Zealand Pharma A/S

Thank you, operator. Welcome, and thank you for joining us today to discuss Zeeland's interim results for the first six months of 2023. With me today are the following members of Zeeland's management team. Adam Steenke, President and Chief Executive Officer, Henrietta Benke, 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, we will be making forward-looking statements that are subject to risks and uncertainties. With that, I will turn the call over to Adam Stainsberg, President and CEO. Adam?

Thank you, Anna, and thanks to everyone for joining today. I will begin on slide three. I'm very proud of what CELAN has achieved in the first six months of 2023. With a strong focus on R&D, We have successfully progressed our product candidates within obesity, rare diseases, and type 1 diabetes. Also, we have significantly strengthened our balance sheet to ensure a cash runway until mid-26. Of course, the big news of today is Bernhard Engelheim's announcement that they are advancing Cevutotide, co-invented with Zealand Pharma, into three global phase 3 clinical trials in people living with overweight and obesity. We are very encouraged by the phase two results presented at this year's ADA conference in June, and certainly share Boehringer's excitement about the potential for Sivertotype and the phase three trials expected to start in the second half of the year. Also in our obesity portfolio, we presented results from the phase one single ascending dose trial at ADA in June, demonstrating profound reduction in body weight after only one week of dosing of our long-acting amylin analog. Then in July, we announced top-line results from part one of the phase one multiple ascending dose trial demonstrating improved weight loss after six weeks of once-weekly treatment with lower doses of CP8396. Based on the significant weight reductions and mild adverse event profile, we have started part two of the multiple ascending dose trial, assessing both longer duration of treatment and higher doses of CP8396. And we look very much forward to seeing those data and announcing them in the first half of 2024. With dasycluvagone, we are excited about the regulatory submissions to the US FDA for the treatment of congenital hyperinsulinism and the regulatory submission to the European Medicines Agency for the treatment of severe hypoglycemia. Moving to slide four, we are well on track to deliver on the strategic objectives that we have had outlined for 2023. In the second half of the year, we expect to submit the new drug application for the US FDA for clopacritide for the treatment of short bowel syndrome. Also in the second half, We expect to initiate the 13-week dose titration trial with dabiglutide, our dual GLP-1, GLP-2 receptor agonist, and complete preclinical activities with CP6590, our GIP analog. The dialogues with potential partners for our rare disease programs are progressing according to plan, and we aim to enter into a partnership agreement for Dasikluogon in congenital hyperinsulinism in the second half of this year. Moving to slide five, I will now turn over the call to our CMO, David Kendall, to present our R&D pipeline and the recent results from our BCT portfolio. David.

