Zealand Pharma A/S

Welcome and thank you for joining us today to discuss Zeeland's results for the first quarter of 2024. With me today are the following members of Zeeland's management team. Adam Steenspert, President and Chief Executive Officer, Henrietta Winnecke, Chief Financial Officer, and David Kendall, Chief Medical Officer. You can also find the related company announcement and interim report on our website at zeelandpharma.com. As described on slide two, I caution listeners that we will be making forward-looking statements that are subject to risks and uncertainties. Moving to slide three, I will turn the call over to Adam Steensberg, President and CEO. Adam?

Thank you, Anna, and thanks to everyone for joining today. I'm very pleased with the performance of our business in the first month of 24. The progress we have made sets us up for an extremely exciting next few months with key clinical results from all our programs targeting obesity and continuous productive interactions with the FDA on our two rare disease programs. We have completed the phase 1B multiple ascending dose trial with protrinitide and the investigator-led dream trial with dapiglutide. Both programs are on track for top-line results here in the second quarter. For betrinotype, we aim to develop this molecule as an alternative to the GLV-1-based therapies for weight loss and, importantly, weight maintenance, as we believe the specific mode of action could provide a better patient experience and address some of the shortcomings associated with GLV-1-based therapies. With dapiglutide, we have a truly differentiated GLP-1 containing molecule designed to provide significant weight loss with the added potential to address the low-grade inflammation associated with metabolic diseases. Through the DREAM trial, we expect to mainly gain mechanistic insights into the effects of the GLP-1 and GLP-2 receptor components. as this trial only included lower doses of dabigrutide and thus will be less informative on the weight loss potential. In the second half of the year, however, we expect top-line data from a 13-week dose titration trial investigating significantly higher doses of dabigrutide. In February, our partner, Berner Ingelheim, reported groundbreaking top-line results from a Phase II trial with servilutide in mesh, providing evidence of effect on fibrosis and thus a clear differentiation that positions Cervulotide as a potential future leading incretin-based weight loss medication. Results from this trial will be presented at the ESO Congress here in early June. In rare diseases, we now have PDUVA goal dates for both dasyclogon in congenital hyperinsulinism and for plipactotide in short bowel syndrome in the fourth quarter. Lastly, we significantly strengthened our balance sheet through a private placement with two renowned international investors in early January, securing a runway into 2027. Moving to slide four. With the strong start of the year, we remain on track to deliver on our key priorities for 2024. We look forward to important clinical results for both quaterniontide and dabiglutide that we anticipate will position us to advance into large comprehensive Phase IIb trials and thus significantly expand our efforts towards developing the next generation of obesity treatments to address what we believe is the largest healthcare challenge we have seen in modern times. For the past year, we have already made significant investments into the organizational capabilities required to deliver on this next development phase and we expect to accelerate those efforts as we progress through the year. Our two rare disease assets, dasyclogon in congenital hyperinsulinism and Gepakrutide for short bowel syndrome, are an active review by the FDA with the DUFA dates in Q4. In parallel with the regulatory process, we are engaging in partnership discussions for future commercialization. We are also advancing our preclinical programs targeting chronic inflammation towards the clinic and expect to initiate first in human trials with our K1.3 iron channel blocker this year. We intend to provide an update on the potential next steps with the complement C3 inhibitor in due course. Moving to slide five, I will now turn over the call to our chief medical officer, David Kendall, to discuss our R&E pipeline. David.

