically into those at the appropriate doses, once we have established dose. So the next step for this program is to start a larger phase two b study, and then in parallel with that, we expect to run studies that are assessing these opportunities. Because, of course, if you can have a molecule that preserves muscle mass to a large extent when you lose weight, that is a very, very interesting concept, especially for weight maintenance, for two reasons. First of all, we know it's good to have functional muscle, and here I must highlight functional. It's not just about, you can say, big muscles, it's actually a muscle that works.
And then the other thing, because that can contribute to also maintaining your resting energy metabolism and thereby having a more, you can say, normal maintaining a more normal weight loss.
Okay. And then those, both of those assets, so GLP-1, GLP-2, and then your amylin analog are both unpartnered right now. Could you kind of just help us think about how you, how you're kind of strategizing the partnership process from here? I mean, you've been clear that that is the, the plan.
Yeah. So of course, when you are going after an opportunity that is as big as obesity, as I said in the start, we actually consider it the biggest healthcare challenge that we have seen in modern time. It makes sense to partner at one point, and then the key question is, of course, when and with whom? And if for Dapiglutide, which has a GLP-1 backbone, it is a more complicated development program because you have to differentiate on clinical outcomes like in NASH or Alzheimer, and other areas. So here, it probably makes sense to engage in a partnership somewhat earlier. For amylin, it could be later, or it could be earlier, because it's a more simple development in the sense that it's a new category.
You just need to show that you have got good enough and differentiate it towards the first category. And, so for me, the most important thing when we partner this is that we have, you can say, a dedicated partner who have the same vision for the opportunities as we do. Not just trying to play a game of catching up with the current leaders, but actually trying to define a winning strategy to become a future winner instead of just somebody who stays behind all the time. So it's about ambition, I would say, and right partnerships. And because we have differentiated molecules, I think it's fair to have a, at least a dream about being a future winner.
Okay. In terms of the process, and kind of I realize you can't say too much on that, but is it something that you're actively engaging in right now, or are you waiting for data sets to mature as we get through the year?
We have a lot of dialogues, as you can imagine. I mean, as you started out saying, there's only two players who are really on the market today. Then we have Boehringer, who looks to be the next company who could actually get a product on the market, our GLP-1 glucagon, if it succeeds all the way. But so of course, there's a lot of other large pharma companies who have to consider or are considering how to play in this game, and we are in dialogue with several of those. We are not pushing it into very, you can say, detailed discussions yet, but it's because I do think that there's a lot of value in generating the next data sets from our end to truly, you can say, build evidence around the potential.
Okay. And then just on kind of thinking about what an ideal partnership may look like from your perspective, is kind of the deal that you have in place with Boehringer on Survodutide a good guide, or would you want kind of more economics or some kind of commercial exposure going forward?
Yeah. That partnership that we have with Boehringer is one we established more than 10 years ago. It was a preclinical opportunity. It was actually targeting diabetes at that time, so it was a very different, you can say, setting, and also at a preclinical stage. So of course, we are pursuing a different kind of partnership ultimately, and also with different financial surroundings, since we are talking about very unique clinical assets approaching Phase 2b now.
I would also say, in particular with amylin, I think when I look at this, if what we have seen so far are confirmed in the next data readout after the 16-week, I think we need to have some strategic rights because it becomes such a big opportunity that it would be important for Zealand to stay involved going forward.
Okay. And particularly at kind of the end of last year, there was a kind of a step-up in deal activity within obesity. How does that influence your strategy? Do you feel that there's kind of potentially more pressure to enter into a partnership because the potential partners are hoovering up assets, or even from a competitive perspective, that these bigger players may be able to kind of invest behind the assets and it may kind of, you know, reduces the head start that you may have?
Yeah, not really, to be honest, because what we're seeing right now, I think, is deals that are focused on products that are similar to what is already on the market or oral versions of what is on the market. So I don't think coming back to what I started out saying, that in the future we should have 10 different modalities. We should have a lot of different opportunities, so, and that's what we have at Zealand. It's not like me-too compounds or things that looks more or less similar to the products that are already on the market. So I don't feel an increased pressure. I think it's important that Big Pharma starts to take steps into this.
