Good afternoon, everyone. Thank you for joining for the last session of the day. My name's Rajan Sharma. I cover European biotech and pharma for Goldman Sachs. My coverage is Zealand Pharma, and I'm pleased to have Adam Steensberg, CEO, with us this afternoon. So, Adam, lots to talk about, so maybe we'll jump straight into it. Kind of big upcoming catalyst for you. You have the long-acting amylin petrelintide data coming up. Could you maybe just frame expectations?
Yeah, I mean, it's, of course, the data readout. We look [audio distortion] 16-week phase I -B study, which we have completed, and now we're just waiting for data readouts later this week. It's, of course, you can say expectations are based on what we observed also in the 6-week study, where we had 5% weight loss at lower doses. Now we test even higher doses. We know we have achieved higher doses. We also observed in the 6-week study a very tolerable profile with very, you can say, mild side effects with regard to nausea and vomiting, only mild events. We kind of try to not guide too much on expectations, but the number that I have put out is, of course, this range of 7%-9%, but that's very much based on the target profile of the product I want to develop.
That is a product that would give you, let's say, Tier one-like weight loss of 15%-20% weight loss, ultimately with a more tolerable profile. If you want to achieve that in a long-term study, you probably need to be in that range at the shorter-term time point, which we are reporting soon.
Okay. There's obviously a lot of focus on the 7%-9% that you've kind of put out there as a target. So can we just think about either side of the range there? So if the data come in slightly below that 7%, what does that tell you? Is that kind of, is there a reason that you may still continue to a phase II trial? And then at the other side of things, if it came in higher than that expectation, does that change anything in terms of the company's planning?
We have really thought about this program a lot. Really, if you consider what it is we want to develop, that is an alternative to the Tier 1 class. They are very successful medicines as they are launching right now. They provide significant weight loss and are helping a lot of patients achieve their goals when it comes to losing weight, which is something a lot of people are struggling with in this world. The flip side of those products is that they have quite significant side effects associated with nausea and vomiting, which a lot of patients experience. You have 20%-30% of people who drop out early during the course of treatment due to side effects. We also know now that within a year, maybe up to 70% have stopped taking these medicines for different reasons. We are developing an alternative.
And if I come, as long as I believe I will be able to develop a product that gives you this north of 15%, and I'm guiding on the 15%-20% range in weight loss, which is similar to the Tier 1 and with a better tolerability profile, we will proceed into phase II-B. And of course, when you look into small data sets, you can be lucky to have patients who are driving a data set in one direction. You can also be unlucky to have a few patients who are driving it in a different direction. So personally, I will not pay too much attention to that specific number, as long as we have a profile that suggests that we can get Tier one-like weight loss in phase III with a more benign tolerability profile.
Okay. Then you mentioned the point on tolerability. So again, conscious that this is a phase I-B trial, 16 weeks, what is a good tolerability outcome in that data set?
Yeah. That's, of course, another key question. I mean, as I said, for our 6-week study, we achieved 5% weight loss with lower doses, and we only had mild nausea and I think maybe one event of mild vomiting, which is not something you cannot achieve with a Tier 1 medicine. We already now know that amylin is more tolerable. What we don't know is, as we are approaching significant higher doses in this study, if there are specific titration steps where we experience or where the patients will experience some nausea, that's something we would then be able to handle in a phase II setup when we can then adjust the titration scheme. But for me, it's just a validation that nausea, vomiting, GI side effects are significantly more benign than what you see with a Tier 1 . That is what we will be looking for.
Okay. You mentioned the titration. How does the titration schedule for a long-acting amylin compare to the GLP-1 products that we know exist right now?
Yeah. That is, of course, also what we look forward to evaluate further in this study as we are evaluating a number of titration steps here. We are pretty aggressive because you want to reach maximum exposure, so you also secure steady-state exposure in this relatively short study. And of course, we can change this for phase II. I think one of the key things that is worth noticing is, while you need to be very careful with how you initiate treatment on a GLP-1 and also how you titrate it, you basically have to start with inferior doses that don't give you real weight loss in order to get used to the experience of a GLP-1. With amylin, as we saw with the 0.6 mg dose, we actually were able to achieve 5% weight loss with that dose and with only mild nausea.