Thank you very much, Adam. Today, I would like to focus my remarks on the continued advancement of our obesity program and also provide an update on the regulatory progress with our two rare disease assets. Turning to slide six, I will begin with petrolentide, our long-acting amylin analog. Amylin agonism provides a unique and distinct mechanism for achieving weight loss in people with overweight and obesity, and represents an exciting potential alternative to incretin-based treatments. Amylin agonism reduces body weight by enhancing satiety and restoring leptin sensitivity, in contrast to the reductions in appetite and prospective food intake that are observed with GLP-1-based therapies. Furthermore, non-clinical data have demonstrated that amylin agonists, including petrolentide, offer the potential to preserve lean body mass and therefore provide higher quality weight loss when compared to incretin-based treatments. In addition, both our own observations and clinical observations with other amylin analogs have demonstrated improvements in cardiovascular risk factors such as blood pressure, lipids, and markers of vascular inflammation without increasing heart rate supporting the potential for improving cardiovascular risk. We have previously presented data demonstrating a mean weight loss of more than 5% in healthy, lean, and overweight and obese individuals after weekly doses of both 0.6 and 1.2 milligrams administered for six weeks, with these data presented in full at Obesity Week 2023. We remain both optimistic and excited about the potential for our amylin analog and are very encouraged by the significant weight loss observed, which is similar to results reported in initial short-term studies of GLP-1-based therapies. Importantly, we also believe that the tolerability profile of petrolatide offers the opportunity for a considerable improvement compared reported in clinical trials, and experienced in real-world settings with incretin-based treatments. We are on track and expect to report top-line data from the 16-week trial of petrolentide late this quarter. In this Phase 1b trial, we are exploring significantly higher doses of petrolentide using a dose titration scheme. and we anticipate this trial will inform both doses and dose titration schemes planned for a comprehensive Phase IIb trial, which is expected to initiate in the second half of 2024. In line with Adam's initial remarks, GLP-1-like weight loss after 16 weeks would reinforce our conviction that petrolentide has the potential to be an effective monotherapy We truly believe that with petrolentide, we have a unique opportunity to establish a new class of therapies for the treatment of overweight and obesity. Turning to slide seven and turning our attention to dapiglutide, our first-in-class and only-in-class dual GLP-1, GLP-2 receptor agonist. Dapiglutide is designed as a potent GLP-1 agonist targeting significant weight reduction and offers the potential to also leverage GLP-2 pharmacology and improve gut barrier function, as well as addressing the low-grade inflammation associated with metabolic disease, representing a truly differentiated incretin asset. In obesity, low-grade inflammation is thought to further drive many common comorbidities, and we believe that dual GLP-1, GLP-2 receptor agonism can play an important potential role not only targeting weight loss, but also directly affecting a number of key obesity-related comorbid conditions, including liver disease, cardiovascular disease, and neurodegenerative disease, including Alzheimer's. We anticipate reporting top-line data from the investigator-led Phase IIa DREAM trial in the coming weeks. DREAM was specifically designed to provide an initial assessment of the potential of dapiglutide to both reduce body weight and target low-grade inflammation, as well as address the well-described abnormalities in gut barrier function. The initial top-line data will focus on weight loss as well as safety and tolerability, and we look forward to further detailed results assessing inflammatory markers and gut biopsy findings, which will be presented at future scientific meetings. Speaking to the weight loss potential of dapiglutide, it is important to highlight that the DREAM trial is exploring dose strengths of DAPI up to 6.0 milligrams, which were also assessed in the previously reported multiple descending dose trial, where a mean relative reduction in body weight of 4.3% was observed after weekly doses over four weeks. In the ongoing Phase 1b trial, we are exploring significantly higher doses of dapaglutide over 13 weeks of treatment using a dose titration scheme and expect top-line data in the second half of 2024. These data will be used to more fully inform plans for the larger Phase 2b trial, which is expected to begin in the first half of 2025. Turning now to slide eight in the servodutide program, the glucagon GLP-1 receptor dual agonist being developed by Beringer Ingelheim. Beringer reported the exciting and impressive top line data from the phase two trial with servodutide in people with metabolic dysfunction associated steatohepatitis, or MASH, in February. These data demonstrated that 83% of participants treated with servodutide showed an improvement in biopsy measures of MASH without worsening of fibrosis, stages F1, F2, and F3, after 48 weeks when compared to placebo. Importantly, servodutide also met all secondary endpoints, including a statistically significant improvement in liver fibrosis. This is the first report demonstrating an improvement in fibrosis with a GLP-1-based therapy, providing evidence for differentiation among GLP-1-containing weight loss medications. We look very much forward to seeing these data presented in full at the upcoming European Association for the Study of the Liver Congress in Milan on June 7. Based on the positive results from the 46-week phase 2 trial in people with obesity and overweight presented last year at both the American Diabetes Association and the European Association for the Study of Diabetes, as well as the positive results from the previous 16-week phase 2 trial in type 2 diabetes patients, servodutide is now in phase 3 for the treatment of obesity and overweight, with recruitment into the trials progressing very well. Behringer have also communicated that they anticipate moving forward with Phase III studies in MASH as quickly as possible. Now turning to Slide 9 for an update on the regulatory status of our program for dosiglucagon in congenital hyperinsulinism. Following the complete response letter issued by the US FDA in December of last year identifying deficiencies at a third-party manufacturing facility that were not specific to dosiglucagon, have now resubmitted part one of our NDA, so-called original one, which targets dosing of daziglucagon up to three weeks duration. This NDA has now been accepted by the US FDA with the PDUFA goal date October 8, 2024. This represents a significant opportunity for Zealand to address a major unmet medical need for these children and their families. If approved, we plan to make daziglucagon available to U.S. healthcare professionals and patients as soon as possible and continue to actively engage with potential partners for future commercialization. We also expect to submit the additional analyses requested by the FDA from existing continuous glucose monitoring datasets in support of part two of the NDA for dosing beyond three weeks in the second half of 2024. We anticipate that longer-term therapy will be necessary for the vast majority of children living with congenital hyperinsulinism. Turning to slide 10 in clopaglitide, our long-acting GLP-2 analog that we believe has the potential to be the best in-class therapy for the treatment of adult patients with short bowel syndrome and intestinal failure who are dependent on parenteral support. As we have previously shared, the NDA for glipaglutide was submitted in December 2023 and is now under active review at the FDA with the PDUFA goal date of December 22nd, 2024. As with our CHI program, we are actively engaged in partnering discussions for glipaglutide. And with that, I would like to now turn the call over to our Chief Financial Officer, Henrietta Venicky, to review financial results for the first quarter of 2024. Henrietta?

