Standing by. Welcome to the Zealand Pharma Top Line Data from phase II ZUPREME-1 Trial webcast and conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you will need to press star one and one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one and one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Adam Langer, Vice President, Investor Relations. Please go ahead.
Thank you, operator. Welcome, everyone. We are excited to have you joining us today to discuss the positive top-line results from the phase II ZUPREME-1 trial of our amylin analog, Petrelintide. Petrelintide is being developed under our co-development and co-commercialization partnership with Roche. You can find the related company announcement on our website at zealandpharma.com. Turning to slide 2, which outlines the agenda for today. Joining me to present and discuss the data are Adam Steensberg, President and Chief Executive Officer, David Kendall, Chief Medical Officer. Our Chief Financial Officer, Henriette Wennicke, is also on the call today for the Q&A session that will follow after the presentation. As described on slide 2, as always, I would like to remind listeners that today's presentation and discussion will include forward-looking statements that are subject to risks and uncertainties. With that, please turn to slide 4.
I would like to hand over the call now to our CEO, Adam Steensberg. Go ahead, Adam.
Thank you, Adam, and thanks everyone for joining the call. We are very pleased to report the top-line results of placebo-like tolerability and safety with double-digit weight loss for Petrelintide in this phase II trial. These data brings us a significant step forward in addressing the gap in treatment options for the millions of people living with overweight and obesity. Did we anticipate to see 1% or 2% more weight loss in the trial? Yes. Does it change anything? Not at all. We do expect to address this in the phase III trial design, and thus demonstrating Petrelintide's potential to ultimately deliver mid-teens % weight loss. These results therefore reinforce our conviction in the potential of Petrelintide as a future foundational first choice treatment option and a clear alternative to GLP-1 based therapies for weight loss, and importantly, weight maintenance. Turning to slide 5.
Obesity remains one of the greatest healthcare challenges of our time, with high and growing prevalence. While treatment penetration is only 3% - 5% in the United States today. In other chronic disease areas, there's a broad range of therapeutic options that can be tailored to individual needs. In obesity, we are still in the very early stages, relying on one single therapeutic category. While the GLP-1 based therapies have clearly advanced the field, they have not yet delivered what ultimately matters the most: long-term treatment persistence, doable weight maintenance, and ultimately sustained improvements in health outcomes for the most people living with obesity. As an industry, we have placed significant emphasis on the magnitude and the speed of weight loss. However, this focus does not reflect the goals of most people living with overweight and obesity.
Data tells us that current GLP-1 users only aim to lose up to 20% of their body weight, with one in five targeting 10% weight loss and about 60% aiming for weight loss between 10% and 20%. In the real world, only a minority of patients escalate to the highest approved GLP-1 doses. This may reflect several factors, including tolerability challenges and variability in treatment experiences. Real-world data shows that treatment persistence with GLP-1 based therapies remain a major challenge, with about 30% of GLP-1 users stopping treatment within the first month. By one year, nearly 80% have discontinued treatment. Remember, this is in today's world where there are no alternative treatments available.
There are a number of reasons why people discontinue GLP-1 based therapies, but with Petrelintide, we are addressing the number one reason for negative treatment experiences and discontinuation: gastrointestinal effects such as nausea, vomiting, constipation, and diarrhea. Moving to slide 6. Today's data further strengthens our conviction that Petrelintide can play a leading role in addressing this treatment gap. What we are seeing is sustained double-digit weight loss with expectations of greater efficacy in upcoming phase III trials, which will be designed to show the full potential of Petrelintide while maintaining the excellent tolerability profile. Importantly, the observed tolerability and safety profile is what we believe will set Petrelintide apart and ultimately will set a new standard for people's expected weight management experience. With that, let's move to slide 7 as I turn over the call to our Chief Medical Officer, David Kendall, who walk us through the results.
David.
Thank you, Adam. Again, thanks to all of you for joining us. I am very pleased to share additional details on the top-line results of the phase II ZUPREME-1 trial and also share our collective excitement to bring these data forward and continue to progress Petrelintide through development. The top-line data shared today build on the consistent and very encouraging clinical results for Petrelintide, demonstrating double-digit weight reduction paired with an exceptional safety and tolerability profile, reaffirming both the potential of Petrelintide's role in chronic weight management and bringing a new foundational therapy forward for those living with overweight and obesity. Moving to slide 8. Importantly, amylin-based therapies offer a number of unique physiologic and potential pharmacologic effects when compared to incretin-based therapies.