Thank you, Adam. Today, I will focus my remarks on the most recent results from two of our product candidates targeting obesity, namely the Phase 2 results with the dual glucagon GLP-1 receptor agonist, Cervodutide, presented at the American Diabetes Association Scientific Sessions in June, and the top-line results from Part 1 of the Phase 1B Multiple Ascending Dose Trial with our long-acting amylin analog, ZP8396, announced in July. Turning to slide six, most people living with overweight and obesity who are candidates for pharmacologic therapy will benefit from weight loss of between 15% and 25%. While there are several promising pipeline candidates from a number of companies targeting weight loss in this range, there remains a significant treatment gap and unmet medical need to target the complications of obesity and improve tolerability of treatment. Bringing differentiated anti-obesity treatments to the market that address the different needs of obesity subpopulations and improve tolerability will be critically important. Please turn your attention to slide seven. Obesity is a complex disease that is amenable to pharmacologic treatments that target a number of unique metabolic pathways. We anticipate that the future treatment landscape in obesity will contain several categories of molecules Today, this is dominated by molecules with a GLP-1 receptor backbone, including dual and triple agonists that target several important metabolic pathways. We are incredibly excited about the potential for our amylin agonist in the management of overweight and obesity and firmly believe that amylin agonism holds significant potential for offering substantial weight loss and the potential for a better tolerability profile when compared with the GLP-1-based therapies. Amilin is a validated non-incretin mechanism and has been shown to be very effective both as monotherapy and in combination with GLP-1-based treatments. We also believe that the success of future anti-obesity treatments will be determined by their effects on both body weight and important features of differentiation, including targeting comorbidities, improving tolerability, and offering alternatives to these incretin-based mechanisms. On slide eight, we outline our portfolio of novel and differentiated assets for the potential treatment of overweight and obesity, highlighting the mechanistic rationale behind each molecule. Our therapeutic approach aims to, one, achieve increased weight loss, and two, provide additional effects to address specific comorbidities, and three, improve tolerability. Each molecule is differentiated through peptide target, design, or formulation. Turning to slide 9 and recent clinical data, positive results from the Beringer-Ingelheim-sponsored Phase II dose-finding trial with servodutide, the glucagon GLP-1 receptor dual agonist targeting energy intake and energy expenditure, were presented at the American Diabetes Association Scientific Sessions in San Diego in June of this year. This study in individuals with overweight or obesity demonstrated significant and dose-dependent reductions in body weight of up to 19% after 46 weeks of treatment. Up to 40% of participants receiving servodutide achieved body weight reductions of more than 20% at the end of study. As illustrated by the figures, body weight reductions had not yet plateaued at week 46, indicating that further reductions are likely to be observed with longer treatment duration. Please now turn to slide 10. In July, we announced additional positive topline results from Part 1 of the Phase 1b Multiple Ascending Dose Trial with our long-acting amylin analog, ZP8396. demonstrating mean weight loss of more than 5% in healthy, lean, and overweight people with multiple doses of ZP8396 at both 0.6 and 1.2 milligrams administered once weekly over six weeks. These data compared to the mean weight loss of 2.6, 3.6, and 4.2% observed following single-dose administration of 0.7, 1.4, and 2.4 milligrams of ZP8396 administered in the single ascending dose trial reported earlier this year. In the most recent Phase 1b study, ZP8396 was judged to be well tolerated with no serious or severe adverse events and no withdrawals from the study. Gastrointestinal side effects were the most common adverse event reported, all were mild and most occurred within two days of the initial dose. We are very encouraged and believe that the weight loss observed are on par with the results reported in initial studies of incretin and GLP-1-based therapies. In addition, we believe that the tolerability of ZP8396 offers the possibility of a considerable improvement over the adverse event profiles reported with these incretin-based therapies. We have recently initiated Part 2 of the Multiple Ascending Dose Trial, which is a 16-week study exploring significantly higher doses of ZP8396 utilizing a dose titration scheme, and these study results are expected in mid-2024. With these data, our confidence in the potential of our long-acting amylin analog to achieve substantial weight reduction in people living with overweight and obesity has significantly increased. And we believe that ZP8396 can play an important role as monotherapy to achieve and maintain weight loss and thus provide an alternative to GLP-1-based therapies. In addition, ZP8396 may play an important role in combination with incretin-based therapies in those individuals who will benefit from additional weight loss and help in maintaining that weight loss. Now turning to slide 11. My final remarks today are related to our congenital hyperinsulinism program and the new drug application for doziglucagon, which we are pleased to have submitted to the US FDA in June of this year. We believe that doziglucagon, if approved, can be an important and effective treatment option for this rare and devastating disease. This program represents a significant opportunity for Zeeland to address a major unmet medical need for these children and their families As Adam has mentioned, discussions with potential partners are progressing as planned, and we aim to enter into a partnership agreement for dasi glucagon in congenital hyperinsulinism in the second half of this year. With that, I would now like to turn the call over to our Chief Financial Officer, Henrietta Venike, to review our financial results for the first six months of 2023. Henrietta?