Even though we still have to titrate to reach the higher doses, we can probably start at a more therapeutically relevant dose. Thereby, you can say titration schemes become less relevant from the patient experience because they will actually start to experience the weight loss at relevant doses, even the first dosing steps.
Okay. Just you mentioned kind of 6-week data where you saw the 5% body weight reduction. Just kind of, again, thinking about the range that's out there and where people are kind of anchored to, why is it not the right thing to do to kind of just extrapolate? So if you're at 5% at 6 weeks, then at 16 weeks, why would that not mean that kind of 7% is not easily achievable?
Remember that at the 6-week time point, both this 0.6 mg and the 1.2 mg dose actually achieved the 5% weight loss. I'm not sure we would have gone to a higher number even if we applied a higher dose. Maybe we would, but that would perhaps have been driven by some nausea and vomiting at that stage without titration. So I'm just careful here to not guide an expectation. And reality, as it doesn't, as we discussed in the start, change my view on how I want to develop this product as an enabler that in the future, the vast majority of obese patients who get on treatment will be looking for a weight loss of this 15%-20%, not more than that. Yeah.
Okay. And I realize we went kind of straight into the data and the readout there, but maybe just take a step back and looking at the bigger picture. How do you that profile that you're looking for, why are you looking for that? How do you think amylin fits into the treatment algorithm? What are the differentiations?
Yeah, but I think the clear differentiation, and that's also not, it's not only about the products which are already on the market, but also a lot of the products that are in development, they all carry GLP-1 as a backbone. And then they have built on additional pharmacology to address specific needs and potential differentiation. But if you have GLP-1 in your molecule, you will have side effects associated with nausea, vomiting, and those things. So for us, it's really the future is about developing, you can say, novel modalities as well, which can help the patients who find out that a GLP-1 is perhaps not for them. And that's where amylin comes in. And so novel modalities is incredibly important when you think about new opportunities in this space.
The other thing I think that people have underestimated for some time as we have been pursuing this more and more and more weight loss all the time, there is one way that we achieve these weight loss today, and that is by reducing calorie intake. My personal opinion is that there is a limit to how much people are actually ready to reduce the calorie intake in the long run. Maybe not in the initial weight loss phase, but when you talk about weight maintenance, if you are to maintain a 25% or 30% weight loss, you have to reduce your calorie intake so much that I'm not sure that most people are ready to maintain that.
I think, and I think that's also the experience we see with the current use of these medications, that a lot of people, they say, "When I get to this 15%-20%, that's enough for me. I don't need more because then these products will become a little bit more tolerable for me, and I can also engage more in food experiences." And talking about that experience, you can say with the GLP-2, once you lose your appetite, that means you turn over at the buffet and you basically decide, "I will not eat because I have lost my appetite." We believe that with amylin, it could have a more, you can say, pleasant way of reducing calorie intake because it works in satiety. So that feeling of fullness, that means that you will engage in your food experience, and then you will just stop eating earlier.
So eat less calories every time you eat. So we think that's a more pleasant way to actually reduce the calorie intake. But pursuing that more and more are faster, faster weight loss. I think that is, you can say, the view of the past is not where this space will go in the next generation. Medicines is about helping patients get to the targets that they want. And of course, ultimately, the reason that we are in this is to address comorbidities. The good news is that we can actually, we have already now seen with the first-generation molecules that there's a lot of benefits on comorbidities by just having a 15%-20% weight loss.
Okay. And then the other piece of the amylin story, and it's something that people have increasingly focused on, is kind of potential for muscle sparing and a better kind of quality of weight loss. And it's something that's being investigated in certain ways. So first question on that, to what extent do you think that is a real issue? And then secondly, do you think there's an opportunity here to differentiate and why?
