Zealand Pharma A/S

Good day and thank you for standing by. Welcome to the Zeeland Pharma results for Q3 2023 conference call and webcast. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, please press star 1 and 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 and 1 again. Please note that today's conference is being recorded. I would now like to have the conference over to your first speaker, Anna Krasovska, Head of Investor Relations. Please go ahead.

Anna Krasovska Thank you, Operator. Welcome, and thank you for joining us to discuss VLIN's interim results for the first nine months of 2023. With me today are the following members of VLIN's management team. Adam Steinsberg, President and Chief Executive Officer, Henrietta Vinica, Chief Financial Officer, and David Kendall, Chief Medical Officer. You can also find the related company announcement and interim report on our website at www.lilandpharma.com. As described on slide 2, we will be making forward-looking statements that are subject to risks and uncertainties. With that, I will turn the call over to Adam Steensban, President and CEO. Adam?

Thank you, Anna, and thanks to everyone for joining today. I'll begin on slide 3. In the third quarter, we saw strong progress across several programs in our pipeline, supported by a solid financial development. Subrutatide advancing into global phase three trials is an important step in Sealand's long-term commitment to bring forward novel therapies for obesity and obesity-related diseases. With the launch of the synchronized trials, Boehringer will be only the third company to initiate a phase three program in this new era of weight loss therapies. We see obesity and related comorbidities as the biggest healthcare challenge of our time. And we believe that CELAN is uniquely positioned to help address this global pandemic, which we'll be discussing further in details at our obesity R&D event in December. In early October, we presented clinical data from multiple ascending dose trials with our long-acting amylin analog at Obesity Week. The data we have seen so far strongly support our confidence in this molecule as a next-generation treatment for overweight and obesity, with potential for weight loss comparable to the GLP-1-based therapies with improved tolerability. For dapaglutide, We have initiated the 13-week dose titration trial to evaluate higher doses than those investigated in the ongoing investigator-led DREAM trial. Dabiglutide is a truly differentiated GLD1-containing molecule, and we are very excited about evaluating its potential to address not only obesity, but also low-grade inflammation associated with metabolic disease. In the third quarter, We have also secured significant regulatory progress on our rare disease assets, including a U.S. FDA priority review and a PDUFA date of December 30th for part one of our NDA for dashing luergon in congenital hyperinsulinism. Henriette will review the financial results in details. Here, I will just mention the revenue recognized in the third quarter for milestones from existing partnerships, which contribute to our solid financial position. Moving to slide four, we are delivering on the strategic objectives that we outlined for the year and remain on track to submit the glipagrutide new drug application for short bowel syndrome to the US FDA this quarter. The C-Land team has also completed non-clinical activities to support potential first in human clinical trials with our GIP analog as well as the KV1.3 ion channel blocker and the complement C3 inhibitor partnered with Alexion. On partnering, we remain engaged in discussions for dasigruvin in CHI, while also preparing for making the product available to patients in the US as soon as possible after a potential approval. While we do believe that FDA's decision to split the NDA into two parts secures the most efficient regulatory review process, this has introduced some complexity in the partnering discussions. And our focus is to secure a partnership that best supports our long-term strategic goals and maximizes value creation. We therefore recognize that a partnership may be pushed into 2024 when we have further clarity on the label and importantly, a PDUFA decision on part one of the NDA. For Gepaglutide in SPS, we expect to engage in more detailed discussions with potential partners once we have submitted the NDA to the FDA. Moving to slide five, I will now turn over the call to our Chief Medical Officer, David Kendall, to discuss our R&D pipeline. David.

Thank you, Adam. Today I will discuss my remarks on three specific areas, the Phase III trials with cervidutide, the dual glucagon GLP-1 receptor agonist, the recent results from our long-acting amylin analog, ZP8396, as well as activities related to dosiglucagon. Please turn to slide six. Our major focus is on obesity, which is increasingly recognized as a complex chronic disease which is amenable to treatment using pharmacologic agents that target a number of unique metabolic pathways. We believe that the success of weight loss therapies will be determined by various differentiating factors catering to specific segments of people living with overweight and obesity. Therefore, our therapeutic approach aims to, one, achieve significant weight loss, two, provide additional effects that can address specific comorbidities, three, improve tolerability, and four, offer alternatives to incretin-based obesity therapies. Each molecule in our portfolio is differentiated through peptide target, design, or formulation. On slide seven, we outlined the three global phase three trials with cervidutide, the glucagon GLP-1 receptor dual agonist, sponsored and designed by our development partner, Beringer Ingelheim. in people living with overweight and obesity. The trials Synchronize 1 and Synchronize 2 include people with obesity or overweight with at least one comorbidity. Synchronize 1 will enroll participants without type 2 diabetes, and Synchronize 2 will enroll participants with type 2 diabetes. Both trials will assess the percentage change in body weight and the proportion of people who achieve categorical body weight loss of 5% or more. at week 76 as the primary endpoints. Six hundred participants will be randomized one-to-one-to-one to weekly subcutaneous doses of either cervidutide using monthly titration schedules to reach a maximum dose of either 3.6 or 6 milligrams for maintenance treatment or matched placebo. Recall that the maximum maintenance dose in the Phase II trial in people with overweight or obesity was 4.8 milligrams and that the total treatment duration was 46 weeks. In that trial, body weight reductions had not yet appeared to plateau after the 46 weeks of treatment, indicating that further reductions are likely to be observed with longer treatment duration and higher doses. The third phase three trial is a long-term cardiovascular safety study that will enroll nearly 5,000 individuals with overweight or obesity with cardiovascular disease, chronic kidney disease, or risk factors for cardiovascular disease. The primary endpoint of this trial is five-point major adverse cardiac events, or MACE, defined as the time of the first occurrence of any one of five major adverse cardiovascular events, cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, ischemia-related coronary revascularization, and heart failure events. Please turn now to slide eight in our amylin program. At this year's Obesity Week, held in mid-October, we presented the results of the first two cohorts, or so-called part one, of our Phase 1b trial, assessing weekly doses of ZP8396. These data demonstrated mean weight loss of more than 5% in healthy, lean, and overweight people with very low doses of either 0.6 or 1.2 milligrams administered weekly for six weeks. We are very encouraged by these data and the magnitude of weight loss achieved, which we believe is on par with the results reported in initial short-term studies of GLP-1-based therapies. On slide 9, we show additional tale of the adverse events reported in this Phase 1b trial, with the results showing that ZP83-96 was well tolerated with no serious or severe adverse events and no withdrawals. Gastrointestinal side effects were the most common adverse events reported. All were mild and most occurred within two days of the initial dose. Based on these data and the results from our previously reported phase one single ascending dose trial, we believe that ZP8396 offers the potential for significantly improved tolerability when compared to the known adverse event profile of incretin-based therapies. The emerging clinical profile supports our conviction that ZP8396 can play an important role as monotherapy to achieve and maintain weight loss and thus represent an alternative to GLP-1-based therapies. Turning to slide 10, our focus now is on the execution of the ongoing 16-week multiple ascending dose phase 1b trial, exploring significantly higher doses of ZP8396 using a dose titration scheme. We are very pleased with the progress on this trial to date and expect to report top-line results in mid-2024. Now turning to slide 11. My final remarks today are related to our DASI glucagon program for the treatment of congenital hyperinsulinism. We submitted the NDA for the prevention and treatment of hypoglycemia in pediatric patients with congenital hyperinsulinism ages 7 days and older in June of this year. The FDA subsequently recommended that the regulatory review should be conducted in two parts under the same NDA. Part one, or original one, relates to dosing of doziglucigon for up to three weeks, and the FDA has granted a priority review with the PDUFA date on December 30th of this year. I am very encouraged by the progress our team is making and the continued engagement with the agency as we approach the final steps towards potential approval. In parallel, in support of part two or original two of the NDA, we are preparing and analyzing the continuous glucose monitoring or CGM data sets that were included as an additional measure of glycemic outcome in each of our two pivotal phase three clinical trials as well as in the long-term safety study. This work is expected to be completed and submitted to the FDA in the first half of 2024 to support the review of part two of this NDA. The sentiment and the strong support for the potential benefit of dosiglucagon for the treatment of CHI were reaffirmed during a recent meeting that convened the clinical investigators from our CHI program who represent the leading experts in CHI from the U.S. and across Europe. Therefore, as Adam stated, we will work to ensure that dosiglucagon is available to U.S. healthcare professionals of our CHI MDA. With that, I would now like to turn the call over to our Chief Financial Officer, Henrietta Venneke, to review our financial results for the first nine months of 2023. Henrietta?