Thank you, David, and hello, everyone. Let's move on to slide 12 and the income statement. Revenue for the first six months of 2023 was 24 million BKK, which was mainly driven by the license and development agreement with Novo Nordisk for Sigalov. The submission of the marketing authorization application to the European Medicines Agency in June triggered a milestone payment of 15 million BKK. The operating expenses for the period were 388 million BKK, driven by the progression of the late-stage rare disease assets towards submission and the obesity programs. Sales and marketing expenses as well as administrative expenses are significantly lower than what we saw in the same period last year, following the restructuring announced in March 2022. Almost 80% of OPEX are now allocated to R&D activities and to progress our programs. Net financial items for the period resulted in a loss of 152 million DKK, driven by the final repayment and termination of the loan agreement with Oberland Capital in May this year. Let's move on to slide 13 and the cash position. As of June 30, cash, cash accounts and market hold securities were approximately 1.7 billion Danish crowns. This significant increase compared to year-end is driven by the capital rate in April of 1.5 billion DKK and partly offset by the cash used for operating activities during the first six months of the year and the repayment of the Oberland loan in May. With the revolving credit fertility of 350 million DKK, we now have approximately 2 billion DKK in cash. which combined with the near-term upcoming milestones from our existing partners result in a runway to mid-2026. I am very satisfied with the fact that we have now managed to both strengthen and clean up our balance sheet in the first six months of 2023. We now have a solid foundation to engage in more detailed partnership discussions, ensuring that we maximize the value of our assets. Let's move on to slide 14 and our financial guidance. Our guidance is unchanged and we continue to guide for net operating expenses of between 800 and 900 million EKK in 2023. We do not provide guidance on revenue anticipated both from the system and potential new license and partnership agreements due to uncertainty related to the time as well as size of this kind of revenue. That said, we do expect to receive additional milestones from existing partners in the second half of 2023. And with that, let's move on to slide 15, and I will then turn the call back to Adam for some concluding remarks.

Thank you, Henriette. So these first six months of 2023 has been exceptional for Sealand Pharma. And looking ahead, I expect an equally exciting next 12 months with several important events and catalysts across the therapeutic areas. Just to name a few, we expect to submit the new drug application for clopacrutide in short bowel syndrome to the US FDA in the second half of 2023. We expect initiation of phase three trials in obesity with serututide in the second half of the year with details of the trials to be disclosed by Boehringer prior to initiation. In addition, we expect top line results from the phase two trial in NASH first half of 24. In the first half of 24, we also expect top-line results from part two of the 16-week phase one multiple ascending dose trial with amylin and top-line results from the investigator-initiated phase two trial with dapiglutide. Next year, we also expect to initiate first in human clinical trials, both with our GIP analog for obesity and with product candidates in the inflammatory space. Turning to slide 16, I would like to thank all our employees for their dedicated work towards achieving our strategic priorities. Likewise, we appreciate our partners for the strong collaboration and our current and new shareholders for their continuous support and trust. Finally, I would like to express my sincere gratitude to those who have participated and are participating in our clinical trials. One final note on slide 17, we are planning to host an obesity R&D event in the fourth quarter of 2023, where we look very much forward to elaborate more on our obesity portfolio. Please stay tuned for further information on that. Thank you all. I will now turn over the call to the operator for questions.

Thank you. 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. Please stand by while we compile the Q&A roster. We will now go to your first question. And your first question comes from the line of Thomas Bowers from Danske Bank. Please go ahead.

Yes, thank you very much. A couple of obesity-related questions. So firstly, sort of an overall strategic consideration here in the wake of the Vigovi Select trial. Is there anything that has sort of made you look differently on your proprietary pipeline in the wake of this top-line result? And then just on the amylin, so now you have a number of very interesting data early, maybe also a little bit early to call before we have the 16-week data readout. But still, is there any way – do you actually see a potential for a meaningful weight loss with the preclinical and currently available clinical data? And I mean, of course, as a potential standalone product, so maybe comparable to – a pure GLP-1, what do you see here as actually a potential weight loss after one year? And then just on dabiglutide, so sequence derived from GLP-2 peptide backbone, can you maybe just comment, maybe I've just missed it, but can you comment on the actual bias towards each receptor component? So just like you have said with, I think it's 8 to 1 with the ratio with the GLP-1, so those are BI45 candidates. So anything you can disclose here. Thank you.

