Q3 2025 Zealand Pharma A/S Earnings Call
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Speaker #1: relations of Zeeland Pharma.
Speaker #2: Thank you, operator, and thank you to to slide three and today's conference over to your speaker, call, we will be making forward-looking uncertainties. Turning today are the following members of Zeeland Pharma's management team: Adam website at Steensberg, president and chief executive officer; Henriette Wennicke, chief financial officer; and David Kendall, chief medical officer.
Speaker #2: everyone for joining us today to zeelandpharma.com. As described on slide two, Please be advised that discuss Zeeland Pharma's results for the
Speaker #2: first nine months of today, Adam Lange, investor related company announcement on our
Speaker #2: Four, I will now turn the call over to Adam Lange. Moving to slide... All speakers will be the CEO.
Speaker #3: Adam.
Speaker #3: 2025 has been a quarter of strong execution and Thank you, continued momentum in our partnership with
Speaker #3: class of drugs for weight the potential to lead in the next currently analog supported by the clinical data to 2025.
Speaker #3: Graham, CEO of Roche partnership process, we Steensberg, president and partner for Zeeland Pharma and patronified. Turning to slide Surrogate is licensed to burn identified Roche as the ideal why to a highly competitive seven.
Speaker #3: Roche at their Pharma Day in You can find the September convey to you their strong commitment to become a top three player in therapies.
Speaker #3: renal, and metabolic obesity. markets. We're excited to see next major pharma company to more than 130 Last month, Zeeland Pharma had the with a truly differentiated tier two one co-invented with Zeeland phase therapy Pharma.
Speaker #3: Week. Week and Atlanta last Engelheim, a leading family-owned company, demonstrated their strong presence at the obesity event. The scale and complexity of obesity make it a distinct disease area, in which we identified different market segments to enter.
Speaker #3: In the prescriber-driven segment, a key motivation for prescription is focused on This leads me to slide relative weight loss. We comorbidity risk reduction, potential to be uniquely believe surrogate has the positioned within this is patient-driven.
Speaker #3: In the prescriber-driven segment, a key motivation for prescription is focused on This leads me to slide relative weight loss. We comorbidity risk reduction, potential to be uniquely believe surrogate has the positioned within this segment.
Speaker #3: significant focus here is personal weight loss goals and how individuals achieve deliver the weight loss that the The larger segment, however, and obesity desire, combined profile and an excellent vast majority of people with overweight them.
Speaker #3: patient experience, we believe patronified is ideally positioned segment. I'm highly encouraged by the to lead in such a potential of both of our leading obesity programs, which holds potential to With potential to weight management in key segments.
Speaker #3: And with that, let's move to slide nine as I turn over the Thank you, David.
Speaker #3: Call to our Chief Medical Officer, David Kendall, to discuss our R&D pipeline.
Speaker #4: leading programs, patronified and Adam. so, I would like to begin by providing a Today, I will focus my remarks on brief update on our two late-stage surrogate.
Speaker #4: rare disease programs and the continued advancement of our two GLP-2 receptor dual agonist program. For doxyglucagon in congenital hyperinsulinism, our third-party manufacturers' facility Before doing has not yet received the anticipated classification upgrade, and as shared previously, we have implemented a supply contingency plan, including the qualification of an alternative supplier to ensure we can bring this important therapy to patients in need as quickly as possible.
Speaker #4: For glipaglutide, our GLP-2 receptor agonist in development for the intestinal failure, the treatment of short bowel syndrome and phase three ease five trial remains on track to initiate before the end of the year.
Speaker #4: With the purpose of supporting regulatory submission in the US. We remain encouraged and excited by the clinical profile of glipaglutide as a potential best in class long-acting treatment for patients living with short bowel syndrome and intestinal failure.
Speaker #4: And look forward to confirming completed ease one the positive findings of the previously trial. We have made the decision to pause the current development of dapiglutide.
Speaker #4: This decision is a result of a discipline portfolio review and prioritization. Seeking to focus our obesity portfolio investment on programs with the greatest potential for clinical differentiation and those offering the greatest potential for long-term impact for patients living with overweight, obesity, and related dapiglutide has demonstrated the potential for a competitive weight loss profile based on the results of clinical trials completed to date, the GLP-1 based therapeutic space has become comorbidities.
Speaker #4: differentiation for assets which even greater and clinically meaningful would be launched in the 2030s and beyond. While there is compelling scientific rationale, for GLP-1, GLP-2 dual agonism to modulate low-grade inflammation more effectively than GLP-1 alone, the clinical requirements needed to demonstrate this differentiation in a dedicated obesity-related comorbidity would be long, complex, and expensive.
Speaker #4: significant opportunities in both the Amylan and Incretin-based therapeutic space with our leading programs, including patronified, the fixed dose combination of patronified and Roche's GLP-1 GIP dual agonist Although CT388, and We have surrogate as well as an early-stage pipeline that includes novel and inflammation with the ultimate mechanisms targeting obesity goal of restoring and maintaining metabolic health.
Speaker #4: Please turn to slide 10 and beginning with patronified. Our strong confidence in patronified is grounded in its overall efficacy, safety, and tolerability profile. While Amylan-based therapeutics can deliver clinically meaningful weight loss, we are not seeking to deliver the highest possible weight loss with patronified, but rather seek to target the weight loss that the vast majority of people with overweight and obesity desire and to do so with an excellent patient experience.