Weight loss programs in general will be associated with loss of fat and muscle. I mean, in particular, you lose muscle if you lose weight and you don't start to exercise more because you carry less weight, meaning you lose your muscle, you use your muscles less. You can say on the Tier 1 class, there has been a lot of speculation that if do you have more muscle wasting as compared to other weight loss programs. I think the debate is still open, I would say. Reality is we have seen with some of the outcome studies that it's not at least creating a safety issue because we have benefits on some of the key parameters like heart and so on. The issue from the patient perspective in my mind is that if you lose too much muscle, you will also drop your resting energy metabolism.
And that means that you actually have to even maintain a lower calorie intake in order to maintain your weight. And it becomes more difficult to maintain that weight loss in the long run. And in particular, if you stop taking these medications, of course, you would have a tendency to actually put more weight on afterwards. So I think it's an issue, but for me, it's more about an opportunity to maintain a higher resting energy metabolism if you can maintain your muscle mass and prevent the weight gain long term. And with amylin, I think there's very, very strong preclinical evidence for muscle preservation. There's a number of animal studies where that has been shown with a number of different molecules, different amylin molecules, that animals preserve muscle mass when they lose weight as compared to a GLP-1 weight loss in animal.
Okay. And then just kind of thinking about amylin, there's obviously a few other programs in development. I think kind of for obvious reasons, people are focused on Eli Lilly's developments there. Novo are obviously kind of have an amylin, slightly different strategy. AstraZeneca talked about taking one to phase II. How do you think petrelintide fits within that? What gives you confidence that this is a best-in-class asset?
Yes. Our focus with the petrelintide is really monotherapy as an alternative to the Tier 1s for those patients who cannot tolerate it. And there, I believe you need an effective amylin. And that means one that can give you weight loss long term in the 15%-20% class. And our experience and the design principles we applied when we made this molecule was that you need to hit not only the amylin receptor, but also the calcitonin receptor. That is the same that human amylin is doing, amylin that is released from the beta cells. So we are trying to copy that. And the experience is built on knockout studies, which suggests that if you don't have the calcitonin receptor available or engaged here, then you cannot achieve the same degree of weight loss. And it's also preclinical.
You can see studies with a number of different amylin analogs we created. So we firmly believe you need to be on both receptors to have the most weight loss with this class. And that's where we think we have a unique, you can say, a very strong molecule. Our understanding is that petrelintide has the same properties. It's also working on both receptor systems, both the amylin and the calcitonin receptor system, and has the higher doses, which is not being pushed into phase III, but the highest dose of petrelintide did, you can say, provide 10.5% weight loss over 26 weeks, similarly weight loss in my mind. If you look into the other approaches where we have not seen the data yet, but I mean, I think more qualitative statements from Astra and Lilly, they say they are more targeting only the amylin pathway.
Our expectation would be that potentially that could be less efficacious approaches and maybe not that well suited for monotherapy, but could still be something you could use for combination therapies.
Okay. Okay. And then thinking ahead to the phase II trial that we may potentially have for petrelintide, obviously, you've got to get through the initial data readout and make sure that kind of the profile fits. But to what extent is that already in planning and what are the considerations?
We have extremely well planned for the phase II-B study with the petrelintide. We, of course, need now to see the data to set the final doses and also to have the final view on the titration scheme that we have anticipated. But we are, I would say, very developed in that protocol and expect to have the first patients dosed in the second half of the year.
Okay. And then just thinking about the muscle preservation endpoints, how do you think about incorporating that into a clinical trial? Of course, we're not going to get it in the phase I-B that's imminent, but in phase II and beyond, how are those implemented?
Yeah. So it is, of course, a very important parameter if we can show that we can preserve muscles because we can help patients maintain their resting energy metabolism. And the way we will assess it in the phase II-B study is by applying an MRI, so as a way to assess lean body mass. So that's a dataset which I will be looking very much forward to seeing to see if we can confirm the literature on animals. Yeah.
Okay. And then in terms of other endpoints, and you talked kind of comorbidities related to obesity, are you confident that amylin should have benefits on kind of external effects, so kind of cardiovascular, renal, as we've seen with the GLP-1s? What gives you that confidence?