So far, I've seen what I would describe as rather conservative steps in the sense that they are playing in the same space that has already been defined by the two leaders, and we are trying to do something more than that. I think we would be complementary to any of those ideas.
Okay. You mentioned oral GLP-1s. How do you think those could impact the treatment landscape? And I guess secondly, is there internal capabilities at Zealand to play in the oral game if you needed to?
You know, I do think all medicines for management of obesity will become important in the future. I think we are overstating, you can say, the impact of it today, because historically, actually, if you look into any chronic therapy area, the biggest barrier to get an injectable is to start treatment. And that's, obesity is a very different animal because people are extremely motivated to get on treatment. So it's not a big barrier to get people to take an injectable. And once they're on it, they actually very often don't. It don't matter too much because it's so such a simple procedure. So I don't think orals will revolutionize which patients would like to get treatments, as you have seen in other chronic therapy areas.
And on the other hand, I would also say the reason that I do think they should play a role is, of course, if you have small molecule or medicines for the future, you could consider cheaper productions and actually reaching broader patient groups with small molecule therapies. But we only work in peptides. It's a, it's a cumbersome process to make a peptide orally available. You very often, even with very, very a lot of work going into this, you will only achieve very low bioavailability. So of course, we can do it. It's something we will do in partnerships. I think it will be, you can say, not the biggest drivers going forward.
I would also challenge people to think about if you ask patients on the current obesity medications, what are the few things that are the three or five things that you would like to see from a next generation molecule? Oral would not be the first answer. That would be less nausea, less constipation, maybe something that doesn't remove my appetite, so I can actually be at a dinner and without having to skip two-thirds of the meals. So then after that, maybe they would mention, "Could I get an oral pill?" So I think we are overstating the opportunity for orals, but I do think they will play a role. I would say in ten years from now, I would still think that injectables are the biggest category by far.
Okay, helpful. Then just going back to amylin, because I know that's kind of a molecule in your pipeline that you're particularly excited about, and we get kind of informative data this year. One of the other interesting things there is that you're targeting a monotherapy strategy. One of your competitors, as we know, is looking at a combination with a GLP-1. Could you just maybe talk to your confidence in that monotherapy strategy?
You know, our confidence comes from the data that we've seen thus far with 5% weight loss after six weeks. We have seen data from a competing program from Novo Nordisk, where they have shown, I would say, weight loss that is comparable to a, to a, to a GLP-1, but they're amylin analog, so around 11% after 26 weeks. So and, and so the bigger opportunity, we believe, is really in creating a new category distinct from the GLP-1 class. For those patients who cannot tolerate a GLP-1, those patients who would like something else, weight maintenance, those who would like to have perhaps a better quality weight loss with muscle preservation. So focusing on creating that new category is more important than just doing a fixed-dose combination, where we lock our molecule into one specific GLP-1, if you will.
So having said that, that does not mean that we would not also pursue combination therapies, and that would be a natural thing to do in a phase III program, where you combine, let's say, our amylin petrelintide with a market-leading GLP-1. That's what you have done in other chronic therapy areas. Then you show if there's added synergetic effects, and then ultimately, you could also do consider fixed those combinations. We have actually designed our amylin, so it can be co-formulated with all the GLP-1s we know of because it has a, it's stable at neutral pH. That's in contrast to other amylins. So I'm not saying that we will not do it. I'm just saying it's not logical to pursue that as the first indication.
Unless you have a market-leading GLP-1, such as Novo have, then maybe it does make sense to try and protect that franchise. But for us, it's much more important to create a new category, of weight loss medications.
Okay. And then on the topic of combination therapy, how do you think that lands kind of in the long term? So we've seen dual agonists like yourselves, we've seen triple agonists. Is there a point at which we kind of get too many agonists in a single, in a single kind of dose? And how do you think that all of these mechanisms can exist in harmony?
