Ipsen Aktie

Excellent. Thanks, everyone, for joining, and hello. I am pleased to welcome you this afternoon to our corabotase LANTIC Phase II glabellar line KOL presentation, which will also be found on ipsen.com. Please turn to Slide 2. Please take note of our forward-looking statements, which outline the routine risks and uncertainties contained within this presentation.

Please turn to Slide 3. I am delighted to be joined by Professor Kerscher today, the PI for the global Phase II LANTIC trial, who will present the aesthetic proof-of-concept data. We will both be available to take your questions at the end. I will start by introducing our first-in-class Recombinant NeuroInhibitor, corabotase.

Please turn to Slide 4. The external validation of corabotase is an important milestone for aesthetic innovation. The USAN and INN have designated corabotase as a custom-engineered Recombinant NeuroInhibitor recognizing the novelty of this first-in-class molecule. If approved, it would be the first therapy in a new botase class, reflecting a differentiated engineered molecule rather than a naturally occurring toxin. It is fully designed, engineered and manufactured in-house at Ipsen, which is critical to quality control and consistency. Built from engineered functional domains of catalytic domain A and binding domain B, every element of this structure has been deliberately optimized to increase receptor affinity, enhance uptake and improve resistance to degradation, reinforcing the scientific milestone reached in this naming designation.

Please turn to Slide 6. Corabotase is a precisely engineered Recombinant NeuroInhibitor developed using advanced protein engineering through Ipsen's proprietary technology platform. It was designed to deliver rapid onset of action, compelling efficacy, sustained duration of effect with prolonged symptom relief. Corabotase draws on insights from nature, but it is not a naturally occurring molecule. It has been purposefully engineered. This approach enables a highly replicable product with minimal variability compared to naturally derived molecules. It is supported by a controlled, high-quality and reproducible manufacturing process.

Structurally, it combines optimized functional domains and active catalytic domain A and a binding domain B. The B domain uniquely targets the Syt2 receptor, enabling binding to higher density neuronal Syt2 receptors and improving binding affinities through amino acid sequence optimization. This engineering is intended to drive higher receptor affinity and a greater probability of receptor engagement, faster and more efficient cellular uptake and less extracellular tissue diffusion. Together, these properties translate into sustained inhibition of neurotransmitter release and a sustained reduction in muscle activity.

Please turn to Slide 7. As you can see, in our growing neuroscience pipeline, we focus on both development in therapeutic and aesthetic indications. I want to draw your attention to the ongoing Phase III registrational trial for corabotase in aesthetic glabellar line opened earlier this year and recruiting very well. I will now hand over to Professor Kerscher to run through the LANTIC proof-of-concept data in glabellar line that was presented at the SCALE Symposium in Nashville over the weekend. Please turn to Slide 8.

Over to you, Professor Kerscher.

Yes. Hello, everyone. Absolutely excited to present here again the data we have shown last weekend at SCALE meeting in Nashville. Well, it is the first data that has been obtained in subjects with glabellar lines, the proof-of-concept data. Next slide, please. And you have been already introduced to corabotase. For us, as aesthetic physicians and dermatologists, it's really important because aesthetic injections of botulinum toxin are worldwide since decades, the most often performed procedures in aesthetics. So seeing something new on the horizon is quite important for us.

And corabotase from a scientific point of view, is absolutely interesting as it is the first Recombinant NeuroInhibitor combining the binding domain of botulinum neurotoxin type B and the catalytic domain of botulinum neurotoxin type A. And through amino acid modifications, this NeuroInhibitor binds to the synaptotagmin receptors at the nerves. And this means they are more abundant there than, for example, the receptors conventional neurotoxins bind to. And this means that we have enhanced binding and uptake and then after internalization, the catalytic domain of botulinum neurotoxin type A within corabotase causes muscle relaxation.

At the conference, I had the chance to first report the data from the LANTIC trial. Please next slide. And the LANTIC trial has really a very complex study design. It is a 3-stage study design, including or starting first in patients with glabellar lines and then moving up to treating also horizontal forehead lines and lateral canthal lines. And this study is still ongoing and is conducted at 9 sites in France and Germany. We at the University of Hamburg are one study site from the very beginning and the LANTIC study is a study that evaluates safety on the one hand side and efficacy of corabotase.

Next slide, please. And I'm now reporting the data from stage 1 step 3. This means data that have been obtained in a study setting that assesses different doses. So it was a dose-finding trial, and it has been assessed versus placebo, just injection of saline solution and versus abobotulinum neurotixin type A (sic) [ abobotulinumtoxinA ], and it has been done in a double-blind study design, was randomized, and placebo and gold standard control. We included in this clinical trial adult patients from 18 to 65 years, all having moderate and severe glabellar lines and all patients or subjects within the clinical trials being dissatisfied with their glabellar lines.

Next slide, please. The primary endpoint of this clinical trial has been the response to treatment at week 4. And this response to treatment has to be measured as a so-called composite response of at least 2 grade improvement. This means if someone started, for example, with moderate glabellar lines, 2-point grade improvement means no glabellar lines in the end. For sure, not only the primary endpoint has been assessed, but a lot of other endpoints, including composite response at the other time points up to week 24 and longer than treatment response. This means an investigator live assessment, the ILA was none or mild. Then subject satisfaction, that's really important in daily clinics and time to onset of response, and this has been evaluated through a patient diary. Safety endpoints included treatment-emergent adverse events, serious adverse events and adverse events of special interest during the whole period of the clinical trial.

Next slide, please. We directly walk now through the results. And first, we have to look at the participant or subject characteristics, that subjects that have been included in this clinical trial. And these characteristics were, in general, absolutely consistent with those in prior studies in subjects with glabellar lines. So mostly female subjects, 82.5% with a mean age of 46.8 years. It's quite important to also look at the investigator live assessment score at baseline because due to the study protocol, patients with moderate and severe glabellar lines could be included. And as you can see here for the corabotase group, 1/3 had moderate glabellar lines, while 2/3 came with severe glabellar lines.

Next slide, please. And now the response rate at the primary endpoint, this means the response rate at week 4. As you can see here in the columns, 66% of subjects that have been treated with 50 nanogram of corabotase showed an at least 2 grade improvement as composite response as compared to 0% with placebo and 54.3% with abobotulinumtoxinA. This is a high percentage of patients responding to treatment using this specific endpoint of at least 2 grade improvement.

Next slide, please. Let's now have a look at the response to treatment at week 24, and this is a quite important criterion because this reflects duration of treatment effect. And as we can see here on the columns or also on the graph on the right-hand side is that almost 61% of patients or subjects treated with corabotase 50 nanogram had a clinically meaningful response at week 24. Here, assessed as investigator live assessment as a treatment response of none or mild. And this comes again in daily clinics because patients are satisfied if they have no glabellar line at all or just mild glabellar lines. And again, this treatment response is really clinically meaningful, and it is absolutely high also as compared, for example, to the group that has been treated with abobotulinumtoxinA and has a treatment response that is lower, just 36.7%.

Next slide, please. Quite important, especially for the patient is also the onset of effect. And as you can see on the left-hand side, median onset of effect with corabotase is less than 1 day, 0.84 days as compared, for example, to onset of effect with abobotulinumtoxinA that is 1 day longer. For me, the most important result of this clinical trial so far is if you have a look at patient satisfaction or subject satisfaction.

This is the linear graph on the right-hand side. And here, we can see that the patient, they are very satisfied or satisfied over a plateau of almost 32 weeks. This means that subject satisfaction is higher and takes longer than the treatment effect. And if we compare the orange line with the green line, we see that treatment satisfaction gradually decreases with treatment, for example, with abobotulinumtoxinA, while it remains on a very high level up to week 32. And this is really an interesting and clinically very meaningful treatment response to corabotase.

Next slide, please. Subject safety is always quite important, especially as soon as new drugs come on the aesthetic market because we have to have in mind we are treating in general, healthy patients that are dissatisfied with aesthetic factor with some lines and wrinkles in their face. But in general, they are healthy. So we are not treating a disease. We are treating just a skin condition that dissatisfies our patients. But in this clinical trial so far, corabotase was very well tolerated, absolutely no safety concerns with any of the evaluated doses.

Next slide, please. So far, we can conclude that stage 1 step 3 of the LANTIC trial achieved very good clinically meaningful results for corabotase in glabellar lines. Data so far support an onset of action less than 1 day, a peak effect that is consistent or at least consistent, even better with one, with abobotulinumtoxinA and a sustained duration of effect with the majority observed to have a line severity score of none at week 24 and reported being satisfied or very satisfied with the treatment. The safety profile corabotase was consistent with that observed for marketed botulinum toxin A products so far. And this first aesthetic data certainly support the initiation of Phase III trials in glabellar lines, and the first patients have already been enrolled in February this year.

Next slide, please. So in my opinion, corabotase is really important scientifically, absolutely interesting molecule within the always emerging market of botulinum toxins and neuroinhibitors. Thank you so much for your attention.

Thank you, Professor Kerscher. Please turn to Slide 22. And let me tell you a little bit more about the LAURITE registrational trial. The Phase III program is underway, marking an important step as we move from the Phase II learnings into late-stage development. As shown on the slide, these studies are designed to confirm efficacy and safety and to support potential future filings.

Please turn to Slide 23. Over the next 3 years, we expect multiple readouts from across our neuroscience programs in both aesthetics and therapeutic indications, including the beyond migraine program for Dysport and further Phase II and Phase III data in aesthetics as well as a key proof-of-concept readout in 3 therapeutic indications for corabotase.

Please turn to Slide 24. To conclude this presentation, we are continuing to maximize the potential of our portfolio of botulinum toxins while exploring the full potential of our purposefully designed first-in-class Recombinant NeuroInhibitor, creating a truly unique opportunity in Ipsen's neuroscience pipeline.

With that, we are pleased to take your questions.

[Operator Instructions] First question we have is from Victor Floch.

Maybe starting with a question on Dysport, which seem to have performed particularly well in the trial, especially at 6 months on treatment response and despite less favorable baseline mix. So what do you think drove that result? And could it also have influenced corabotase's outcomes?

And my second question, maybe more for Professor Kerscher. Can you discuss the feedback from your peers on the data and which aspect was most positively received? Was it onset of action or durability?

Maybe I'll start addressing this question. So the first one is a question regarding abobotulinum A in our trial. So I'd like to start by saying it's not really possible to compare data from the Phase III registrational trial run with Dysport in 2007, where there were 100 patients treated with our active comparator arm in a Phase II proof of concept. There are many differences between those 2 studies. And one key is the number of patients, but also the treatment paradigm was very different at the time of Dysport registrational trial. And I'd like to bring Professor Kerscher at this time to maybe comment on the difference of injection paradigm.

Yes, absolutely right. And thank you for this question. It's really important from a medical point of view, and it has already been explained 20 years ago, we had completely different injection protocols. If you have a look in the publications, then you might see that the 5 injection points in the glabellar area 20 years ago were injected in a V-shape. So this means from our knowledge by today that we injected the corrugator points, the lateral corrugator points more within the frontalis muscle and not within the corrugator muscle and the corrugator muscle has to be relaxed for getting rid of the glabellar frown lines.

And this reduces the outcome, especially in -- if we compare and have a look on the duration of effect because if you have a look at week 4, week 4, we have a high concentration of NeuroInhibitor in the area around the synapses, also in the corrugator muscles. So this effect doesn't show up. However, as soon as the molecules were needed at the synapses, less molecules are present at the corrugator muscle if we inject in a V-shape and not directly over the bony orbital rim. So this is mostly due to the development of new injection protocols nowadays. On the other -- I think the injection volumes, but it's mainly to our -- now to the knowledge of anatomy.

Thank you for this complementary answer, Professor Kerscher. To the other part of your question regarding the duration of action, I would say the detailed comparison at isolated late time points should really be interpreted with caution. The study was not powered for that level of granularity and the sample size are limited. The more meaningful comparison is across the duration window, where we see a very clear and consistent signal, particularly at the week 24.

So the next question is from Ben Jackson.