As Adam noted, there is a clear and growing need to leverage novel classes of treatment in weight management and approach this complex metabolic disease of obesity in new and better ways. amylin therapy offers a fundamentally different approach by enhancing satiety and by restoring leptin sensitivity. This capacity to leverage the body's natural sense of fullness is a meaningfully different effect when compared to GLP-1-based therapies, which primarily act by suppressing appetite. On to slide nine, which outlines the design of our phase II ZUPREME-1 trial. In ZUPREME-1, Petrelintide was evaluated in a randomized, double-blind, placebo-controlled phase II dose-finding trial. The study evaluated and compared five different maintenance doses of Petrelintide to placebo, with dose escalation executed every fourth week to achieve maintenance dose.
The primary endpoint was the percentage change in body weight at week 28. Treatment continued through week 42, followed by a nine week safety follow-up period. Secondary and exploratory endpoints include body composition assessed by magnetic resonance imaging or MRI. Assessment of cardiovascular risk factors. Today's presentation focuses on top-line results. Additional analyses will be shared as the full data set is finalized. These data will be presented in publications and at upcoming scientific congresses. Turning now to slide 10. The top-line demographic characteristics in ZUPREME-1. As previously shared, ZUPREME-1 randomized 493 participants with a balanced distribution of men and women with a mean body weight of 107 kg. An average BMI of 37 kg per meter squared with a mean age of 47 years. Randomization maintained this balance across all treatment groups.
Moving to slide 11 and the weight loss results across placebo and the 5 active treatment arms. Treatment for a total of 42 weeks resulted in significant weight loss across all doses of Petrelintide, with mean weight loss ranging from 8.7% to 10.7% from baseline and with no obvious weight loss plateau observed by week 42, supporting the potential for continued weight loss with extended treatment. Maximum efficacy with Petrelintide was observed in dose group 3, and we are similarly encouraged by the weight loss efficacy seen even with the lowest treatment doses tested. Moving now to slide 12. The data from ZUPREME-1 are incredibly encouraging and provide us with critically important insights into the plan design for phase III studies.
Studies that we firmly believe will demonstrate that longer-term treatment with Petrelintide can achieve even greater weight loss, targeting mid-teen % reductions in body weight while preserving the excellent tolerability profile. Importantly, the treatment estimand results in this trial were consistent with the efficacy estimand results, likely driven by both a high retention rate and a high completion rate. Notably, and consistent with the results reported in our phase I trial, nearly all trial participants receiving active Petrelintide treatment achieved some body weight loss during the course of the trial. It is also important to note that several trial-specific conditions likely impacted the efficacy outcomes reported.
While greater proportions of women are known to enhance weight loss in clinical trials, the ZUPREME-1 trial focused on dose identification for phase III and on assessing the potential for a significantly improved long-term treatment experience for all those living with overweight and obesity. In ZUPREME-1, female participants did in fact achieve a much greater weight reduction as compared to males, with women losing on average approximately six percentage points more weight than male participants on a placebo-adjusted basis with the maximally effective dose. There was also a larger than expected geographic variation noted in the mean treatment response at maximal dose, with approximately three percentage point greater weight loss for participants from the EU versus US study sites. With the weight loss observed in the EU study subjects achieving reductions more consistent with our predictions.
Let's turn to slide 13 for a look at the details of the safety and tolerability profile observed in ZUPREME-1. Shown here are placebo-corrected rates of the GI adverse events that are both most commonly reported in studies of weight loss therapies and which are one of the main drivers of treatment discontinuation of incretin-based therapies in the real world. Data reported today demonstrated Petrelintide's placebo-like tolerability for the common GI adverse events of constipation, diarrhea, and vomiting. Notably, while predominantly mild nausea was reported with Petrelintide therapy, overall rates were low, and reports of nausea were most common during dose initiation and escalation. Most importantly, I wish to highlight that no episodes of vomiting were reported in any participant treated with the maximally effective dose of Petrelintide.