Yeah. I think there's a limit to how much weight loss patients want. I guess there's a natural limit at one point. But of course, I think you can say the dual acting is probably we are reaching when we get to these 25% weight loss, which we can achieve. I think we are at least reaching the goal for most patients. Then you can consider adding an amylin and get closer to 30% or 35% maybe later on, for those few patients who truly need that. But there is a limit to how much weight we should achieve, and I think the more important thing is, of course, how we address comorbidities.
So ultimately, you also need to understand if you are providing even better outcomes with those degrees of weight loss compared to what you can do with a 15%-25%. That remains to be seen, to be honest. So, I would say it remains to be seen. I do see an opportunity. I would stress that if you go beyond dual pharmacology in a single molecule, you are really on thin ice on predicting how it will go from animals to humans, because there's so many parameters you play on. It's not just about which receptors you hit, it's also the relative balance and also via signaling and so on. So it becomes extremely complicated, and probably you will also need a little bit of luck to get it right at when you get into those matrices.
Yeah. And in terms of kind of GLP-1, GLP-2, could you just kind of remind us of the key events this year?
Yeah. So we have a Phase 2a study reading out this first half year, where we have dosed obese individuals for 13 weeks and with two different doses and placebo. So of course, here we will learn a little bit more about the weight loss potential, but we have also included a lot of biomarkers, including intestinal biopsies, to better understand how the GLP-2 component contributes to controlling low-grade inflammation. And then later in the year, we actually have a Phase 1b study that reads out where we have dosed even higher. So the combined data sets from the Phase 2a and this Phase 1b study, where we dose even higher, will then allow us to move into a phase 2b.
Okay. And the 13-week data, I guess it's a relatively short trial. Do you think that's going to be predictive of what you may see in longer term trials?
You know, for the weight loss component, I think we can make projections based on what we've seen with other GLP-1 containing molecules. And then for the ability to control inflammation, it will be more hypothesis generating than it providing evidence, I would say. But of course, we will be looking to see if we can confirm some of the findings we have from animal studies.
Okay. And then you talked about comorbidities being an important part of the treatment paradigm. Is that something that you consider in the early stages of development? Do you feel that you need to, even if it's pre-clinically, to at least have a kind of hypothesis for treating cardiovascular outcomes, renal outcomes, for example?
You know, ultimately, it has to be about comorbidities to obesity. This is why we're treating, and this is why we see it as the biggest healthcare challenge that the world have faced, this obesity pandemic. And I think, again, when you really think about it, then the comorbidities to obesity that we are seeing today are the result of people who became obese in the middle age, so in their forties, thirties or forties. What we will see in a not so distinct future will be the consequence of people who were obese when they were children or adolescents. And, you know, it's not just about being obese and not obese, it's also the time you're obese. That is where your organs will ultimately end up with organ damage and organ failure.
So that's why as I really think for any new modality, you need to focus on how can that help address the comorbidity aspects. And ultimately, of course, you can get into a preventive medicine state where you treat people early on when they are just about to become or have just become obese, to try and prevent them developing these comorbidities later on.
Okay. And I guess if you think about these potential comorbidities, is there one that's more important, or do you kind of think they're all as important as each other?
I mean, right now, of course, cardiovascular risk reduction is important. I think there's a little bit of historic reason for that in the sense that for some time in diabetes, so in the metabolic space, there were FDA guidance showing that you had to show that you would not increase the risk of cardiovascular death. And then we started to see with the GLP-1 class, that you could actually, you can say, decrease cardiovascular risk, both with the GLP-1s, but also the SGLT2s. And now we have seen with semaglutide as well, that in an obese population can also, to a large degree, actually decrease cardiovascular events. So that is an important one. But it's also quite important to understand that it's probably only 10%-15% of obese individuals who are cardiovascular risk patients. If you...