Speaker #4: deliver 15 to 20% weight of patronified to We remain fully confident in the potential loss in phase three clinical clinical efficacy, safety, trials and also remain highly confident in patronified's consistent Underscoring its unique value proposition and the potential to become the and tolerability.
Speaker #4: Leading amylin-based treatment and a foundational therapy for weight management. I'm extremely pleased with the strong execution and advancing the patronized clinical program at full speed.
Speaker #4: In late September, we reached a key milestone in the large phase two supreme one trial, which evaluates the efficacy and safety of patronified in people with overweight or obesity without type two diabetes.
Speaker #4: With the last randomized participant having now completed the 28-week primary endpoint visit. Additionally, earlier in the month, we completed participant enrollment in the phase two supreme two trial, which evaluates the efficacy and safety of patronified in people with overweight or obesity and coexisting type two diabetes.
Speaker #4: These achievements put us well on track to report 42-week top line results in the first half of 2026. Report top line results from the supreme two trial in the second half of 2026 and to initiate the phase three program with patronified monotherapy, also in the second half of 2026, together with our partner Roche.
Speaker #4: Let's move to slide 11. We also look forward to exploring the potential of patronified as a backbone for future combination therapies unlocking its full value potential.
Speaker #4: Patronified CT388 is the first combination product under our alliance with Roche. This program will target individuals who and/or improve glycemic control seek even greater weight loss while optimizing the dose of each component.
Speaker #4: We anticipate that use of higher doses of patronified and optimized doses of the Incretin-based therapy CT388, a potential best in class GLP-1 GIP receptor dual agonist, can provide both robust efficacy while maintaining excellent tolerability.
Speaker #4: Zealand and Roche remain on track to initiate the phase two trial with patronified CT388 combination in the first half of 2026. Now turning to slide 12 and surrogate.
Speaker #4: A potential best in class glucagon GLP-1 receptor dual agonist in late stage development for the treatment of obesity and MASH. The phase three synchronized program of surrogate in obesity consists of six clinical trials, all of which are expected to complete in 2026.
Speaker #4: In the phase two obesity trial, surrogate demonstrated the potential to deliver highly competitive weight loss with doses of up to 4.8 milligrams. Notably, the phase three trials are evaluating a higher maximum maintenance dose of six milligrams.
Speaker #4: This leads me to slide 13. Following the last participant's last visit in the 76-week synchronized one trial, which evaluates the efficacy and safety of surrogate in people with overweight or obesity, but without type two diabetes, we are rapidly approaching top line results from this trial in the first half of 2026.
Speaker #4: At the obesity society annual meeting in Atlanta last week, Dr. Karl LaRue presented the baseline characteristics of participants in this trial. Which are also shown on this slide.
Speaker #4: We are very pleased that Dr. LaRue has agreed to join us at our upcoming capital markets day next month, where he will share more insights on the potential of surrogate to represent the next frontier in the management of obesity and MASH.
Speaker #4: Now turning to slide 14. We remain exceedingly optimistic in our very excited about the ongoing phase three program with surrogate in people with metabolic dysfunction associated steatohepatitis or MASH.
Speaker #4: A serious obesity-related comorbidity with significant unmet medical needs. Shown in this slide is an indirect cross-trial assessment of the registrational clinical trials for the two approved therapies in the US for MASH today.
Speaker #4: The thyroid hormone receptor beta agonist resmeteram and the GLP-1 receptor agonist semaglutide. In the phase two trial with surrogate in people with MASH and liver fibrosis, 38.6% of adults with moderate to advanced scarring achieved a placebo-adjusted biopsy-confirmed improvement in fibrosis without worsening of MASH after 48 weeks of treatment.
Speaker #4: We believe this represents the most compelling and strongest clinical data set to date. On the critical endpoint of improvement in liver fibrosis. With these groundbreaking phase two data and a comprehensive ambitious phase three program now underway, the so-called liverage program, which includes two large trials, one in people with moderate to advanced fibrosis F2 and F3, and one in people with cirrhosis.
Speaker #4: F4. We believe surrogate has the potential to become the therapy of choice in this large and growing market segment, offering a much-needed treatment option for people living with MASH and obesity.
Speaker #4: With that, thank you very much for your attention. I would now like to turn the call over to our chief financial officer, Henriette Wennicke, who will review our financial results for the first nine months of 2025.
Speaker #2: Thanks, Henriette. David. And hello everyone. Let's turn to slide 15 and the income statement. Revenue for the first nine months of $9.1 billion EKK, 2025 was driven primarily by the initial upfront payment received under our collaboration and license agreement with Roche.
Speaker #2: Of the $9.2 billion EKK in upfront payment received in the second quarter, $124 million EKK was deferred as of September 30th, as it relates to the progression and completion of the phase two trials with patronified.
Speaker #2: Net operating expenses total $1.5 billion EKK for the first nine months of 2025, with 73% of that amount dedicated to research and development. R&D expenses were mainly driven by the ongoing development of Patronified, including the last phase two trials and preparation for phase three.
Speaker #2: Net financial items amounted to negative $62 million EKK for the period, primarily reflecting exchange rate adjustments related to the US dollar deposit and currency revaluation.
Speaker #2: This was partly offset by interest income from investment in marketable securities. Moving to slide 16 and the financial position. As of September 30th, 2025, our cash position totaled $16.2 billion EKK, a significant increase from the $9 billion EKK at the beginning of the year.