Thanks David and hello everyone. Let's move to slide 11 and the income statement. Revenue for the first quarter of 2024 was 15 million DKK. This was mainly driven by the license and development agreement with NOA Nordisk for Sigalov. Operating expenses for the period were 266 million DKK, driven by research and development expenses, which represented 72% of Xenon's OPEX. The increase in research and development expenses compared to the same period last year is driven by the clinical advancement of our wholly owned obesity pipeline and activities supporting the regulatory review by the US FDA of the late-stage rare disease asset. Selling and marketing expenses primarily lead to activities associated with dasyclogagon, which Xenon will make available to patients in the US once approved. The increase in admin expenses is a result of a strengthening of the IT infrastructure and organizational capability in selective corporate functions, as well as legal expenses related to our patent portfolio. Net financial items in the first quarter of 2024 of 26 million DKK are mainly driven by interest income from investment in marketable securities. Let's move to slide 12 and the cash position. As of March 31st, cash, cash equivalent and marketable securities were approximately 3.2 billion DKK and 3.6 billion DKK, including the ongoing credit facility. In Q1, the balance sheet was significantly strengthened. In January, we raised 1.45 billion DKK from a direct issue and private placement of new shares. And in March, TransA off the loan facility with the European Investment Bank was disbursed representing 50 million euros. With a cash runway into 2027, Zealand has never been in a stronger financial position. And this solid foundation allow us to invest in our old wholly owned obesity programs with the right speed and quality as we conclude phase one and embark on initiating last phase two B trials. At the same time, we are in a strong position to continue the more detailed partners in discussion for our rare disease programs. And this takes me to slide 13 on our financial guidance. Let me keep this brief as our guidance is unchanged. We continue to guide for net operating expenses of between 1.1 and 1.2 billion DKK. And with that, I will move to slide 14 and turn the call back to Adam for concluding remarks.

Thank you, Henriette. We are rapidly approaching some of the most exciting weeks and months in the history of Sealand. Our differentiated obesity asset holds a transformational potential and could elevate the company into a new league. For Protrinatide specifically, we have an opportunity to create an entirely new class of medicines for weight management and thus play an important role in framing the future landscape for treatment of obesity. Within the next 12 months, we expect to be well into large and comprehensive phase 2B trials for both Protrinatide and dabiglutide We have invested significantly in setting up the organization for this next phase of development. Ceylon is ready to move ahead with speed and quality. Also, within the next 12 months, our two rare disease programs will have completed the regulatory review process in the U.S. With both dashyglucan and congenital hyperinsulinism and Kepaglutide in short bowel syndrome, we have an opportunity to address major unmet medical needs for patients. Finally, Our next wave of peptide innovation targeting chronic inflammation will have ended early clinical development. Thank you all. I'll now turn over the call to the operator for questions.