I mean, have all the risk factors that we are, that we are considering when you are considering cardiovascular risk. If you look into an organ like the liver, there's probably around 35% of obese individuals who have MASH or NASH. And this is where I see the bigger opportunity, because there's no treatments today for these indications. Then you can look into Alzheimer's, which is also a huge challenge to society, and I don't think that many people actually know that there's a very close relationship between obesity and Alzheimer's, well, due to probably the neuroinflammation. So there's these, these comorbidities that are well- less well known to the public, which I think are probably gonna be even more important than the cardiovascular risk reduction in the future, because we have tools to address the cardiovascular risk, actually.
Okay. Conscious of time, so I just wanted to touch on the rare disease pipeline as well. You have two late-stage assets there. For one of those, dasiglucagon in CHI, there was a CRL at the end of last year. Could you just provide a little bit more color around that?
Yeah. So we are developing dasiglucagon, a glucagon analog, as a continuous infusion therapy for small children with congenital hyperinsulinism, which is an ultra-rare indication with a huge unmet medical need. And we submitted the NDA as June last year with a PDUFA date in December. So just before Christmas, actually, Christmas, December 22nd, we got a notice from FDA that they issued a complete response letter due to observations at a third-party manufacturer. Unrelated to dasiglucagon, but it's related to a different product from that company. So that was, of course, a huge disappointment to us. We have known about those observations for some time, but there's historic, you can say, a precedent for products being approved regardless if they target a, an unmet medical need as CHI.
So we had actually not seen it as a huge risk for this program. We are confident in the manufacturer's ability to also address these questions and hope that this will be done in the next few months. They have already issued a letter to the FDA stating that they believe they are ready for re-inspection. So we are, of course, hugely disappointed, but also confident that the manufacturer will solve these things, and we are working closely with them to understand this, and then also, of course, now with the FDA to discuss timelines for resubmission and getting the file back on track. Importantly, as you also remember, then the NDA was always split into two, one which focused on the three-week indication and then for the chronic indication.
We still aim to submit the chronic indication this first half, as has been the plan all the time, and that is where the biggest opportunity is. So for the, you can say, for the bigger opportunities, we don't believe we will see a bigger change in the opportunity.
Okay. And then there's also glepaglutide, and one of the questions that we were getting at, at the end of last year was if there's any cross read from the CRL in CHI to the glepaglutide filing. Is it the same CMO that you're using?
It is the same CMO, but as I said, we are very confident that they will solve this. It's a CMO that has been inspected several times by the FDA. They already have products on the market in the U.S., which is still there. They can supply for clinical trials. This is a technical thing where FDA can decide not to approve new NDAs when this is ongoing, and history would suggest that these things are normally solved within a year's time, which we will reach very soon.
Okay, perfect. And both of those two assets are kind of wholly owned by Zealand right now. Again, the intention has been to partner those. Could you perhaps just give us an update as to where you are with partnering discussions?
Yeah. So we are still having good dialogues. We had actually made preparations to make the CHI commercially available by ourself here in the first half in the US, if it had been approved. So of course, that has been pushed a little bit now, but the dialogues we have with potential commercialization partners, they continue. We have one of your competing competitors having a conference next week, where we will of course continue those dialogues as well. So I think things are continuing as planned. And we do have the capabilities to make all the preparatory steps. Until a few years back, we had full commercial infrastructure in the US, so it's not something we see as hugely urgent.
The more important part for me is to find a partner who can make a difference in the commercialization, and then also that whatever deal we make here will be able to contribute in a meaningful way to what we want to achieve in obesity.
Okay. And on that point, I guess, is there any difference in what you may be looking for from a potential partner in rare diseases relative to obesity?
Yeah, very much. I would also say even between the two rare disease assets, CHI is an ultra-rare indication. There's only a very few clinics, so I mean, that could be any commercial stage biotech company or pharma company which has a presence in rare diseases because you don't need a big sales force or anything. For glepaglutide, which is a somewhat larger opportunity, but also one which requires more commercial effort and a broader scope in your sales, we would probably be looking for a larger entity as a preferred opportunity. For obesity, it's of course a completely different game. I would say it can only be among the biggest pharma companies of the world, otherwise, we might as well do this ourselves.