Speaker #2: This increase was, of course, driven by the initial upfront payment of $9.2 billion EKK from Roche, partly offset by the operating expansion during the period and the purchase of treasury shares to support GL Pharma's long-term intensive programs.
Speaker #2: I would like to remind everyone that in addition to this very solid financial position, we are entitled to receive a total of $250 million US dollars in anniversary payments over the next two years under the Roche collaboration, as well as potential development milestones of up to $1.2 billion US dollars.
Speaker #2: As I stated in our last quarterly earnings call, I am very pleased with our capital preparedness. We are fully able to honor all obligations under the comprehensive Roche collaboration for patronified, while at the same time accelerating investments in our early stage pipeline to build the next wave of innovation.
Speaker #2: Finally, let's turn to slide 17 and the outlook for the year. Net operating expenses for the year are now expected to be between $2 and $2.3 billion EKK, excluding other operating items.
Speaker #2: The financial guidance has been narrowed from the $2 to $2.5 billion EKK, reflecting the decision to pause the development of dairy glutide. Previously planned to advance into phase two B development in 2025.
Speaker #2: This decision, as David also mentioned, reflects our active portfolio management and our sharp focus on investing in assets with the highest potential for clinical differentiation, commercial impact, and long-term value creation.
Speaker #2: And with that, I will move to slide 18 and turn the call back to Adam for concluding remarks.
Speaker #3: Thank you, Henriette. We are now at the cusp of the most pharma's history. In just the first half of 2026, we expect to catalyst rich period in seed and see phase three enabling data for patronified, phase three data for surrogate, and phase one data for what could become one pillar in the next wave of innovation from seed and pharma, our highly potent and specific KB1.3 ion channel blocker.
Speaker #3: Moving to slide 19, I can only encourage you to join us at our capital markets day on December 11th, where we will set the stage for the rapidly approaching data readouts.
Speaker #3: We will also share more about our ambitious research strategy, which builds on seed and pharma's unique expertise in peptide R&D and our strong foundation to lead the next wave of innovation in obesity and related diseases.
Speaker #3: And to continue our journey towards becoming a generational biotech company. I'm excited that we will be joined by Jonathan Ruth, a pioneer in amyloid leptin biology as well as Carole Leroux and Louis Aron, recognized thought leaders in the field of obesity.
Speaker #3: They will join us on stage to share their valuable insights. I will now turn over the call to the operator, and we'll be happy to address your
Speaker #3: questions. Thank you.
Speaker #4: As a reminder to ask your question, you will need to press star one, one on your telephone, and wait for your name to be announced.
Speaker #4: To withdraw your question, please press star one, one, again. We will take our first question. And the question comes from the line of Kirsty Ross Stewart, from BNP Paribas.
Speaker #4: Please go ahead. Your line is open.
Speaker #4: Please go ahead. Your line is open.
Speaker #5: questions. So two on patronified, please. Hi there. Good So with the laurel and tide trial now published, I think interested to hear your thoughts on kind of the differences in the setup of the two trials in terms of baseline characteristics, titration, doses being explored, and how your, or how you would encourage us to look at your own data set in the context of Lilly's data to kind of make a fair comparison there.
Speaker #5: And then also, David, you highlighted in your opening remarks that you're not targeting the highest possible weight loss with patritumab, which seems quite in contrast to what Lilly has tried to do with their Laurel and Tide trial.
Speaker #5: I think there are some people that have sympathy with that message, but maybe you could argue as well that there's still some way to go to convince the market of the validity or the strength of that message.
Speaker #5: So I guess my question is, can you provide some feedback from your discussions with regulators or takeaways from market research with physicians and patients that may help to convince this move away from, as you call it, the weight loss Olympics?
Speaker #5: Thanks very much.
Speaker #3: Thanks for your question. And then maybe I can start and then hand over to David. We were extremely encouraged to see the laurel and tide data last week, which we really see building on what we already saw with patronified last year.
Speaker #3: We remember normal demonstrated that patronified can be delivered 12% weight loss, and we consider with a 2.4 milligram dose, which we consider very low dose.
Speaker #3: And it really, you can say, underscores the potential that we have been communicating all the time around the amyloid class that with amyloids, we have the potential to actually develop a new class of medicines that will provide patients with likely a 15 to 20% weight loss.
Speaker #3: And those are two alternatives to the GLP-1s. And very importantly, we expect this weight loss to be a more pleasant weight loss experience with significant less side effects, but also the major in which the patients would reduce their food intake we think would be superior in the amyloid class in the sense of feeling full faster, versus having lost their appetite.
Speaker #3: So we are extremely pleased and you can say it actually increases our excitement around the upcoming phase two data with patronified and our efforts to prepare for the phase three trial conduct really been moving towards for a very long time.
Speaker #3: And David, maybe you underscoring what we have want to touch a little bit upon important trials design specifics.
Speaker #2: Yeah. Thanks, Kirsty. And a trial design specifics, I'll reiterate what Adam said. I think 15 to 20% weight loss when we came forth with patronified's potential to achieve this, I think at first there were actually some skeptics that looked at this and said that can't be possibly achieved.
Speaker #2: We've seen early CAGRI data. But I think the data we saw recently from another compound in this class clearly demonstrates that GLP-1-like weight loss percentages are achievable.