Thank you, Thomas. I will start to reply and then I will hand over to David for further comments. Maybe just first on dataglutide on the balance between GLP-1 and GLP-2. We have not presented that. We have just disclosed the general principle here at Celan. When we have TRP1 in our molecules, we have designed them towards TRP1 activity and less activity on the, you can say, second receptor. So that you can at least... That is also the case for this molecule, but we have not yet released the actual balance. And then maybe on your question on select, let me start on this one. and I would say we were of course pleasantly, we're really happy to see the outcome of that study. I think it really underscores the potential and I would also say what we have been pursuing all the time with these medications that we have in development that is of course far more than just weight loss. It's about clinical outcomes and of course very importantly cardiovascular outcomes that we are trying to address in our pipeline. So I would say It does not change our approach or how we have been thinking about these things, but it underscores how important it is to actually be active in this space. And before I hand over to you, David, I will just mention with amylin, I think this is, as David also highlighted today in the call, and I think something we'll talk much more about at our R&D day later in Q4, we do think there's a significant potential as amylin as a monotherapy, and if you Compare across tribes, you will see that early data both from our program but perhaps also from other long-acting amylin analogs suggest that you should be able to get into GLP-1 like weight loss medications and perhaps with a more benign profile when it comes to tolerability. It's something we will elaborate further on at our R&D day but maybe David, do you want to put some more thought into both the question on SEDEC and Amadine?

Yes, and thank you, Thomas. I'll reiterate what Adam shared. Certainly, the select trial results are, in our way of thinking, a significant positive for the overweight, obesity, pharmacologic environment and the approach to treatment, and not surprising in some ways, given the known benefit of GLP-1-based therapies on cardiovascular risk in the diabetes population, but I think this opens the door in a very important way to target not just body weight as a number, but in fact target those with overweight and obesity to improve outcomes, and in this case very important outcomes, cardiovascular risk of events and cardiovascular death. And I think it will have significant implications on how clinicians, prescribers engage patients in those conversations about the potential benefits of therapy. And we will wait to see how this affects the reimbursement environment. But I see it only as a positive and very positive move forward with regards to making these therapies available to those at highest risk. Adam also said it hasn't changed our perspective on the portfolio. We believe both the servodutide program and our own dapiglutide program, which have a strong GLP-1 receptor agonist component, are in great part designed on the assumptions that GLP-1-based therapies could and would have these beneficial effects. And finally, with amylin, I think for those of us who've grown up through the oral anti-obesity medication era, expecting single-digit weight loss, we're now in a phase with the incretin-based therapies, and as Adam suggested, early and mid-stage data with amylin agonists that suggest that they do have the potential to achieve incretin-like weight loss And there we're talking double digits of weight loss. And while it would be premature to project, I think looking back at the early clinical trials, both with Kregrelentide and many of the GLP-1 agonists that achieved mid-teens to close to 20%, early results were on par with what we've seen with our MLIN program. So we are very encouraged by that potential.

Great, thank you. And maybe if I just may sneak in one additional question, just on BI45, so the phase three, are you able to give us any color on the design, just if there's anything that sort of materially differ from what we've seen with the Vigovian and also in relation to whether there are some issues with the glucagon part, any special requests from the FDA that you are aware of?

So we are not aware of any special issues, if you will. We can share that we see that Beringer is extremely excited and they're extremely committed to put this molecule into phase three and excited about the potential for this molecule to address both weight loss and the benefits we have just discussed here that was also evident with the SELECT study, but also in the efforts in the NASH space On the specific design of the phase three program, we cannot share more beyond the fact that Weringa have released now that we are talking about three phase three trials that they are working on, but they do expect to present further details on the trials before they initiate them later this year. So we will have to stay tuned there. Sorry for that. Will do. Thank you very much.

Thank you. We will now go to our next question. And your next question comes from the line of Lucy Codrington from Jefferies. Please go ahead.

Hi there. Thank you for taking my questions. Just firstly, a quick clarification because I think I missed it in the prepared remarks. The cash runway to mid-2026, does that include any anticipated milestones and or use of the credit facility available to you? Secondly, you mentioned about the potential in NASH and we talked about the ratio of GLP-1 to glucagon. And I guess given the importance of glucagon activity for the liver effect, how do you kind of expect results in NASH to fare versus the competitor assets with greater activity on the glucagon side of things? And then finally, on the artificial pancreas timings, I see the report still expects the trial to start this year. Is that based on any new information, or is that just a maintenance of the prior commentary? Thank you.