Two questions from my side, please. Could you perhaps just provide a little bit more information about the dosing of Dysport that was used in the actual trial and how that differs or perhaps differs from how it's used in the real world? And then also on your own dosing of corabotase, it's obviously been noted that it's, I think, 50 nanograms. It seems slightly bigger than what we typically would use for a neurotoxin. So perhaps you could talk us through what it is within the profile of corabotase that allows you to do that and whether that could increase importance of longer term and reinjection data to improve the knowledge around that?

And then secondly, can I just also ask if you've looked at the subject live assessment at all in the study and how this perhaps differs from the investigator responses that you were looking at? And is one more important than the other in the real world when it comes to decisions around which product is given to which patient?

Thank you, Ben, for this question. I'll start with the dosing question, then we'll hand over to Professor Kerscher to talk about dose used in the study and assessment. So Ben, we actually cannot compare at all the doses in the sense that natural occurring toxins are dosed by units and those are units of activities. We have engineered a fully recombinant protein and our doses are expressed in nanogram, but they are not comparable to whatever equivalent you're thinking of with the natural toxin. So we really cannot draw any conclusion from this.

Professor Kerscher, would you like to comment on the choice of dose for abobotulinumtoxinA in our study and also the assessment?

Yes. Thank you very much for this question. Absolutely important. And I think, well, the nanogram -- 50 nanogram has already been explained. This is due to the fact that it's a completely different molecule. For abobotulinumtoxinA, 50 Speywood units have been used, and this is exactly the dose that is recommended for treatment of glabellar lines.

Then I think if there is nothing open about this point. The second part of your question was the subject live assessment in comparison to the investigator live assessment. And I think this is a phenomenon that we observe in all the clinical trials that are performed in patients with glabellar lines or also horizontal forehead lines and periorbital lines also in nasolabial patients do a different assessment if they have to have a look for their own wrinkles, and they tend to see them a lot milder than the physicians rate the wrinkles.

And this means that subject live assessment often is, for example, if you, as a physician, see it's severe or maybe even very severe patients sometimes even deeming it is mild for them. And as a physician, you are not allowed to explain and you are not allowed to communicate to the study subject how you, as physician rate the wrinkles, even if patients ask, I cannot tell them anything. So they are just alone to rate their own wrinkles and then they have a tendency to do this in a more positive way.

And this is all the fact that this composite evaluation often has very low percentages, even if we are happy with the 66% response in general. And as physicians, we might see a more than 90% response because we see that the patient perfectly responds to the treatment. But having in mind that then the subject may be just improves in their own decision from a 2 to a 1, this then is lost for a treatment response.

So the next question comes from the line of Xian Deng. Xian?

So two, please. First one for Professor Kerscher. Just wondering, I mean of course, this is Phase II data, very small sample size and everything. So just wondering, given the data so far, how do you generally feel about corabotase versus Relfydess? This is the first question.

And the second one is specifically for this data. So just wondering the chart where you actually show the response to treatment at week 24. So the 2 curves, I think, between corabotase and Dysport has a bit of separation, but there's a lot of overlaps with [indiscernible]. Of course, this is a small sample size, the 2 line doesn't seem to have much separation. But then the next slide, the subject satisfaction, there is a very kind of quite significant separation of the 2 curves. So just wondering what do you see as the reasons that contributes to a better satisfaction for corabotase versus Dysport?

Well, thank you for these questions. I start off with the first part of your question, meaning corabotase versus relabotulinumtoxinA. So as this study was a double-blind study, as injector and physician involved in the trial, I didn't know whether a patient had corabotase or abobotulinumtoxin. So I just could assume over the period of time, but you also have to have in mind in some phases of this clinical trial, we also had different doses of corabotase. So clinically, I have no idea how it behaves in comparison to relabotulinumtoxinA, because study setting is completely different.

What we have seen in the clinical trial with corabotase is that we had a percentage of patients showing really long-lasting clinical effects. And even -- and I'm still completely blinded, so I can just assume that this has been the group of subjects that have been treated with 50 nanograms of corabotase. So clinically, so far, it is not on the market. So no chance to compare it in a direct clinical setting with relabotulinumtoxinA. And then the response at week 24 concerning patient satisfaction with corabotase. Well, I think here, patients even if they don't rate their wrinkles in a way we as physicians do it and have a tendency to rate their own wrinkles a bit milder than they are in real life, concerning their satisfaction, patients have clearly shown that they are satisfied over a long period of time.

And this was what they told us. At least some of the patients we have treated. We also had patients with placebo being very disappointed. But the others told us, whatever you gave me as soon as this is on the market, I would like to have it because I'm absolutely satisfied and its injection has been 6 months ago and still I have a much better outcome and can't move as I did it before. This explains why patient satisfaction is on a high level over a long period of time.

So apologies, everyone. I've just been informed that the Zoom meeting will actually be cutting in 4 minutes. Sorry for the logistical error. But if it cuts, can we just all dial back into the same link and we should be back online.

But the next question is from Simon Baker.

I'll be quick. Two questions, if I may, please. Firstly, for both of you. I was just wondering if you could give us perspectives on the translation of Phase II results into Phase III studies typically for neurotoxins.

And then secondly, one for Professor Kerscher. I just wondering if you could give us the considerations that you make as a clinician in deciding what neurotoxin to use for a given patient? And also the role of the patient in deciding that. Is this something where it is principally clinician led? Or is it determined more by the request of the patient/consumer?

Thank you, Simon. So maybe I'll start with the Phase II, Phase III question and then hand over to Professor Kerscher. So this Phase II LANTIC stage 1 step 3 has actually delivered exactly what we were looking for, which is proof of concept that corabotase is fast acting, has sustained efficacy and show really strong patient satisfaction. So based on those results, we're really encouraged and have started 2 parallel Phase III trials. And those trials will further establish efficacy and safety. So we're very encouraged from this proof-of-concept data.

Now I'm going to hand over to Professor Kerscher to comment on the second part of the question.

Thank you. I think the second part of the question, especially deals with the fact which neurotoxin or which NeuroInhibitor to choose for our patients in a clinical setting, having in mind that all the different drugs are approved. Then for me, it's -- the most important thing is safety. So safety counts always first, even over efficacy and duration because we have to have in mind, we are treating young patients, we are treating healthy patients. So we see from statistics, from worldwide statistics that the average age on which patients start with their botulinum injections, it decreases more and more. So we have young patients whose 23, 25 years having their toxin.

And then we have to have in mind that they might need this NeuroInhibitor over decades. And in later life, they also might need it for the therapeutic indication. So safety is really important. And among safety, it's mostly immunogenicity that counts, especially for me. So it's absolutely important that we just have the pure 150-kilodalton protein within the corabotase and this gives us more patient safety than having a conventional neurotoxin with the core protein and complexing proteins.

Thank you very much. I think we've lost it now. So if you could all dial back in, sincere apologies for this technical glitch.

[Technical Difficulty]

Apologies for the technical glitch. Christelle, I see we have you back.

I am indeed, and I can hear you.

I know we had a question from Yihan. [Operator Instructions] Victor has another question. So maybe we can go to Victor's question while we wait for Yihan to rejoin.

Maybe just a follow-up because I think in my 2 questions I've asked, I've asked about like physician feedback. I'm not sure I got that. But if ever Professor Kerscher can just discuss what was the feedback from your peers on data will be quite useful. And as well, maybe just a quick follow-up on dosage, and I do understand that it's maybe tricky to compare the 50-nanogram to what we've seen from Dysport and like more classic type A toxin in the past.

But I was just wondering whether we can discuss the potential implication in terms of immunogenicity. I mean for now, data looks pretty reassuring. But with this kind of toxin loads over the longer term with -- I mean more -- with the frequency of dosing and everything, do you think it's something that you begin to have to follow up closely in the future? Are you like worried about this? Or I mean just how should we think about like immunogenicity causing the toxin load?

So I didn't know if Professor Kerscher has rejoined yet, but I can start by addressing your question regarding immunogenicity. So first of all, I think Professor Kerscher mentioned, one of the key advantage of our fully Recombinant NeuroInhibitor is that it is a 150-kilodalton protein, just one protein, while every naturally occurring toxin is actually purified from a bacterial [indiscernible] and comes often in complex with other proteins, complex that is difficult to fully control. So that is one first advantage is that we know exactly what protein is produced. Second is in repeat dosing preclinical studies in NHPs, we have not seen any sign of immunogenicity.

Second, we are, of course, running repeat dosing, and that is important. And should there be any signal, that's where we would see them. But so far, we have already conducted repeat dosing in Phase II. There are no signals to date. And again, the dose cannot be compared and 50 nanogram is not a large dose in terms of what we're injecting. We also, of course, as you can imagine, optimize the sequence to minimize immunogenicity risks within the boundaries of what is known in protein engineering. But we have taken this into account. And so far, there are no signals. So we don't have a particular concern.

Kerscher, have you rejoined?

I think she might be having issues rejoining. In the absence of that, we can go to the next question from Yihan Li.

Yihan Li from Barclays. So 2 from me, I guess. So the first one is on the data baseline. So it seems like -- I know it is like a very small sample size, but it seems like the prior -- for example, Dysport exposure was around 25% in the corabotase arm versus over 50% in Dysport prior slice. I'm just curious, like could prior toxin exposure potentially affect patient reported onset or satisfaction or any response rates? So that's my first question.

And the second one, I think it is just like a follow-up question. Just curious like what -- it seems like corabotase have a pretty good combination of sub 1-day median onset of action and also the sustained 24 weeks response. Just from a clinician perspective, how should we think about its profile versus other long-acting toxins such as DAXXIFY? Yes. And what kind of data we should see in Phase III to be competitive or potentially differentiated?

So maybe I'll take the first half of the question, and then I'll hand over to Professor Kerscher. So in terms of pretreatment or not, this is a Phase II. And in the Phase II proof of concept, we did not stratify our patients. So I can really not speculate on this at present. There is no data within this study that would support any kind of speculation. So I won't. I'd like to hand over to Professor Kerscher to maybe comment on how to think about the [ duration of ] action.

Professor Kerscher, I'm just trying to unmute your line again. Please unmute. I think we've lost Professor Kerscher. So maybe we can try to come back to that later on.

If we come to the -- another question from Ben Jackson.

I also dropped out briefly. So apologies if I'm asking again, feel free to skip it if I am. But just 2 further from me. Could you just remind us about how prior toxin use can impact aesthetic results in this context? Obviously, it differs by arm, but more interested to think about repeat dosing over time. Does it become more difficult to build a response? Or does it improve with the frequency of prior botulinum toxin use? And then secondly, can you just remind us about diffusion around injection sites, specifically for corabotase? What do patients and physicians want in terms of diffusion? And how can corabotase be positioned to actually build on that too?

So I don't know if Professor Kerscher has rejoined. Again, Ben, thank you for that question. I won't speculate on whether pretreatment or not has had any impact on the Phase II results because we did not stratify our population. In practice, I'd like Professor Kerscher's opinion on this question. Obviously, she is a treating physician. In terms of tissue diffusion, so we have engineered corabotase so that it has a very high affinity binding to the Syt2 receptor.

And that allows us to do 2 things. One is to bind very tightly and to internalize fast. And these properties really allow to have less local tissue diffusion, something we measured in preclinical settings. And this is in order to give us a good therapeutic index. So it was engineered so that it really gets in the cell rapidly and it does not diffuse. So those are the properties that were built in. I wonder if Professor Kerscher has rejoined us and can address the other part of the question.

We seem to have lost her. We're still trying to connect. [Operator Instructions] At the moment, there are no outstanding questions. Unless, Ben, you have another question?

All okay from my side.

Okay. It looks like we have no further questions. Sincere apologies for the technical glitch today, and we will come back to you on those other questions through Martina -- through Professor Kerscher, if possible. Thank you very much for participating today, and apologies again.

Thank you very much, everyone. Have a good rest of the day.

Hello, and welcome to Ipsen's Conference Call and Webcast on Q1 2026 Results.

I'll now hand you over to David Loew, Ipsen, CEO.

Thank you, operator, and hello, everyone. I'm pleased to welcome you this afternoon to our Q1 sales presentation, which can also be found on ipsen.com.