Additionally, approximately 70% of the participants on the maximally affected dose did not report any gastrointestinal adverse events during the course of the trial. Highlighting the superb tolerability profile of Petrelintide treatment observed. Petrelintide treatment was judged to be safe and extremely well tolerated. No unexpected or novel safety signals were identified, and rates of alopecia, fatigue, and neuropsychiatric adverse events were very low or non-existent. The study also demonstrated very low rates of injection site reactions with an incidence similar to placebo injections. Slide 14 shows the treatment discontinuation rates for placebo, pooled Petrelintide, and the maximally effective doses of Petrelintide treatment. It is noteworthy that treatment discontinuation was similar in those treated with active drug as compared to placebo, and that no participant who discontinued the maximally effective dose of Petrelintide did so due to gastrointestinal adverse effects.
Once again underscoring the tolerability and usability we observed with Petrelintide. Moving now to slide 15 and a summary of these exciting and compelling results from ZUPREME-1. At Zealand Pharma and with our partner, Roche, today's data further strengthen our conviction that Petrelintide can establish itself as the next true foundational approach to weight management. Petrelintide demonstrated sustained and clinically meaningful weight reduction at all doses, with no obvious plateau in the pattern of weight loss. The data also support a pristine and exceptional safety and tolerability profile for Petrelintide, with rates of adverse events generally similar to or lower than those observed with placebo. Equally important, there were no discontinuations due to gastrointestinal adverse events and no episodes of vomiting among those treated with the maximally effective dose.
Petrelintide treatment was also associated with favorable improvements in cardiovascular risk factors, including lowering of blood pressure, improvements in lipid profiles, no increase, and in fact, a 2-beat per minute decrease in heart rate, and reductions in markers of systemic inflammation. We are extremely excited to continue to advance the Petrelintide monotherapy with full ZUPREME-1 data to be presented in detail at an upcoming scientific meeting in 2026. We expect to initiate the phase III program in the second half of 2026, with trial conditions optimized to achieve maximum clinical response while maintaining a highly differentiated and exceptional tolerability and experience profile while enhancing long-term treatment adherence. With that, I would now like to move to slide 16 and turn the call back over to Adam for closing remarks.
Thank you, David. Please turn to slide 17. In conclusion, I want to emphasize that the combination of double-digit weight loss and the placebo-like tolerability profile places Petrelintide in the ultimate sweet spot for the future treatment paradigm for chronic weight management. Petrelintide is not about chasing headlines for who can achieve the greatest weight loss number. It is about redefining the weight management experience and creating a future foundational and first-choice medicine for the millions of people who live with overweight and obesity. Let's turn to slide 18. Before joining this call, I had a great conversation with Thomas Schinecker and Teresa Graham from Roche, where we acknowledged the importance of this significant milestone in our partnership. As you may know, next week marks the first anniversary of the partnership announcement, and today's news has only added to the strong commitment and collaboration between the two companies.
We are excited about building our customer-focused commercial and medical affairs presence in the U.S. as we advance Petrelintide and the Petrelintide CT-388 combo through development and ultimately into the hands of patients. Let's move to slide 19. Today's news is only the first of many catalysts that we expect throughout the year, including initiation of the Petrelintide phase III program and the phase II program with Petrelintide in combination with CT-388, and importantly, the full phase III data readout for survodutide in obesity. With that, I will now turn over the call to the operator and will be happy to address your questions.
Thank you. To ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. We will now go to our first question. Our first question today comes from the line of Andy Hsieh from William Blair. Please go ahead.
Thanks for the update and thanks for taking our question. So I have a question regarding kinda the dose forward. So looking at across different dose groups, there are five. It seems like the highest three, there appears to be some sort of ceiling in terms of weight loss. You know, I'm looking at the tolerability profile. It seems like, hey, that's suggesting you can add more on the dosing front. But then on the dose response, there seems to be a ceiling. I'm just curious about your view on the interpretation of that and also just kind of forward in the phase III setting, you know, what are some possible doses that you're hoping to tease out? Thank you so much.
Thank you for your question. Maybe David, you will start by addressing it.
Yeah. Andy, thanks for the question. I think an important part of understanding amylin pharmacology versus amylin biology, it's quite clear our observations reflect yours that at the three highest doses we achieved very comparable efficacy. Yet, the tolerability profile obviously was quite favorable even at dose group three. Ultimately carrying doses forward, both through regulatory review but also to bring forth to patients requires the optimum balance of safety and efficacy. Whether we have, you know, reached the asymptote of the dose response curve, as has been observed with other therapies, in particular pramlintide at its very high dose exposures in studies completed 20 years ago. I think it also speaks to the high bioavailability that we know exists with Petrelintide.