Thank you, Lucy. I will again start by addressing your questions and hand over to both Henrietta and David. On the artificial pancreas, there's no change in guidance. As you know, we are depending on Beta Bionics moving forward here, and it is our belief that they will move forward based on conversations with them. But it's not new belief or anything, so we are just retaining it and keeping the guidance. When it comes to the cash runway, I will let Henriette elaborate on that.

Yes. Hey, Lose. Thanks for the question. So the cash runway to mid-2026, of course, is our current cash position, including securities. And then it also includes a near-term milestone for existing partners. So not for new partners, but existing partners where we expect milestones in the second half of this year.

And then before, I will hand over to you, David, on the relative balance of GLD1, gluagon, where we do have an 8 to 1. I think it's extremely important to remember that in order to get meaningful weight loss with GLD1-based therapies, we know we need to have very, very high exposure. and also higher exposures than what you would need in a Type II setting, for instance. And therefore, of course, with the profile that we have and the very high exposure to GLP-1 we achieve in the program, we would expect that the GLP-1 component will be sufficient to also drive effects on the liver, despite the fact of the balance. That's why we designed it that way, to be able to push the ones with those highest doses while getting meaningful gluagon exposure. But David, I do elaborate a little bit more also compared to data that we have seen from other studies and so on, and why we're still encouraged.

Yeah, thank you, Lucy. And Adam, I agree that Clearly, one of the greatest impacts on NASH and NASH progression has been demonstrated with bariatric surgery and the weight loss associated. So having a potent GLP-1 component, we have deemed and our partners have deemed that that is a critical piece to achieve weight loss that in the obesity studies was up to 19%. I think the glucagon component and the effects on fat metabolism and liver fat trafficking is important, and we believe we have dialed in an appropriate amount. Remember, too, that many patients with fatty liver disease and or NASH also have coexisting glucose intolerance so excess glucagon agonism would be expected to have less beneficial effect on the glucose metabolism and as a consequence free fatty acid metabolism obviously with the bi compound the cervodutide data in type 2 diabetes clearly an effective glucose lowering agent so not any evidence of excess glucagon impairing the glycemic response. So, importantly, the Phase II data, which we'll read out in the first half of next year, will be biopsy-based primary endpoint data in that NASH trial. And I think we'll answer your questions well beyond the speculation that I or Adam can answer. But we have great confidence in the balance of the two receptor agonists in this molecule.

That's great. Thanks very much.

Thank you, Lucy.

Thank you. We'll now go to your next question. And your next question comes from the line of Michael Novot from Nordea. Please go ahead.

Thank you very much. It's Michael from Nordea. A couple of questions. So first of all, trying to dig down a bit further into the Phase 3 plans. I know I respect that you can't say that much, but Is it fair to speculate that there will be also a dedicated cardiovascular outcomes trial related to cervidutide? Because a cardiovascular outcomes trial is not a registrational requirement. So could it be fair to assume that they do three registrational trials and then on top of that a cardiovascular outcomes trial? And then secondly on the NASH sort of release timing. Would you mind sort of speculating when this could be? I think we have the European liver. meeting in May or late May, early June next year. So should we expect all of the same progression in releases from Berger-Engelheim, you think, as they did on the obesity data, so spring-wise and then presentation during the summer? And also timing-wise, do you expect or is it fair to assume that there will be data at ADA on both the piclotide and also set P8396? Then I have a follow-up. But let's take the first three ones.

Thanks for the questions, Michael. We cannot comment more on these things. We really have to honor also the relationship with BI, and they do expect to present the details of the programs before they start the Phase 3 program. I think a lot of the considerations you shared are good considerations, but it's not something we can comment on. I'm sorry for that. And with regard to data presentation for our own I think we are right now comfortable guiding that we expect results in the first half next year. When we will present the data, we will have to wait just a little bit longer before we can commit to specific conferences.

Okay.

I cannot be more precise here.