Thank you. As a reminder, to ask a question, you will need to press star 1 and 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 and 1 again.

We will take our first question.

Please stand by. Your first question comes from the line of Rajan Sharma from Goldman Sachs. Please go ahead. Your line is open. Hi.

Thanks for taking the question. I think it's actually the second quarter in a row that there's been kind of new obesity data on the day of your quarterly results. So similar question to last quarter. Could you just provide your thoughts on the extent to which the Roche data this morning, as well as kind of other competitor readouts, recently changed the dynamics in terms of the profile that you think you need to achieve with petrolintide and dapaglutide, if at all. And then just kind of a second follow-up on partnering discussions on dasaglucon and glapaglutide. Now that you have the PDUFA dates for both and more clarity on the competitive landscape in short bowel syndrome specifically, Should we expect updates on those processes during 2024? Is that likely to come after the respective PDFAs? Thank you.

Thank you all for those questions. I will start and maybe David will add some flavors also on the, you can say, data readouts on the BCC in the BCC space. If I start with the updates on the rare disease programs and partnering discussions, then At this call, we now communicate our PDUFA date for the original one, which is the three-week indication and also our intention to submit original two in the second half. And we continue to have good dialogues there in parallel as Henriette also expressed and David as well. We are preparing for making this product available to patients once approved and continue partnership discussions with the full ambition of having a commercial partnership established at the right time so we have a good dialogue. On glipakrutide, we have just started those discussions following the acceptance of the Biduva file and also data readout from one potential competitor. So we are happy with where we are in those discussions. They have been now started and we have a significant interest, as you can imagine, with a potential to have... a best-in-class molecule to address unmet medical needs for patients with short bowel syndrome that is of high interest, I would say. So we will, of course, communicate to the market once those discussions materialize, but we will not provide specific guidance on when. I will share that also that we are, of course, in parallel with those discussions, also making all the commercial preparedness to be able to launch the product. but we will provide updates as we progress those discussions. Regarding clinical data readouts, I think it is no surprise to us, and I don't think it should be to any, that we will continue to see more and more data readouts in this space as we see more players being active here. An important thing for Sealand Pharma is that we are truly focused on developing differentiated assets and not, you can say, things that are carrying the same mode of actions of medicines that you already have on the market or in late stage development. And I think that is where, from our point of view, data sets regarding molecules that are based on a GS1-DIP backbone is not something that really changed our view on how we would position or develop our molecules, because you can say it's already, you already have, you can say products like that, either on the market or in development. Our focus is to come up with novel, differentiated products that either target comorbidities to obesity in a differentiated way compared to the existing incutin-based, and that is mainly for products where we have DRT1 as a backbone, like with Cervalutide or with Dapaglutide. And then, of course, as we continue to discuss more and more about amylin as an alternative and novel class. And here I would say the data for any DLT1 would not change our scope here and opportunity to develop something for those patients who don't have perhaps the optimal experience on the DLT1. We don't think any of the other DLT1s would be, for many of those patients, the obvious choice, but a novel non-incretin-based mechanism would be. So for us, it doesn't change our plans, and I would also say, in my mind also, it doesn't change the future healthcare space, or you can say in the sense that there will be plenty of opportunities to differentiate with novel modalities in the future. David, do you want to add anything to this?

Yeah, thank you, Adam, and I agree wholeheartedly that these data from Roche and other either our perspective or the landscape. It's a follow-on to what has now been reported with terzeptide in many settings. But to Adam's point, I think for us, the data readouts and the advancement of information, for example, of Lilly's amylin agonist and the combined amylin GLP-1 program at Novo have added further strength to our position, which is that our amyl and agonist petrolentide still has a very important potential role to play. And so this unique mechanism, as Adam referred to, with distinctive mechanisms of action and potentially a distinctive tolerability profile with efficacy that we would hope would at least mirror that of the GLP-1 alone class. For us, that is really the information that has added strength to the story that we believe petrolentide and amyloid mechanism can play a critically important role.

Thank you.

Thank you.

We will take our next question. Your next question comes from the line of Lucy Codrington from Jefferies. Please go ahead. Your line is open.