Please turn to Slide 2. Please take note of our forward-looking statements, which outline the routine risks and uncertainties contained within this presentation. Also, all of my comments on growth will be based on constant exchange rates.

Please turn to Slide 3. I'm going to take you through our first quarter sales performance and provide you with a business update, after which our CFO, Aymeric Le Chatelier, will join me for the Q&A session. Let's begin by taking a look at today's highlights.

Please turn to Slide 4. We delivered a strong top line growth in Q1. Total sales grew by 22.6% this quarter, driven by all 3 therapeutic areas. We're pleased to see the very strong performance of our portfolio outside Somatuline, which grew by 27.5% in the 3-month period. Based on this continued solid momentum and strong growth, we confirm our 2026 guidance with total sales growth greater than 13% at constant exchange rates and a core operating margin greater than 35% of sales.

Turning to the pipeline. We were delighted to announce the approval of Ojemda following the positive CHMP opinion in the European Union as the first targeted therapy in relapsed or refractory pediatric low-grade glioma regardless of BRAF alteration. Looking ahead, 2026 promises to be an exciting year for our pipeline with several key milestones, including 3 pivotal Phase III readouts expected in H2 2026 as well as the launch of 3 late-stage programs starting this year.

Please turn to Slide 5. Our Q1 sales delivered solid 22.6% growth, fueled by all 3 therapeutic areas. The portfolio outside of Somatuline grew by 27.5% in the quarter. Oncology performed well with sales up 13%, driven by the strong performance of all products. Rare Disease continues to stand out, propelled by the sustained performance of Iqirvo and Bylvay. Neuroscience with Dysport delivered 18.5% growth this quarter.

I will now turn to oncology for more detail. Please turn to Slide 6. Starting with Somatuline sales were up by 12.8% in Q1. Both the U.S. and Europe continued to benefit from shortages of generic lanreotide in addition to a solid performance in Rest of the World. We do anticipate lanreotide generic competition to resume in H2 2026. Cabometyx sales were up by 16.4% with solid performance in Europe and in Rest of the World. NET launch in Europe continues to progress with additional launches planned this year. Decapeptyl sales were up by 8.4% as we experienced volume growth in Europe and China, despite continued competition and some pricing pressure in some countries.

Now let's turn to Rare Disease. Please turn to Slide 7. In rare disease, Iqirvo continued to track very well with sales reaching EUR 79 million this quarter. In Q1, we continue to see strong growth in the U.S. We believe that the switching of Ocaliva patients on to PPARs has now happened and took place mostly during Q4 last year. On the European side, we observed a sustained momentum with more countries coming online and further reimbursements achieved.

Turning to Bylvay. We continue to perform well with Q1 sales of EUR 61 million, growing by 51.5%, driven by strong demand in the U.S. in addition to Europe and some Rest of World countries such as Japan, where we recently opened a new affiliate. We're also starting to see benefits as the dedicated field force comes fully online in the U.S.

Moving to neuroscience. Let's turn to Slide 8. Dysport performed very well in aesthetics this quarter with sales up 24.3%. We have seen continued growth in most territories, augmented by share gains in some countries. European markets have remained robust. The good performance includes positive phasing of shipments in the Rest of the World. In therapeutics, Dysport sales grew by 10.5%, driven by both Europe and the U.S. This concludes the review of sales.

Now let's turn to the pipeline. Please turn to Slide 9. We have a well-balanced pipeline across the 3 therapeutic areas. I will cover the late-stage assets shortly. But you can see we are building an early to mid-stage pipeline, including several Phase I oncology assets and an extensive program across both aesthetics and therapeutics for our long-acting recombinant molecule IPN10200, now known by its generic name, corabotase.

Please turn to Slide 10. Now I will provide more detail on the key readouts expected in the second half of this year. We have pivotal Phase III readouts for Dysport in chronic and episodic migraine, Iqirvo in the less severe PBC patients, Bylvay in biliary atresia. And lastly, further data from our Phase II LANTIC trial for corabotase in 2 additional aesthetic indications of forehead lines and lateral canthal lines.

Please turn to Slide 11. We're excited to be starting 3 late-stage trials with a view to registration. Following the acquisition of ImCheck Therapeutics last year, we're initiating activities for the Phase IIb/III trial in frontline unfit AML. For Iqirvo, following encouraging Phase II data in PSC, we have initiated the Phase III trial. Given it is a long-term outcome study, we anticipate the readout in 3 to 4 years.

Finally, for the long-acting recombinant molecule, corabotase, following last year's proof-of-concept data, we have started the Phase III program in glabellar lines with patients enrolling quickly. The data from the Stage 1 of the Phase II LANTIC trial in glabellar line will be presented at the SCALE Symposium in Nashville in May.

I would now like to conclude. Ipsen has delivered a strong start to 2026. We are on track to build further momentum in our transformation and to achieve our objectives for the year. Our top line continues to deliver, driven by the launches and continued portfolio performance. We're increasing our investment in our launches and our preparations for upcoming launches as we advance our pipeline. To further strengthen our pipeline, we will continue to diligently evaluate external innovations, leveraging our increasing firepower with priorities unchanged.

With that, please turn to Slide 13. This concludes our presentation, and we will now take your questions. Operator, over to you.

[Operator Instructions] And your first question today comes from the line of Yihan Li from Barclays.

Congrats on the quarter. Yihan Li from Barclays. So I guess I have 3 questions, if I may. So the first one is [ Forlax ] Somatuline business. So we saw it is very strong this quarter. So could you please help us to understand how much of that was onetime in nature versus a more sustainable improvement in the base business? And with this performance improving across a number of products, so what makes you cautious on potentially raising the guidance at this stage?

And my next question is on corabotase, the IPN10200. So could you please help us to understand how much the strategic flexibility it that has around the future commercialization in aesthetics? Or more broadly, how should we think about the options to maximize the value of the asset? Is that still possible to collaborate with other companies other than your current aesthetics partner?

And the last one, I just wanted to clarify on the timing of Iqirvo Phase IIa data readout in the second half. We saw the primary completion in June. So just curious, are we going to potentially see the data in the third quarter?

Okay. Yihan, thanks a lot. On Somatuline, we indeed had a strong quarter. This was driven by, of course, the stockouts of the generics. Now this allowed us to recapture market share volume, obviously, through market share, but also price. So there is a -- your question on, okay, how much is this a onetime versus sustainable lift.

I think we have guided the market to say we expect around Q3, Q4 generics to come back. We know that Amneal has announced yesterday that they plan to intend to launch in Q3. I just want to remind everybody, it's a really hard to produce product. You have seen that over the past years, several of the generic producers were struggling. So we have to see how this is going to develop. And so therefore, we are a bit cautious on raising the guidance right now. So you will have to just be a bit patient and we have to observe what's going to happen and that might influence what we're going to tell the market.

On the corabotase, we have strategic flexibility. The arbitration was clear. We fully own the product. We are not going to elaborate now on what we are going to do in terms of partnering or not. I just want to remind you that we're also still in dose findings in some of the indications in aesthetics with FHL and LCL, as I said, where we're going to show results towards the end of the year. And then also in the therapeutic space, we also have still the dose finding.

And to your third question on Iqirvo in Phase III -- so we are going to unblind this summer. Indeed, as you say, we assume that we would submit the data to AASLD, which is, I think, in Q4, if I recall it right, in November. So you will probably see a press release when we unblind and then you're going to see the data towards the end of the year. Thank you.

Sorry, I just wanted to clarify on my first question. I think I was asking about the business outside of Somatuline. So what is the onetime in nature versus sustainable improvement?

When you have an increase in sales, and we have seen that the market is growing, we have taken back market share. Of course, if you get affected by generics, that will have that effect of the lift that you come from a higher level will have a carryforward effect, we have to assume. So there's partially -- there is a carryforward on this beneficial effect. Next question?

Your next question comes from the line of Xian Deng from UBS.

Okay. Could you hear me now?

Yes, we can hear you.

Xian Deng from UBS. So 2, please. So first, both on Bylvay. So first one is Bylvay did really, really well this quarter with EUR 16 million growth from Q4 2025. So just wondering, is this rate of growth something that we can expect for the rest of the year? Or do you think this will more sort of stabilize a bit?

And then the second one is the Phase III readout for Bylvay in BA. So just wondering if you could comment on your thoughts on the probability of success and commercial opportunity here, that would be great.

Sorry, if I can maybe just squeeze one in quickly, kind of a follow-up from the previous question. So Decapeptyl and Dysport you got a bit of positive phasing for Q1. Just wondering if you could maybe quantify the size of positive phasing, please?

Thank you, Xian. So on Bylvay growth, we are very pleased, obviously, with the dynamic. As you have heard us say, we have a dedicated field force that we have put in place in September last year. So the rollout started. And so clearly, it does have an effect. Now it's a bit early days to say, okay, is that going to totally change the trajectory? Or was there a bit of a catch-up on some of the patients. So we -- I think we have to observe that, but we are definitely very pleased with the dynamic of the drug.

On the Phase III on biliary atresia, I mean, as you know, the hurdle is relatively high on biliary atresia because we have a very hard end points on liver transplant. And so therefore, we will have to see that the children need to have a Kasai procedure. And sometimes the liver functions properly after this Kasai procedure. Sometimes it doesn't fully function. So this is also why the hurdle on BA is relatively high. The commercial opportunity that we have guided is about as big as PFIC and Alagille together. So it's a significant upside if we hit it.

And then on your third question on Decapeptyl and Dysport phasing, I'll let Aymeric comment.

Yes. So thank you, David. Thank you for the question. Yes, it is true to invest that the performance of Decapeptyl, as you can see, has been boosted, especially in Rest of the World by some extra shipment, especially related to supplying the Middle East market. So I think you should not expect Rest of the World to continue to grow at a very strong double digit, while at the same time, the product is doing very well, including in China.

Regarding Dysport, you have the same effect on the aesthetic sales where you see that we are growing by 35%. This is also based on very high level of shipments for the quarter. Having said that, we also are very happy with the performance both of Galderma and on the Ipsen territory for rest of the world of Dysport.

Thank you. Operator, next question, please.

Your next question comes from the line of Sophia Graeff Buhl Nielsen from JPMorgan.

Could you talk about how you see the growth potential of Iqirvo going forward now the impact of the Ocaliva withdrawal is largely behind us? In the second half, we have the Phase III ELSPIRE study in second-line PBC patients with lower ALP coming up. Just how you're thinking about the market expansion opportunity for this and the potential for Iqirvo from this trial? Is there any use of the product already in these patients?

And then just also any additional color you could share in terms of market share developments for Dysport aesthetics in Europe would be great.

Okay. Thank you, Sophia. So taking your first question on Iqirvo. What's going to be the dynamic now that Ocaliva withdrawal has basically washed out. So what you have observed is that we had a very nice growth in Q1 to mid -- let's say, middle of Q3. And then Ocaliva was withdrawn and Q4 was a notable significant acceleration. So what you should think of looking forward now is that the growth, which we are going to see from, let's say, Q2 to Q4 is going to be probably around the speed that you have seen at Q1 to Q3 last year because this jump that we have done on Q4 has lifted up on the next level, on a much higher level. And of course, we're going to continue growing on this higher level. So that is probably how you need to think about.

And then comes on top of it, the unblinding of ELSPIRE. So what I was just saying on the growth rate was just relating to the above 1.67. Now if you now assume that we will have a positive readout of ELSPIRE in the below 1.67, that would give an additional lift.

Just to give you a bit of an idea in terms of the size of the pools that we have in these different populations. So when you take the U.S., PBC overall are about 100,000 patients, out of which in second line then in the above 1.67, we estimate to have about 30,000 patients and in the below 1.67, you have about 20,000 patients. So it's a sizable business opportunity, adding to the 30,000 where we can be used, 20,000 on top of it.

Now some of those are potentially not going to be eligible because they're very close to 1, but there is a good part of the patients that are eligible there, and they also sometimes have symptoms despite being below 1.67. And it, therefore, constitutes a clear market expansion opportunity. We do see and we estimate that on our current sales, we have about 20% of the scripts coming from the below 1.67 already. So there is already some use there.