So I think personally, I have a lot of confidence in amylin, not only from a weight loss perspective, but also driving benefits and comorbidities. And again, it's built on, you can say, the datasets from petrelintide, where you can see reductions in the classical risk factors for cardiovascular disease, such as blood pressure, lipids, CRP, cholesterol is all pointing in the right direction. And I would say, in contrast to the GLP-1 class, amylin doesn't carry the liability on heart rate. I mean, with GLP-1s, we know that there are some increases in heart rate. Some GLP-1s have very significant increases in heart rate. With the amylin's, we don't. So I think that's at least an early kind of positive. But the risk factors that we normally would look into are all pointing in the right direction that we should see some cardiovascular protection as well with this class.
Okay. And then just in terms of partnering and commercialization and kind of longer term on amylin, obviously, as we talked about Novo, Lilly, AstraZeneca are kind of within this market. At what point do you kind of seriously consider a partnership for petrelintide and considering that these companies with kind of billion dollars of R&D spent that you're competing with?
Yeah. We have a very, very good idea about how we want to develop this molecule and also for which patients we want to develop it, like an alternative for the GLP-1s. But it's clear that we need a partner at one point, and you can say that should be before we enter phase III development. But that is more to secure, you can say, a global reach, positioning, of course, but perhaps most importantly, also investments into manufacturing and factories in order to, you can say, meet the demands of a potentially leading future weight loss medication. So it's not that we will be out shopping this around now, trying to find somebody to take over and drive things forward.
We will be looking for the right partner, somebody who will have the same vision as we do for how this space will develop, and also, of course, somebody who would view petrelintide as a product that could actually help frame the future management of obesity. So we are looking for a true partnership and one where we will continue to play a very strategic role going forward. And so I look forward to having those discussions as we progress into the next period. Yeah.
Okay. Perfect. And just a few kind of housekeeping bits on petrelintide to kind of tie up. So timing, obviously, this quarter is what you've communicated. So are data in-house? Where are you in terms of the process?
We will have the data here in June. The study is completed. There's a team analyzing the data. At one point, they will unblind them and present them to a group of people, and then we will release it to the market.
Okay. Just on that release to the market, what should we expect the top-line release to look like? Will it be kind of data by dose? Will there be AE data in there as well?
Yeah. I think if you also look into our prior releases, we'll be making sure that we have a balanced release here, which represents the data as they come out, both from the benefit and the risk perspective. So it will be weight loss, of course, as everybody will anticipate it, but also, of course, the side effect profile, nausea, vomiting, and data on that. Yeah.
Okay. And then just thinking about kind of the broader pipeline that you have, both internally and kind of the competitive landscape, amylin, kind of how focused are you on a monotherapy? Is there a point in time when it might make sense to start to do kind of combination trials with other GLP-1-based products or otherwise?
I think we have seen data that the combination of an amylin and a GLP-1 looks to be a very promising opportunity. And there are, of course, two ways you can do that. It's either fixed dose product where you have to give them as one, you can say, product, or you can do loose dose combinations, which is actually how most combination therapies are applied in chronic diseases. Most are actually you get on one therapy, and if you need more, then you add one on top of that. We have designed our molecules, so it can also be co-formulated with all the GLP-1-containing molecules we know of because it's stable at neutral pH. So it's only natural that at one point we would also consider co-formulation, but it's not going to be the primary scope of this program.
Our focus is to develop petrelintide as a leading future brand monotherapy that could be also used for those patients who need more as an add-on to other therapies. Ultimately, it could also be relevant to consider fixed dose combinations. I will not use my amylin as a lifecycle management tool around another GLP-1. In our view, amylin should be the backbone of obesity treatment in the future and not the other way around.
Okay. Okay. That's clear. As I said, kind of there are a few other assets in the pipeline. Before we go to survodutide, I just wanted to kind of touch on dapiglutide, the GLP-1, GLP-2. We saw some data from an investigator-led trial last month. Could you just put that into context for us?