Hi there, thank you for taking my questions. Just then, following on on amylin, and we've obviously seen Lily move into phase two, just wondering if you could talk us through the relative importance of activity on amylin and calcitonin, all these long-acting amylin assets, and how you think petrolintide may be differentiated from some of the other assets out there. Secondly, noticed beringer has started a small non-biopsy based phase three study in obese subjects with mash i presume this is separate to to a larger study that would be planned i just wonder if i appreciate it not your study but any thoughts on on the rationale for that specific study um Then just on the recent collaboration with Beta Bionics and Xeris and what the potential implications are for dazoglucon in an artificial pancreas, given that their deal does appear to be exclusive for use of Xeris' future glucagon and whether we should therefore, what that would mean for the phase three that may or may not start this year. And then, sorry, one more quick one just on Glepper. I presume, given the lack of commentary, that unlike Desert Music on this isn't something you would consider making available whilst you wait to seek a partner. Just confirmation there. Thank you.

Thank you, Lucy. Maybe I will start and then David will add as well to this. If we start with the Glepper side, we are, you can say, engaging in the pre-launch activities needed to be ready to... that any party would need to initiate to be ready to launch the program. It is, of course, our key ambition to have a partner on board before we launch the molecule. And we have good discussions here. And it is a different, you can say, animal, if you will, than launching into an ultra-rare indication like CHI. So you're correct on those assumptions. On the basis of ionic collaboration, We also expect to provide further updates in the coming months to the market as we progress discussions with Beta Bionics. I think it's important to note that we have a non-exclusive collaboration, meaning that we could work with any pump company in this space. And our understanding is that Beta Bionics or Xerox is now engaged in an exclusive collaboration regarding their gluobon. With that, that should not change our, you can say, collaboration, but again, for us, it's important to have non-exclusivity to work with any pump manufacturer in the future for this indication, and we'll provide updates as we progress through the year on this one. I can also, on your observation on the smaller phase three, start, you know, these individuals with servitude types who also have mesh. That is also our understanding that this is more a program that is targeting the obesity indication, and we should expect additional activities specifically related to mesh development. But again, it will be up for Berger to comment on those things. Lastly, and I'm sure that David will add something here as well on the amylin and calcitonin. We, of course, have a very good idea what we have, and we also have some idea about caprillin type because that has been around for a long time, and at least our belief is that you have to to have the most effective molecules, you need to be addressing both receptors, both in the right balance. And we will provide further updates to the market on how we have addressed that relative balance and other aspects of the molecule. For the lily molecule and other molecules, we don't have the same insights yet. And you can say, ultimately, I guess clinical data will inform us. What I can say is that the translation that we have observed from the animal studies into the initial clinical evidence of weight loss has been very reassuring in our minds that we at least are onto something that looks very right. David, any comments to that?

Yeah, I'm happy to add a couple of notes to that, and Lucy, you're U.S. colleagues provided a short summary the other day on the importance of understanding the receptor biology. I think we're in the early stages of that understanding, but to Adam's point, we do believe that, you know, this complex receptor system with amylin calcitonin, that activation at both receptors, not true DACRAs, but the amylinol mimetic compounds activating both amylin pure amylin receptors, pure calcitonin receptors, we believe is one of the components that is important for promoting significant weight loss. As Adam also alluded to, we will provide further characterization over time of our molecule. And I think that also ties back to Other components of these molecules beyond receptor biology, long half-lives with stable drug exposure or pharmacokinetics, has demonstrated in other classes of medicines and we believe will be demonstrated with long-acting amylin analogs. that will be another important contributor to the impact on body weight. And then finally, the mechanisms I alluded to in my prepared comments, namely that this is a very distinct mechanism, the mechanism of satiety versus the loss of prospective food intake or the desire to eat with GLP-1 or incretin-based therapies, as well as the leptin-sensitizing nature of amylin agonism, we believe can contribute both to the experience at the patient level in terms of how they feel when they're taking the medication, the side effect profile we've already talked about, and then maintaining that weight loss through each of those mechanisms. So for us, it is uniquely positioned based on much more than just the receptor biology, but an important question nonetheless. So thanks for your questions, Lucy.

Thank you. Thank you. We will take our next question.

Your next question comes from the line of Thomas Bowers from Danks Bank. Please go ahead, your line is open.