So the ELSPIRE trial is really going to turbo boost the penetration in the below 1.67 because it's going to add data. To help you, we don't need to wait until we would have a label update because the label is actually not restricted to the above 1.67. So this is why you see already some use in the below 1.67 despite the fact that the PPARs didn't have data yet. Both companies are going to show data, and that's probably going to significantly enlarge the market because with data in hand, physicians are probably going to increase the use in a significant manner in the below 1.67.

And then to the market share question, if I understood right, Dysport, Ax, I'll let Aymeric answer.

Yes. So thank you, David. So regarding the question on market share, I think you should ask our partner, Galderma. We are not commenting on market share. What you can see is that we are very pleased with the performance of Dysport in aesthetic in Europe, growing by 9.5% this quarter and we expect that to continue for the year.

Your next question comes from the line of Victor Floch for BNP Paribas.

Victor Floch, BNP Paribas. Maybe first one on Iqirvo. I think in the past, you've been strictly pointing out to a base case LOE around 2031. But if I'm not mistaken, there is a large family of patents that could extend the IP protection of Iqirvo. So any chance you could discuss the different option you have and whether we could expect a common up data on this at some point?

And my second question is on Somatuline. So I think Amneal has said yesterday that they were actually asked the FDA to accelerate the review of their filing. So just wondering whether you think that the Q3 is still a reasonable timing for a potential entry? And also whether we should assume that the long-term contracting that you have in the U.S. should also be helpful when it comes to protect your market share in this market?

Thank you, Victor. So on Iqirvo, as you have seen from our UDR document, we have the base patent expiring in 2031, but there are method of use patents, which indeed can go significantly longer. So we are not expressing ourselves as a company on what our assumption is. I think you have to make your own decisions here.

What I can say in addition is that if we would hit it in primary sclerosing cholangitis, we would launch the drug, elafibranor under a different brand name given that it's a different dosing and given that the tablets are not split tablets, we assume that the generics are not going to penetrate there on PSC, and we have orphan drug protection. So you would have an additional 7 years on top of this for the PSC indication.

Then on Somatuline, I mean, Amneal asking FDA to accelerate, you have seen the FDA stating that they want to accelerate some drugs, but I don't think that they talked about generics. I mean they have talked about some real breakthrough drugs like when you have massive overall survival benefit with a new drug, et cetera. I mean that was basically the discussion. So I would certainly not assume that they would come any time earlier than what they have said. They have also a little bit of a track record of having delays. As you know, I mean, they gave originally the date of Q1, then they pushed it out to Q2. And then they said in Q2, now it's Q3. So let's see what's going to happen there.

To your question then on the long-term contracts, I mean, of course, we're not going to comment on what our strategy is. So you have to make your assumptions here yourself. Thank you.

[Operator Instructions] And the next question comes from the line of Charlie Haywood from Bank of America.

Charlie Haywood with Bank of America. I have 3 questions, please. So the first is just on the potential to commercialize 10200 alone, which I know is an option for you and obviously would be a significant strategic decision. So if you were to go it alone, how do you think about your ability to compete commercially and the feasibility of scaling up that sales force? And then any sort of magnitude or phasing of costs to ramp that up?

Second question on sort of Galderma, recent commentary post the arbitration, there looks to be a slight sort of discrepancy in who has the rights to the commercialization. I guess, any color on that from your side or if it's been clarified with the party? And would there be a potential need for another arbitration down the line to resolve that issue?

And then third question, if we only see one Soma generic in '27 and let's say, we assume it's Amneal, how should we broadly think about the Somatuline outlook for '27? It feels like one generic would not be your sort of mid-teens to 20% annual decline needed for 2 to 3 generics. So is that closer to sort of flat, slight decline? Is that fair? Or how should we think of a good proxy there?

Okay. So I start with your first question on IPN10200, which we now call corabotase. So it has a generic name. We don't need to remember any fancy figures anymore. So it's corabotase.

And on our go-to-market strategy, I mean, we're evaluating all scenarios. So we're not going to comment on what we are going to do. So as I said, we're also still in the dose finding on some of the aesthetic indications, but also on the therapeutic indications that we also want to see more data.

Of course, we could choose to invest ourselves. I mean we have what is needed. But as I said, I mean, this is something that we have to carefully evaluate in the light of what I just said before.

Regarding the legal statements, I do not comment on legal statements from Galderma. What I can tell you is that the arbitration was very clear. We have full rights on corabotase ourselves.

And then on the third one, I hand over to Aymeric.

Yes. So thank you, David. So regarding the potential impact, if there were to be only one generic to launch by the end of this year, I think you should anticipate that there will be an impact on 2027, especially given the very strong baseline for 2026. Having said that, we're not going to provide the guidance today. Just reminding you that only one generic will be a progressive erosion as we characterized it in the past.

It's only if we see more than one that we see a potentially more accelerated erosion for Somatuline. So let's wait and see what happened, as David said, regarding a first generic to be able to launch because this is still a challenging space for companies to manufacture and to secure approval both in the U.S. and also outside the U.S.

Let's perhaps just to add something to remember. It's an Autogel, which needs to have the right viscosity. If it's too viscous, you can't push it through the syringe. If it's not viscous enough, you have leakage syringes. And we have also observed that some of the generic producer had some air bubbles in there, et cetera. So the yields that you get and the compliance of the product, et cetera, the quality controls that you need to do has been an issue as testimonied by the several 483s and then OAI. So Pharmathen got an OAI and Sun Pharma as well. So it's not really an easy product to produce. The next question.

Your next question comes from the line of Simon Baker from Rothschild & Co.

This is Qize Ding speaking for Simon. I have 2 questions. The first one is on Bylvay. So is the Bylvay sales force change complete? Or is there more to come?

And my second question is on the 10200. So what's the overall appetite for the long-acting toxin based on your discussion with prescribers? And does that differ from -- between aesthetics and therapeutics?

Okay. I didn't quite get your second question. Can you just repeat this?

Yes, yes, sure. No problem. So regarding the 10200, what's the overall appetite for the long-acting toxin based on your discussion with prescribers? And does that differ between the aesthetics and therapeutics?

Okay. Great. Thank you. Okay. So on Bylvay, yes, I can say the field force implementation is complete. So they have been deployed last autumn. So now they're going in the field, and we clearly see the first effect. So we are very pleased with that.

On 10200, as I said, it's called corabotase now. We see a very, very high interest for that drug on both the aesthetics and the therapeutics. As I said, we have started the Phase III glabellar line trial, and it's recruiting extremely fast. The investigators are enthusiastic and you're going to see the data at the conference in May. We're probably also going to have an IR event at that time.

And the same feedback we're getting in the therapeutics. I mean that's a real game changer in therapeutics because, for example, if you're a migraine patient or cervical dystonia or spasticity patient, if you do only inject every 6 months instead of every 3 months, that makes a massive difference; a, for the patient; b, for the physician because there are not that many physicians which know how to inject. It requires a very specific know-how how to inject. It's complex to get trained and to do this procedure.

So it's going to unlock a lot of additional capacity in the health care system, and it's going to make the health care system more effective. So for payers, this is also a very interesting new option. So I think this can be a drug which is really significantly changing Ipsen if everything works out as we want to. So I'm very, very excited about this drug. Thank you.

And I think, operator, that was our last question, correct?

That is correct. Back to you now.

Okay. That wraps up our Q1 results conference. Thank you for having participated. Bye-bye.

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

Good day, and thank you for standing by. Welcome to Ipsen's Conference Call and Webcast on full year 2025 results. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to your speaker today, David Loew, Ipsen's CEO. Please go ahead.

Thank you, operator, and hello, everyone. I'm delighted to welcome you to our presentation this afternoon, which can also be found on ipsen.com. I want to use the time we have together to focus on the progress Ipsen delivered in 2025 and on the future opportunities and platforms for growth.

Please turn to Slide 2. Please take note of our forward-looking statements, which outline the routine risks and uncertainties contained within this presentation. Also, all of my comments on growth will be based on constant exchange rates.

Please turn to Slide 3. I'm going to take you through the presentation of our latest business update followed by our CFO, Aymeric Le Chatelier, who will take you through the financials. And finally, I will provide an R&D update. At the end of the presentation, we will open the Q&A session. Let's begin by looking at today's highlights.

Please turn to Slide 4. Turn to Slide 5. Today's headlines illustrates how we are continuing to deliver strong and sustainable growth. In 2025, total sales grew double digits by 10.9% and performance driven mostly by the strong performance of our portfolio, excluding Somatuline, which grew by 14.2% over the year. Regarding margin, we delivered a core operating margin of 35.2% of total sales.

Turning to regulatory highlights. This year was marked by the EMA regulatory submission of tovorafenib for pediatric low-grade glioma in the first quarter. EU approval of Cabometyx in neuroendocrine tumors in July and importantly, by the announcement of the first data for our first-in-class differentiated long-acting molecule IPN10200 in September. Looking ahead, 2026 promises to be another exciting year for our pipeline with 5 key milestones, which includes 3 pivotal readouts in addition to the highly anticipated full data presentation of the Phase II data for IPN10200 in first aesthetics indication Glabellar lines at an upcoming medical meeting.

Lastly, we are expecting another year of double-digit sales growth for 2026, supported by accelerated performance across the entire portfolio and the better outlook for Somatuline given the production challenges faced by generic competition. Aymeric will provide more details in his section.

Please turn to Slide 6. Our full year sales delivered a solid 10.9% growth and 7.5% in Q4 fueled by all 3 therapeutic areas with an improvement of performance for neuroscience and rare disease this year compared to last year. The portfolio, excluding Somatuline, grew at 14.2% this year and by 19.6% in Q4. Oncology performed well with sales growth of 4.1% but were down in the last quarter due to a decline in Somatuline sales versus a very high baseline in 2024. Rare disease performed very well with sales doubling this year. Neuroscience with Dysport continued to deliver high single-digit growth.

I'll now turn to oncology for more detail. Please turn to Slide 7. Starting with Somatuline, sales were up by 4.3% for the full year. Both Europe and the U.S. continue to benefit from shortages of generic lanreotide, and we saw a strong performance in Rest of World. As we have previously communicated, we are aware of recent updates on the potential challenges with regards to the manufacturing and availability of generic lanreotide in several markets, and this is factored in our guidance. Cabometyx sales were up by 5.1% with solid performance in Europe, driven by renal cell carcinoma growth and boosted by the neuroendocrine tumor launch despite increased competition in rest of world. Decapeptyl sales were up by 2.7% as we experienced volume growth in Europe and China despite continued competition and some pricing pressure in some countries. Onivyde sales grew by 6.2%, with expansion of use in the U.S. driven by the first-line metastatic pancreatic ductal adenocarcinoma indication. We expect sales to continue to grow modestly, but acknowledge that we are now unlikely to reach EUR 500 million in peak sales.

Now let's turn to rare disease. Let's go to Slide 8. On rare disease, Bylvay continues to perform well with annual sales of EUR 180 million, growing by 36.3%. Growth was driven by both PFIC and Alagille syndrome indications in the U.S. Additionally, we saw a strong double-digit growth in both Europe and in Rest of World. Q4 sales growth was impacted by ongoing competitive challenges in the PFIC indication and we expect to see the positive effect of the new pediatric field force we put recently in place in the coming months in the U.S. Iqirvo continues to track very well with annual sales of EUR 184 million, with growth coming from all regions.

Let me go into a bit more detail on the next slide. Please turn to Slide 9. As you can see, we have demonstrated strong quarter-on-quarter growth since the launch just over 1.5 years ago. In the U.S., we have seen a significant number of Ocaliva patients switching to Iqirvo, on top of a growing PPAR market. We believe that the new data published at AASLD this year has further strengthened Iqirvo's profile as a drug with both long-term efficacy and safety, including improvements in pruritus, fatigue and fibrosis. In Europe, we are continuing the launch across many countries. We're also very pleased with how well the launches are progressing, capturing new patients and contributing to expand the market.

