Thank you, Operator. Thank you to everyone for joining us today to discuss Zealand Pharma's results for the first nine months of 2025.

You can find the related company announcement on our website at zealandpharma.com. As described on slide 2, we caution listeners that during this call, we will be making forward-looking statements that are subject to risks and uncertainties.

Turning to slide 3 and today's agenda. With me today are the following members of Zealand Pharma's management team: Adam Steensberg, President and Chief Executive Officer; Henriette Wennicke, Chief Financial Officer; and David Kendall, Chief Medical Officer.

All speakers will be available for the subsequent Q&A session. Moving to slide 4, I will now turn the call over to Adam Steensberg, President and CEO.

Thank you, Adam, and welcome, everyone. The third quarter of 2025 has been a quarter of strong execution and continued momentum in our partnership with Roche.

We achieved a key milestone in the petrelintide phase 2 Supreme-1 trial in people with overweight and obesity, which put us well on track to report 42-week topline data in the first half of 2026. We are also rapidly approaching data from several phase 3 trials with survodutide in obesity, starting with topline results from the 76-week SYNCHRONIZE-1 trial in the first half of 2026.

Meanwhile, we are gearing up to outline our path towards becoming a generational biotech company at our Capital Markets Day next month. Moving to slide 5.

Two years ago, we laid out our vision to become a key player in the management of obesity through innovation that address one of the greatest healthcare challenges of our time. Central to this vision was developing an alternative to GLP-1-based therapies and to end the weight loss Olympics by focusing on the most important unmet medical need, a therapy that patients can and will accept to stay on.

What excites me today is that Zealand and Roche has the potential to lead in the next class of drugs for weight management. We are very confident in the profile of petrelintide as a potential best-in-class amylin analog, supported by the clinical data to date and the large, robust phase 2 program currently underway.

We are rapidly approaching phase 2 data with petrelintide and phase 3 obesity data with survodutide, alongside an impressive phase 3 MASH program that is well underway. I look forward to this next catalyst-rich chapter and to sharing more from these programs at our upcoming Capital Markets Day, where we will also discuss our intensified, early-stage efforts to build a generational biotech company.

Let's turn to slide 6. Six months have passed since we kicked off our alliance with Roche, and I'm highly encouraged by the energy and commitment we have seen from both sides of the partnership.

The agreement with Roche is more than just a deal. It's a shared commitment to redefine the future of weight management and to establish leadership in what could become the next foundational class of therapies.

Last month, Zealand Pharma had the pleasure of welcoming Teresa Graham, CEO of Roche Pharmaceuticals, to our offices for an engaging fireside chat about exactly this. I was also pleased to see Roche, at their Pharma Day in September, convey to you their strong commitment to become a top three player in obesity.

This is the reason why, through a highly competitive partnership process, we identified Roche as the ideal partner for Zealand Pharma and petrelintide. Turning to slide 7.

Survodutide is licensed to Boehringer Ingelheim, a leading, family-owned biopharmaceutical company with a strong legacy in cardiovascular, renal, and metabolic diseases, and a global presence across more than 130 markets. We're excited to see Boehringer Ingelheim potentially becoming the next major pharma company to enter the obesity market with a truly differentiated GLP-1-based therapy co-invented with Zealand Pharma.

We were also highly encouraged by their strong presence at ObesityWeek in Atlanta last week. This leads me to slide 8.

The scale and complexity of obesity make it a distinct and complex disease area in which we identified different segments. In the prescriber-driven segment, a key motivation for prescription is focused on comorbidity risk reduction, improving health outcomes, and relative weight loss.

We believe survodutide has the potential to be uniquely positioned within this segment. The larger segment, however, is patient-driven.

A significant focus here is personal weight loss goals and how individuals achieve them. With potential to deliver the weight loss that the vast majority of people with overweight and obesity desire, combined with an acceptable tolerability profile and an excellent patient experience, we believe petrelintide is ideally positioned to lead in such a segment.

I'm highly encouraged by the potential of both of our leading obesity programs, which holds potential to redefine the near-term future of weight management in key segments. With that, let's move to slide 9 as I turn over the call to our Chief Medical Officer, David Kendall, to discuss our R&D pipeline.