80% plus bioavailability likely, allows us to maximally leverage the amylin receptor system for clinical effect. Obviously we will look to take forward the dose that optimizes efficacy and maintains the tolerability profile that we spoke so much about.
That's helpful. Thank you so much.
Thank you. We'll now go to the next question. Your next question comes from the line of Thomas Bowers from SEB. Please go ahead.
Yes. Thank you very much for taking my question. Maybe I just want to follow up a little bit on the dose response. Do you believe you already have the, you would say the maximal pharmacological effect of Petrelintide? Also keeping in mind that we know that Novo very recently shared on their conference call on cagrilintide that they actually see limited effect from dosing higher of cagrilintide 2.4 milligram. Are we maybe seeing here this fear that you could see a darker ceiling effect here on the weight loss?
Maybe just to follow up on that, in regards to your ambitions for the phase III, you have previously stated 15%-20% was the target. I just wanted to confirm whether you said in your prepared remarks that you are now aiming for mid-teens in phase III. Is that correct? Thank you.
Thank you for your question, Thomas, and maybe I can start, and David, you can fill in. I hope, number one, I think it's really important to note, as David also highlighted in the prepared remarks, that in our study where we had a gender balance of 50/50, we actually observed that females achieved 6% more weight loss than males on a placebo-corrected basis, and also that we have observed lower than expected weight loss across some U.S. sites, which are, of course, all things we will address and account for in our phase III design. We by no means believe that we have exhausted or demonstrated the full potential of Petrelintide when it comes to a weight loss potential. Also, as was communicated by David, we have not seen a weight loss plateau.
We expect to see also with continuous dosing that we see more effect. It's also really important to note when you if you wanna compare across amylins that Now, as David also alluded to in the prior question, we have much higher bioavailability, so we are dosing extremely high as we have also communicated before with the nine milli with the top dose that we pursued in this study. I think it's fair to assume that David's also said that we have probably demonstrated the maximum potential of amylin biology, but under some study conditions which do not demonstrate the maximum potential of the product. I would also like to highlight that there are other program based on the same balanced approach that has demonstrated also in efficacy in higher ranges.
We by no means think we have exhausted it. We think the study conditions is a major driver. What excites us the most and what really this study was about was to find the doses to take into phase III, and we believe we have those. Importantly, we are seeing a tolerability and a safety profile, which is even more benign than what we have experienced in earlier studies. Actually, no safety, you can say, findings, which is a major milestone as you progress into phase III. David, do you wanna add something?
Yeah. Thomas, I think, to echo what Adam said, you know, in this study population, given the caveats that it is balanced for men and women, that we did see some unanticipated findings by geography. I think it also underscores that with amylin biology and particularly amylin pharmacology, we are not as limited by GI tolerability issues to push milligram dosing. Similarly, we and others have not demonstrated any limitations on increase in heart rate, and I emphasized that in my prepared remarks. The challenges that come with, I will say, maximizing incretin-based therapies to much higher doses can be limited by adverse events and other, if you will, off-target effects like increasing heart rate.
In this case, we identified that the three top doses, to your point and Andy's, clearly had comparable efficacy, even in a population that was not entirely reflective of what will be the clinical population, which is predominantly female. We think in phase III, optimizing for those conditions can give a clearer picture, but also go back to what Adam opened with. I think there is still intense focus on winning this weight loss numbers game, when in fact, one of the greatest predictors of long-term outcomes will be persistence of the weight maintenance that individuals achieve. With something that has placebo-like tolerability, I think the dose issues aside, that capacity to get to long-term persistence is what gives us the confidence that, yes, in fact, mid-teens efficacy is achievable.
Okay, great. Thank you very much.
Thank you. Your next question comes from the line of Mohit Bansal from Wells Fargo. Please go ahead.
Great. Thank you very much for taking my question. Thanks for this update. Just two questions from my side, if I may. One, how do you see the potential of amylin in the light of this data, more in terms of is it, is it going to be a monotherapy drug, or do you think combo has a better potential in combination with CT-388? The second one is there's a little bit of change, if I am sensing right that in the... Earlier, you were talking about 15%-20% weight loss, but today you are talking about mid-teens.
Am I sensing it right that your target profile is more like mid-teens now, in light of the data or, this is what you, is a fair target for an amylin-based therapy? Thank you.