Speaker #2: And we think, as Adam referred to, that higher milligram dose exposure, higher bioavailability and the excellent tolerability profile we've seen to date with patronified up to nine milligrams once weekly can certainly hit that sweet spot.
Speaker #2: You also mentioned what does the market seek? One simply needs to do some math. If somebody weighs 150 kilos, 30 kilogram weight loss or 65 pounds of weight reduction is substantial.
Speaker #2: And I think five years ago, the world would have thought that's unachievable with what we've seen to date. Including with loraglutide. So both in speaking with clinicians and in speaking with the vast majority of patients who seek weight management therapy, that's 10 to 20% weight loss figure comes up repeatedly.
Speaker #2: They may not say 10 to 20%, but they will give you a number of desired number of pounds or an end target weight that generally reflects that.
Speaker #2: I think as some of the data from Triple G, high dose GLP-1-based therapies which we believe suffer from challenges with tolerability can get you to the 20 plus percent range.
Speaker #2: But that serves a vast minority of the patients seeking this. And finally, to your question characteristics, just recall that with about the baseline patronified phase one B, predominantly male participants predominantly are leaner, mean population with a BMI just under 30 kilograms per meter squared.
Speaker #2: Both of those factors, we believe, could have significantly muted the response we saw in Phase 1B. We will have a much more balanced gender distribution in Phase 2, and a much higher baseline BMI, as we reported in the last quarter's call.
Speaker #2: And the likely contribution of a predominantly female very high BMI population I think is well worth considering. It may amplify the observed results rather than mute as a predominantly male and leaner population.
Speaker #2: I think it's also important to read the details of both diet and exercise instruction in the trial. We achieved our results in Phase 1B with limited to no other intervention.
Speaker #2: So I encourage you and others to look at the full construct of all of these trials before jumping to just top line numbers. So I'll stop there.
Speaker #1: Thank you. We will take our next question. Your next question comes from the line of Hakon Hem Bro Jorgensen from Danske Bank. Please go ahead.
Speaker #1: Your line is open.
Speaker #4: Great. Hakon Hemme, Danske Bank. I also have a question regarding the patronified study design. The data from last week demonstrated that patients did not experience a weight loss plateau like we see with the GLP-1 treatments.
Speaker #4: Likely to the restoration of leptin sensitivity by MLN. So how does this influence your consideration on the trial duration for patronified in phase three?
Speaker #4: And how do you see the trade-off between potentially achieving greater weight loss with a longer study compared to bringing patronified to the market sooner?
Speaker #3: Question, Hakon. I'll let David. Thanks for that.
Speaker #3: answer. Thank you, Hakon.
Speaker #2: And I think two very important observations. The absence of plateau which I think was readily evident both in our short phase one B studies with patronified, but certainly offers that potential where longer exposure, some of it required for regulatory review and approval, out to beyond 68 to 72 weeks will allow us to assess whether this is a continued effect and I think importantly speaking back to the mechanisms that Adam discussed, a sense of satiety or fullness where one feels full faster and stops prospective food intake as opposed to a food aversive signal that hits suddenly and may be consistent at least in theory could contribute to a continued gradual weight loss over longer periods of time.
Speaker #2: So in both our own visual extrapolations and I think now looking at the ALORA high dose data noting that the higher doses were perhaps less well tolerated than the three milligram dose, you see not only progressive weight loss, but GLP-1-like effects something we've been talking about for most of the past two or three years.
Speaker #2: So I think it will be important to observe what we pull out of our 42-week phase one trial and then the design for the longer phase three trials will directly answer your question, but would expect the potential for progressive weight loss.
Speaker #2: Out beyond one year of
Speaker #2: treatment.
Speaker #3: Thank you,
Speaker #3: Hakon.
Speaker #1: Thank you. We will take our next question. Your next question comes from the line of Lucy Codrington from Jefferies. Please go ahead. Your line is open.
Speaker #5: Hi. Thank you for taking my questions. Sorry. Sticking with the ALORA data from last week. So in light of that data, do you have any updated thoughts on the importance of the receptor activity that has previously been discussed?
Speaker #5: you're confident it will still be best in And you mentioned that class. I just want to know what drives that confidence given the data we've seen so far for ALORA.
Speaker #5: Then secondly, just following up on the trial design, just to confirm this trial will have no lifestyle interventions. Is that correct? And then secondly, related to the trial, did you specify to have a balanced just sex ratio in the trial or is that happenstance?
Speaker #5: And then on Dapaglutide and the decision there, I just wonder you're obviously not short of cash. So kind of what was the thought process in terms of stopping this study?
Speaker #5: Was there any discussion with Rosh about this? I appreciate you not partnered, but did you discuss it with Rosh? And also any thoughts on potential combination with patronified down the line and what studies would be needed to do done in order to enable that?
Speaker #5: Thank you.
Speaker #3: question. I was the first Thank you. Thank you for the that. I think it's very evident and it one. capital market day that we have what we Pause on believe really a leading opportunity in the GLP-1 space with the surrogate type, which we have license to bring out, which do not only have a huge potential for weight loss, but actually also addressing liver health and in particular mass and potentially other organ damages by activating lipolysis.
Speaker #3: So it actually has a strong profile towards managing comorbidities to obesity. And now with the Roche partnership, we also, as you know, got shared economics on the combination product with CB388.
Speaker #3: That GLP-1 DIP, meaning that's going to be the combination opportunity we are going to focus on. And thus that became less relevant for combinations with over the summer was Amylin.