Thanks, David, and hello everyone on the call. Let's move to slide 12 of the income statement. Revenue for the first nine months of 2023 was 320 million DKK. This was mainly driven by the recognition of a 30 million euro milestone from BI, as well as a 10 million US dollar milestone from Sanofi. Both milestones are expected to be paid in the fourth quarter of the year, but are recognized in Q3 due to the fulfillment of the contractual obligations. Operating expenses for the first nine months of 2023 were 633 million DKK. compared to 676 million DKK in the same period of 2022. The decrease was driven by lower sales and marketing expenses as well as lower administrative expenses due to cost reduction efforts following the restructuring last year. This was partially offset by significantly higher R&D expenses. Almost 80% of OPEX was allocated to R&D activities in the first nine months of 2023. This was driven by the progression of the late-race rare disease assets towards submission and significant investment in our wholly owned obesity programs. The net financial items for the first nine months of the period resulted in a loss of 125 million DKK. This was mainly driven by the final repayment and the termination of the loan with Oberland Capital. So let's move on to slide 13 and the cash position. As of September 30, 2023, cash, cash equivalents and marketable securities were approximately 1.6 billion DKK. The increase compared to year-end 2022 was driven by the capital raise in April of 1.5 billion DKK and partly offset by cash use and operating activities during the first nine months as well as the repayment of the Oberland loan in May. With the revolving credit facility of 350 million DKK provided by Danske Bank, we now have approximately 1.9 billion DKK in cash, which, combined with the expected payment of 285 million DKK in milestones in Q4 for BI and Sonove, results in a runway to mid-26. I am very satisfied with our financial position and the solid foundations it provides us to ensure we maximize the value of our assets. So let's move to slide 14 and our financial guidance, which is unchanged. So let's keep this very short. We continue to guide for net operating expenses of between 800 to 900 million DKK in 2023. And with that, I will move to slide 15 and turn the call back to Adam for some concluding remarks.

Thank you, Henrik. Building on the progress In the first nine months of the year, I expect an equally exciting next 12 months with several important events and catalysts. Just to name a few, rounding off the year in rare diseases, we expect to submit the new drug application for glipaglutide in short bowel syndrome, and we have the PDUFA date for dasiglurgan in CHI. Looking into next year, we expect results from the sublutide phase 2 trial in NASH, the 16-week clinical trial with our amylin analog, the investigator-led phase 2 trial with dapaglutide followed by results from our 13-week dose titration trial, and initiation of new first-in-human clinical trials. Importantly, we will also continue to engage in partnership discussions. A final note on slide 16 before we take questions. We really hope that you can join us for our obesity R&D event on December 5th in person in London or online. We have a very strong lineup of three leading experts in the field, Professor Daniel Drucker, Lou Aron, and Carole Leroux. Together, we will share perspective on the scientific, rational, and clinical potential of C-Lens obesity assets. Personally, I look very much forward to this event and hope to see many of you there. Please contact us or go to our website to register. 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, you can please press star 1 and 1 again. Once again, please press star 1 and 1 if you have any questions or comments. Thank you. We are now going to proceed with our first question. And the questions come from the line of Michael Novot from Nordea. Please ask your question. Your line is opened.

Thank you very much. It's Michael Novot from Nordea, Copenhagen. So two questions, one relating to DARS-CoV-2 in CHI. So maybe not a big surprise that it's going to be pushed in given the due date of 30th of December. So it's going to be pushed into 24 paths. Can you talk about sort of what kind of interest you're seeing? Have you seen sort of a declining interest after the FDA decided that you had to do the NDA in two parts? And should we expect that a potential partnership will not materialize after the part two has been filed with the FDA as well, or the data that is needed for that? And then secondly, to the amylin analog. So it was obvious from discussions at Obesity Week that you are likely going up to around six milligrams in part two. Can you talk about, if you see that being well tolerated, is there a possibility that you can take it even further? I know it's probably then going to take a bit longer time, but can you talk about whether you can push the dose even further than six milligrams? Thanks a lot.