David?

Thank you, Adam. Today, I will focus my remarks on the continued advancement of our two leading programs, petrelintide and survodutide.

Before doing so, I would like to begin by providing a brief update on our two late-stage rare disease programs and dapiglutide, our GLP-1/GLP-2 receptor dual agonist program. For dasiglucagon in congenital hyperinsulinism, our third-party manufacturer's facility 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.

For glepaglutide, our GLP-2 receptor agonist in development for the treatment of short bowel syndrome and intestinal failure, the phase 3 EASE-5 trial remains on track to initiate before the end of the year with the purpose of supporting regulatory submission in the U.S. We remain encouraged and excited by the clinical profile of glepaglutide as a potential best-in-class, long-acting treatment for patients living with short bowel syndrome and intestinal failure, and look forward to confirming the positive findings of the previously completed EASE-1 trial.

We have made the decision to pause the current development of dapiglutide. This decision is a result of a disciplined 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 comorbidities.

Although 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 increasingly crowded, requiring even greater and clinically meaningful differentiation for assets which 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.

We have significant opportunities in both the amylin and incretin-based therapeutic space with our leading programs, including petrelintide; the fixed-dose combination of petrelintide and Roche's GLP-1/GIP dual agonist, CT-388; and survodutide; as well as an early-stage pipeline that includes novel mechanisms targeting obesity and inflammation with the ultimate goal of restoring and maintaining metabolic health. Please turn to slide 10, and beginning with petrelintide.

Our strong confidence in petrelintide is grounded in its overall efficacy, safety, and tolerability profile. While amylin-based therapeutics can deliver clinically meaningful weight loss, we are not seeking to deliver the highest possible weight loss with petrelintide, 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.

We remain fully confident in the potential of petrelintide to deliver 15% to 20% weight loss in phase 3 clinical trials, and also remain highly confident in petrelintide's consistent clinical efficacy, safety, and tolerability, underscoring its unique value proposition and the potential to become the leading amylin-based treatment and a foundational therapy for weight management. I'm extremely pleased with the strong execution in advancing the petrelintide clinical program at full speed.

In late September, we reached a key milestone in the large phase 2 ZUPREME-1 trial, which evaluates the efficacy and safety of petrelintide in people with overweight or obesity without type 2 diabetes, 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 2 ZUPREME-2 trial, which evaluates the efficacy and safety of petrelintide in people with overweight or obesity and coexisting type 2 diabetes.

These achievements put us well on track to report 42-week topline results in the first half of 2026, report topline results from the ZUPREME-2 trial in the second half of 2026, and to initiate the phase 3 program with petrelintide monotherapy, also in the second half of 2026, together with our partner Roche. Let's move to slide 11.

We also look forward to exploring the potential of petrelintide as a backbone for future combination therapies, unlocking its full value potential. Petrelintide/CT-388 is the first combination product under our alliance with Roche.

This program will target individuals who seek even greater weight loss and/or improved glycemic control while optimizing the dose of each component. We anticipate that use of higher doses of petrelintide and optimized doses of the incretin-based therapy CT-388, a potential best-in-class GLP-1/GIP receptor dual agonist, can provide both robust efficacy while maintaining excellent tolerability.

Zealand and Roche remain on track to initiate the phase 2 trial with petrelintide/CT-388 combination in the first half of 2026. Now turning to slide 12 and survodutide, a potential best-in-class glucagon/GLP-1 receptor dual agonist in late-stage development for the treatment of obesity and MASH.

The phase 3 SYNCHRONIZE program with survodutide in obesity consists of six clinical trials, all of which are expected to complete in 2026. In the phase 2 obesity trial, survodutide demonstrated the potential to deliver highly competitive weight loss with doses of up to 4.8 mg.

Notably, the phase 3 trials are evaluating a higher maximum maintenance dose of 6 mg. This leads me to slide 13.

Following the last participant's last visit in the 76-week SYNCHRONIZE-1 trial, which evaluates the efficacy and safety of survodutide in people with overweight or obesity, but without type 2 diabetes, we are rapidly approaching topline results from this trial in the first half of 2026. At the Obesity Society Annual Meeting in Atlanta last week, Dr.