Speaker #3: addressing segments of the obese patients which were suffering from specific What we have been exploring comorbidities. And in doing those in-depth evaluations, it's very clear that it will require a stable also set very large investments and long commitments before getting to understand the full potential for differentiation and if you then consider GLP-1, the GLP-1 marketplace in five, six years from that it's a very crowded place and now, you will see we came to the conclusion that the level of clinical differentiation we would have to show by coming that late into a GLP-1 market was not worth the efforts in particular not because we have such a rich early pipeline and fantastic ideas which you will hear more about that we want to invest in and apply our capital so we basically believe we can apply our capital better in those early programs.
Speaker #3: So I would say it's a very, you can say considered decision and one which allows us to invest even more in our early stage pipeline as we mature the company towards a generational biotech.
Speaker #3: When thinking upcoming data for patronified, we about the confident in the potential to deliver these 15 to 20% weight loss, which we know will address by far the vast majority of the weight loss that patients are desired.
Speaker #3: And as I said before, the data that came out last year last week underscores the potential that we also saw with patronified last year remember patronified was only 2.4 milligrams, which is a very low dose compared to where we take patronified today.
Speaker #3: And so the confidence in the best in class potential comes from when we look at the consistency of the data we have seen across our early stage clinical trial readouts.
Speaker #3: The balance between efficacy and tolerability has been outstanding in our minds and then the potential to dose high and continue into the longer are soon to report gives us that confidence.
Speaker #3: term study that we report supreme one, we have applied diet and exercise and we do have a gender balance of around 50/50 as opposed to the 80% females that were reported in the study last week.
Speaker #3: But again, that has been done from a very firm development perspective that you want to have exposures in both genders to make the best possible decisions for your phase three design.
Speaker #3: You actually introduce a lot of risk by because you don't get to learn about your molecule in both genders if you screw it too much in phase two.
Speaker #1: And Lucy, I'll take the question about the
Speaker #1: differentiation. I think Thomas Lutz said it quite well in his introductory talk saying there's still quite a bit to understand. having very few of one gender ALORA based on data reported by Lily has about a 12-fold higher And affinity for the amylin receptors than calcitonin.
Speaker #1: But I think it's important to note that improvement in tolerability the proposed or the hypothesized was clearly not demonstrated. There was significant nausea, I think up to 64% in one of the treatment groups.
Speaker #1: Relatively moderate doses. Similarly, if one looks in the appendix, there's not just a transient, but a small decrease in serum calcium, which is also indicative of some calcitonin effect.
Speaker #1: So our own conclusions are that with balanced agonism, as we have seen with patronified, we have seen one of the best, if not the best tolerability and safety profile and that it does not sacrifice tolerability, y, particularly around GI side effects.
Speaker #1: I think the other comments that Thomas Lutz made which is all of this receptor biology work and knockout activity in animals really requires confirmation in clinical testing.
Speaker #1: with a predominantly And to our end female higher BMI population, treated with high doses, there was no substantial difference. I think based on the author's conclusions in tolerability versus historic GLP-1 programs, and we would at least posit that some of the changes including the drop in serum calcium indicates some and perhaps significant calcitonin receptor activity in clinical treatment.
Speaker #1: So we will continue to explore how these may differ. But I think as Thomas Lutz concluded, the answers will come from the clinical
Speaker #2: Thanks, Lucy. trials.
Speaker #3: Thank you so
Speaker #4: Thank you very much. We will take our next question. The next question comes from the line of Andishi from William Blair. Please go ahead, your line is open.
Speaker #5: Thanks for taking our question. So it's about the patient experience that you comment frequently about. So in the context of co-formulation with CT388, I'm curious about your take on how important it is to harmonize the number of steps ups between let's say patronified and CT388.
Speaker #5: In the titration step, especially given the tolerability profile in cretins will likely need a more prolonged titration number two has to do with another adverse event profile that was raised during the conference, which period.
Speaker #5: fatigue. Based on our one of the KOL discussions, I think this is probably is overlooked adverse events affecting patients' quality of life. That number appeared to be numerically higher than what we've seen.
Speaker #5: So I'm just curious about your take
Speaker #6: and hand over to you again, So that's question number one. David. I think as we have also said
Speaker #6: recognizing that we work with extremely fast. potent biology, as David also mentioned before, That could be fluid that you Question
Speaker #6: 20% weight loss with a pharmacological intervention just a few years back? And here we are. But you have to be careful and otherwise you may see things you don't like.
Speaker #6: So that is a clear observation. When we look at our studies, we have not seen it in our program thus far signs of fatigue.
Speaker #6: So again, let's see, we, as you know, apply actually titration throughout our entire phase, all cohorts in our phase two study. Something that was has not always been done with other programs.
Speaker #6: And so far, we have not seen it on the titration steps. Before handing over to you, David, I also just want to mention, I mean, what we have seen thus far is that amylin is actually delivered weight loss even at the initial doses.
Speaker #6: And it's, of course, clear that ultimately when we titrate together with the GLP-1, it will be the GLP-1 that determines how to titrate. Because those are the ones that really need titration from an GI tolerability approach.
Speaker #1: Yeah, I'll David. reemphasize that fairly Andy and harmonizing those I think gives us the opportunity as I said to find what is the most applicable dose escalation scheme for patronified to get to what we hope is maximal dose with very good tolerability as Adam said.