Thank you, Michael. I will take the first question and then I'll hand over to David to discuss your question on amylin. As I mentioned on the in the prepared remarks, then of course with the splitting of the NDA, that introduced some complexity in our partner discussions. But having said that, you can say our confidence in the assets has not changed. I would say actually on the contrary. And the way we see this now is that our main focus is of course to secure the PDUFA date for part one, and then do all the preparative work and submit part two. The feedback, or you can say maybe not feedback, but more our observations will be that having a better understanding of the full label potential will be helpful in some of these discussions we had earlier on before this decision was taken. I remind you that the first part is only treatment for up to three weeks, whereas the latter part, part two, will support chronic use. We see a huge need for both situations, but it is clear that a lot of the CHI patients, especially those with diffuse disease, they are in need for chronic therapies. That's why we are so focused on also getting to part two. So it is quite difficult for me to guide on the specific, you can say, considerations for the potential partnership companies. What I can say is that CLAN's focus, as I said, will be to secure the value creation that we believe we have with this asset and we will not compromise on if people view the potential different than we do. Having said that, that also means that we have taken means to make the product available to patients at PDUFA once we have the PDUFA part one. But I can only confirm that we have continued good discussions Whether this will happen this year, next year, early on when we have the PDUVA data only after we have submitted part two, I cannot guide on right now. But we remain very confident in the opportunity. And David, I will hand over to you to discuss the amylin potential for significant, for dosing levels and so on, even though we are in the midst of the study. I know we cannot share maybe everything, but David.

Thank you, Adam, and thank you, Michael. I'll add to Adam's comment on the DASI and CHI. It obviously does require additional work getting the supplemental data, as we discussed, but from our perspective, that does not increase uncertainty. It just pushes the timeline for that full review and to leverage the full value of that asset clinically. Obviously, both acute and chronic therapy is of great interest to us and of great interest to potential partners with whom we're discussing it. Your question about amylin dosing obviously will be ultimately guided by the results of the Phase 1b and seeing where in multiple ascending dose we can and will take the doses of amylin. Obviously, the Part 2, as we've described, of the Phase 1b that's ongoing will extend treatment out to 16 weeks, and while that's relatively short-term for obesity trials, we believe that will give us a great perspective on not only what doses are achievable, certainly we believe higher than 0.6 and 1.2 that have already been reported. I can't speculate yet on where the maximal dose might take us. And obviously with those results in hand, we'll put together a final protocol that we believe pushes to the optimal doses, both as high as feasible, but also as we've stated throughout to maintain what we already see as a very favorable tolerability profile. So, more to follow in the first half of next year. Great. Thanks a lot. Yep. Thanks, Michael.

Thank you. We are now going to proceed with our next question. And the questions come from the line of Lizzie Codrington from Jefferies. Please ask your question.

Hi, thank you for taking my questions. Just following up on the partnership with the CHI discussions, I do appreciate that there is a lot of unknown here. But in terms of a couple of things, when you say you would want to wait for the partners might want to wait for the full label, does that then mean we need to wait for the part two approval? And is that part two also under priority review and therefore could still come next year, or could that end up coming in 2025? And just on your plans to make it available as soon as possible after the 30th of December without waiting for a partner, is that feasible to do without a significant investment required on your part? Then secondly, just in terms of the server due tied phase three, and I appreciate you're not in charge here, but in terms of the timing, it seems kind of conservative perhaps to what I was expecting in terms of the primary readout. Do you think there is scope for an earlier readout than end of 2025, early 2026? And then finally, on the current R&D rate, there was quite a significant step up in the third quarter. Should we be thinking about that as a sensible level going forward, or should I be thinking about anything else kind of into the next quarter and then on into 2024? Thank you.

Thank you, Lucy. I will address your first question and then hand over to David afterwards to address server, and then Henriette will address your last question on the R&D spend. Full label, let me put it this way. Of course, with part one, once and if approved, that will be, of course, de-risking the program significantly because, of course, part of the part one NDA review includes all the quality, all the device, a lot of the clinical questions which will be cleared and will be very, very important label elements. So just having the PDUFA date, December the 30th, will de-risk, of course, a lot of label considerations. Once we have, as David discussed, all the existing data from this continuous glucose monitoring data evaluated in the ways that we are agreeing with FDA, that will further provide a significant de-risking of the potential future of ABL because then we know, you can say, to which extent we have potential claims to support and so on for specific areas. So that will, of course, also provide some further clarity. And ultimately, you can say, of course, it comes with a potential approval of Part 2. Then we will have all the clarity. So I would say this is not black and white. We believe that just getting the initial label in place and having a full oversight of all the data that FDA requested provides a lot of clarity on the potential future label for this program. So I'm sorry I cannot be more precise right now. I hope it's clear that our confidence in what we are working on here remains very high, but also that we will not compromise on the value potential and the strategic opportunity for us on this asset in this partnering process. And as I mentioned, and thanks for that question, we have and we are taking means to make the product available in the US as soon as possible after a potential approval also of part one. And it's not something that will carry a huge spend for us also not going into next year if that is the case. So this is something that we feel that we are on top of and we will do what's needed. David, will you, I hope this answers your question, and then, David, just, will you address the question on and so on?

I'm happy to. Thanks, Adam, and thanks, Lucy, for your questions. One added comment on to Adam's discussion around the current NDA and original one and original two, remember that this remains part of the same NDA. for which the part one, original one, was granted priority review. So while we cannot speculate that part two will receive the same, because it is under the same NDA, that is and remains a possibility. And obviously, both for us and for the agency, the review of You know, these detailed but existing data from CGM and more data collection will be part of that. So pending their acceptance of that second file, we'll know and understand that it remains under the same NDA where a priority review is possible. Can't speculate on whether it's likely or possible. Servodutide, the phase three program readouts to your question on timing. Obviously, the endpoints and the readouts are dependent on a number of variables, which you know quite well, primarily getting sites up and running, actively recruiting, and recruiting at an acceptable or rapid rate. And it is not about the first patient and first visit to the clinic. It's about the last patient and their last visit. So with that, I think these readouts, which obviously are in the hands of our BI partner, and their timing are probably based on their current estimates using the sites that have been identified and will get up and running. So I think one comment to that end is we have seen that the majority of trials in overweight and obesity tend to recruit quite quickly. So our hope obviously is with that program and our other obesity programs that that rate of recruitment into clinical trials will remain vigorous and that that can move the readout timelines forward as much as possible so I'll leave it at that and obviously additional questions probably best answered by those on the clinical side FBI and then I'll turn the financial question on the step up in our R&D expenses over to Henrietta if she has a comment

Yes, thank you, David, and thank you, Lucy, for the question. You're correct. Our R&D spend in the quarter is stepping up compared to what we saw in the first and second quarter. As you know, always with R&D activities, there can be certain swing factors depending on where you are in your clinical activities, but also research activities. When that is said, then it's clear. We do invest heavily into obesity, and we have good progression of our programs there. Currently at the same time, of course, we are investing our rare disease assets to get them over the finish line. So there will always be swing factors, but we are, of course, investing heavily at the moment.