Carel le Roux presented the baseline characteristics of participants in this trial, which are also shown on this slide. We are very pleased that Dr.

le Roux has agreed to join us at our upcoming Capital Markets Day next month, where he will share more insights on the potential of survodutide to represent the next frontier in the management of obesity and MASH. Now turning to slide 14.

We remain exceedingly optimistic and are very excited about the ongoing phase 3 program with survodutide in people with metabolic dysfunction-associated steatohepatitis, or MASH, a serious obesity-related comorbidity with significant unmet medical need. Shown in this slide is an indirect cross-trial assessment of the registrational clinical trials for the two approved therapies in the U.S.

for MASH today: the thyroid hormone receptor beta agonist, resmetirom, and the GLP-1 receptor agonist, semaglutide. In the phase 2 trial with survodutide 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.

We believe this represents the most compelling and strongest clinical dataset to date on the critical endpoint of improvement in liver fibrosis. With these groundbreaking phase 2 data and a comprehensive, ambitious phase 3 program now underway, the so-called LIVER-EG program, which includes two large trials, one in people with moderate to advanced fibrosis, F2 and F3, and one in people with cirrhosis, F4, we believe survodutide 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.

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.

Henriette?

Thanks, David, and hello, everyone. Let's turn to slide 15 and the income statement.

Revenue for the first nine months of 2025 was DKK 9.1 billion, driven primarily by the initial upfront payment received under our collaboration and license agreement with Roche. Of the DKK 9.2 billion upfront payment received in the second quarter, DKK 124 million was deferred as of September 30 as it relates to the progression and completion of the phase 2 trials with petrelintide.

Net operating expenses totaled DKK 1.5 billion 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 petrelintide, including the large phase 2 trials and preparations for phase 3.

Net financial items amounted to negative DKK 62 million for the period, primarily reflecting exchange rate adjustments related to the U.S. dollar deposits and current currency revaluation.

This was partly offset by interest income from investments in marketable securities. Moving to slide 16 and the financial position.

As of September 30, 2025, our cash position totaled DKK 16.2 billion, a significant increase from the DKK 9 billion at the beginning of the year. This increase was, of course, driven by the initial upfront payment of DKK 9.2 billion from Roche, partly offset by the operating expenses during the period and the purchase of treasury shares to support Zealand Pharma's long-term incentive programs.

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 in anniversary payments over the next two years under the Roche collaboration, as well as potential development milestones of up to $1.2 billion. 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 petrelintide while at the same time accelerating investments in our early-stage pipeline to build the next wave of innovation. 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 DKK 2 and 2.3 billion, excluding other operating items. The financial guidance has been narrowed from the DKK 2 to 2.5 billion, reflecting the decision to pause the development of dapiglutide, previously planned to advance into phase 2b development in 2025.

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. With that, I will move to slide 18 and turn the call back to Adam for concluding remarks.

Thank you, Henriette. We are now at the cusp of the most catalyst-rich period in Zealand Pharma's history.

In just the first half of 2026, we expect to see phase 3-enabling data for petrelintide, phase 3 data for survodutide, and phase 1 data for what could become one pillar in the next wave of innovation from Zealand Pharma, our highly potent and specific Kv1.3 ion channel blocker. 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. We will also share more about our ambitious research strategy, which builds on Zealand Pharma's unique expertise in peptide R&D and our strong foundation to lead the next wave of innovation in obesity and related diseases, and to continue our journey towards becoming a generational biotech company.

I'm excited that we will be joined by Jonathan Hogg, a pioneer in amylin-leptin biology, as well as Carel le Roux and Louis Aronne, recognized thought leaders in the field of obesity. They will join us on stage to share their valuable insights.

I will now turn over the call to the Operator, and we will be happy to address your questions.

Hi there, good afternoon. Thanks for taking my questions.

Two on petrelintide, please. With the eloralintide 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 you would encourage us to look at your own dataset in the context of Lilly's data to kind of make a fair comparison there.

Then also David, you highlighted in your opening remarks that you're not targeting the highest possible weight loss with petrelintide, which seems quite in contrast to what Lilly have tried to do with their eloralintide trial. 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.

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? Thanks very much.