Speaker #1: We've seen less fatigue than in a placebo-treated subjects in the phase one trial. And very limited GI tolerability issues. That would allow you to either very low dose incretin-based therapy so it would further slow down to get to not a maximal dose as is often done in simplify the addition of phase two trials or phase three to see the maximal weight loss.
Speaker #1: But an optimized dose let's say dose three of the 388 compound and dose five of the patronified compound is what the alignment looks like.
Speaker #1: We would base that on the patronified dose in phase two and phase three. So the question is then, how do you formulate a fixed dose combo to get to the optimized, not maximal, dose of escalation scheme? Monthly is what we're testing 388.
Speaker #1: So this is not simple math. I think we have our manufacturing team on edge for the types of combinations that are possible. But this work is well underway and I think will allow us to do exactly what we set out to do, which is to find a very effective therapy that optimizes tolerability while still leveraging the efficacy of both components.
Speaker #5: Thank you so much.
Speaker #4: Thank you. We will take our next question. Your next question comes from the line of Kerry Holford from Berenberg. Please go ahead, your line is open.
Speaker #7: question. Mine is more bigger picture with regard to Oh, thank you for taking my here. So we've clinicians, we are the last update had nearly Trump deal.
Speaker #7: We now have clarity on pricing. In the US, at least the market at least by the cash pay and the Medicare channel. So I would just be interested to hear how that deal and the details that we have so far may be impacting yours and pushes forecasts for the opportunity for your next gen obesity pipeline assets.
Speaker #7: Will it essentially now be more difficult for you to unlock the value and deliver strong returns in this market? Just your thoughts from that bigger picture perspective.
Speaker #7: Thank
Speaker #7: you.
Speaker #6: Thank you for that
Speaker #6: question. And we will actually at our capital markets day in December 11th address our considerations about the current market dynamics in more detail. But maybe just to share a few considerations.
Speaker #6: I think it's a very dynamic market right now. We have already seen that a very large part of the uptake has been in a direct-to-consumer space where list prices.
Speaker #6: And we've also seen rebating in this space when it comes to the commercial channel. prices have been lower than the So it's actually a blessing to be where we are right now where we can learn from these dynamics and then design our programs and go to market strategy together with Rose according to those dynamics and how we think they will play out in the future.
Speaker #6: That allows us to actually define the future instead of just trying to tap into something that will. On the value opportunity, I think the key single most important parameter to unlock the value in this market and actually truly address the obesity pandemic, that is to develop therapies that patients will stay on and thus increase the volume of patients who get to these therapies.
Speaker #6: It's a huge problem that in today's market many patients would use the GLP-1, GLP-1-based offerings as a little bit of an event-based therapy, with the majority of patients being off therapy within a year. A lot of that has to do with side effects we know from IQ data.
Speaker #6: So the focus to unlock the value of this market and to get excitement into this space again, I truly believe is by making sure you develop therapies that people can stay on and thus you will see the volumes go up.
Speaker #6: then the And pricing part that people like to discuss so much is less of an issue as long as people stay on therapy. It's only an issue if you only stay on therapy for one to three months and then you need to go out and find a new patient to that value you lose by the patient stopped capture taking it.
Speaker #6: So we actually like to the clarity that you see more and more clarity. We understand that it's still a very dynamic market. We would expect to see a significant number of changes in the coming years.
Speaker #6: And together with Rose, we would build our go-to-market models accordingly. Thank
Speaker #4: Thank
Speaker #4: you. We will take our next question. And the question comes from the line of you. Prakar Agwa from Cantor Fitzgerald. Please go ahead, your line is open.
Speaker #8: Hi, thank you for taking my questions and congrats on the quarter. So I had a few, maybe firstly going back to receptor biology. Let me say having Alura as a more selective emblem or especially on emblem one receptor and seems to be balanced on emblem three and calcitonin.
Speaker #8: So maybe if you could talk about whether potently targeting Emblem One versus Emblem Three receptors has any clinical implications in obesity and beyond. And if you can remind us about Better Than Diets' activity on Emblem One versus Three receptors.
Speaker #8: And secondly, on the trial for phase two B supreme one, if you can talk about how the discontinuation rates are trending as it has been an issue with some of the recent trials and when you disclose the data next year, whether you will disclose both efficacy and treatment regimen estimate and when the data are disclosed.
Speaker #8: Thank
Speaker #8: you. I
Speaker #6: I just thought I'd hand it over to you to you, David. And we do expect to disclose the top line efficacy data from both estimates, I would expect, including this relevant safety observations.
Speaker #6: When we disclose the data, on the receptor profiles, if you look into preclinical data, I remind you that both we and Nova have had a firm effort for many, many years and came out with balanced profiles towards these receptors.
Speaker #6: And as David just alluded to, probably quite a few of the molecules we're looking at right now have some receptor activation on all three.
Speaker #6: We have one which is quite similar we believe to the one that has ultimately we need to say it also says to see clinical data.
Speaker #6: When we look at the early clinical exposure for which we have actually had among the different molecules, that is where we see get a lot of confidence in our approach if you start to compare let's say the single ascending dose studies across the different molecules where we have data now available and published both from us but also the competing programs.
Speaker #6: And if we then account for females who male BMI and other aspects, but the single ascending dose data probably some of the more honest data sets here where there's bias, that gives us a lot of confidence.