Thanks very much.

Thank you. We are now going to proceed with our next question. And the questions come from the line of Rajen Sharma from Goldman Sachs. Please ask your question.

Hi. Thanks for taking my questions. I've just got a couple on cervidutide and the synchronized phase 3. So as you mentioned that there's a higher maintenance dose in the phase 3 relative to what we saw in phase 2. Could you just kind of help us understand the rationale for this? If you're able to, could you perhaps give us any color on the titration schedule? I think the Phase 2 used a biweekly titration. Is this the case in the Phase 3, or will that be a slower titration? And could you also confirm if the trial will allow for antiemetic therapy? And then just on glupaglutide and thinking about partnership there, how should we think about timing? And I guess one of the gating factors here is that that partners are waiting for submission or potentially an approval? And is it fair to assume that any potential partners may be waiting for top line data from your potential competitor at Ironwood?

Thanks, Rajan, for your question. I will address your Glipa question, and then I'll hand over to David on the Servo question. So on partnerships for Glipa, as I mentioned on the call, We are on track to submit the NDA later this year and it's only after then we will, you can say, progress significantly on the partnership discussion. At least if what I'm aware of then, Ironwood are expecting to see top-line results or report top-line results from their program in March. So I think it's probably fair to assume that it's not likely to have a partnership before that, whether partners' interest and so on will depend on those. I mean, of course, to some extent, I think we are equally as interested and as you know, we feel very comfortable in our assets. So I think it's a fair assumption that a partnership will only happen after that event, but perhaps equally driven by just the process that we are running right now and which will only be really started after we submit the NDA. David, will you take the questions on server?

Happy to, and thanks as well for the question. Yeah, you're correct, the higher dose going up beyond what was utilized in Phase II. Obviously, these Protocols and I'm speaking now obviously on behalf of our bi partner who done the negotiating at end of phase two those discussions Have to occur with the FDA to get approval on the protocol both for the treatment population and the doses used And you need obviously the appropriate pharmacology and clinical pharmacology studies as well as safety and tax tax studies, which are allow those doses. I think two things emerged from Phase 2. One you've alluded to, which is the titration schedule, and monthly titration will be used. The comments and specific details on antiemetic use will obviously be part of the protocol, but suffice it to say that, yes, all will be done to ensure that the dose assigned at randomization is titrated on that monthly schedule and is maintained for as long as possible. I think it now has essentially become the standard in clinical trials where you're forced titrating to these doses that anti-medic and other measures for titration can be used. So the higher doses obviously are supported. This protocol is signed off and moving forward, and I think given what we saw from phase two, particularly in the overweight and obese population, but also in the shorter type two diabetes study, that both the effects on body weight and the potential effects on glycemic control in those with diabetes will be enhanced by pushing to these top doses.

Thank you very much.

Thank you.

Thank you. We're now going to proceed with our next question. And the questions come from the line of Charlie Mabbitt from Morgan Stanley. Please ask a question.

Hi. Thanks very much for taking my question. It's Charlie Mabbitt from Morgan Stanley. Firstly, on the cardiovascular outcomes study, please could you just go into a little bit more detail on the study? I appreciate you didn't design it specifically, given it sort of includes patients with cardiovascular disease or chronic kidney disease or cardiovascular disease risk factors at baseline, it seems like quite a lot more complicated than I guess other cardiovascular studies we've seen. So could you just explain the rationale for that and why sort of the CKD studies and see cardiovascular disease studies might not be done separately. And then I guess, secondly, I guess, how do you think about trial duration in like a phase three, 2A study for something like dapiglutide. I guess, does a 13-week study give you enough information to know if there's an additive benefit of GLP-2 versus GLP-1, and would a larger phase 2 therefore be needed before going to phase 3? Thanks very much.

Yeah, I'm happy to start, and Adam, please add additional details. On the CBOT, Charlie, a good question. I think it's worth noting that our BI colleagues have now achieved indications with the Invagliflozin franchise in both cardiovascular disease, heart failure, as well as in CKD with their recent outcomes and approvals. So, as partners, they have a great understanding of these populations. I think it's also important to note that chronic kidney disease, particularly in the absence of diabetes, and remember these are obesity studies first and foremost, confers cardiovascular risk that in many cases approaches that or is similar to that of preexisting cardiovascular disease. I think the other component that RBI partners look to achieve in this study population is is a more representative population of those with overweight and obesity who have comorbidities that relate to cardiovascular risk, so including cardiovascular risk factors, previous cardiovascular events, and CKD. I cannot comment on whether CKD will have a secondary outcome measure, but obviously renal function and renal outcomes will be an important safety measure in all these trials. I think it's also important to point out that the previous CBOTs that have been designed, say, with the assets from Novo and Lilly, are with assets that were previously evaluated for cardiovascular outcomes in diabetes. So whether those sponsors also wanted to demonstrate effects separate from the diabetes-related cardiovascular effects or not, uh, noting that for silver dew tide, this will be the first potential approval in overweight and obesity. Uh, so a slightly broader population, um, with a slightly broader outcome, the five point base, uh, makes very good sense, uh, at least to me. And I think, uh, to us collectively in the BI Zealand partnership, um, in terms of that cardiovascular outcomes study, um, or the, uh, second question on, uh, GLEPA and, uh, Its potential, or I'm sorry, DAPI and its trial design, obviously you are correct. Phase 1B and shorter 13 to 16-week studies that are often done are generally only directional in giving you a sense of both dosing tolerability and the potential for weight reduction. As we get into Phase 2, both the requirements for, and we believe, the understanding that longer-duration Phase II trials out 36, 42, even 48 weeks in duration give you a much clearer assessment and are required by the FDA to help you design Phase III. So Phase Ib will be directional. We hope to have very clear insights from both the DREAM investigator-led study and our own program at the higher doses. But obviously, the duration of exposure will be relatively brief, as it is with many in Phase 1b, even in obesity.