Thanks for your question, Kirsty. Maybe I can start and then hand over to David.

We were extremely encouraged to see the eloralintide data last week, which we really see building on what we already saw with cagrilintide last year. Remember, Novo demonstrated that cagrilintide can deliver 12% weight loss with a 2.4 mg dose, which we consider very low dose.

It really, you can say, underscores the potential that we have been communicating all the time around the amylin class that with amylins, we have the potential to actually develop a new class of medicines that will provide patients with likely a 15% to 20% weight loss and thus a true alternative to the GLP-1s. Very importantly, we expect this weight loss to be a more pleasant weight loss experience with significantly less side effects, but also the nature in which the patients would reduce their food intake, we think would be superior in the amylin class in the sense of feeling full faster versus having loss of appetite.

We are extremely pleased, and it, you can say, actually increases our excitement around the upcoming phase 2 data with petrelintide and our efforts to prepare for the phase 3 trial conduct, really underscoring what we have been moving towards for a very long time. David, maybe you want to touch a little bit upon trial design specifics, et cetera.

Thanks, Kirsty. Trial design specifics, I'll reiterate what Adam said.

I think 15% to 20% weight loss, when we came forth with petrelintide'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. We've seen early cagri data.

I think the data we saw recently from another compound in this class clearly demonstrates that GLP-1-like weight loss percentages are achievable. We think, as Adam referred to, that higher milligram dose exposure, higher bioavailability, and the excellent tolerability profile we've seen to date with petrelintide up to 9 mg once weekly can certainly hit that sweet spot.

You also mentioned, what does the market seek? One simply needs to do some math.

If somebody weighs 150 kg, a 30 kg weight loss or 65 lbs of weight reduction is substantial. I think five years ago, the world would have thought that's unachievable with what we've seen to date, including with liraglutide.

Both in speaking with clinicians and in speaking with the vast majority of patients who seek weight management therapy, that 10% to 20% weight loss figure comes up repeatedly. They may not say 10% to 20%, but they will give you a number, a desired number of pounds, or an end target weight that generally reflects that.

I think 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, but that serves a vast minority of the patients seeking this. Finally, to your question about the baseline characteristics, just recall that with petrelintide phase 1b, predominantly male participants, predominantly are leaner, mean population with a BMI just under 30 kg/m^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, much higher baseline BMIs we reported in last quarter's call, 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. 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. I encourage you and others to look at the full construct of all of these trials before jumping to just topline numbers.

I'll stop there.

Great. Håkon here, Danske Bank.

Also a question regarding petrelintide study design. The eloralintide data from last week demonstrated that patients did not experience a weight loss plateau like we see with the GLP-1 treatments, likely due to the restoration of leptin sensitivity by amylin.

How does this influence your consideration on the trial duration for petrelintide in the phase 3? How do you see the trade-off between potentially achieving greater weight loss with a longer study compared to bringing petrelintide to the market sooner?

Thanks for that question, Håkon. I'll let David answer.

Thank you, Håkon. I think two very important observations.

The absence of plateau, which I think was readily evident both in our short phase 1b studies with petrelintide, 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. 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.

In both our own visual extrapolations and I think now looking at the elora high-dose data, noting that the higher doses were perhaps less well tolerated than the 3 mg 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. I think it will be important to observe what we pull out of our 42-week phase 1 trial, and then the design for the longer phase 3 trials will directly answer your question, but with respect to the potential for progressive weight loss out beyond one year of treatment.

Thank you, Håkon.

Hi, thank you for taking my questions. Sorry, sticking with the elora data from last week.

In light of that data, do you have any updated thoughts on the importance of the receptor activity that has previously been discussed? You mentioned that you're confident it will still be best in class.

I just want to know what drives that confidence given the data we've seen so far for elora? Then secondly, just following up on the trial design, just to confirm, this trial will have no lifestyle interventions, is that correct?

Then secondly, related to the trial, did you specify to have a balanced sex ratio in the trial, or is that just happenstance? Then on dapiglutide and the decision there, I just wonder, you're obviously not short of cash, kind of what was the thought process in terms of stopping this study?

Was there any discussion with Roche about this? I appreciate not partner, but did you discuss it with Roche?