Speaker #6: And the robustness of our observations where we have not seen some side effects in one study and then others in another one, the first one disappearing, we have a very robust data set, which suggests that we have a profile of a drug that has found the right balance between efficacy and safety tolerabilitys.
Speaker #6: So and we will review more of this at our capital markets day, which will answer probably in more detail some of these questions and maybe I don't know if you have more to say.
Speaker #1: Thanks, Prakar. And I think as you and we are learning this receptor biology when it's assessed in vitro, looking at receptor occupancy and activation, doesn't necessarily provide the entire clinical picture.
Speaker #1: As Adam said, Kagri and Petrel and Tide are clearly balanced receptor agonist activate all three receptors in our hands. With equal potency, the KUBRA now have the asset is similar in our hands, slightly greater predilection for the emblem than the calcitonin receptor.
Speaker #1: And the Lilly molecule, Alura Lintide, while touted to be emblem more specific, it clearly had GI tolerability issues associated with it, something that calcitonin receptor dialing back has been touted to improve, but hasn't been demonstrated clinically to demonstrate.
Speaker #1: I think the other point that Adam makes that’s critically important is, regardless of this, how does the clinical safety, tolerability, and efficacy profile line up?
Speaker #1: Using the Alura data as an example, there were in the early phase trials an increase in the number of headaches whereas with Petrel and Tide we've seen less headache than with placebo.
Speaker #1: The newly reported adverse effects of bradycardia, bradyarrhythmia, and syncope reported in the Alura trial are unique amongst this class, to my knowledge. I have no idea if that's related to receptor biology or other mechanisms.
Speaker #1: Again, the clean profile and the balanced agonism of both Kagrel and Tide now through phase three and our phase one B data and beyond for Petrel and Tide give us great confidence that that is not only an acceptable receptor profile, it is an incredibly effective and well tolerated
Speaker #1: profile. Thank
Speaker #6: you. Thank
Speaker #4: you. We will take our next question. Your next question comes from the line of Yihan Lee from Barclays. Please go ahead, your line is
Speaker #4: open. Hey, Yihan
Speaker #9: Lee from Barclays: Thank you so much for taking our question. We have two. The first one is about the petrolene-type phase three timing.
Speaker #9: So it seems like you have already completed the end of phase two meeting with the FDA. So just curious if you could walk us through what remains before initiating the phase three monotherapy trial.
Speaker #9: Which is now planned in the second half of next year. Especially given competitor Eli Lilly actually they move very fast for the phase three will start by year end.
Speaker #9: Yeah, thank you. And the second question actually is Alura Lintide being mass data. So again, they showed 60 to 70% of the mass reduction from metallose and also the other 30 percentage from the B mass.
Speaker #9: However, an interesting thing is that it doesn't seem to have a continued decline in the B mass from the week 24 to week 48.
Speaker #9: So suggesting the B mass loss could potentially stabilize after 24 weeks. I'm just curious, does this suggest maybe emblem-based therapy could inherently preserve B mass better over time?
Speaker #9: Like any thoughts will be appreciated because I'm just thinking like emblem could be used as a post-GLP-1. So just curious what your thoughts there.
Speaker #9: Thank you very much.
Speaker #6: Thank you for that question and I can reassure you that we are moving as fast as possible forward to copay three initiation with Petrel and Tide right now.
Speaker #6: Right now our expectations would be a second half of next year and as we have communicated today we have the primary endpoint of the study and we are of course also anticipating a meeting with FDA as fast as possible once these data have been analyzed and progressing as fast as possible.
Speaker #6: So and top line data will be available first half next year. So it's a shared commitment from Rose and us to accelerate as much as possible to get these treatments to patients ultimately and help achieve the health goals.
Speaker #6: So this is progressing with a high sense of urgency. But the phase three start is set for second half next year. I think we need to actually wait for our phase two data with Petrel and Tide before we will comment more on the balance between muscle and fat preservation.
Speaker #6: use MRI as an assessment of body composition, which is a much more precise mechanism than the DEXA scans Remember we that have been used utilized by other companies.
Speaker #6: We as everyone know have seen extremely strong preclinical evidence for muscle preservation with the emblem class and we need to now see human evidence before addressing this more and we think we will get some at least high quality data from our phase two study, which will be able to address this in more detail.
Speaker #6: Thank
Speaker #6: you. Thank
Speaker #4: You. We will take our next question. Your next question comes from the line of Theodora Robedo from GS. Please go ahead, your line is.
Speaker #4: open. Hi, thank
Speaker #10: you very much for taking my questions. Both on Zapigli Tide if that's okay. So firstly, why did you take the decision now to pause the development of Zapigli Tide rather than further exploring the potential anti-inflammatory benefits?
Speaker #10: Has there been some data generated internally, for example, that could drive that decision? And then secondly, could there be developments elsewhere in the space that change your thinking on Zapigli Tide?
Speaker #10: So specifically thinking about if Novo show a benefit in Alzheimer's in the evoke trial. Thank
Speaker #10: You. Thank you for that question.
Speaker #6: and as you have indicated today we have decided to pause the program because we do recognize that it's a very attractive profile both for the clinical profile we have seen thus far and also its potential to lower inflammation even further than the existing GLP-1s.
Speaker #6: We actually think it's probably the most differentiated GLP-1 containing mid-stage development candidate. The decision has been reached now partly as I explained due to the fact that we have seen the 388 where we can as you will combine with emblem also of course very much because we see now we see several side approaching.