Okay. But then just a follow-up in terms of partner discussions. So you describe potential partner discussions and also signing something for DAS Glucagon in GHI this half year. With regards to glipaclutide, how dependent is sort of the timing of the deal going into the first half of next year on the ironwood invective bio apaclutide data? I mean, in terms of sort of how competitive will the process be with negative data for ironwood invective or ironwood versus sort of very positive data. How do you see that playing into a potential attractiveness of the deal and timing of the deal for your asset?

First of all, with regard to CHI, as you know, we submitted the NDA in June and we could then have an approval first half next year. That, of course, also that it's a good timing for us to establish the partnership this second half of the year, which has been part of the plan all the time. And as we are announcing with this call and confirming with this call, then we are in good discussions and progressing according to plan with that one. With regard to Gepagrutide for short bowel syndrome, we have also been very clear on the fact that we're going to have our pre-NDA meeting, or we will have our pre-NDA meeting in this second half and also expect to submit the NDA in the second half of the year. We have not started confidential discussions with partners for GLEPA yet, but we do expect to start that very soon and also start to open up data rooms. So that also means that we have not had the confidential discussions or disclosed or shared confidential data with any party until now. Regarding the readout of the phase three program for apraglotype, whether that will impact our timelines, it's not something I can comment on right now. We believe we have a very, very competitive profile with our product having been developed in an auto-injector, very simple injection and some very compelling clinical data that we have presented at clinical conferences throughout the first half of the year. So we think we have a product that is very competitive and that, of course, has to be confirmed also in future discussions. But of course, ultimately, if APROS weaves out positive in the Phase III study, we will see that as a competitor in the state, another long-acting GLP-2. But still, I would argue that we have a very competitive profile of our product and actually see the potential for a market leader with the Pacro site. Great.

That's all for me. Thank you very much.

Thank you. We'll now go to the next question. And your next question comes from the line of Rajen Sharma from Goldman Sachs. Please go ahead.

Hi, thanks for taking my question. I've got a couple too. So firstly on cervidutide, there's obviously been some concern in the market on the drug's tolerability post the phase two data that we saw at ADA specifically on the discontinuation. Could you just help to put that into context for us? And I realize that you don't lead development of the drug and you're not leading to phase three, but I guess in theory, what could practically be done to reduce those discontinuations in the phase three trial? And then similarly, just kind of coming out of ADA again, there was obviously data from Lilly's GGG. Could you just talk about how you think about Servitude Tide's competitiveness and your wider portfolio's competitiveness relative to that? And then I've just got a follow-up on complement, but maybe we could take those first.

Thanks for the question. I will start by addressing the competitive landscape maybe a little bit and then hand over to you, David, to also address the discontinuations and how we believe that Berger can handle that in Phase 3. I think, as David also alluded to in his remarks on one of our slides, then first of all, obesity and obesity-related comorbidities are a very complicated area of treatment. And there will be the need for many different approaches in the future. And I think that's extremely important to note. There will be some patients who will need 30% weight loss. Others might benefit more from a 15% weight loss or 25% weight loss. And you can say the relative balance to also where you then see effects and comorbidities and so on, the balance between solubility side effects, how do we affect heart rate, how do we affect other aspects, all those things ultimately will play into how these future medications will be used in a landscape. So we can just say with what we have seen with service so far, it looks like a very competitive product also compared to the programs that were releasing early data at ADA this year from competitors. And we are, you can say, of course, close to BI, and we know they feel the same way. So we see that Servo has a very strong profile. The data that was presented from competitors at ADA doesn't change that picture. I think we have moved beyond just looking at who can give you the most weight loss. It's really about how can you differentiate, how can you address specific patient needs. And I think that is where the conversation will go in the coming period, also in this field in general. But David, I will hand over to you to also address these continuations and perhaps provide further considerations on that.