Also any thoughts on a potential combination with petrelintide down the line, and what studies would be done in order to enable that? Thank you.

Thank you. Thank you for the questions.

I'll start with the first one on on the pause on dapi. I think it's very evident, and it will be even more so at the Capital Markets Day, that we have what we believe really a leading opportunity in the GLP-1 space with survodutide, which we have licensed to to Boehringer, which to not only have a huge potential for weight loss, but actually also addressing liver health and in particular MASH and potentially other organ damages by activating lipolysis.

It actually has a strong profile towards managing comorbidities to obesity. Now with the Roche partnership, we also, as got shared economics on the on the combination product with CT-388, their GLP-1/GIP, meaning that's going to be the combination opportunity we are going to focus on, and thus dapi became less relevant for combinations with with amylin.

What we have been exploring over the summer was addressing segments of obese of obese patients which were suffering from specific comorbidities, and in doing those in-depth evaluations, it's very clear that it will require, as David also said, very large investments and long commitments before getting to to understand the the full potential for differentiation. If you then consider GLP-1, the GLP-1 marketplace in five, six years from now, you will you will see that it's a very crowded place, and 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.

We basically believe we can apply our capital better in that in in those early programs. I would say it's it's a 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 being a generational biotech.

When thinking about the upcoming data for for petrelintide, we remain and we are even more confident in in the potential to deliver this 15% to 20% weight loss, which we know will address by far the the the vast majority of the weight loss that patients are are desired. We, as I said before, the data that came out last year last week underscores the potential that we also saw with cagrilintide last year.

Remember, cagrilintide was only 2.4 mg, which is a very low dose compared to where we take petrelintide today. 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.

The balance between efficacy and tolerability has been outstanding in our mind. When the potential to dose high and and continue into the longer-term study that we're soon to to report gives us that confidence.

In the phase 2 study that we will report, ZUPREME-1, 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. Again, that has been done from a very firm development perspective that you want to have exposures in both genders to make make the best possible decisions for your phase 3 design.

You actually introduce a lot of risks by having by having very few of one gender because you don't get to learn about your molecule in both genders if you skew it too much in phase 2. Lucy, I'll take the question about the receptor biology and receptor differentiation.

I think Thomas Lutz said it quite well in his introductory talk, saying there's still quite a bit to understand. Elora, based on data reported by Lilly, has about a 12-fold higher affinity for the amylin receptors than calcitonin.

I think it's important to note that the proposed or the hypothesized improvement in tolerability was clearly not demonstrated. There was significant nausea, I think up to 64% in one of the treatment groups at 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. Our own conclusions are that with balanced agonism as we have seen with petrelintide, we have seen one of the best, if not the best, tolerability and safety profiles, and that it does not sacrifice tolerability, particularly around GI side effects.

I think the other comments Thomas Lutz made, which is all of this receptor biology work and knockout activity in animals really requires confirmation in clinical testing. To our end, with a predominantly female, higher BMI population treated with high doses, there was no substantial difference, I think, based on the authors' conclusions in tolerability versus historic GLP-1 programs.

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. We will continue to explore how these may differ, but I think, as Thomas Lutz concluded, the answers will come from the clinical trials.

Thanks, Lucy.

Thanks for taking our question. It's about the patient experience that you comment frequently about.

In the context of co-formulation with CT-388, I'm curious about your take on how important it is to harmonize the number of step-ups between let's say, petrelintide and CT-388, in the titration step, especially given the tolerability profile, incretins will likely need a more prolonged titration period. That's question number one.

Question number two has to do with another adverse event profile that was raised during the conference, which is fatigue, based on our KOL discussions, I think this is probably one of the overlooked adverse events affecting patients' quality of life. That number appeared to be numerically higher than what we've seen.

I'm just curious about your take on this and also what you've seen with petrelintide clinical trial experience. Thank you.

Thanks for the questions. Maybe I can just start and hand over to you then, David.

I think, as we have always said all the time, it is about time to move beyond the weight loss Olympics, not only because it's not what patients are looking for, but is also a clear observation at our end, at least, and I would also say maybe you see that in some of these datasets, if you go too aggressive with very potent biology as we have today, especially in the start, you might actually introduce situations you're not looking for. Our observation, and you will also see that in earlier study data from several amylins, you don't want to push this too much in the start.