Moving to neuroscience, please turn to Slide 10. Dysport delivered another year of solid performance with sales growth of 9.7% for the full year. In aesthetics, sales grew by 13.7%, driven by continued strong sales in most territories, including the U.S. and rest of the world and by strong performance from our partner, Galderma, who continued to gain market share in key countries and a solid growth in our Ipsen territories. On the therapeutic side, Dysport grew by 4.2%, driven by strong growth in the U.S. and Europe. Reported sales were, however, down in rest of world impacted by adverse phasing of orders in Brazil.

That concludes the review of sales. I'll now hand over to Aymeric, who will provide you more details on our full year financials. Please turn to Slide 11.

Thank you, David, and hello to everybody. I will now take you through more details of our 2025 financial performance and our guidance for 2026. Please turn to Slide 12.

We delivered another set of strong financial results this year across sales, profitability and cash flow. First, our total sales, which exceeded EUR 3.6 billion, grew by 10.9% at constant exchange rate. Our core operating income grew by 16.7% to EUR 1.3 billion, in line with our free cash flow increasing by 29% to reach EUR 1 billion. Given the strong performance and our solid balance sheet with no debt, we had EUR 3.2 billion of firepower available for external innovation.

Let's take now a closer look at those financials in the next slide. Please turn to Slide 13. Starting with the P&L to core operating income. I would like to highlight that we implemented this year a slight reclassification of our distribution expenses. These costs have been moved from SG&A to cost of sales and therefore now impact our gross margin. This change brings our reporting in line with common practices of most of our industry peers. You have all the details in the appendix of that presentation. Now if we look at the figures, the growth in total sales of 10.9% at constant exchange rate translated into 8.1% at current rates, given the adverse currency movements. Gross margin increased by 2.1 points driven by the earlier level of other revenue by EUR 80 million, mainly due to commercial and regulatory milestone received from ex U.S. partner for Onivyde and some other products and the growth in royalties received primarily from Dysport partner.

SG&A costs increased by only 6.9%, with a ratio to sales at 31.6% improving by 0.3 points, reflecting an increased investment to support the launches, especially Iqirvo and Bylvay and the impact of our ongoing efficiency program. R&D costs increased by 9.8% to reach 20.5% of total sales, driven mainly by increased investment to support the development, mainly in neuroscience and early-stage oncology assets. As a consequence, our core operating income increased by 16.7% with a core operating margin standing at 35.2%, increasing by 2.6 points.

Please turn to Slide 14. Turning to IFRS consolidated net profit. This year, we recognized impairment losses for about EUR 350 million before tax mainly driven by, first, Tazverik for which we no longer expect to achieve the EUR 500 million peak sales given the recent competitive developments. Secondly, by fidrisertiband following the negative readout in December 2025 of the pivotal Phase II trial and thirdly, by the discontinuation of some of our early-stage assets. Despite this impairment, IFRS operating income and consolidated net profit increased by 26% and 28%, respectively.

Please turn to Slide 15. Finally, on cash flow. We continue to generate strong free cash flow this year and maintain a solid balance sheet with a cash position of more than EUR 500 million at the end of December. Free cash flow increased by 29% to EUR 1 billion, driven by EBITDA growth, sound management of capital expenditures and working capital. Net investments included the acquisition of ImCheck Therapeutic for about EUR 350 million and some regulatory and commercial milestones. As a consequence, with a net cash position of exactly EUR 560 million at the end of December and based on the maximum of 2x net debt-to-EBITDA we had an available firepower of EUR 3.2 billion for external innovation at the end of 2025.

Let's now move to 2026 guidance. Please turn to Slide 16. For this year, we anticipate another year of double-digit sales growth with a high level of profitability. For total sales, we expect growth of more than 13% at constant exchange rates. This year, we also anticipate adverse impact of around 2% from currency based on the January exchange rate. This guidance on sales is assuming an accelerated sales growth of the portfolio, excluding Somatuline. This will be driven by Iqirvo, Bylvay, Dysport but also Cabometyx as well as the continued growth from Somatuline. Given the recent challenges with regard to the manufacturing and availability of generic lanreotide, we assume limited generic supply in 2026 with a potential entrant only in the second half of this year.

On profitability now, we anticipate a core operating margin greater than 35% of total sales. We will continue to leverage our top line growth with moderate increase in SG&A and R&D ratio to stay around 20% of sales. However, currency rates and a lower level of other revenue will have an adverse impact on our margin in 2026. Regarding our midterm outlook, we are highly confident to exceed our total sales average growth of at least 7% per year for the period '23 to '27 and our 2027 core operating margin greater than 32% given the higher-than-expected Somatuline sales due to continued generic loyalty challenges and the stronger performance of our broader portfolio across our 3 therapeutic areas.

With that, I will now hand over to David. Please turn to Slide 17.

Thank you, Aymeric. I will now provide an update on our R&D efforts. Please turn to Slide 18. We have another exciting year for our pipeline. We have seen strong expansion in oncology with 4 active Phase I programs evaluating promising new modalities in solid tumors and the addition of IPN60340 formally known as ICT01, which came through the acquisition of ImCheck. In rare disease, following the positive Phase II trial, we have opened a Phase III program evaluating elafibranor in primary sclerosing cholangitis, which I will share more on in a moment.

In neuroscience, our broad programs continue to advance across both Dysport and our long-acting molecule IPN10200 with new Phase III programs expected to open in H1.

Please turn to Slide 19. In oncology, a growing focus of our pipeline is on precisely modulating the immune system through multiple synergistic routes. I would like to highlight a couple of new molecules entering Phase I. Our antibody drug conjugates, IPN60300 targets a novel tumor antigen known to be expressed on multiple solid tumor types, and we are pleased to confirm first patients have been dosed in this trial. We also have our T-cell activator IPN01203, a potential first-in-class asset that selectively activates V beta 6 T cells through TCR and IL-15 R pathways.

Please turn to Slide 20. Moving to rare disease and primary sclerosing cholangitis or PSC, an area with no approved treatment options and the majority of patients requiring a liver transplant. Following the promising Phase II data, we are excited to announce a Phase III study, elascope, which will be the only global study in PSC looking at the long-term clinical outcomes as primary objective. Elascope will evaluate the efficacy and safety of elafibranor 120 milligrams versus placebo in patients with PSC based on time to first occurrence of clinical outcome events and multiple secondary endpoints.

Please turn to Slide 21. Turning to neuroscience following the announcement of our Phase II first proof of concept in Glabellar lines in September '25. We are on track to open 2 global Phase III trials for IPN10200 in Glabellar lines. Both trials will evaluate the efficacy and safety of IPN10200 at week 4 and 24 with key secondary endpoints, including patient satisfaction scores and onset of action.

Please turn to Slide 22. We remain diligent in our external innovation efforts and announced strong additions to the oncology pipeline as we closed '25. We are delighted that the lead program IPN60340 from our acquisition of ImCheck Therapeutics was awarded U.S. FDA Breakthrough Therapy designation in January, recognizing investigational therapies with evidence of a substantial clinical improvement. A global licensing with Simcere Zaiming outside of Greater China brings another antibody drug conjugate into our pipeline, which is expected to enter Phase I soon. Finally, reinforcing the strength of our ongoing partnership, we added further 2 research programs with IRICoR, evaluating MAPK-related inhibition.

Please turn to Slide 23. As you can see, we have several milestones to look forward to over the coming years. Firstly, we await the EU regulatory decision for tovorafenib in the first half. In the second half, we see many Phase III unblindings for Bylvay in biliary atresia, Iqirvo for PBC patients with an ALP of between 1 and 1.67 and Dysport in migraine and also for the Phase II data for IPN10200 in forehead lines and lateral cancer lines. Then as we look to next year, we have more proof-of-concept readouts for our long-acting neuromodulator, IPN10200 in the therapeutic indication as well as Phase III unblinding for Tazverik and tovorafenib.

With that, please turn to Slide 24. We continue on our strong momentum and remain firmly on track to achieve our ambitions. I'd like to leave you with 2 key messages. First, we delivered strong '25 results with double-digit sales and profit growth fueled by the performance of our existing portfolio and launches. This consistent growth reflects our focus on execution and our ability to deliver across both commercial and medical fronts. We will further strengthen our R&D investments and grow our internal pipeline while investing to support our current and future commercial launches.

Secondly, the outlook to 2026 is strong with double-digit sales growth guidance, multiple regulatory and clinical milestones to come and significant firepower to pursue external innovation. We look forward to another year of accelerated growth as we continue on our transformation.

Turn to Slide 25. This concludes our presentation, and we will now take your questions. Operator, over to you.

[Operator Instructions] We will now take our first question from the line of Charles Pitman King from Barclays.

Charles King from Barclays. Two questions from me, please. Firstly, just on your guidance, I think it's quite noteworthy that your guidance in FY '26 is significantly ahead of that midterm growth outlook. So firstly, just is it fair to say your guidance philosophy is less conservative this year? And given the double-digit growth in FY '25 and guided to '26, just wondering kind of why you're not looking to readdress and raise that midterm target into '27?

Then just secondly, on the kind of aesthetics neurotox business, can you just confirm -- in the press release, you talked about product mix dynamics seen in the U.S. given this is a single product, I'm just wondering kind of what these are, if you could provide a little bit more clarity. And then beyond that, I know you're unlikely to comment, but just if you're able to give us any further thoughts on the potential partnership discussions you're having with Ipsen 10200 within the aesthetics indication, that would be great.

Okay. Thank you, Charles. I will let Aymeric answer on your guidance question.

Yes. So thanks for the questions, and maybe I will clarify. I think that our guidance is today our best estimates regarding first Somatuline on one side. for which we are still expecting potentially some generics to be able to be on the market in the second half of the year. So I will say we are pretty balanced. And I think we have also a great ambition to continue a very strong growth of the portfolio ex Somatuline, where we expect to be able to accelerate the growth, and we deliver 14% growth this year.

Regarding the midterm target, as you remember, the midterm target was to exceed 7% annual growth and to exceed 32% margin by 2027. So I think the message today is very clear that we are highly confident we're going to do better than this number, but this is still going to be exceeding. And I don't think we want to provide 2 guidance for 2 consequential year. So we are clearly highly confident to 2027. I will provide a guidance for 2027 when it's going to be time in a year time.

On the product mix, maybe I can just answer the product mix and let you answer. So I think the product mix is more related to the product and sample of Dysport in aesthetic as you know, we're providing our partner with both products and sample and the economics are slightly different. That explains what we qualify as a product mix in our communication.

Then on your third question on our long-acting neurotoxin. As you know, in January 26, the arbitral tribunal of the International Chamber of Commerce issued a final decision in favor of Ipsen dismissing the claims brought by Galderma in connection with Ipsen's termination of the R&D agreement. And so the Tribunal confirmed also Ipsen's full rights to its clinical stage toxin programs in the aesthetics field, including therefore, the IPN10200 that you were alluding to. So basically, we continue to assess all options and we can't give you more information at this point, but we're going to come back as soon as we have made progress on this.

We will now take the next question from the line of Xian Deng from UBS.

It's Xian from UBS. Two questions, please. So both on Iqirvo. So just wondering, the first question -- the first question is just wondering, Iqirvo previously you guided for EUR 500 million peak sales. And -- but of course, now the drug is doing really, really well. So I was just wondering, would you say now your peak sale guidance there is very conservative? And if you could maybe give us some color on what assumptions did you have when you set the guidance and what has changed since then? So that's the first question.

And the second one is also on Iqirvo. Actually, just wondering about the patent or exclusivity situation. So my understanding is that the compound patent has already expired in the U.S. right now is protected by offer exclusivity on PBC. So just wondering, given now you are also running -- you already started the Phase III in PSC. So just wondering how should we think about the exclusivity/patent protection on this one, please? Sorry, just can I just quickly clarify -- did I hear that right? You mentioned on Somatuline you are expecting potential generics to come back in second half this year. So is that conservative as well? Have I heard that right?

Okay. Thank you, Xian. So on Iqirvo, the EUR 500 million peak sales guidance. So yes, we are very pleased with the performance, I have to say. We are going to observe how this goes. And especially also we have the ELSPIRE trial, which is going to read out in the mid of this year. And then subsequently, once we have seen that, we're going to look at potentially looking at changing the guidance if required. For now, we say it's above EUR 500 million. But I have to say we're extremely pleased with what we are seeing and with the performance that we have in the U.S. and ex U.S., yes.