Yeah, thank you, Adam. And I'll add one more comment on the GGG, as Adam said, the relatively high rates of GI intolerance in that study, the heart rate concerns that were raised by some, but I also think In that retatrutide data, there is confirmation of GLP-1 and glucagon in a single molecule, which to us adds strength to the cornerstone that cervodutide has established. Back to the discontinuation rate, a couple of very important things to consider, and we have, with our partners, looked at this in detail. This was a very rapid titration scheme by GLP-1 and encryption-based therapy standards, going every other week to relatively high doses and maintaining them there. There were some unique components of the protocol. that allowed patients to hold at a lower dose, which we think may have limited the capacity to understand the higher doses, but that fast titration over two weeks with a GLP-1-based therapy is one that not only our BI colleagues but others in this space have learned is likely quicker than need be. And remember, across these trials, some allow use of anti-medics, anti-nausea therapies, Some do not, and not allowing that may result in slightly higher discontinuation rates in a clinical trial program. But overall, I would say qualitatively, and we have looked at other Phase II programs, both the rates of nausea and discontinuation we assess to be qualitatively quite similar. And we believe that in the Phase III program, the consideration of a much slower titration scheme to maximal dose and assuring that efforts are taken to enable tolerability can and will be part of the program to both minimize the impact of the potential GI side effects and understand just how high adherence and persistence can be.

Perfect. Thank you. And then just to follow up on complement inhibitor. In terms of kind of the preclinical activities you're expecting to complete by the end of the year, the data that's being generated, do election or, I guess, Astra now have ongoing visibility onto that? And have they sort of indicated that they expect to progress development? And if so, would there be a milestone to Zealand with that?

So it's been a collaboration where we have been responsible for most activities until now. Once we deliver, you can see the phase one ready package, Alexia and AstraZeneca will take over most of the development efforts, but we will continue to contribute in a few areas. They have been very engaged. Our assessment is that they share the same excitement about the lead molecule that we have now progressed and will soon give over to them so they can progress it into clinical testing. of course we don't have all insights into the executive rooms, but we see a lot of excitement and we anticipate to hand over the program to them quite soon and then they will take it from there. So that's our clear ambition that they will also, expectation that they will push this into phase one.

Thank you.

Thank you. We will now go to your next question. And your next question comes from the line of Jasper Ilse from Carnegie. Please go ahead.

Great. Thank you. Firstly, a follow-up to the question on the partnership status on clopacalcite. um so trying to ask in a different way has ironwood's phase three data delay to march 24 instead of late 23 has that sort of changed to intern timelines because i guess that may drag discussions out a bit versus previously And then just on the partnership timeline from here, can just help us prepare the market how you intend to communicate on the partnership process in the coming quarters and on how you progress and whether there's any progress at all. And then just a question on the R&D event, just to preview this. Will this simply be an educational event or will there be any incremental updates? And then just on timing, why already in Q4? Is there any particular reason or is that just because you are excited to share some stuff? Thank you.

So just on the obesity R&D day, it will of course be hopefully a very educational day where we will also try to put all our data a little bit more in context into where the field is moving. So We do not plan to announce significant new data updates that would normally be in a press release since it is so, you can say, defining for our activities right now. With regard to the three months or so delay in data readout from the APRA Phase 3 that was announced by Ironwood, it has not changed anything to As we have also, as I said, communicated, we have all the time thought there was a little bit of a stretch to have data in late this year since the studies were not completed. So this is probably more in line with what we had thought all the time. And we do not see a specific connection to our partnership discussions. But again, that is, of course, up to partners. We think we have a very competitive profile. We are looking for a collaboration where we'll continue to contribute. We have a lot of confidence in Glippe. And so we believe partners will have once we get to partnership discussions. And as I said, we have not gone to the confidential or data sharing level yet.

Thank you. Thanks so much.

Thank you. We will now go to your next question. And your next question comes from the line of Charlie Mabbot from Morgan Stanley. Please go ahead.

Thank you. Hi, it's Charlie Mabbot from Morgan Stanley. Thanks for taking my questions. So I guess, firstly, on DAPI glutide, one of the major benefits cited has been on leaky gut. And post the select data, this may perhaps be even more interesting given the potential effects on inflammation. I was just wondering what evidence you'll be able to gather on dapaglutide utility here, given the short length of the current programs, and if there's anything you sort of expect to see in these studies that might support that. And then secondly, I was wondering if you could provide a little bit more color on the new phase one, the ion channel blocker, if there's any insight into the indication being targeted. And then also, I guess, where your other preclinical efforts are now being focused, that would be helpful. Thanks very much.