Could that be driving some of the fatigue that you're seeing? Maybe if you have a, let's say, 4% weight loss over one week, that's probably not fat, that could be fluids that you lose, and how would that make the patients behave?

Recognizing that we work with extremely potent biology, as David also mentioned before, who would have thought that you could achieve a 20% weight loss with a pharmacological intervention just a few years back, and here we are. You have to be careful, and otherwise you may see things you don't like.

That is a clear observation when we look at our studies. We have not seen it in our programs thus far, signs of fatigue.

Again, let's see. We, as apply actually titration throughout all cohorts in our phase 2 study, something that has not always been done with other programs.

Far, we have not seen it on the titration steps. Before handing over to you, David, I also just want to mention, what we have seen thus far is that amylins actually deliver weight loss even at the initial doses.

It's of course clear that ultimately when we titrate together with a 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. David, maybe?

I'll reemphasize that, Andy. Harmonizing those, I think, gives us the opportunity, as I said, to find what is the most applicable dose escalation scheme for petrelintide to get to what we hope is maximal dose with very good tolerability.

As Adam said, we've seen less fatigue than in our placebo-treated subjects in the phase 1 trial and very limited GI tolerability issues. That would allow you to either simplify the addition of very low-dose incretin-based therapies, it would further slow down to get to not a maximal dose, as is often done in phase 2 trials or phase 3 to see the maximal weight loss, but an optimized dose.

Let's say dose 3 of the 388 compound and dose 5 of the petrelintide compound is what the alignment looks like. We would base that on the petrelintide dose escalation scheme.

Monthly is what we're testing in phase 2 and phase 3. The question is then how do you formulate a fixed-dose combo to get to the optimized, not maximal dose of 388.

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.

Thank you so much.

Oh, thank you for taking my question. Mine is more bigger picture with regard to the market and your expectations here.

Clearly since the last update, we've had the Novo Lilly Trump deal. We now have clarity on pricing in the U.S.

obesity market, at least via the cash pay and the Medicare channel. I would just be interested to hear how that being in the details that we have so far may be impacting yours and Roche's forecasts for the opportunity for your next-gen obesity pipeline assets.

Will it essentially now be more difficult for you to unlock the value and to deliver strong returns in this market? Just your thoughts from that bigger picture perspective.

Thank you. Thanks

thank you for that question. We will of course we will actually at our Capital Markets Day in December 11th address our considerations about the current market dynamics in more details.

Maybe just to to share a few considerations. 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 prices have been lower than the list prices, and we have also seen rebating in this space when it comes through through the commercial channels. It's, it's actually a blessing to be where we are right now where we can learn from these dynamics and then design our our programs and go-to-market strategy together with Roche according to those dynamics and how we think they will play out in the future.

That allows us to actually define the future instead of just trying to tap into somethings that that that were. 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 these therapies.

It's a huge problem that today 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 majority of patients being off therapy within a year, and a lot of that has to do with side effects. We know from IQVIA data.

We just focus to unlock the value of this market and to change to get excitement into this space again, I truly believe is by making sure you develop therapies that people can stay on, and thus we will see the volumes go up. Then, the the pricing part that 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 1 to 3 months and then you need to go out and find a new patient to capture that that the value you lose by the patients not taking it. We actually like the to to the clarity that is that is that we 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, and together with Roche, we would build our go-to-market models accordingly.

Thank you.

Hi, thank you for taking my questions, and congrats on the quarter. I had a few.

Maybe firstly, going back to receptor biology, Lilly says having elora as a more selective amylin, especially on amylin 1 receptor, and seems to be balanced on amylin 3 and calcitonin. Maybe if you could talk about whether potently targeting amylin 1 1 versus amylin 3 receptor have any clinical implications in obesity and beyond?

If you can remind us about petrelintide's activity on amylin 1 versus 3 receptors? Secondly, on the trial for phase 2b of ZUPREME-1, can you talk about how the discontinuation rates are trending as it has been an issue with some of the recent trials?

When you disclose the data next year, whether you will disclose both efficacy and treatment regimen estimand when the data disclose? Thank you.