On your -- on the exclusivity question, we have orphan drug protection until '31. There are additional patents, which exist as well. Just to help you also on PSC on that question because PSC, and I think you're alluding to this, might report shortly before that date of the '31 that you have given. You need to keep in mind that, first, we have gotten orphan drug designation for PSC so there is a separate protection for PSC. It's a different dose. It's 120 milligrams, not 80. So that's already very different. There will be a different tablet as well. It's a different packaging, et cetera. So we think this is going to confirm quite good protection, and this is why we have given a go to that trial besides being excited about the data, obviously.

And then on your third question regarding Somatuline, H2, it's hard always to exactly know what's happening with these generic companies. What I can say is that we have said that in the past, and I think it becomes very obvious, it's a very difficult product to produce because the gel is very viscous. It shouldn't be too viscous. It shouldn't be too liquid. So it's hard to produce. You have also seen that there have been FDA 483s and [indiscernible] on some of our competitors. So I think -- for the moment, it is reasonable to say that we're anticipating generics entering in H2.

We will now take the next question from the line of Simon Baker from Rothschild & Co Redburn.

Three, if I may, please. Just going back to Somatuline. You've indicated that at best, there will be some generics later in this year. But I'm looking at this from a slightly different perspective, where does this leave you in terms of long-term contracting with your customers? Because it's all fine and dandy to have a generic available at a significant discount. But if the manufacturer can't deliver and can't manufacture it, it's rather academic for the customer and creates a lot of inconvenience. So does this really open up the possibility for tying in your customers into long-term contracting where you alone in the market can guarantee quality and supply. Any thoughts on that would be very helpful.

And then just a couple of quick ones. You gave us the patient incidents of PSC in the state. I just wondered if you could give us a little bit more detail on and point us on how big you think this opportunity is. Some have suggested this is a $1 billion opportunity. And as you say, there are no existing treatments. So any thoughts there would be helpful.

And then finally, on Iqirvo, if you could just give us an update on the sort of commercial dynamics share of voice in that category because your competitor there is rather preoccupied with launching another product in another category. I just wanted to see if you -- if there's been any change to marketing intensity by competitors in that space.

Thank you, Simon. On Somatuline, we, of course, do contracting with several of the customers, especially in the U.S., of course, that's a current practice, I would say. And this has, in the past, already helped to mitigate somewhat the penetration of the generics. So I would say we have done this already before, and you have seen the effect of it. So it all comes down, I would say, can they actually deliver or not and in what kind of quantities.

On your second question, to give you a feeling on PSC.

PSC is about the same market opportunity as PBC. And why do I say this? In PBC, it's a second-line indication that we and Gilead are having currently and so we are talking roughly 30,000 patients in the above 1.67 and about 20,000 in the below 1.67. And then in PSC, you have 40,000 patients, prevalent patients. And so that means that today, all these prevalent patients, they have no solution in PSC and we're actually going to be first line contrary to PBC where we are a second line. So basically, that explains why the market opportunity is about equal as the whole PBC pool. So for us, quite an exciting opportunity, I would say.

And then on your third question, the dynamic share of voice. So for the moment, we don't see a change on Gilead's presence. They are heavily present, I would say, so as we are, right? So I think we performed very well, and we are very pleased with the performance that we are seeing.

We will now take the next question from the line of Richard Vosser from JPMorgan.

A few, please. Just returning to Somatuline. I wonder if you could just talk about price and volume thoughts in '26. Clearly, lack of generics means potentially you could raise price. So if you could talk about that and how that might impact also on '27. And for '27 on Somatuline, you talked about exceeding the margins. Just -- any thoughts to the extent of generic competition of Somatuline you might be thinking in '27 would also be helpful.

Second question, just on Iqirvo as well. Just thinking about the growth, which has been stellar, what bolus do you think you've got from Ocaliva and how that might feed into growth expectations for the second half of '26.

And then finally, on business development M&A, you've highlighted the EUR 3.2 billion firepower. And I think previously, you've highlighted thinking about strengthening the oncology business. But maybe you could give us an idea of latest thoughts around business development and what you're looking for and how that might impact R&D spend going forward.

Yes. Thank you, Richard. So on Somatuline price volume, I'll let Aymeric answer.

Yes. So Richard, on Somatuline, I'm not going to be able to provide you all the detail of our assumption. But clearly, the lack of competition will allow you to -- will allow us to regain volume both in Europe and in the U.S. I think that's the trend on top of a very dynamic market that we see for NET, where it's still a market that is growing in the 4% to 5% per year with very strong position for lanreotide.

On the price side, I think there are opportunities, probably more in the U.S., and David was talking about on the prior questions regarding the contracting. As you know, there is significant rebate which have been negotiating in the U.S. We have also passed a price increase at the beginning of the year. Ex U.S., I will say the situation is more complicated. In many countries, it's probably difficult to change the pricing, and there may be some markets where we have tenders, and we are still assessing that opportunity.

The second part of your question was regarding the margin in 2027. So as I said, I'm not going to provide a guidance for 2027. As you know, we are very confident to exceed the outlook. Now the shape of 2027 will depend at what pace the generics are going to be able to make it, how many generics are going to be able to make it, if any, in the second half of this year and in 2027 and that could have an impact on the level of profitability. But we are very confident that in any case, we will be exceeding to some extent, the 32% target that we gave.

Then on your third question regarding Iqirvo growth and the bolus of Ocaliva. So what you have seen in terms of sales acceleration from September to December, is really the delta in terms of the acceleration came from the Ocaliva switches. We think the Ocaliva switches are mostly done. So we are on a higher level and that higher level should carry forward, of course, into 2026 because we are seeing still new patients, which are new to second line coming on to Iqirvo. So we're very pleased with that. And this is why we are very confident on Iqirvo and we observe a very strong dynamic.

On mergers and acquisitions. So as you pointed out, we have a bit more than EUR 3.2 billion of firepower. We intend to use this if we see the right opportunities. As I stated before, at JPMorgan, we are looking at oncology late-stage opportunities that we want to bring on board. And then, of course, in our guidance, as you remember, we already include the preclinical and early clinical in that guidance and in the margin. So you will also see us use part of this firepower for some of the earlier deals.

We will now take the next question from the line of Victor Floch from BNP Paribas.

Victor from BNP Paribas. A couple of questions on IPN10200. So I mean, I think it's fair to say that the optimal target profile for that one differs quite a lot between aesthetics and therapeutic use and notably when it comes to duration of action. So now that you have the full Phase II data in hand, I was just wondering whether you can discuss whether IPN10200 delivered an optimal profile, keeping its commercial potential impact in both opportunities. And then I understand that you don't really want to discuss your option, but I mean just to understand what would be like the tipping point when it comes to either go with a partner or either go with yourself? Is it just about like economics and whether that you want to protect at least the kind of economics you have on Dysport with that one?

And finally, on M&A, I was just wondering whether you can discuss whether you would be open to potentially stretch your firepower in your balance sheet beyond 2x EBITDA, if the right opportunity arise.

Perhaps, Victor, on your first question, can you just clarify why you are saying that the optimal target profile will be different. That's not something that we would subscribe to.

Okay. I mean I think it's -- I mean what do we understand in the past that for aesthetics use, I mean physicians were pretty happy with the 6 months duration of dosing, even though at the same time for therapeutic use, I think we're all looking for the longer duration as possible. So maybe you don't agree with that, but so I was just wondering whether you could discuss the target profile you've seen with the IPN10200.

Yes. First, I would like to bring this back to data, right? When you look at none or mild in aesthetics at 6 months. Most of the bond As have actually shown that you can go and look at the labels of these different drugs, most of them are between 20% and 30%. And so here, what we have said is we have seen a majority of patients achieving none or mild. And so that data is going to be presented. So in that sense, why many companies are saying, well, some patients are satisfied or they see still some effects and et cetera, I would just bring this back to the endpoints of none or mild because that's usually what is being measured in the clinical trials.

So in that sense, with that statement, I think the profile that we want to see in aesthetics and therapeutics is actually the same. You want to see a very rapid onset of action. You want to see a good 1 month efficacy and you want to see a prolonged duration. This is important, not just in aesthetics, but also in therapeutics, obviously, for example, in spasticity, migraine or cervical dystonia, where it can also help alleviate the health care system utilization because patients need to get less often to the doctor. So I don't know if that answers your question.

Definitely.

Then on your second, as I said, we are looking at all options. We are not going to comment on this right now. And then on your third question on the use of our firepower, I'll let Aymeric comment on the stretching the firepower.

Yes. So Victor, just to clarify, we are today operating clearly on the maximum debt of 2x EBITDA, which is fully in line with our investment-grade rating. This gives us a EUR 3.2 billion firepower on top of our very strong free cash flow, EUR 1 billion this year with a very ambitious guidance that we have this EUR 1 billion should even increase 2026. So we don't see any reason for using more than the 2x EBITDA. Having said that, the Board has always said that we consider if there were to be a unique opportunity and ability to slightly stretch that, but this is not today our priority.

We will now take the next question from the line of Lucy Codrington from Jefferies.

Just I was wondering if you could go into a bit more detail in terms of your expectations that Dysport this year, both in terms of aesthetics and therapeutics. And with that, any potential impact that you might expect as the Relfydess launches continue. And then any update on what the aesthetics environment is like in the U.S. and other markets at the moment?

And secondly, on Somatuline when you talked about the guide, you said growth. So I know you're -- it's somewhat dependent on the entry of generics, but should we be expecting growth on the numbers reported in 2025? Or still some decline?

And then second -- finally, any milestones that we should be factoring in for this year?

Thank you, Lucy. On Dysport, we are expecting good high single-digit growth in both markets, aesthetics and therapeutics. We do not anticipate any impact from Relfydess because that's a -- it's a different market. There is a market segment, which is open for liquids. I would say the majority of the market is on great constitution because many of the physicians actually like to dilute to their liking. We have seen this with the Alluzience launch as well. So we don't really foresee any cannibalization. It's quite the contrary. I think both are going to drive growth.

Then on aesthetics in the U.S. The market has slowed down a little bit, but our partner, Galderma is performing very, very well, gaining market share. So we are very pleased with that performance. On Somatuline, yes, we do anticipate growth versus 2025 because of what Aymeric just said before is you have -- of course, the volume gain of the generics not being there, but you also have some potential pricing upside. So there is this kind of double effect, if you want, versus the baseline of '25. And then I wasn't quite sure I understood your milestone question.

I think I get the question on milestone. I think this is related to our other revenue which, as I said during the presentation, have increased significantly in 2025. Our other revenue are made of both royalties that we received from partners and some milestones -- some of the milestones are nonrecurring. That's why we were indicating that our margin in 2026 is going to be slightly impacted by a slightly lower level of milestones and other level of other revenue, while we still continue to have a strong dynamic on the royalty side which is directly linked to the high single-digit expected growth for Dysport with our partner.

Thank you, Lucy. I think we have no more questions. So this wraps up our 2025 conference. Thank you for your attendance. Back to you, operator.

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

Hello, and welcome to Ipsen's Conference Call and Webcast on Q3 2025 Results.

I'll now hand you over to David Loew, Ipsen's CEO.

Thank you, and hello, everyone. I'm delighted to welcome you this afternoon to our year-to-date and third quarter sales presentation, which can also be found on ipsen.com. It's a pleasure to take you through the progress we are making this year.

Please turn to Slide 2. Please note of our forward-looking statement, which outlines the routine risks and uncertainties contained within this presentation. Also, all of my comments on growth will be based on constant exchange rates.

Please turn to Slide 3. I'm going to take you through our brief presentation, and then our CFO, Aymeric Le Chatelier; and our Head of R&D, Christelle Huguet, will join me to answer your questions.

Let's begin by taking a look at today's highlights. Please turn to Slide 4. Today's highlights illustrate how we are continuing to deliver strong growth. Total sales grew by 13.7% this quarter and by 12.1% in the first 9 months. We are very pleased to see a strong performance of our portfolio outside Somatuline, which grew by 12.3% in the 9-month period. Based on this continued solid momentum and strong growth, we are pleased to further upgrade our full year 2025 guidance. We now expect total sales growth around 10% at constant exchange rates as compared to our last guidance from July of sales growth above 7%. Regarding margin, we now expect the core operating margin around 35% of total sales as compared to more than 32% in our last guidance.