Yep. And given kind of the prominence of obesity and the importance and kind of commercial opportunity that potentially exists, how committed are you on the rare disease side of things? Is that kind of... If you think about your R&D organization, for example, how much of their resource and their time is spent in obesity and metabolic diseases relative to rare disease?
I mean, we have two groups who are entirely focused on the regulatory processes for glepaglutide and CHI. When it comes to new initiatives and really the future of Zealand, it's really all about when it comes to the clinical phase, obesity. But then I also have to remind you that we actually have two chronic inflammation assets that will enter the clinic this year, hopefully. And those are some of the new opportunities that you will see also from Zealand. So we're not entirely focused on obesity, but we do spend the majority of our R&D time today on it. But in order to secure future value drivers, I would say we have now leveraged our peptide platform to also move into inflammation.
Okay. And one of those is the kind of product which is partnered with AstraZeneca Alexion. Is there anything that you can kind of say on there, any kind of in terms of visibility that you have and which or what updates we may get during 2024?
Unfortunately not. It is really up to AstraZeneca Alexion to make those announcements. But, I mean, per the agreement, we were responsible for all activities up to the clinical phase, and then they will take over and drive from there, and we believe we are ready for that. That's also why we expect that the phase 1 studies will start this year. We cannot communicate on which indications, but it's a high-profile target. It's a complement C3 inhibitor, so we think it's a very interesting target, but it's really up to our collaborator to announce the progress from here.
The other molecule we are fully owned is a Kv1.3 inhibitor, which is a broad anti-inflammatory target, which you can say could go into many different autoimmune diseases, that we will provide further updates on as we move into the year.
Okay. And then just to kind of wrap up, I wanted to talk about cash and cash runway. So current guidance is to mid-2026. Where does that take you operationally in terms of kind of progressing the obesity pipeline?
So that allows us to, you can say, continue with the current planned activities, including initiation of the phase 2b study with amylin that we discussed before. So it's kind of in that ball game. You can say what we have not built into that communication is potential upfront or milestones or what have you from when we partner out the rare disease assets. So that, of course, could bring in extend the runway. It does also not completely build in all the activities from the obesity pipeline that we would need to initiate late 2025, if you really want to push on all cylinders towards phase three. I mean, not meaning that we have to do phase three ourselves, but all the activities needed to get into that.
It's a rather conservative but balanced forecast.
Okay. And I guess how comfortable are you with that? And I, I'm conscious your CFO is not here to answer that question, but, you know, obviously more is always better, but how comfortable are you with your current runway and the ability to kind of-
I'm very, very confident, and for several reasons. I mean, we have the rare disease assets, which can bring in additional capital. We have existing partnerships which can contribute. We have fantastic opportunities in obesity, so there's a lot of opportunity. We have, like, opportunities everywhere, if you will. So we feel that we are at a very, very good start. And from a historic perspective, I don't think Zealand has been in a stronger position also from a cash perspective, ever.
Okay. And maybe just thinking again about the split between kind of the R&D, between obesity and rare disease. You know, near term, the things that we don't have visibility on, if there are new assets coming through the pipeline, is that likely to be obesity or metabolic diseases?
I mean, the first two assets will be in inflammation. Then you probably should expect to see a few more obesity assets as well in the coming years. But so it will be in inflammation and in obesity. You should expect the next larger indications. You should expect the next opportunities. But of course, when it comes to resources in the next few years, it will really be obesity that is driving. It's the thing that I've probably spent, and my management team has spent the most time on last year, is to build our organization, set up our organization to be able to execute on these obesity opportunities.
In terms of kind of a trials perspective and the ability to execute on these trials, given that, you know, there's a huge interest both, both from a patient perspective and an industry perspective in obesity, do you think that's beneficial to your ability to recruit into these trials and execute them on time?