Well, thanks very much.

Yep. Thanks, Charlie.

We have no further questions at this time. I will now hand back to Adam Steensberg for closing remarks.

Thank you. And with that, we'd like to thank you all for attending and for your questions today. We look very much forward to seeing you on the road and connecting at our obesity R&D event in London on December 5th and on future announcements and updates. Thank you.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect your lines. Thank you. you Thank you music music

Welcome, and thank you for joining us to discuss Zeeland's interim results for the first nine months of 2023. With me today are the following members of Zeeland's management team. Adam Stainsberg, President and Chief Executive Officer, Henrietta Vinica, 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 Steensban, President and CEO. Adam?

Thank you, Anna, and thanks to everyone for joining today. I'll begin on slide three. In the third quarter, we saw strong progress across several programs in our pipeline, supported by a solid financial development. Savutatide advancing into global phase 3 trials is an important step in Sealand's long-term commitment to bring forward novel therapies for obesity and obesity-related diseases. With the launch of the synchronized trials, Berger will be only the third company to initiate a phase 3 program in this new era of weight loss therapies. we see obesity and related comorbidities as the biggest healthcare challenge of our time. And we believe that CELAN is uniquely positioned to help address this global pandemic, which we'll be discussing further in details at our Obesity R&D event in December. In early October, we presented clinical data from multiple ascending dose trials with our long-acting amylin analog at obesity week. The data we have seen so far strongly support our confidence in this molecule as a next-generation treatment for overweight and obesity, with potential for weight loss comparable to the GLV-1-based therapies with improved tolerability. For dabiglutide, we have initiated the 13-week dose titration trial to evaluate higher doses than those investigated in the ongoing investigator-led DREAM trial. Dabiglutide is a truly differentiated GLD1-containing molecule, and we are very excited about evaluating its potential to address not only obesity, but also low-grade inflammation associated with metabolic disease. In the third quarter, we have also secured significant regulatory progress on our rare disease assets, including a US FDA priority review and a PDUFA date of December 30th for part one of our NDA for dashing luergon in congenital hyperinsulinism. Henrietta will review the financial results in details. Here, I will just mention the revenue recognized in the third quarter for milestones from existing partnerships, which contribute to our solid financial position. Moving to slide four. We are delivering on the strategic objectives that we outlined for the year and remain on track to submit the glipagrutide new drug application for short bowel syndrome to the US FDA this quarter. The C-Land team has also completed non-clinical activities to support potential first in human clinical trials with our GIP analog as well as the KV1.3 ion channel blocker and the complement C3 inhibitor partnered with Alexion. On partnering, we remain engaged in discussions for DASIG rule in CHI, while also preparing for making the product available to patients in the U.S. as soon as possible after a potential approval. Moreover, while we do believe that FDA's decision to split the NDA into two parts secures the most efficient regulatory review process, this has introduced some complexity in the partnering discussions. and our focus is to secure a partnership that best support our long-term strategic goals and maximizes value creation. We therefore recognize that our partnership may be pushed into 2024 when we have further clarity on the label and importantly, a PDUFA decision on part one of the NDA. For Capacritide in SPS, we expect to engage in more detailed discussions with potential partners once we have submitted the NDA to the FDA. Moving to slide five, I will now turn over the call to our chief medical officer, David Campbell, to discuss our R&E pipeline. David.

Thank you, Adam. Today I will discuss my remarks on three specific areas, the phase three trials with cervidutide, the dual glucagon GLP-1 receptor agonist, the recent results from our long-acting amylin analog ZP8396, as well as activities related to dosiglucagon. Please turn to slide six. Our major focus is on obesity, which is increasingly recognized as a complex chronic disease, which is amenable to treatment using pharmacologic agents that target a number of unique metabolic pathways. We believe that the success of weight loss therapies will be determined by various differentiating factors catering to specific segments of people living with overweight and obesity. Therefore, our therapeutic approach aims to, one, achieve significant weight loss, two, provide additional effects that can address specific comorbidities, three, improve tolerability, and four, offer alternatives to incretin-based obesity therapies. Each molecule in our portfolio is differentiated through peptide target, design, or formulation. On slide seven, we outline the three global phase three trials with cervidutide, the glucagon GLP-1 receptor dual agonist, sponsored and designed by our development partner, Beringer Ingelheim, in people living with overweight and obesity. The trials synchronize one and synchronize two include people with obesity or overweight with at least one comorbidity. Synchronize 1 will enroll participants without type 2 diabetes and Synchronize 2 will enroll participants with type 2 diabetes. Both trials will assess the percentage change in body weight and the proportion of people who achieve categorical body weight loss of 5% or more at week 76 as the primary endpoints. 600 participants will be randomized 1 to 1 to 1 to week using monthly titration schedules to reach a maximum dose of either 3.6 or 6 milligrams for maintenance treatment or matched placebo. Recall that the maximum maintenance dose in the Phase 2 trial in people with overweight or obesity was 4.8 milligrams and that the total treatment duration was 46 weeks. In that trial, body weight reductions have not yet appeared to plateau after the 46 weeks of treatment, indicating that further reductions are likely to be observed with longer treatment duration and higher doses. The third phase three trial is a long-term cardiovascular safety study that will enroll nearly 5,000 individuals with overweight or obesity with cardiovascular disease, chronic kidney disease, or risk factors for cardiovascular disease. The primary endpoint of this trial is five-point major adverse cardiac events, or MACE, defined as the time of the first occurrence of any one of five major adverse cardiovascular events, cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, ischemia-related coronary revascularization, and heart failure events. Please turn now to slide eight in our amylin program. At this year's Obesity Week, held in mid-October, we presented the results of the first two cohorts, or so-called Part 1, of our Phase 1b trial, assessing weekly doses of ZP8396. These data demonstrated mean weight loss of more than 5% in healthy, lean, and overweight people with very low doses of either 0.6 or 1.2 milligrams administered weekly for six weeks. We are very encouraged by these data and the magnitude of weight loss achieved, which we believe is on par with the results reported in initial short-term studies of GLP-1-based therapies. On slide 9, we show additional tale of the adverse events reported in this Phase 1b trial, with the results showing that ZP83-96 was well tolerated with no serious or severe adverse events and no withdrawals. Gastrointestinal side effects were the most common adverse events reported. All were mild and most occurred within two days of the initial dose. Based on these data and the results from our previously reported phase one single ascending dose trial, we believe that ZP8396 offers the potential for significantly improved tolerability when compared to the known adverse event profile of incretin-based therapies. The emerging clinical profile supports our conviction that ZP8396 can play an important role as monotherapy to achieve and maintain weight loss and thus represent an alternative to GLP-1-based therapies. Turning to slide 10, our focus now is on the execution of the ongoing 16-week multiple ascending dose phase 1b trial, exploring significantly higher doses of ZP8396 using a dose titration scheme. We are very pleased with the progress on this trial to date and expect to report top-line results in mid-2024. Now turning to slide 11. My final remarks today are related to our DASI glucagon program for the treatment of congenital hyperinsulinism. We submitted the NDA for the prevention and treatment of hypoglycemia in pediatric patients with congenital hyperinsulinism ages 7 days and older in June of this year. The FDA subsequently recommended that the regulatory review should be conducted in two parts under the same NDA. Part one, or original one, relates to dosing of doziglucigon for up to three weeks, and the FDA has granted a priority review with the PDUFA date on December 30th of this year. I am very encouraged by the progress our team is making and the continued engagement with the agency as we approach the final steps towards potential approval. In parallel, in support of part two or original two of the NDA, we are preparing and analyzing the continuous glucose monitoring or CGM data sets that were included as an additional measure of glycemic outcome in each of our two pivotal phase three clinical trials, as well as in the long-term safety study. This work is expected to be completed and submitted to the FDA in the first half of 2024 to support the review of part two of this NDA. The sentiment and the strong support for the potential benefit of daziglucagon for the treatment of CHI were reaffirmed during a recent meeting that convened the clinical investigators from our CHI program who represent the leading experts in CHI from the U.S. and across Europe. Therefore, as Adam stated, we will work to ensure that daziglucagon is available to U.S. healthcare professionals and patients as soon of our CHI NDA. With that, I would now like to turn the call over to our Chief Financial Officer, Henrietta Venneke, to review our financial results for the first nine months of 2023. Henrietta?