Turning to the pipeline. We are delighted by the first data for our first-in-class differentiated long-acting molecule, IPN10200, enabling the initiation of Phase III trial in aesthetics. In rare disease, we were pleased to receive the approval of Bylvay in Japan for PFIC, offering a nonsurgical treatment option for infants, young children and adults. Also in July, we announced the European approval of Cabometyx in NETs, an area where Ipsen has a strong legacy. We're also excited to announce the addition of ICT01 into Ipsen's clinical oncology pipeline following the intention to acquire ImCheck Therapeutics.

So let me provide you more details on this deal. Turn to Slide 5. This deal is focused on the lead clinical stage program, ICT01, in first-line unfit patients with acute myeloid leukemia, including high-risk patients who are ineligible for intensive chemotherapy, another strong addition to our pipeline as we expand our leadership in oncology. ICT01 is a first-in-class monoclonal antibody targeting BTN3A, a key immune regulatory molecule broadly expressed across cancer and follows strong data presented by the ImCheck team at ASCO 2025. ICT01 is currently in Phase II trials for AML, and we hope to be able to start the Phase IIb/III trial in 2026.

Ipsen proposed to acquire all issued and outstanding shares of ImCheck Therapeutics for a closing purchase price of EUR 350 million and downstream payments contingent upon achievement of regulatory and sales-based milestones with an expected closing by the end of the year or early 2026.

Turning to Slide 6. Our Q3 month sales delivered a solid 13.7% growth and 12.1% in the year-to-date, fueled by all 3 therapeutic areas with an improvement of performance for Neuroscience and Rare Disease this quarter compared to last quarter. The portfolio outside of Somatuline is growing at 16.7% in the quarter and 12.3% year-to-date. Oncology performed well with sales growth of 7% this quarter and 6.6% in year-to-date. Rare Disease continued to have the most impressive performance of our portfolio with sales doubling both this quarter and in year-to-date. Neuroscience with Dysport continued to deliver high single-digit growth.

I'll now turn to Oncology for more details. Please turn to Slide 7. Starting with Somatuline, sales were up by 11.7% year-to-date. Both Europe and the U.S. continue to benefit from shortages of generic lanreotide. While we do anticipate lanreotide generic competition with potential new entry next year, it is apparent that it is a complicated product to manufacture. Cabometyx sales were up by 2.9% with solid performance in Europe from increased volumes, offset by shipment phasing and increased competition in rest of world. Q3 performance was at 9.3%, including the rest of world returning to growth. NET's launch in Europe is progressing well with the first patients treated in Germany and additional reimbursements to come soon. Decapeptyl sales were up by 2.2% as we experienced volume growth in Europe and China despite continued competition and some pricing pressure in some countries. Onivyde sales grew by 4.8% with moderate growth in the U.S. driven by the first-line metastatic pancreatic ductal adenocarcinoma indication. We continue to expect challenges in the U.S. as communicated previously.

Now let's turn to Rare Disease. Please turn to Slide 8. In rare disease, Bylvay continues to perform well with year-to-date sales of EUR 135 million, growing by 46%, driven by strong demand in the U.S. and in Europe in both PFIC and Alagille syndrome indications despite increased competition. We're pleased to soon also launch in Japan, where so far, we didn't have an Ipsen commercial presence and where Bylvay will be the first of several drugs to be launched by our new affiliates, opening up this important market.

Turning to IQIRVO. We continue to track very well with sales reaching EUR 107 million this year. In Q3, we saw strong growth in the U.S. with a 46% growth quarter-over-quarter, driven by an increasing uptake from new patients. We also note the recent withdrawal of OCALIVA for PBC from the U.S., and we expect to see many of these patients transition to IQIRVO towards the end of this year and into 2026. The Europe launch gains momentum with more countries coming online with reimbursements achieved now in several countries.

Moving to Neuroscience. Let's turn to Slide 9. Dysport is performing well in aesthetics, where sales are up by 12.3%. We have seen continued growth in most territories, augmented by share gains in some countries. European markets have remained robust with a good performance despite negative phasing of shipments to our partner. In therapeutics, Dysport sales grew by 5.2%, both in Europe and in the U.S. Rest of the world performance was impacted by phasing of inventories in Brazil in the first half, but delivered solid growth in the third quarter. We are very pleased with how well Dysport has performed overall this year, and we are committed to high single-digit growing forward.

That concludes the review of sales. Now let's turn to the pipeline. Please turn to Slide 10. We have a well-balanced pipeline across the 3 therapeutic areas. The deal announced today will further strengthen our hematology pipeline. I would like to spend some time now focusing on the update for our long-acting program.

Please turn to Slide 11. In September, we announced the proof-of-concept data for IPN10200, Ipsen's uniquely engineered recombinant first-in-class molecule. These first data in glabellar lines follow the completion of Stage 1 of the ongoing Phase II LANTIC trial. We announced that patients treated with IPN10200 experienced a statistically significant improvement in response at week 4 versus placebo, the primary endpoint. A longer duration of effect was also observed with a substantial majority of patients experiencing a clinically significant response at week 24 compared with placebo and Dysport defined as none or mild off-line severity at week 24. IPN10200 was shown to be well tolerated with no safety concerns reported with any of the evaluated doses of IPN10200 across Stage 1.

Furthermore, the data demonstrated a rapid onset of action documented by patient diary data and superior patient satisfaction scores versus placebo and Dysport. The full data will be shared at the scientific conference in the first half of 2026 and Phase III start-up activities in aesthetics have been initiated. The Phase II LANTIC trial remains ongoing with Stage 2 currently recruiting patients to evaluate the safety and efficacy of IPN10200 compared to placebo in 4 headlines or lateral cancer lines. Phase II development continues for therapeutic indications, including adult upper limb spasticity, migraine and cervical dystonia.

Turn to Slide 12. We're expecting an update in Rare Disease, where we should report the pivotal FALKON trial results for fidrisertib in FOP in the coming months. Looking ahead to 2026, it is going to be a busy year for the pipeline with several anticipated Phase III data readouts across all 3 therapeutic areas, including for Bylvay in biliary atresia, IQIRVO in PBC as well as migraine trial readouts for Dysport.

Please turn to Slide 13. I would now like to conclude. We continue to deliver strong momentum and remain firmly on track to achieve our ambitions. There are 2 key messages. First, we are delivering strong financials with double-digit growth of our top line, fueled by the performance of our existing portfolio and launches as well as we upgrade our sales and margin guidance today. This consistent growth reflects our focus on execution and our ability to deliver across both commercial and medical fronts.

Second, we continue to expand the pipeline with the proposed acquisition of ImCheck Therapeutics, progression of IPN10200 and multiple catalysts to come over the next 18 months.

Finally, we have significant firepower to pursue external innovation. We remain disciplined but ambitious, and we are well positioned to seize the right opportunities to further strengthen our portfolio. We're committed to advancing science with purpose to bring the benefits patients are looking for as we believe everyone deserves a life fully lived.

With that, please turn to Slide 14. This concludes our presentation, and we will now take your questions. Operator, over to you.

[Operator Instructions] Our first question comes from the line of Charles Pitman-King from Barclays.

Charles Pitman-King from Barclays. Two, please. Maybe just to start off, just wondering if you could give us a few more thoughts on the kind of Dysport phasing at this point. I'm wondering if you're able to kind of quantify the impact here of 3Q versus 4Q. Can we expect that there's going to be some form of catch-up there? I'm just wondering if you can provide a little bit more color on the end market dynamics for Dysport across aesthetics and therapeutics versus peers, including specifically just how you're currently viewing Galderma's positioning of Dysport versus Relfydess given that's where a lot of investors are focused as of our feedback this morning.

Second question, please, then on Somatuline and guidance. The guidance that you provided today reflects limited impact expected from generic erosion for the rest of the year. I'm just wondering how that compares to your assumption behind the guidance at 1H '25. And given the degree of margin expansion guidance between 1H and 3Q, can we assume this is entirely driven by Somatuline not facing as high erosion as you had anticipated? And what this could mean for 2026, given your expectation that generics could ramp up over that -- over next year, could margins decline year-on-year? Any commentary would be great.

Thank you, Charles. Perhaps I start with the market dynamics of Dysport, and then I hand over to Aymeric for the Dysport phasing estimation and the assumptions on the more limited impact on Somatuline.

Regarding market dynamics, we see that we're performing well, Galderma and ourselves in the territories that we have in the aesthetic market. We see market share gains in the U.S. and performance is also very well in Europe. Relfydess has just started with the launch. So it's a little bit early to comment on this one, but we are very satisfied with the Dysport performance.

On Dysport phasing then, I hand over to Aymeric and also for the Somatuline impact assumptions for Q4.

Yes. So thank you, David. So Charles, to answer your questions, yes, the Dysport performance, as you see, we're delivering a very solid over 9% growth, both on the quarter and year-to-date, and this is really our guidance for Dysport to continue to deliver high single digit.

Having said that, if you look quarter-by-quarter, we are impacting by phasing of shipments. So I will say both on the therapeutic and the aesthetic, we believe that both therapeutic and aesthetic will continue to perform very well. David was talking about the aesthetic performance. I think on the therapeutic also, we're confident. You see the U.S. continue to deliver double-digit. I think the rest of the world has been impacted by Brazil. So the Q3 was really strong with some catch-up. I think it should normalize in Q4. But overall, we are pretty strong here.

On the aesthetic side, there is also some shipment issue. As you know, we're shipping to Galderma, our partner. And depending on the phasing of shipment, the level of inventory also at the end of last year, this is significantly impacting. So as you see, the overall performance for the first 9 months is minus 13%. And I think that all of that, not to say more than that, is related to phasing and shipments. So that was your first question.

Regarding your second question, I think there is a lot of question into your question, which is really trying to understand better the assumption behind our guidance and potentially what could be the impact for 2026 on the group profitability. So I think you're right to say that today, upgraded guidance is to a large extent related to the better performance of Somatuline. We were anticipating that there will be more generic to come in the market, and there will be also more impact of the existing generic on both the U.S. and the EU. Today, we see a much slower erosion than what we anticipated. So this is the reason why our guidance on sales has been increased. And this is also what you see as a translation in our core operating income. This is combined with some other impact. The rest of the portfolio continue to perform pretty well, and David was talking about IQIRVO and also we get some other revenue that are very strong in 2025.

Going into 2026, as you know, I'm not going to provide the guidance for 2026, but we are comfortable with the momentum that we have on the rest of the portfolio, even if there were to be more impact of generic potentially because, as David said, it's very difficult to predict because the product is complicated to manufacture. We believe we will be able to continue to grow. But should the pressure and erosion from generic be more important in 2026, we should see some lower level of profitability in 2026 than the 35% that we are guiding for this year. We'll provide more detailed numbers in February when we provide the guidance for 2026. I hope it answers your several questions on Somatuline.

Our next question comes from the line of Simon Baker from Rothschild & Co Redburn.

2.5, if I may, please. Firstly, on ImCheck and the impressive ICT01. I just wonder if you could share your thoughts not only on the potential in the lead indication, AML, but it's also in development for DLBCL, mantle cell lymphoma and multiple myeloma. Are they areas of equal interest? Would they be areas that you would promote on your own? Or would there be potential for partnership there?

Secondly, looking at the FOP opportunity for fidrisertib. I just wonder how that's changed, if at all, in light of the Regeneron garetosmab data?

And then finally, just a quick one. We're starting to see a gentle stream of letters doing deals with the White House on drug pricing. I just wondered if you could give us an update on your own experiences there.

Thank you, Simon. So regarding ImCheck, we are indeed enthusiastic about this one. What we have modeled currently, which is why we determined that we wanted to make the deal is the potential in first-line unfit really. We're not guiding on peak sales yet, obviously, because we have to now see much more data in Phase IIb and III. So it's a bit too early here. What I can say is in terms of helping the modeling a bit, in the U.S., you have about 7,000 patients, which are in AML in first-line unfit not eligible for high-dose chemotherapy. And then inside of that pool, we have assumed that there will be targeted therapies coming. So we have actually taken only 60% of the 7,000, which we consider eligible.