Thanks for your question, Charlie. I'll start and then I'll hand over to you, David. So on the KU1.3 iron channel inhibitor, we do expect to initiate phase one development next year, and we are extremely excited about the potential. If you look through the literature, it actually has potential in a number of inflammatory conditions, severe chronic conditions. We are not at a stage yet where we will announce where we will take it, but there are many avenues, as you will see, and we have, of course, ideas, but we will wait with sharing those until we are a little bit closer to phase one initiation. On dapaglutide, I completely concur with you that the select data, of course, underscores the potential with this molecule and with the low-grade inflammation we know has been a major or is a major driver of cardiovascular disease. And also, if we look into NASH and the NASH space, they're basically believed to be two things that are causing NASH to develop in the obese or metabolic state, and that is excessive fat on nutrition and inflammation. With the one gluobal we address the excessive fat, with DAPI we address the inflammation. So it also, we believe, has potential opportunities in NASTIS molecule. But maybe, David, you can elaborate a little bit more on what we could expect to see from the Phase II study that we have ongoing.

Thanks, Charlie. And I'll reiterate what Adam said. I think the select data and the implications for high-risk cardiovascular disease populations not now just diabetes, but diabetes and obesity. And to your point, the effects of GLP-2 both on gut barrier health, but also more broadly the inflammatory environment. Many know that those at highest risk for heart disease have markers of inflammation, HSCRP, but how one modifies that inflammatory environment beyond statin therapy and blood pressure lowering We will, in the current investigator-led Phase 2 study, have what we believe is a broad brush look at a number of critical inflammatory disease markers or markers of systemic inflammation, both those that primarily affect the liver and vascular bed. And we believe that will, at a minimum, give us insights about the potential anti-inflammatory effects. Obviously, the ultimate test of this is a cardiovascular outcomes trial, and we're a ways away from that, just starting phase 2A. But suffice it to say that we are aligned with your perspective that the leaky gut, improving gut health, perhaps the gut microbiome, and affecting these markers of systemic inflammation can be critically important in both cardiovascular disease and NASH.

Great, thanks very much. And also, just as a follow-up, I was just wondering on your initial perspectives on whether you think amylin could add cardiovascular benefit.

So, again, this is going to be an important topic for our R&D day coming up in October, but I think that's already now substantial evidence in the literature that if you treat with a long-acting amylin analog, then you will see very significant reductions in cardiovascular risk factors, such as decreases in blood pressure, neutral to actually decrease in heart rate, which is in contrast to what you see with the THC-1, significant effects on C-reactive protein, which is a known driver of cardiovascular risk. And then importantly, studies also demonstrating very beneficial effects on VLVL, triglycerides, and then increases in HDL, which is a good cholesterol. So if you put all those data together, you will actually see an incredible strong profile when considering amylin as an agent that can not only induce weight loss, but could also be very strong when it comes to cardiovascular benefits, perhaps even beyond the weight loss that you see with these molecules.

Great, thanks.

Thank you. We'll now go to our next question. And your next question comes from the line of Luisa Morgado from Landschott Kempen. Please go ahead.

Hi, this is Luisa dialing in for Susana. I have one single question. So regarding GLEPA, could you provide us with some more... Sorry, not GLEPA, DASI. Could you give us a better understanding on what are you looking here for...

um in a partnership in chi thanks for your question louise and we we we are looking for a partner who have commercial relatives infrastructure either you can say just regional so us europe or other regions or global infrastructure so that is that is the that's what we don't have we have the capacity to manage manufacturing and thus supply finished product. We can support on the medical aspects. We have very deep ties into the community, both the patient communities and the patient prescriber, potential future prescriber communities, and deep insights into the disease area. So we can help there. So we are looking for true collaborations, but we are looking for a company where rare disease commercial infrastructure, and those are the companies that we are discussing with right now.

Very clear. Thank you.

Thank you. This concludes the Q&A session for today. I will now hand the call back to Adam Steensberg for closing remarks.

Thank you. And with that, we would like to thank all of you for attending and for the questions. And we look very much forward to connecting at our BCT R&D event in the fourth quarter and to future announcements and updates. So thanks a lot and have a good day.