Yes, thank you very much. A couple of questions here from my side. So kicking off with Amelin, so the phase two B trial design, I know I'm a bit early out here, but I'm just trying to get a bit of understanding on future timelines here. So are you potentially targeting, you know, 40 plus minus weeks or could you maybe even see a potential reduction given that you might be able to try trade faster? just to get a feeling on how to advance as fast as possible toward the pivotal trials here. And then just on GLEPA, I'm just wondering whether you had the mid-cycle review yet and do you have any indications from GFDA regarding a possible outcome here? And then on DAPI, you mentioned it in your prepared remarks, but I just wanted to double-check. So the top-line data we get from the DREAM there's not going to be any information data at all in those top line data. So that will only be safety and weight reduction. And then just lastly, very quickly here, just on the complement C3, is there something in that that you see that you want to advance on your own or has the competitive environment changed given that ASTRA is not pursuing this after all? Thank you.

Thanks for your questions, Thomas. I will start with the C3. We cannot provide further comments on these programs. We are negotiating the return of the asset with Election Astra, so we will provide updates as those discussions are being completed. it will be the top line weight and safety data from the lower dose that will be reported and the mechanistic data will be presented at later scientific conferences. So you're correct in that note and then of course in the second half you'll have the phase 1b with titration and significant higher dose exposure that will also be reported this year. For glipakglutide the mid cycle review is still ahead of us but it's of course approaching and We have no indications of that yet. And then for amylin, again, it's a bit early for us to provide all the comments on the Phase IIb design. What we have said and what we also maintain is that this will be a very large and extensive Phase IIb study, which really has to be designed with quality in mind and speed, of course. So I would say It will also require the number of weeks needed to fully understand the potential of a molecule like amylin before we move into phase three with this opportunity, and also the appropriate titration and so on. So you can expect a very thorough phase two study. Thank you, John.

That's great. Thank you very much. Thank you.

Thank you. We will take our next question. Your next question comes from the line of Laura Hindley from Berenberg. Please go ahead. Your line is open.

Hi, Laura from Berenberg. Thanks for taking my question. My question is on your partnerships in obesity. Has there been any change in the cadence of your interactions with potential partners for your obesity drugs so far this year versus last year? Can you remind us of what you see as the ideal time to do them to find partners for petrolintide and daphyglutide, and then how your thinking is evolving on this and do competitor readouts have any bearing here? And then as a follow-up on amylin, is there a floor value for weight loss that you'll need to see in this phase 1B trial to go ahead with your planned phase 2B? And final one on NASH. So Novo has been confident that Wegovy can deliver significantly significant fibrosis benefit in NASH in its larger and longer phase three trial. If Regobi does show this significant benefit, how confident are you that Cervidutide can still differentiate? Thank you.

Thanks. I will again start and then maybe David have some additional comments. If I start with the partnership discussions, our minds have not changed here in the sense that we for some time, of course, have had in formal discussions with a number of large pharma companies and trying to understand their views on this market and where it should go. And of course, I think it should be of no surprise to anyone that there's a huge interest in this space as such. So we have had those discussions, but we have also been very clear that we didn't want to move on to more concrete discussions until we have the next data set. what we are doing from an internal perspective is that we set our organization and all our efforts up so we can completely deliver on the phase 2b programs and we will move these programs forward but but of course as we get data here in this quarter we will also engage in in discussions and see when is the right time to find a partner for us it's it's the right time really will be also defined on that we are reassured that we have partners with the right, you can say, ambition. We truly believe we have opportunities, as I said in my prepared remarks, to frame the future of obesity management. We think we sit with some very unique, differentiated assets, and we will only partner with somebody who have an ambition of winning in this space and not just playing in this space. So we actually think It's such a unique and rare situation. We sit in here that we will be, you can say, really also looking for the commitments from such a partner before defining what time is right for this. But it's clear to us that there is significant interest, as you can imagine. On the amylin phase 1b study, Remember, it's a small study. I think it's reasonable to expect, I mean, seven to nine, then we are in line with others, as we have said repeatedly, percent weight loss. If it's lower, we would have to look into it. There could be study specific reasons for that. But I mean, maybe David will provide further comments. I will just maybe before I hand over to you, David, address the mass trial and say, I think it's pretty well established that weight loss per se are related to mass improvements overall. So of course, you should expect that weight loss programs will provide some mass benefits and potentially also some improvements in fibrosis. As we have said all the time, by adding glucagon to that weight loss program, as has been the case with Cervulotype, then you get a liver-specific reason to get energy out of the liver. And thus, we would at least expect general weight independent benefits on liver and thus significantly higher benefits. So we don't think it will change anything. It will just underscore, you can say, the potential of indirect weight loss, but it will still, you can say, position the product that is most effective in addressing MASH as a potential future leader because MASH is going to be such a huge issue with obesity in the future. David, do you want to add something to this?