Yeah. So dapiglutide is one of the, you can say, most, you can say, differentiated probably GLP-1-containing molecules in clinical development right now. I mean, there's a lot of, you can say, GLP-1 monoagonist and GLP-1/GIP co-agonist. And then there's the GLP-1 glucagons, which I think with survodutide, Boehringer Ingelheim as leading. But GLP-1, GLP-2 is really leveraging the benefits of GLP-1, which I think most people are aware of, and then adding further anti-inflammatory potential with the GLP-2 component. And that is both by improving the gut integrity, meaning that you have less bacterial translocation that drives low-grade inflammation at the liver level, but it's also direct anti-inflammatory actions of GLP-2 on, you can say, both systemic, but also organ levels. So by activating stellate cells in the liver, for instance, and so on.
So the focus here for this program is really to develop, you can say, a weight loss agent that gives you, let's say, tirzepatide like weight loss, but have an even greater opportunity to address organ damages, low-grade inflammation associated with metabolic diseases. So it's really working on the, you can say, the comorbidities to obesity.
Okay. And then I guess timelines on dapiglutide, so your own company-sponsored phase I data is expected second half of the year?
Data is still expected second half of the year. We reported the data from the investigator-led trial, which was really with inferior doses. So we were not really getting into the weight loss range of where you need to be on a GLP-1. The good news is that with the phase I-B multiple ascending dose study, we have already more than doubled the exposure compared to where we were in that study, and we expect to go significantly higher. So that study will read out in the second half, and then we plan to start a phase II-B study in the first half of next year with this program.
Okay. And then, of course, you talked about kind of the inflammation benefits that come with the GLP-2 component. Similar question, how do you demonstrate that in a clinical trial? Is that in an obesity trial, or do you run a separate trial to do that?
Yeah. So the first study will be a study that just focuses on obesity and also, you can say, learning how to titrate this molecule, as you know, you have to do with all these GLP-1s and so on. We will have to do additional studies in parallel with that, which targets more on some of the, you can say, significant comorbidities to obesity to truly show the differentiation potential. So, of course, this is a longer, you can say, game, if you will, before we have the final proof of the differentiation potential of this molecule.
Okay. And then similarly, on partnering on that side, is that a focus for Dapiglutide? And is it kind of reasonable to expect that there might be, it might make more sense to partner that earlier than relative to petrelintide, given there's probably more work to do to validate it?
There's no question that if you want to develop a GLP-1-containing molecule today, you need more development power. You need more ability to differentiate your molecule because you will launch such a molecule into a space where there's a lot of other GLP-1 products out there. So in order to convince a future prescriber that this GLP-1 that contains additional pharmacology is the product to be prescribed, you need significant muscles that big pharma are normally very good at. So it's a completely different development opportunity compared to amylin. They're both great, but of course, you need more power. And therefore, you're right, there we could probably benefit from a partner earlier rather than later.
Okay. Moving to survodutide, we're just coming out of EASL, where we had full phase II data for that asset. Could you just characterize the data that were presented at EASL and kind of your confidence, the sense that we got coming out of the conference was there was a huge amount of interest, and particularly from a physician perspective, but could you put it into context, especially related to competitor data?
Yeah. But we were extremely impressed with the data. Remember this program that Boehringer Ingelheim is running? It's one of the companies who have invested the most into the MASH space, recognizing the huge issue that we are dealing with here globally. And I must say that personally, I was extremely happy to see the data, how they read out. I think we are really looking now into potential solutions for these patients, of which there have not been a lot so far. It's, in my mind, the strongest dataset that we have seen in this category. And I really look forward to seeing Boehringer Ingelheim moving forward into the next development phase. And I think it's speaking specifically to what we also discussed before. I mean, here we have a GLP-1-containing molecule, which has shown a great weight loss, but it's not really why you need this molecule.
It's really its ability to actually address liver disease in obese individuals. Remember, 35% of all obese and overweight individuals, they have MASH, some degree of MASH. It's one of the most overlooked and undertreated, underrecognized diseases associated with metabolic diseases. I really think the world is in need of more therapies in this space. We need, just as in obesity, we need many different modalities to address this issue. Personally, MASH, I think, is one of the diseases we'll start to see much more of in the future because we're going to be faced soon with the consequence of childhood obesity, meaning that people have lived with obesity for many more years. Those people are the ones who are really at risk, in my mind, of developing MASH earlier in life than what we're used to seeing.