Thank you for your question. I will start, and maybe David will add a little bit. I would say, as we indicated also in the prepared remarks, we have actually increased our confidence in Petrelintide as an alternative and a future foundational and first-choice therapy for the many people who live with overweight and obesity. Remember, most people are not seeking weight losses above 20%. Most people are looking for weight loss below 20. We think with the profile that we have seen thus far, we can deliver the weight loss that most patients are looking for, and importantly, in a completely different experience where you don't have to be concerned about GI tolerability effects. Physicians don't have to adjust doses based on individual experiences. You don't need maybe to consider getting off drug before you go for a birthday party.
This is about turning the weight loss Olympics into chronic weight management. This is about delivering the weight loss that the majority of patients are looking for and changing the weight loss experience. This is exactly what Petrelintide as a monotherapy can do. On the combination product, we remain also, and you can say, of course, an important component of that combination product is the benign safety and tolerability profile of Petrelintide. Our confidence in the combination with CT-388, also after Roche has announced some of the key data from that program has just also increased in the recent months. It's back to this opportunity to build Petrelintide into the leading amylin franchise, and this data that we have seen today reinforces that potential.
Highlighting not only tolerability, but also the safety aspects where we have not seen anything, if, that would suggest that we are, you know, the safety profile is placebo-like. This is back to our firm belief that this is the way the B.C. market is going. David, maybe you wanna add.
Yeah. Mohit, I think, very important questions. To Adam's point, a reminder that our partnership with Roche is 50/50 on both the monotherapy and the combination. We believe both will have important roles to play. Obviously, preserving the, as I described, a pristine tolerability profile of amylin monotherapy, will be part of the focus of putting that asset forward as a foundational therapy. That does not preclude, as with many other chronic metabolic diseases, that the combination of therapies that best serves an individual patient will be desirable in having that potential combination with our partner, Roche, to us makes great sense.
I think your other question regarding, you know, have we reached an asymptote with all amylin agonists, I'll give you my best perspective from days looking at pramlintide, a very short-acting agent now to cagrilintide, and Petrelintide with data in the public domain. I think if one looks across those not at the highest doses with higher rates of either discontinuation or challenging tolerability, using, for example, the 3-milligram dose of liraglutide with a placebo-corrected treatment estimate of about 10.5%, not in the mid-teens to 20% that sort of captured the headlines. I think this class of therapies, with Petrelintide standing out, in our opinion, with the most favorable tolerability profile. Can all readily achieve that mid-teens if the right doses can be utilized.
You're not limited, by either formulation, injection site reactions or the potential for antibody formation. I would apply the answer to that more broadly to long-acting amylins in general based on the data available today. Again, we remain quite encouraged that the weight loss that the vast majority of people desire, if it can be achieved as comfortably, as acceptably as possible with an asset like Petrelintide, that will reshape the way we think about this. One last comment. If you go back to things like hypertension, even the management of type two diabetes, the game at first was to lower blood pressure as much as possible. You can do that with vasodilators that are fraught with adverse effects.
We now have very well-tolerated classes of therapies that are used alone and in combination, and I think I see us in that same evolution in the weight management space.
Helpful. Thank you.
Thank you. Your next question today comes from the line of Kirsty Ross-Stewart from BNP Paribas. Please go ahead.
Hi there. Yeah, good evening. Thanks for taking my questions. So firstly, you've highlighted the difference in weight loss across women and men in the trial, but interested if you saw any differences in safety profile across men and women. Thinking through to phase III trial design, you've alluded to kinda plans to increase the proportion of women in the phase III trial. Just interested in, you know, Why you're taking that kind of different approach that you've taken in phase II and what are the other kind of key changes that you're thinking about as you go into phase III or the learnings that you're taking from the phase II data, and in combination with data from kind of competitive datasets as well. Thank you.
Thank you. David, will you?
Yeah, very quickly, Kirsty, to your first question. No differences across males and females in terms of the safety tolerability profile, adverse effects, completer rates, all of the above. In regard to the population anticipated to be enrolled in our phase III program, I alluded to it already. One, to reflect the population as accurately as possible that seeks weight management today, but also understanding that the regulatory environment requires a certain proportion of exposure to, you know, all populations, men and women, various populations by geography, by comorbidities, et cetera.
As we alluded to and we've maintained in phase II, we wanted to best understand dosing that could take us into phase III rather than to win some election or game, in phase II, realizing that it is phase III that the regulatory authorities will ultimately use to judge safety and effectiveness.
Thank you.