I will start and hand over to you, David. We do expect to disclose the topline efficacy data from both, as I would expect, including this relevant safety observations when we disclose the data.

On the receptor profile, if you look into preclinical data, I remind you that both we and Novo have had a firm effort for many, many years and came out with balanced profiles towards these receptors. As David just alluded to, probably quite a few of the molecules we're looking at right now have some receptor activation on all trees.

We have one which is quite similar, we believe, to the one that cagrilintide has. Ultimately, we need, as David also said, to see clinical data.

When we look at the early clinical exposure for which we actually have among the different amylin molecules, that is where we 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, and if you then account for female to male, BMI, and other aspects, but the single ascending dose data are probably some of the more honest datasets here where there's less bias, that gives us a lot of confidence 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 dataset which suggests that we have a profile of a drug that has found the right balance between efficacy and safety tolerability. We will review more of this at our Capital Markets Day, which will answer probably in more detail some of these questions.

David, I don't know if you want to add more to this? Thanks, Prakhar.

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. As Adam said, cagri and petrelintide are clearly balanced receptor agonists, activate all three receptors in our hands with equal potency.

The GUBRA now AbbVie asset is similar in our hands, slightly greater predilection for the amylin than the calcitonin receptor. The Lilly molecule, eloralintide, while touted to be amylin 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.

I think the other points that Adam makes that's critically important is regardless of this, how does the clinical safety and tolerability and efficacy profile line out? Using the elora data as an example, there were in the early-phase trials an increase in the number of headaches, whereas with petrelintide, we've seen less headache than with placebo.

The newly reported adverse effect of bradycardia, bradyarrhythmia, and syncope reported in the elora trial is unique amongst this class, to my knowledge. I have no idea if that's related to receptor biology or other mechanisms.

Again, the clean profile, the balanced agonism of both cagrilintide now through phase 3 and our phase 1b data and beyond for petrelintide give us great confidence that that is not only an acceptable receptor profile, it is an incredibly effective and well-tolerated profile. Thank you.

Hey, Yihan Li from Barclays. Thank you so much for taking our questions.

We have two. The first one is the petrelintide phase 3 timing.

It seems like you have already completed the end of phase 2 meeting with the FDA. Just curious if you could walk us through what remains before initiating the phase 3 monotherapy trial, which is now planned in the second half of next year, especially given competitor Eli Lilly actually been moving very fast for the phase 3 will start by year end.

Thank you. The second question actually is on the eloralintide lean mass data.

Again, they showed 60% to 70% of the mass reduction from that fat loss, and also the other 30%-ish from the lean mass. However, an interesting thing is that it doesn't seem to have a continued decline in the lean mass from the week 24 to week 48.

Suggesting the lean mass loss could potentially stabilize after 24 weeks. I'm just curious, does this suggest maybe amylin-based therapy could inherently preserve lean mass better over time?

Any thoughts will be appreciated because I'm just thinking amylin could be used as a post-GLP-1, just curious what your thoughts are there. Thank you very much.

Thank you for that question, and I can reassure you that we are moving as fast as possible forward for phase 3 initiation with petrelintide. Our expectations will be second half of next year, and as we have communicated today, we have reached 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.

Topline data will be available first half next year. It's a shared commitment from Roche and us to accelerate as much as possible to get these treatments to patients ultimately and help achieve the health goals.

This is progressing with a high sense of urgency, but the phase 3 start is set for second half next year. I think we need to actually wait for our phase 2 data with petrelintide before we will comment more on the balance between muscle and fat preservation.

Remember, we use MRI as an assessment of body composition, which is a much more precise mechanism than the DEXA scans that have been utilized by other companies. We, as everyone know, have seen extremely strong preclinical evidence for muscle preservation with the amylin class, and we need to now see human evidence before addressing this more, and we think you will get some at least high-quality data from our phase 2 study, which will be able to address this in more details.

Thank you.

Hi, thank you very much for taking my questions, both on dapiglutide if that's okay. Firstly, why did you take the decision now to pause the development of dapiglutide rather than further exploring the potential anti-inflammatory benefits?

Has there been some data generated internally, for example, that could drive that decision? Then secondly, could there be developments elsewhere in the space that change your thinking on dapiglutide?