Yeah, I'll follow on, Adam. Thank you. On the MASH piece, I think you're spot on that while there is evidence that there are weight-dependent effects on fatty liver and the components of MASH, as Adam alluded to, targeting the glucagon receptor appropriately improves free fatty acid trafficking, the metabolism of free fatty acids. So there is a unique mechanism added to, we believe, the weight-reducing effects of servodutide that at least allow the potential to differentiate from GLP-1 alone. So I think if there is significant improvement with weight reduction with GLP-1s, that's a positive for the entire class. And then having, if you will, that second signal, in this case, the glucagon signal with servodutide, can and potentially will offer additional benefits over and above the benefits associated purely with weight change and i'll go back to adam's comment on the petroleum program and what we would expect or at least are anticipating and refer you back to the early data with the five plus percent weight loss over short exposures um i think seven to nine percent um if we see weight reductions in that range that is entirely consistent with what has been reported with other amylin agonists and is on par with shorter studies, meaning these 12 to 16-week studies in weight loss with GLP-1-associated or GLP-1-based therapies. Similarly, I think what the pattern of weight loss will receive form phase three really is as important as the absolute number, but given what we have seen previously, anticipating something in that seven to nine percent range for us would fit with how we have modeled this going forward.

That's great. Thank you.

Thank you, Laura.

Thank you.

We will take our next question. Your next question comes from the line of Suzanne Van Voselsen from VLK. Please go ahead. Your line is open. Hi there.

This is Suzanne from Kempen. Thanks for taking my question. I have one more on the upcoming patrilentide readout. Can you elaborate on the considerations around certain baseline characteristics like BMI and gender split, what we should be keeping in mind when interpreting weight loss data? And to what extent will there be information provided on the samples, baseline characteristics, and the topline release?

Thank you for the question, Susanne. And again, I will just start by putting a few comments, and then, David, you can add. But of course, it's known, especially in phase two programs, that both baseline characteristics, gender, amount of, you can say, the base weight and so on are quite significant, you can say, determines of how much weight loss you can achieve. But so is other things related to how you guide the patients and so on. So there are so many things you put into your trial designs when you move into phase 2b, which we have not implemented in a study like this. But I think it's a fair assumption that these are healthy overweight to obese individuals. So we have not been You can say specifically pushing to get the most of these patients into a study like this. So, yeah, if that is what the question is about. David, do you want to add something?

Happy to. And yes, Suzanne, nice to hear from you. And this reminder is a relatively small study and characteristics like gender and the baseline weights, as Adam said. These are otherwise healthy overweight and obese individuals. And while we will obviously at this time or at a future scientific presentation go through those data in detail, I think for us what's critical with the initial readout is looking at the impact on body weight by dose and what the dose titration scheme may have taught us. And obviously the primary measure in phase one, looking at safety and tolerability as carefully as possible. So this would more than likely be a more homogeneous population, and we will share those data both at top lines and at future presentations as appropriate. So thanks.

Got it. And then one follow-up. Can you clarify the number of dosing cohorts that are part of the part two of the MAD study?

David? Yeah. We haven't disclosed the full number of cohorts, but note that there are multiple cohorts, which allowed us to both progress and modify the dosing regimen to get to these, what I'll still call Suzanne, until we have top lines, substantially higher doses. This is not a single cohort study. We're looking, obviously, at significantly higher doses across multiple cohorts.

Got it.

Thank you.

Thanks much.

Thank you. There seems to be no further questions. I would like to hand back for closing remarks.

Thank you. And with that, we would like to thank you all for attending and for your questions. We look forward to future announcements and updates and to connecting in the coming weeks and months. Thank you.