Okay. Within MASH, we obviously have an approval there with Rezdiffra. How do you think about survodutide positioning in MASH relative to Rezdiffra and other kind of liver-directed therapies?
Again, it's really up for Boehringer Ingelheim because they are responsible for development and commercialization of this asset. But you can say, if you add the weight loss component, at least in my mind, you can say the whole, it's easier for patients to consider to be on a product, even in a preventive setting, for a longer time if they also get the weight loss experience as compared to some of the other approaches. But as I said before, I think we need many different tools to address this problem, which I only expect will increase over the coming years. But it is up to Boehringer Ingelheim to kind of communicate if they're going to have more of an obesity angle versus a MASH angle when they go forward.
I think they have very strong data in both, but of course, the MASH data stands out, as you can say, as uniquely impressive.
Okay. In terms of kind of the flip side of the, we've talked about the positive data. There are obviously a few things that people had kind of picked holes in in the dataset. One was the lack of the dose response between the mid-dose and the higher dose on the fibrosis side. We also saw that with tirzepatide SYNERGY- NASH trial. What do you think is the underlying reason for that? Is there something in the baseline characteristics of patients who are more amenable to those higher doses?
I don't know. That's the simple answer. My own reflections is, of course, first, I mean, that I had actually expected more of a dose response with tirzepatide because I think, in theory, at least more of the benefits on the liver could be indirect effects of weight loss versus if you look at survodutide, which has the glucagon component, which should also provide weight-independent benefits on the liver, you could actually expect less of a dose response. Whether that's what we're seeing with survodutide and it's two different things with the two programs. If it's due to dropout rates at the higher doses because of you need to titrate more carefully in the next phases, I mean, we need to see that in phase III before I will judge if this is just a chance finding or something that is real.
Okay. The other thing is discontinuations that some investors have been kind of a little bit concerned on with survodutide, both with the obesity data and then in the NASH or the MASH trial where we saw kind of 20-ish%. Could you kind of put into context why people shouldn't be concerned?
Yeah. But I mean, we have said all the time that we feel very comfortable around that. If you look back to the early studies with some of the, both with Wegovy and with Zepbound, there was also a lot of discontinuation, dropout, nausea in the phase II program before. You can say more appropriate and flexible titration schemes were applied in phase III. And we, of course, expect that Boehringer Ingelheim will apply the same into their phase III program. I think it's also really reassuring if you look into the obesity program in phase II, they only tested up to 4.8 mg. Now they're pursuing up to 6 mg. And you wouldn't do that unless you think you can actually control those things.
So I'm not concerned, but it reminds me a little bit of the same notes that were out from people when the phase II datasets were reading out for these earlier programs where people also said that, well, this is too much, but then it got under control a few years later.
Okay. Now that you have phase II data in hand in both MASH and obesity, as you think about survodutide, which is the bigger opportunity?
Yeah. But again, it's really difficult for me to discuss since it's Boehringer Ingelheim leading this. I would say it's really, really great opportunities, both of them, and they are extremely complementary. So I would say without the MASH data, I think survodutide would not have a great, you can say, opportunity in obesity. And you can say also the other way around. I think the obesity data really supports the opportunity in MASH. So I think they are so complementary. As I said before, 35% of all obese individuals, they have MASH. I don't know the number for how many MASH patients are actually obese, but that is a lot, probably closer to 90% or more. So there's such an overlap here. So I just think that, and it's the most underserved, one of the most underserved consequences of obesity. So I just think it's so complementary.
It's actually difficult for me to differentiate the two.
Okay. Maybe we should talk about the rare disease pipeline as well. I think it's kind of something that's overlooked, and we spent 25 minutes on obesity. What are the latest developments on glepaglutide in terms of your interactions with the agency ahead of the PDUFA at the end of this year?
Yeah. We have good dialogue with the FDA and are progressing those discussions towards the PDUFA date in, as you said, December. We think that that's going according to plans.