Thank you. We will now go to the next question. Your next question comes from the line of Carsten Lønborg Madsen from Danske Bank. Please go ahead.
Yeah, thank you very much. I only have one question left, I think. I was thinking in terms of looking here at the men versus women, there's so much focus on the weight loss you're seeing with the female population. I'm actually more curious to understand why is it that the males in this study and in many other studies get such a low weight loss and whether there could be something that's amylin-specific here because it seems like you're maybe down to something like 4% weight loss in males after 40 weeks. That's really not a lot. I'm wondering if you had an explanation for that.
David, please.
Yeah, thanks, Carsten. I think there are important physiologic reasons and pathophysiologic reasons that we understand regarding the differences in weight loss interventions. Not just pharmacologic interventions, but lifestyle interventions. In general, women have greater degrees of adiposity at baseline. That is a physiologic fact. A greater adiposity likely accounts for a significantly greater potential impact of a weight intervening therapy. I won't go so far as to judge the adherence compliance behaviors of men and women. I think that's outside the bounds of this.
Mm.
Both the greater adiposity, that exists, more lean mass in men, even men who are obese or overweight, likely accounts for a significant proportion of that difference.
In terms of the phase III trial, the things you're going to optimize, obviously this ratio you can optimize. Can you give some other clear examples on other things you can optimize in the phase III trials?
Yeah. I'll take the rest of that. There are very important things beyond the split of men and women, including the proficiency of investigative sites. As a 17-year clinical investigator, it requires both commitment of the sites, their coordinators, and the individuals who are randomized to these trials to invest themselves in these longer-term phase III trials, which all, as you know, extend beyond one year and potentially with open label extensions. It will be site selection, geography, understanding the background environment in which these individuals are treated. Will they have had a great deal of or very little exposure to potential
Weight reducing interventions prior to enrollment in the trial. All those are considerations that, you know, we will and will need to put into this program to ensure that the regulatory authorities can fairly assess, the safety and efficacy in the appropriate population. Study sites, gender distribution, previous exposure to weight loss medications and important comorbidities, and ultimately ensuring, you know, adherence and persistence based not only on the characteristics of the intervention, but the investment of the study sites themselves in ensuring completion of the trial.
All right. Thank you.
Thank you. Your next question today comes from the line of Xian Deng from UBS. Please go ahead.
Hi, thank you for taking my question. Two, please. The first one, just wondering why do you think there is a difference in weight loss between European and US participants? Is that lifestyle or you happen to have different demographics? Given that European participants actually have more weight loss, I'm just wondering how can you actually, how do you plan to manage that at phase III given that FDA would require, you know, enough US participants in the trial? That's the first question. The second one, just wondering, if I look at your phase IB results, you have 8% weight loss at the highest dose, at week 16, and that was only 20% women. Whereas now, it's much longer study and you have 30% more women.
The weight loss is, you know, is 2% more, let's say, incremental. Just wondering, you know, could you actually help us to reconcile the result of your phase IB and phase II, please? Thank you very much.
Thank you for your questions, I'll start, and then David, you can add. On the geographies, of course, we will make sure that we have a fair representation of both US and European patients in the phase III program. I think what we need to understand further when we analyze the data is the reasons why we saw significantly higher differences between the weight loss experienced in the European population and the US population in this study. David alluded to some of the hypothesis which could have to do with priority of the one experience and starting point for people's weight before getting to the study, et cetera.
These are things that we'll continue to evaluate with our good partners at Roche and make sure that we build in systems so we have not only the right sites, but also the right representation of patients in the phase III program, which gives us a lot of confidence that alone can enhance it. You're right on the phase IB study in 16 weeks where we had only 20% females. We reported 8.6% weight loss in that study condition. We actually applied the dose escalation every two weeks. We also had different starting doses. Tolerability profile that we have observed in this phase II study is improved even further compared to what we already saw as a very tolerable approach.
Of course, again, ultimately, as we design our phase III study in dialogue with Roche, we will take into account all these parameters as we design for the profile of the drug we expect best meets the needs of the patients. As we have alluded to several times today, the world is in a much deeper need of a very tolerable approach, which can help people actually stay in therapy rather than just having a short weight loss experience and then a weight regain the months after they stop therapy. These are discussions that we will have with our partner as we design the phase III program, including considerations for doses of course and the escalation. Thank you.
Thank you.
Thank you. Your next question today comes from the line of Yihan Li from Barclays. Please go ahead.