Thanks, David, and hello everyone on the call. Let's move to slide 12 of the income statement. Revenue for the first nine months of 2023 was 320 million DKK. This was mainly driven by the recognition of a 30 million euro milestone from BI, as well as a 10 million US dollar milestone from Sanofi. Both milestones are expected to be paid in the fourth quarter of the year, but are recognized in Q3 due to the fulfillment of the contractual obligations. Operating expenses for the first nine months of 2023 were 633 million DKK. compared to 676 million DKK in the same period of 2022. The decrease was driven by lower sales and marketing expenses as well as lower administrative expenses due to cost reduction efforts following the restructuring last year. This was partially offset by significantly higher R&D expenses. Almost 80% of OPEX was allocated to R&D activities in the first nine months of 2023. This was driven by the progression of the late-race rare disease assets towards submission and significant investment in our wholly owned obesity programs. The net financial items for the first nine months of the period resulted in a loss of 125 million DKK. This was mainly driven by the final repayment and the termination of the loan with Oberland Capital. So let's move on to slide 13 and the cash position. As of September 30, 2023, cash, cash equivalents and marketable securities were approximately 1.6 billion DKK. The increase compared to year-end 2022 was driven by the capital raise in April of 1.5 billion DKK and partly offset by cash use and operating activities during the first nine months as well as the repayment of the Oberland loan in May. With the revolving credit facility of 350 million DKK provided by Danske Bank, we now have approximately 1.9 billion DKK in cash, which combined with the expected payment of 285 million DKK in milestones in Q4 from BI and Sonobi resulted in a runway to mid-26. I am very satisfied with our financial position and the solid foundations it provides us to ensure we maximize value of our assets so let's move to slide 14 and our financial guiding guidance which is unchanged so let's keep this very short we continue to guide for net operating expenses of between 800 to 900 million dkk in 2023 and with that i will move to slide 15 and turn the call back to adam for some concluding remarks thank you henry building on the progress

In the first nine months of the year, I expect an equally exciting next 12 months with several important events and catalysts. Just to name a few, rounding off the year, in rare diseases, we expect to submit the new drug application for glipacritide in short bowel syndrome, and we have the PDUFA-Date for dasyclurban in CHI. Looking into next year, we expect results from the sublutotide phase two trial in NASH, the 16-week clinical trial with our amylin analog, the investigator-led phase 2 trial with dapaglutide followed by results from our 13-week dose titration trial, and initiation of new first in human clinical trials. Importantly, we will also continue to engage in partnership discussions. A final note on slide 16 before we take questions. We really hope that you can join us for our obesity R&D event on December 5th in person in London or online. We have a very strong lineup of three leading experts in the field, Professor Daniel Drucker, Lou Aron, and Carole Leroux. Together we will share perspective on the scientific, rational, and clinical potential of C-Lens Obesity Assets. Personally, I look very much forward to this event and hope to see many of you there. Please contact us or go to our website to register. 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, you can please press star 1 and 1 again. Once again, please press star 1 and 1 if you have any questions or comments. Thank you. We are now going to proceed with our first question. And the questions come from the line of Michael Novot from Nordea. Please ask your question. Your line is opened.

Thank you very much. It's Michael Novot from Nordea, Copenhagen. So two questions, one relating to Darcy, who had gone in CHI. So maybe not a big surprise that it's going to be, potential partners is going to be pushed in given the due date of 30th of December. So it's going to be pushed into 24 paths. Can you talk about sort of what kind of interest you're seeing? Have you seen sort of a declining interest after the FDA decided that you had to do the NDA in two parts? And should we expect that a potential partnership will not materialize after the part two has been filed with the FDA as well, or the data that is needed for that? And then secondly, to the amylin analog. So it was obvious from discussions at Obesity Week that you are likely going up to around six milligrams in part two. Can you talk about, if you see that being well tolerated, is there a possibility that you can take it even further? I know it's probably then going to take a bit longer time, but can you talk about whether you can push the dose even further than six milligrams? Thanks a lot.