Speaker #6: But then also just realizing that the investments needed to show the clinical differentiation and then the need for clinical the amount of clinical differentiation you would have to demonstrate if you don't see GLP-1 based therapy in the 30s it's a very, very high bar to pass due to the competitiveness within the GLP-1 class of medicines.
Speaker #6: And that's coming back to why we are so excited about the emblem class because it's an alternative and it's if you think about how you manage chronic therapies normally if you cannot achieve your goal with one class then you move on to the next and if you need more then you start to combine.
Speaker #6: So and if you then and we will talk much more about that at our capital markets day consider the rich pipeline we have of early stage assets.
Speaker #6: We are really taking a view that there's significant higher value creation opportunities by investing in these next opportunities for which we have some we consider at least very good ideas for how to drive the next wave of innovation and differentiation in this space.
Speaker #6: So it was not as you can imagine an easy decision since the molecule actually looks very strong. But we also think we have so much exciting opportunities in our pipeline that the money actually more wisely spent there.
Speaker #6: Thank you.
Speaker #4: Thank you. We will take our next question. Your next question comes from the line of Alec Ebling from UBS. Please go ahead, your line is
Speaker #4: open. Hi, thanks for taking my question.
Speaker #2: Just on survodatide. So you'll probably cover this more at your CMD, but in terms of the phase three readout in the first half of next year, where do you expect tolerability will likely land considering that in the phase two data we've seen so far there's a pretty high level of GI toxicity?
Speaker #2: Thank
Speaker #2: you.
Speaker #6: Thank you
Speaker #6: for that question and we of course soon will have the data and please also remember that the phase two study design if you compare the safety or tolerability profile with the phase two studies of some of the marketed products you will actually see a quite similar profile of tolerability.
Speaker #6: So, we expect that with survodatide there will be a comparable tolerability profile to the existing molecules and also comparable weight loss. The true opportunity for differentiation is the activation of lipolysis with glucagon, thus providing better liver health, as we saw with the MAST program.
Speaker #6: Also remember that Boehringer is actually pursuing higher doses in the phase two than what the in the phase three than what they did in phase two.
Speaker #6: And that gives us a lot of confidence that by applying the right titration and being flexible around how you titrate, as you have to be with a GLP-1, allows them to go much higher.
Speaker #6: They have already tested that higher dose in the MAST population in phase two, which is applied in the phase three program quite easily. So we have a lot of confidence that the profile will come across as a very strong and effective GLP-1 based therapy with a tolerability profile that is comparable to what's on the market today and a clear edge towards liver
Speaker #6: health. We will
Speaker #4: question. And your final take our final question comes from the line of Mohit Bansel from Wells Fargo. Please go ahead, your line is open.
Speaker #2: Great, thank you very much for squeezing me in and this is my debut on this call. So a couple of questions from my side.
Speaker #2: First of all, so given that with Cagrisemma we saw a little bit of tolerability when you combine GLP-1 with emblem and I fully appreciate the sentiment that combining GLP-1 and emblem could be interesting.
Speaker #2: But at the same time, do you given that emblem does have some GI tolerability issues and it could compound with GLP-1, so do you think the better use of emblem could be more of an immunotherapy versus a combo therapy?
Speaker #2: Maybe in post-GLP setting or maybe as a monotherapy in the frontline setting. So that's first question. And second question is we saw with Eleralindide that I mean phase one was tolerability was better versus phase two we saw a little bit higher GI issues.
Speaker #2: So in that context, I mean what do you expect with paterindide? In terms of tolerability in phase two trial as you see data in more patients.
Speaker #2: Thank
Speaker #6: Thank you for your you. question and we definitely see emblem in particular paterindide having the potential to become a foundational and first line therapy, a first choice therapy I think what many have not really thought deeply about today is that and I think we all recognize that GLP-1 for many patients that is difficult to tolerate.
Speaker #6: therapies today because there's no Many patients accept these alternative. What will the conversation be if there is a more tolerable approach to weight loss?
Speaker #6: Then you don't talk about will you tolerate it, then you will start to have a conversation will you accept the tolerability profile of a GLP-1 if you can actually experience a more pleasant weight loss on a different modality.
Speaker #6: I think that's what you have to think about now. So that and that's what excites us and why we believe we have the potential to drive first choice and foundation therapy.
Speaker #6: So we definitely see as we have said all the time the biggest opportunity for monotherapy as an alternative and a first choice. Treatment for these individuals who want to lose weight and importantly maintain that weight loss because that is the key to unlock the value of this market is to make patients stay on therapy so they don't regain weight and it's also the key then to achieve the health benefits.
Speaker #6: If people don't stay on therapy and they regain weight they will not achieve the health benefits. There's also significant potential for combination therapy but that would be for the most mobile GLPs or patients living for instance with type two diabetes.
Speaker #6: As David also alluded to before, we have a different approach to the combination where we want to max out if you will on the emblem component which we consider the more tolerable part of the combination and then just add a teaspoon of the GLP-1 component.
Speaker #6: And thus we expect to have a more tolerable approach to that combination that maybe has been seen with other approaches to combination. So again on the expectation for our phase two study we have as you can hear we are we have a high level of excitement and high expectations for the
Speaker #1: Thank Time . you
Speaker #1: . Thank
Speaker #2: . This concludes today's question and you I will now hand back for closing remarks .
Speaker #1: Thank you all for attending and for your questions . We