Yeah. It's... I mean, we, we know it's not a, it's not an issue to recruit for these studies. It's actually more an issue to make sure that you get all the sites on board before you have completed enrollment. So it's not about recruitment, it's about doing things right and not making too many shortcuts here, especially if you truly believe you have winners and things that can define the future management of obesity. You have to not pursue the avenue of just, you can say, bypassing important data points before you make decisions. So, so even though there's an urgency to get forward, you also need to, to make the right... have the data to make the right decisions. So that's the fine balance that we are, that we are trying to manage.
Yeah. And then maybe just on that point and kind of going back to the cash position. So I guess current runway allows you to initiate the phase 2s of, for example, the amylin and the GLP-1, GLP-2, but not complete those trials, right?
No, it does allow us to complete them.
Okay.
But then we would be out of cash after that.
Okay. And then in terms of combination, I know we talked about it, but as kind of separate molecules, so is the ability to combine the amylin with the GLP-1/GLP-2, for example, and I guess at what point would you start to do that, in that you're comfortable in the contribution of each of those components?
Yeah. It's an obvious combination since we have both molecules, and they could allow, you can say, that very high weight loss. So this is something you would normally do once you understand the titration scheme and the dosing patterns of each individual molecule, then that's the right time to start to combine them if you have. So that will be, yeah, not this year, maybe next year or the year after.
Okay. And then one other asset that we didn't talk about that you have in the pipeline is the GIP agonist. It's been kind of less in focus. Could you maybe just kind of put that into context?
Yeah. I mean, I think GIP is in contrast to the other two molecules. It doesn't, in our minds, have a standalone potential. It only has potential as a combination opportunity. People don't really know yet what GIP contributes with in weight loss, and I would even say for the dual-acting GLP-1 GIP, tirzepatide, I don't think we completely understand how much each component contribute. There's been some early data now from other GIPs that suggest maybe a 2% weight loss with a GIP, but it could also be that it actually helps manage the nausea and vomiting. So there's a lot of hypotheses here. People don't know if you should have an agonist, an antagonist, so it's super complicated, and it's probably the- it's the- it is the asset which we have the least confidence in. It's...
I don't really, yeah, believe anyone really knows how it plays out-
Okay
- withG IP yet.
But I guess kind of just think from an analyst or an investor perspective, how should we be thinking about that right now? Is it kind of on hold and wait for additional data to read out from a competitive-
From our point of view, it is only a product that can be used for combination therapy and thereby less important for us to focus on right now.
Okay. Okay. And I guess if, for example, again, just thinking about partnerships, and sorry to keep kind of pressing on that point, but is that something that you may be more inclined to partner at an early stage if another company wanted to take that?
Yeah, you can- if you, if you have a... In theory, yes. But again, I maybe just reminding everyone that both Lilly and Novo also have a GIP. So there's a lot- number of companies who have GIPs, and, let's see how they will be utilized in the future.
Okay, cool. Just into the last minute or so, could you just kind of remind us of key catalysts this year, what you're most focused on?
Yeah. So I think the first half is going to be very much about obesity. So we have the NASH phase two data with survodutide, so the 300-patient biopsy-driven study, which is gonna be hugely important, I think, to better understand the differentiation potential that comes out in the first half. Then we have a phase 2a study with our GLP-1, GLP-2, dual glucagon. That also comes out in the first half, and then probably the most important data set, the amylin data set, 16-week phase 1b, where, if that confirms what we've already seen with the six-week data, then that's probably the most important data set in my mind this year. But so that's the first half.
Then, of course, we have the resubmission of the CHI file, both part one, but also submission of part two in the first half. We have continuous progress in the regulatory decision on glepaglutide and hopefully CHI, so PDUFA date coming out in the second half. We have progress on phase three program with survodutide, initiation of a few new phase 1 studies in the second half. So there's actually a lot of catalysts this year.
Okay. Then, of course, there's kind of the wider obesity competitor catalysts that are going on through the year, so lots to look forward to. But I think we're just on time. So Adam, thank you very much.
Thank you so much.