Oh, hi. Thank you for taking my question, Yihan from Barclays. I have two, please. The first one, we just did a very quick calculation. It seems like if we assume 80% of females in your trial, you could potentially reach or something like 12.5%-ish weight loss. It's still like, relatively lower than I expected. Just curious, like what is your, you know, the most recent result in terms of the competitive landscape, especially given there are multiple amylin programs expected to report data this year. The second one, I'm just wondering if we could know the weight loss at 28 weeks please. Just wanted to have a better sense of your weight loss curve. Thank you.
Thank you for your question. We will present the full data at upcoming scientific conferences to provide further insights. We have shared the top line and also what we believe representing the main characteristics of the outcome of this study. When you look into the weight loss that we achieved also when accounting for the gender differences, we do believe we get into the zone of what you could expect from this especially, and of course, in the light of the very tolerable profile. David have in his some of his comments alluded to cross trial comparisons. You have to not only look into the tolerability from a GI perspective, you have to evaluate other safety findings.
You also need to look in the difference between efficacy estimates and effect and treatment estimates, where traditionally we see huge drops in the actual efficacy numbers. With our study, we did not. Again, speaking directly to this thing that we have applied a treatment, and dosing algorithm that patients can actually tolerate and appreciate to be on. That is where, you know, we feel extremely comfortable as we move into phase III, with this profile that it has this potential to set a completely new, standard for what a weight loss and weight maintenance experience can be. David, do you want to add?
I think two points to emphasize further what Adam said. To have essentially 98% of those on the maximally effective dose, both get to maximum dose and complete the trial of 42 weeks on that dose. I can't think of too many other circumstances in my experience where you see that sort of persistence. I think the one when you look at the treatment, and efficacy estimates, they are very, very similar, in contrast to studies where you may lose 10%, 20%, 30% or more of individuals. I think back to a question I believe you raised, we did achieve the primary endpoint at week 28 in all treatment arms as well.
We're sharing the 42 week data because we think that's most germane to guide us into the phase III program.
Thank you.
Thank you. Your next question for today comes from the line of Suzanne van Voorthuizen from Kempen. Please go ahead.
Hi, team. This is Suzanne from Kempen. Thanks for taking my question. About this more benign weight loss journey, it perhaps takes just slightly longer to get to the stronger weight loss numbers seen with other drugs, but with a super clean tolerability profile. I'm wondering if your thoughts evolve on the body composition you expect to see with Petra. Is there reason to believe that a more benign journey could lead to a healthier muscle versus fat loss ratio? I have a small follow-up after that.
Thank you, Suzanne. David, maybe you can address that. The data is being analyzed, and we will of course, release them later. We don't have them at hand yet.
Yeah. I'll add, Suzanne, we're excited to see the body comp out readout, particularly because of the use of the MRI or MRE assessment, which gives a much better look at lean versus fat mass, not just lean mass, and estimates. To the other point, you know, there are historical data, and this is independent of the means of achieving weight reduction, but very rapid weight loss, while it makes for great headlines, also in a variety of interventions, leads to the highest rates of recidivism or weight regain. There are some data that actually suggests that very rapid weight loss is metabolically less advantageous than a gradual and sustainable weight loss. These are studies done years ago at the Pennington Biomedical Research Center and elsewhere.
I'm not saying that losing weight is generally negative. I think in almost all circumstances there are metabolic advantages, but we believe that it is the entire weight loss journey, both for the patient experience, but also potentially for these metabolic advantages. I think we're also excited to get a readout both on the individuals with or without pre-diabetes who take Petrelintide and the ZUPREME-2 trial, where we still believe that given the mechanism of action, we can preserve the weight reducing effects of this intervention in diabetes versus no diabetes. Remembering that if one looks at the semaglutide label, the weight loss in the diabetes population is less than 10%, in phase III trials.
You abrogate a significant amount of the weight reducing therapies of these very effective insulin stimulatory incretin-based therapies, something we look forward to, further elucidating both in phase II and phase III.
Got it. Okay. That's very helpful. Maybe just a small follow-up. I noticed that Roche is PR-ing this better data from the Genentech part of the group. I just wanted to double-check if there has been any change to the partnership or the way that the partners operate within the collaboration. Thank you.
No, there has not been. Remember, Roche Genentech operates as a separate combined entity, but running the U.S. activities out of Genentech.
Thanks a lot.