Okay. On glepaglutide, you've kind of been clear publicly, and you've discussed it multiple times that the strategy is a partnership or a licensing deal. What, firstly, timing, how do you think about that? Is it likely to be pre or post a potential approval?
Yeah. So we are not guiding on this, but what I can say is that we decided not to open data rooms until we had the file accepted with the FDA, which was in late February, and then we were getting so close to also some competitor readouts. So we also decided to just wait for that so we had more clarity on the opportunity, not only focusing on liver, but more the competitive landscape. So now we have initiated the process a few months back and with the data room and so on. So we are in good dialogues, but I would also put it this way. We also actively engaged in the pre-launch activities. This is something we still have the capabilities to do as an organization, even though we closed down our commercial operations a few years back.
So we are not in a hurry, and we will not compromise on the long-term value creation on this opportunity. But on the other hand, from a, you can say, more strategic perspective, I'm fine. It's probably the preferred scenario to have a partner before so we can focus in on the obesity assets. But if we believe we can capture more value by waiting until after approval, we'll do that.
Okay. And then maybe just to kind of push a little bit more on that point, so say in a scenario you get an approval at the end of this year, so you have kind of a commercial-ready product, what are the options there? Could you start to think about an initial launch yourself without a partner?
Yes. I mean, and we actually already communicated that on the CHI opportunity, I mean, which we were making ready to make commercially available ourselves, and we still will if that's approved later this year. So we have the organization to do that. It's not the focus of our strategy. We think we are better served focusing in on the obesity opportunity as we progress into phase II-B. But as I said, we will not compromise on the long-term value creation here, but we are so we can do that, but it's not the focus for us right now. It's actually to see if we can identify the right partner to drive the commercial success.
Okay. Then you talked about dasiglucagon as well. Similar question there. Strategy has been to partner it. If not, would you kind of consider the initial commercial launch? And what could that look like in terms of any OpEx that you may need?
Absolutely. And I will also say dasiglucagon is an ultra-rare disease that's probably six centers in the U.S. who are taking care of, I don't know, 60%-70% of the patients. So that's a very small commercial effort. So we have submitted, we have a PDUFA date for the original one, which covers three weeks of treatment in October. So when we'll have a partnership on that one. And value again here. And the value is with the chronic use label. So let's see when we will engage in a partnership there. But I would say ultimately, it is the ambition for us to have partnerships for the two rare disease assets. We are not forced into a situation where we have to do something to support our short-term needs.
But in particular with Glepaglutide, I would say, because it's a more, you can say, complex commercial operation, it's more, you can say, important for us to find the right partner. With CHI, we can take care of that for some time.
And then just one thing on the PDUFA for Glepaglutide. Well, for dasiglucagon, you got a CRL previously on the manufacturing, and our understanding is it's a contract manufacturer that you're using for both products. Are you confident that that's resolved and it won't be an impediment to an approval?
Yeah, we are. I mean, otherwise, we would not have resubmitted the filing with the FDA for dasiglucagon. Remember, it was not related to our product. It was a different product and a different production line. And our understanding based on the close dialogues with the CMO and also with FDA is that that should be okay.
Okay. So on the last minute on financials, so you said cash runway guidance is to 2027, and that's X, any potential milestones or partnerships. Where does that take you operationally?
Yeah. But that's a guidance that includes, you can say, initiation of the contract of the two phase II-B studies. And also, and this is something people sometimes overlook, is actually including investments in the manufacturing upskaling that we're doing right now. The current R&D budget includes a lot of investments into making sure that we can get commercial scale batch sizes for API and so on. And it's also supporting, you can say, the next wave of innovation, including initiation of a few new phase I studies. And then you can say what it does include is it doesn't include operations associated with commercializing products and so on. But on the other hand, it also does not include, you can say, milestones upfronts and royalties from products that get on the market. So I would say it's a very balanced and perhaps even slightly conservative guidance.
Okay. Perfect. Well, we are right on time. So thank you very much, Adam, and thank you everyone for your attention on the last session and with some storms in the background. Thank you.