Thank you, Michael. I will take the first question and then I'll hand over to David to discuss your question on amylin. As I mentioned on the In the prepared remarks, then, of course, with the splitting of the NDA, that introduced some complexity in our partner discussions. But having said that, you can say our confidence in the assets has not changed. I would say, actually, on the contrary. And the way we see this now is that our main focus is, of course, to secure the PDUFA date for part one and then do all the preparative work and submit part two. The feedback, or you can say maybe not feedback, but more our observations will be that having a better understanding of the full label potential will be helpful in some of these discussions we had earlier on before this decision was taken. I remind you that the first part is only treatment for up to three weeks, versus the latter part, part two, will support chronic use. We see a huge need for both situations, but it is clear that a lot of the CHI patients, especially those with diffuse disease, they are in need for chronic therapies. That's why we're so focused on also getting to part two. So it is quite difficult for me to guide on the specific, you can say, considerations for the potential partnership companies. But what I can say is that CLAN's focus, as I said, will be to secure the value creation that we believe we have with this asset and we will not compromise on if people view the potential different than we do. Having said that, that also means that we have taken means to make the product available to patients at PDUFA once we have the PDUFA part one. But I can only confirm that we have continued good discussions whether this will happen This year, next year, early on, when we have the PDUVA data, only after we have submitted part two, I cannot guide on right now. But we remain very confident in the opportunity. And David, I will hand over to you to discuss the potential for dosing levels and so on, even though we are in the midst of the study. I know we cannot share maybe everything, but David.

Thank you, Adam, and thank you, Michael. I'll add to Adam's comment on the DASI and CHI. It obviously does require additional work getting the supplemental data, as we discussed, but from our perspective, that does not increase uncertainty. It just pushes the timeline for that full review and to leverage the full value of that asset clinically. Obviously, both acute and chronic therapy is of great interest to us and of great interest to potential partners with whom we're discussing it. Your question about amylin dosing obviously will be ultimately guided by the results of the Phase 1b and seeing where in multiple ascending dose we can and will take the doses of amylin. Obviously, the Part 2, as we've described, of the Phase 1b that's ongoing will extend treatment out to 16 weeks, and while that's relatively short-term for obesity trials, we believe that will give us a great perspective on not only what doses are achievable, certainly we believe higher than 0.6 and 1.2 that have already been reported. I can't speculate yet on where the maximal dose might take us, and obviously with those results in hand, we'll put together a final protocol that we believe pushes to the optimal doses, both as high as feasible, but also as we've stated throughout to maintain what we already see as a very favorable tolerability profile. So, more to follow in the first half of next year.

Great.

Thanks a lot. Yep. Thanks, Michael.

Thank you. We are now going to proceed with our next question, and the questions come from the line of Lucy Codrington from Jefferies. Please ask your question.

Hi, thank you for taking my questions. Just following up on the partnership with the CHI discussions, I do appreciate that there is a lot of unknown here. But in terms of a couple of things, when you say you would want to wait for the partners might want to wait for the full label, does that then mean we need to wait for the part two approval? And is that part two also under priority review and therefore could still come next year, or could that end up coming in 2025? And just on your plans to make it available as soon as possible after the 30th of December without waiting for a partner, is that feasible to do without a significant investment required on your part? Then secondly, just in terms of the server duty phase three, and I appreciate you're not in charge here, but in terms of the timing, it seems kind of conservative perhaps to what I was expecting in terms of the primary readout. Do you think there is scope for an earlier readout than end of 2025, early 2026? And then finally, on the current R&D rate, there was quite a significant step up in the third quarter. Should we be thinking about that as a sensible level going forward, or should I be thinking about anything else kind of into the next quarter and then on into 2024? Thank you.

Thank you, Lucy. I will address your first question and then hand over to David afterwards to address server, and then Henriette will address your last question on the R&D spend. Let me put it this way. Of course, with part one, once and if approved, that will be, of course, de-risking the program significantly because, of course, part of the part one NDA review includes all the quality, all the device, a lot of the clinical questions which will be cleared and will be very, very important label elements. So just having the PDUFA date, December the 30th, will de-risk, of course, a lot of label considerations. Once we have, as David discussed, all the existing data from this continuous glucose monitoring data evaluated in the ways that we are agreeing with FDA, that will further provide a significant de-risking of the potential future available, because then we know, you can say, to which extent we have potential claims to support and so on for specific areas. So that will, of course, also provide some further clarity. And ultimately, you can say, of course, it comes with a potential approval of part two, then we will have all the clarity. So I would say this is not black and white. We believe that just getting the initial label in place and having a full oversight of all the data that FDA requested provides a lot of clarity on the potential future label for this program. So I'm sorry I cannot be more precise right now. I hope it's clear that our confidence in what we are working on here remains very high, but also that we will not compromise on the value potential and the strategic opportunity for us on this asset in this partnering process. And as I mentioned, and thanks for that question, we have and we are taking means to make the product available in the US as soon as possible after a potential approval also of part one. And it's not something that will carry a huge spend for us also not going into next year if that is the case. So this is something that we feel that we are on top of and we will do what's needed. David, will you, I hope this answers your question, Lucy. And then, David, just, will you address the servuticide question and so on?

I'm happy to. Thanks, Adam, and thanks, Lucy, for your questions. One added comment on to Adam's discussion around the current NDA and original one and original two. Remember that this remains part of the same NDA. for which the part one, original one, was granted priority review. So while we cannot speculate that part two will receive the same, because it is under the same NDA, that is and remains a possibility. And obviously, both for us and for the agency, the review of You know, these detailed but existing data from CGM and more data collection will be part of that. So pending their acceptance of that second file, we'll know and understand that it remains under the same NDA where a priority review is possible. Can't speculate on whether it's likely or possible. Servodutide, the phase three program readouts to your question on timing. Obviously, the endpoints and the readouts are dependent on a number of variables, which you know quite well, primarily getting sites up and running, actively recruiting, and recruiting at an acceptable or rapid rate. And it is not about the first patient and first visit to the clinic. It's about the last patient and their last visit. So with that, I think these readouts, which obviously are in the hands of our BI partner, and their timing are probably based on their current estimates using the sites that have been identified and will get up and running. So I think one comment to that end is we have seen that the majority of trials in overweight and obesity tend to recruit quite quickly. So our hope obviously is with that program and our other obesity programs that that Rate of recruitment into clinical trials will remain vigorous and that that can move the readout timelines forward as much as possible, so I'll leave it at that and Obviously additional questions probably best answered by those on the clinical side FBI and then I'll turn the financial question on the step up in our R&D expenses over to Henrietta if she has a comment

yes thank you david and thank you lucy for the question you're correct our r d spend in the quarter is stepping up compared to what we saw in in the first and second quarter as you know always with the with r d activities is depending there can be certain swing factors and depending on where you are you know clinical activities but also research activities and then is that that then is clear um We do invest heavily into obesity, and we have good progression of our programs there. Currently, at the same time, of course, we are investing our rare disease assets to get them over the finish line. So there will always be swing factors, but we are, of course, investing heavily at the moment.