Specifically thinking about if Novo show a benefit in Alzheimer's in the EVOKE trial. Thank you.

Thank you for that question. As we have indicated today, we have decided to pause the program because we do recognize that it's a very attractive profile, both with the clinical profile we've seen thus far and also its potential to lower inflammation even further than the existing GLP-1s.

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 CT-388 as we will combine with amylin, also of course very much because we see survodutide approaching, but then also just realizing that the investments needed to show clinical differentiation and then the amount of clinical differentiation you would have to demonstrate if you launch a 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.

That's coming back to why we're so excited about the amylin class because it's an alternative, and 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. If you then, and we'll talk much more about that at our Capital Markets Day, consider the rich pipeline we have of early-stage assets, we are really taking a view that it has significantly 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.

For us 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 are actually more wisely spent there. Thank you.

Hi, thanks for taking my question. Just on survodutide.

You'll probably cover this more at your CMD, but in terms of the phase 3 readout in the first half of next year, where do you expect tolerability will likely land considering that in the phase 2 data we've seen so far, there's a pretty high level of GI toxicity? Thank you.

Thank you for that question. We of course soon will have the data, and and please also remember that the phase 2 study design, if you compare the the safety or tolerability profile with the phase 2 studies of of some of the marketed products, you will actually see a quite similar profile and of of tolerability.

We of course what we expect with survodutide is a comparable tolerability profile to to the existing molecules and also a comparable weight loss. The true opportunity for differentiation is the activation of lipolysis with glucagon and thus providing better liver health as we saw with the MASH program.

Also remember that Boehringer is actually pursuing higher doses in the phase 2 than what they in the phase 3 than what they did in phase 2, and that gives us a lot of confidence that by using applying the right titration, being flexible around how you titrate, as you have to be with a GLP-1, allows them to go much higher. They have already tested that higher dose in the MASH population in phase 2, which is applied in the phase 3 program for obesity.

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 to what's on the market today and a clear edge towards liver health.

Great, thank you very much for squeezing me in, and this is my debut on this call. A couple of questions from my side.

Given that with cagri-sema, we saw a little bit of tolerability when you combine GLP-1 with amylin, and I fully appreciate the sentiment that combining GLP-1 and amylin could be interesting. At the same time, given that amylin does have some GI tolerability issues, and it could compound with GLP-1, do you think the better use of amylin could be more of an monotherapy versus a combo therapy, maybe in post-GLP setting, or maybe as a monotherapy in the frontline setting?

That's first question. Second question is, we saw with eloralintide that phase 1 tolerability was better versus phase 2, we saw a little bit higher GI issues.

In that context, what do you expect with petrelintide in terms of tolerability in phase 2 trial, as you see data in more patients? Thank you.

Thank you for your question, and we definitely see amylins, and in particular petrelintide, having the potential to become a foundational and first-line therapy, a first-choice therapy. I think what the many have not really thought deeply about today is that I think we all recognize that GLP-1s for many patients is difficult to tolerate.

Many patients accept these therapies today because there's no alternatives. What will the conversation be if there is a more tolerable approach to weight loss?

Then you don't talk about will you tolerate, 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? I think that's what we have to think about now.

That's what excites us and why we believe we have the potential to drive first-choice and foundational therapy. We definitely see, as we have said all the time, the biggest opportunity for monotherapy as an alternative and a first-choice treatment for obese 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.

It's also the key then to achieve the health benefits. If people don't stay on therapy and they regain weight, they would not achieve the health benefits.

There's also significant potential for combination therapy, but that would be for the most morbidly obese or patients living, for instance, with type 2 diabetes. 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 amylin component, which we consider the more tolerable part of the combination, and then just add a teaspoon of the GLP-1 component.

Thus, we expect to have a more tolerable approach to that combination that maybe have been seen with other approaches to combination. Again, on the expectations for our phase 2 study, we have, as you can hear, we have a high level of excitement and high expectations for the profile that we will see with our upcoming 42-week data with petrelintide.

Thank you.

Thank you all for attending and for your questions. We look forward to future announcements and updates and to connecting in the coming weeks and months.

Thank you.