Thank you. We will now go to the next question. The next question comes from the line of Jacob Mekhael from KBC Securities. Please go ahead.
Hi there, thanks for taking my question. Maybe just to circle back on the topic of dosing. Given the good safety profile that you have shown, do you think there is potential to potentially skip dose escalation like some of the competitors have done in order to maximize weight loss? I have a also follow-up and on the design of the phase III or on the timelines of phase III. I noticed that Roche was able to move very fast and start a phase III program with CT-388 this quarter once they had their phase II data. Given they were able to accelerate that very quickly, is there any possibility for them to do the same with Petrelintide and accelerate those timelines as well?
Thank you for the questions. I would say, as we have communicated also in the start of the year, we have already worked diligently with our good colleagues at Roche to accelerate on all aspects of getting into phase III. We remain as excited and the, and, you know, now with the data at hand. We maintain our guidance that we expect that the phase III could start in the second half of the year. That's very clear. The other thing that is very clear is that with the data at hand and the very benign tolerability profile we have seen, now we need to evaluate all the nuances of the study and make the last design decisions on the phase III program.
Also considering if we should make some changes to some of the escalations to achieve more. As we have highlighted several times, it will not, we will not do anything that compromises the weight loss experience because we think this is what will actually define and set a new standard for the weight management experience from a patient perspective in the future. If there is a way whereby you can achieve a meaningful weight loss in the future without having these GI side effects, why would you choose a product that gives you a few percent more weight loss but with a terrible GI experience? That is the question I think we should all ask ourselves when we move forward. Thank you.
Thanks. Maybe if I can squeeze 1 more, given the last comment that you just made. Do you still see potential for Petrelintide as a first-line therapy given the relative weight loss difference that we've seen? Or do you think it would be better suited as a maintenance therapy?
I think it's extremely exceedingly well suited for both. We still are extremely excited about the foundational first choice opportunity for Petrelintide. Again, if you can achieve the weight loss you're looking for without having all these GI side effects, without having a very cumbersome titration where you have to step up and step down to get to goal, also knowing that there's most would stop taking that medicine within the first year, why would you not go for the more tolerable weight loss experience? Having said that, the key to unlock the value in the obesity market and get beyond some of the disappointments around not having enough patients, that is weight maintenance. That is where the value is. That is to get patients to stay on therapy.
Why would you not also use a product like this for the weight loss, the initial weight loss, if it can deliver the weight loss you're looking for? Both parts are important, but the value for sure lies in making this becoming a chronic therapy area rather than the event-based treatments that we see is how most use the GLP-1s today.
Okay. Thank you very much.
Thank you. We will now take our final question for today. Our final question comes from the line of Andy Hsieh from William Blair. Please go ahead.
Great. Thanks for taking my follow-up. Just quoting what David said that, you know, Petrelintide showed a pristine tolerability profile. Maybe this is kind of a follow-up to the previous question. From a market segmentation perspective, can you share with us maybe updated thoughts on the maintenance setting? Would it be operationally difficult or maybe characterize, you know, from an operations standpoint, how easy it is to kind of tack on maybe another 52 weeks of maintenance, kind of like what we saw with ATTAIN-MAINTAIN, you know, following the active weight loss phase for CT-388, for example. Thank you.
Thanks a lot for that. These are all very good questions which we will address and which we are addressing with our partner, Roche, as we speak and very strong considerations for the phase III program. I think it's again, really important to take a step back, as we also said in our prepared remarks, and try to envision a world where there's alternatives to GLP-1s, and where you have a lot of patients being the key decision-maker in which therapies you would like to get on and also stay on. We are approaching now, probably soon 50% also out of pocket and with also 60% of prescriptions actually being patient-initiated.
That's a world where we think that most patients would like to get on a product like Petrelintide and see if they can get the weight loss that they're looking for without going through all the hassle you have to do if for many patients at least, if you're on a GLP-1. We think that Petrelintide, with the data that we have seen today and as we expect to show in the upcoming phase III trials, will deliver the weight loss that the vast majority of people living with obesity and overweight are looking for. While the opportunity to unlock the value of the market is in maintenance, and we should have a keen focus on demonstrating that potential and value to the patients, I do not see why patients would not also choose a product like this to initiate their weight loss journey.
Great. That's helpful. Thanks. Thanks, Adam.
Thank you. That was our final question for today. I will now hand the call back for closing remarks.
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.
Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.