Thanks very much.

Thank you. We are now going to proceed with our next question. And the questions come from the line of Rajen Sharma from Goldman Sachs. Please ask your question.

Hi. Thanks for taking my questions. I've just got a couple on server-duty and synchronized phase three. So as you mentioned that there's a higher maintenance dose in the phase three relative to what we saw in phase two. Could you just kind of help us understand the rationale for this? If you're able to, could you perhaps give us any color on the titration schedule? I think the Phase 2 used a biweekly titration. Is this the case in the Phase 3, or will that be a slower titration? And could you also confirm if the trial would allow for antiemetic therapy? And then just on glupaglutide and thinking about partnership there, how should we think about timing? And I guess what are the gating factors here? Is it that partners are waiting for submission or potentially an approval. And is it fair to assume that any potential partners may be waiting for top line data from your potential competitor at Ironwood?

Thanks, Jan, for your question. I will address your Glipa question, and then I'll hand over to David on the Servo question. So on partnerships for Glipa, as I mentioned on the call, We are on track to submit the NDA later this year and it's only after then we will, you can say, progress significantly on the partnership discussion. At least if what I'm aware of then, Ironwood are expecting to see top-line results or report top-line results from their program in March. So I think it's probably fair to assume that it's not likely to have a partnership before that, whether partners' interest and so on will depend on those. I mean, of course, to some extent, I think we are equally as interested and as you know, we feel very comfortable in our assets. So I think it's a fair assumption that a partnership will only happen after that event, but perhaps equally driven by just the process that we are running right now and which will only be really started after we submit the NDA. David, will you take the questions on server?

Happy to, and thanks as well for the question. Yeah, you're correct, the higher dose going up beyond what was utilized in phase two. Obviously, these protocols, and I'm speaking now obviously on behalf of our BI partner who've done the negotiating, At end of phase two, those discussions have to occur with the FDA to get approval on the protocol, both for the treatment population and the doses used. You need, obviously, the appropriate pharmacology and clinical pharmacology studies, as well as safety and tox studies, which allow those doses. I think two things emerge from that. uh phase two one you've alluded to which is the titration schedule and monthly titration will be used the comments and specific details on antiemetic use will obviously be part of the protocol but suffice it to say that yes all will be done to ensure that the dose assigned at randomization is titrated on that monthly schedule and is maintained for as long as possible I think it now has essentially become the standard in clinical trials where you're forced titrating to these doses that anti-medic and other measures for titration can be used so the higher doses obviously are supported this protocol is signed off and moving forward and I think given what we saw from phase two, particularly in the overweight and obese population, but also in the shorter type two diabetes study, that both the effects on body weight and the potential effects on glycemic control in those with diabetes will be enhanced by pushing to these top doses.

Thank you very much.

Thank you.

Thank you. We're now going to proceed with our next question. And the questions come from the line of Charlie Mabbitt from Morgan Stanley. Please ask a question.

Hi. Thanks very much for taking my question. It's Charlie Mabbitt from Morgan Stanley. Firstly, on the cardiovascular outcomes study, please could you just go into a little bit more detail on the study? I appreciate you didn't design it specifically, given it sort of includes patients with cardiovascular disease or chronic kidney disease or cardiovascular disease risk factors at baseline, it seems like quite a lot more complicated than I guess other cardiovascular studies we've seen. So could you just explain the rationale for that and why sort of the CKD studies and see cardiovascular disease studies might not be done separately? And then I guess, secondly, I guess, how do you think about trial duration in like a phase three, 2A study for something like DAPI glutide. I guess, does a 13-week study give you enough information to know if there's an additive benefit of GLP-2 versus GLP-1, and would a larger phase 2 therefore be needed before going to phase 3? Thanks very much.

Yeah, I'm happy to start, and Adam, please add additional details. On the CDOT, Charlie, a good question. I think it's worth noting that our BI colleagues have now achieved indications with the empagliflozin franchise in both cardiovascular disease, heart failure, as well as in CKD with their recent outcomes and approvals. So as partners, they have a great understanding of these populations. I think it's also important to note that chronic kidney disease, particularly in the absence of diabetes, and remember these are obesity studies first and foremost, confers cardiovascular risk that in many cases approaches that or is similar to that of preexisting cardiovascular disease. I think the other component that RBI partners look to achieve in this study population is is a more representative population of those with overweight and obesity who have comorbidities that relate to cardiovascular risk, so including cardiovascular risk factors, previous cardiovascular events, and CKD. I cannot comment on whether CKD will have a secondary outcome measure, but obviously renal function and renal outcomes will be an important safety measure in all these trials. I think it's also important to point out that the previous CBOTs that have been designed, say, with the assets from Novo and Lilly, are with assets that were previously evaluated for cardiovascular outcomes in diabetes. So whether those sponsors also wanted to demonstrate effects separate from the diabetes-related cardiovascular effects or not, noting that for subarbutitis, this will be the first potential approval in overweight and obesity. So a slightly broader population with a slightly broader outcome, the five-point MACE, makes very good sense, at least to me, and I think to us collectively in the BI Zealand partnership in terms of that cardiovascular outcomes study. For the second question on GLEPA and its potential, or I'm sorry, DAPI and its trial design, obviously you are correct. Phase 1B and shorter 13 to 16-week studies that are often done are generally only directional in giving you a sense of both dosing tolerability and the potential for weight reduction. As we get into Phase 2, both the requirements for, and we believe, the understanding that longer duration phase two trials out 36, 42, even 48 weeks in duration give you a much clearer assessment and are required by the FDA to help you design phase three. So phase 1B will be directional. We hope to have very clear insights from both the DREAM investigator-led study and our own program at the higher doses. But obviously, the duration of exposure will be relatively brief, as it is with many in Phase 1b, even in obesity. Well, thanks very much. Yep. Thanks, Charlie.

We have no further questions at this time. I will now hand back to Adam Steensberg for closing remarks.

Thank you. And with that, we'd like to thank you all for attending and for your questions today. We look very much forward to seeing you on the road and connecting at our obesity R&D event in London on December 5th and on future announcements and updates. Thank you.