Of course, there could be an upside. You never know how the data is going to look like. And when you take KEYTRUDA, for example, KEYTRUDA sometimes performed better than some of the targeted therapies. So it could be that this is a conservative forecast model, but this is what we have done. We will look indeed at life cycle management. There are ongoing trials, as you mentioned, but we are also going to look with the team once we have closed the deal at other potential life cycle indications.

Regarding the footprint to your question, I mean, remember that on Taz, we're already present in the U.S., not yet outside of the U.S. But this is in oncology, that's not really a problem because oncology field forces are not that big. I mean you're not talking like GP or high-volume specialty care here. So that wouldn't be a concern for me at all.

To your second question on FOP on fidrisertib, we just need to now be patient to have the readout of the trial. And only then we can really comment regarding your question on Regeneron. Remember, the Regeneron trial was in patients in 18 years and above. And most of the progression of the disease happens already much earlier -- already in early childhood. Our trial was including 5 years of age and above. So if fidrisertib will demonstrate efficacy, then there is certainly an advantage just based on the label. A lot of the disease has already happened up to adulthood, I would say. So there is not such a big benefit after, let's say, 20 years of age because many patients are already in a wheelchair. They have already a lot of their joints locked, unfortunately. So this is just something to keep in mind.

Regarding your third question on deals on MFN, you will remember that the White House sent the letter to the 17 biggest pharma companies. We have seen a couple of deals right now. We heard that more deals are going to happen. When you look at how these deals were structured, they seem to have a very similar pattern. So we have to anticipate that perhaps at one point, this is going to be a bit more common for the whole pharmaceutical industry, but it's too early really to speculate on this one. We have not been contacted so far.

Our next question comes from the line of Lucy Codrington from Jefferies.

I've got 3, if that's okay. So firstly, on Decapeptyl, you commented on the competition and the pricing pressure you're facing. So I just wanted to think about how you're looking at that original mid-single-digit guide you'd given when outlining the midterm aims and if there's any change to that?

Secondly, on Onivyde, I understand that the first-line expansion is taking time, but could you give us more info about how the second-line setting is performing and why growth appears to be stalling a little there?

And then finally, just on the Dysport migraine readouts next year. Firstly, why have they taken so long to conduct? I think the readout has been delayed a year. And then just more generally, is there any reason to expect that these wouldn't work in migraine given we know BOTOX does?

Thank you, Lucy. So on Decapeptyl regarding competition and pricing and our guidance of having a mid-single digit. I think it's going to be a bit in the lower area of the mid-single, I would say, because we see this with the competition. So for example, in China, we have some launches in the 1-month segment. And in Europe, it's mostly pricing negotiation, which we have anticipated. So it's actually fairly in line with our expectations.

On Onivyde, regarding the first-line expansion, it's definitely harder than what we have anticipated. Second-line is not showing such a strong dynamic. We thought the real growth is going to come from the first-line. So we are still looking at this from all angles, trying to do more real-world effectiveness, also some Phase IV studies, but it's definitely a bit harder than what we have anticipated.

On Dysport migraine, I would actually correct that perception. There is no delay that you mentioned on this 1 year. That's wrong. We have never assumed any earlier time line. So we have consistently reported that it's going to be mid next year roughly. We would anticipate that it works as BOTOX does in chronic migraine, but you run the trial to find out if it really does. So we have to just be patient for the migraine data to read out here.

Our next question comes from the line of Sofia Graeff Buhl-Nielsen from JPMorgan.

Firstly, just on the LANT data. Maybe if you could provide some insight on to how you're seeing the efficacy of the profile relative to other toxins on the market beyond Dysport both at 4 weeks and 6 months?

And then just in light of today's acquisition of ImCheck and the target of starting a Phase IIb, Phase III trial next year, how are you seeing R&D spend developing into 2026?

Okay. I'm going to take the first question, and then I will ask Aymeric to comment on the costs for the ImCheck Phase IIb/III spend.

On LANT, so as you know, we have compared the efficacy versus placebo, but more importantly, also, we had Dysport in there. And we have shown that the data looks very attractive versus both of them. I don't want to speculate on cross-study comparisons because we see differences sometimes in the trials that have been conducted a long time ago, like a lot of the BOTOX and Dysport trials have been conducted a long time ago. They didn't all use the same endpoint. So you're going to see the most recent data on Dysport, which looks very good, at the upcoming conference where we are going to submit the trial data in the first half of next year.

And I think we need to stick to these clean comparisons rather than going cross-study comparisons because sometimes you also have slight underlying demographical differences, et cetera. So I think we need to really look at the data as it will stand. And then, okay, I'll let you do cross studies if you want to do that. But I would just caution you that this is always a difficult exercise to do because small underlying demographical differences can sometimes change things. But we are extremely pleased with the IPN10200 data we have to say.

On ImCheck, regarding the spend dynamics, I'll let Aymeric answer.

Yes. So regarding ImCheck, as a reminder, so next year 2026 will be mainly the launch of the Phase IIb, so you should not anticipate very significant expenses. But even going forward, this is going to be a 3 to 4 years study. So you should anticipate that this is a normal Phase III in oncology. And as a reminder, this is for us a mid-stage transaction, which is fully embedded in our guidance. So when we provided the 2027 guidance of at least 32% of sales, this assumes deals preclinical, but also early-clinical to mid-clinical. And this one is fully into our guidance or outlook for margin.

Our next question comes from the line of Xian Deng from UBS.

Xian from UBS. Two questions, if I may. The first one on Somatuline, please. It's just a follow-up on the previous Somatuline question. I wonder if I could maybe push my luck a little bit. Given that we -- you are not expecting very limited erosion for this year. So just wondering how should we think about 2026 erosion purely from a modeling perspective? Because if I look at the consensus now without sort of basically updating after today, right, the current consensus is kind of modeling, let's say, mid-teens-ish erosion for '26, '27. But of course, now if this is actually coming from a much larger base in 2026, I was just wondering how should we actually think about the erosion in '26 onwards? So that's the first question.

And the second one is also just wondering just sort of to follow up on your previous comment on the R&D spending impact fully embedded. But just wondering for full year 2026, of course, understanding that you can't give guidance now, but just wondering if you could maybe remind us some push and pulls in the R&D and SG&A into 2026. So for example, the Bylvay BA study should be winding down? And are you going to prepare some SG&A, et cetera? So yes.

Thank you, Xian. On Somatuline, I mean, as you know, of course, yes, you're pushing your luck. We're not giving guidance on 2026. Having said that, you're right that we're going to be on a higher base. I think what we also observed is that while we have to anticipate more competition coming in, the generics are really struggling with the production of the compound. I mean you have seen Sun Pharma had the registration already since October last year, and they are nowhere to be seen in the market. We see that Pharmathen is struggling to get the volumes up. So I would love to be a fly in their production building to know what's going on. Of course, we cannot know it with precision here. So we just have to assume that there will be somewhat of a gradual erosion next year and potentially with more competition coming in, perhaps Sun Pharma launching or getting the approval in the U.S. next year. So that -- we just want to be carefully guiding on Somatuline, but I have to say we are very pleased with the performance of Somatuline.

Regarding the push and pulls on the spend, regarding your question on R&D and SG&A, I'll let Aymeric answer on this one.

Yes. So your first question was on the R&D cost. So as a reminder, we said that we wanted to get R&D as a percentage of sales to be at least at 20%. I think this acquisition of ImCheck will contribute. You have to keep in mind, if we take the pull and push that some of the large Phase III will start to be at a lower cost in 2026. So there's going to be quite a number of readouts. At the same time, we are accelerating our program in neuroscience. So you should expect a little bit more. And we're still committed to continue to do more deal early stage, mid-stage like ImCheck. But overall, I think you should expect R&D to slightly increase from the 20% in 2026.

Regarding SG&A, I think your question was aiming to, on one side, I think we have the full infrastructure in place. And today, it's more delivering on the existing launches, especially Bylvay, IQIRVO, but also all the infrastructure in oncology. You should not expect significant increase. But at the same time, we're going to prepare for the launch of the potential life cycle management of 2026. These are not going to be massive investments because clearly, most of the investment is going to be more towards '27 when we're going to be actually launching those expected life cycle management.

Our next question comes from the line of Victor Floch from BNP Paribas.

I'm Victor from Paribas Exane. So maybe first one on the arbitration related to IPN10200. So maybe can you help us understand the range of outcomes there and whether it's reasonable to assume that the resolution of that arbitration might not immediately clarify the commercial strategy for that asset, but maybe more likely mark the beginning of a potential broader discussion on your extended collaboration on toxin with Galderma. So that was my first question.

And then my second question on M&A. I mean, congrats for the deal. And I was basically just wondering if we should assume like more deals like this one, which are that you are basically qualifying as mid-stage deals. But should we still assume that you're going to execute on 1 or 2 later-stage production in the near term?

Thank you, Victor. On the arbitration, I will not speculate what the outcome might say and the clarity that we're going to get or not get and et cetera, because arbitrations, they can go sometimes in all different directions. That's just the character of arbitration. We expect the readout towards the end of the year. So we should know more fairly soon. And obviously, we're going to then communicate on the findings on the arbitration. So not much more that I can say at this point.

On M&A, you're right, we have in our strategy, a mix of different deals from the preclinical to early mid-stage clinical, but also late-stage clinical. And yes, we absolutely want to do more mid-stage clinical deals like the one we have just done with ImCheck. But we are also absolutely looking at late-stage deals or on-market deals because we want to make sure that we can continue to expand our pipeline and our footprint in oncology, but potentially also in rare disease. And in neuroscience, you have just seen us with the long-acting neurotoxin results. So clearly, we are looking at late-stage deals, and we have ample firepower still even after this ImCheck deal because we included that, as Aymeric said, we included that in our guidance already. So this is not changing in any way our guidance, the ImCheck deal. It would be the case if we would do a late-stage large deal, then it might influence our guidance.

Our next question comes from the line of Florent Cespedes from Bernstein.

Florent Cespedes from Bernstein. Two quick ones, please. First of all, on ImCheck acquisition. I have a question on the product ICT01, the tolerance profile we see some neutropenia infections. I was just wondering whether this could potentially impact the expansion of the product on different population, notably on less severe patients. So having a product with different side effects, how this could potentially impact the future potential of the product? That's my first question.

And second question, an easy one. When I look at the major coming milestones for 2026, I don't see TAZVERIK on the list on the updated slide. So some comments on this would be great.

Thank you, Florent. So I will actually give both questions to Christelle Huguet, our Head of R&D.

Thank you for the question, Florent. So let's start with ICT01. So when you look at the EVICTION trial and you look at the safety profile, it's, in fact, very well in line with the safety profile of venetoclax plus azacitidine in the AML population. So in fact, it appears that ICT01 does not add to the safety profile and is well tolerated in those patients.

To your second question regarding TAZVERIK, so the SYMPHONY-1 trial is doing well and will be fully enrolled by the end of the year. As you will remember, this is an event-driven readout. And from what we can gather in early interim look, we think that it's going to read out towards the very late end of last year and maybe fall into the first quarter of '27. That's why you're not seeing it on the pipeline for '26. However, the study is going well.

Our next question comes from the line of Natalia Webster from RBC Capital Markets.

Firstly, just a follow-up on your SG&A investment into the IQIRVO and Bylvay launches. Q3 sales are stronger for both of those. So I just wonder if you're able to comment on the impact you're seeing from the investment in your sales force for both of these products in Q3 and then how you expect that to progress in Q4 and into 2026?

And then secondly, specifically for IQIRVO, you said that you're anticipating the U.S. withdrawal of OCALIVA to benefit sales from Q4. Are you able to comment on how you expect this benefit to be split between IQIRVO and competitor Livdelzi?

Thank you, Natalia. On the investment of IQIRVO, so we have indeed invested adequately, I would say, the push on IQIRVO because we are very excited about the product. and we have seen a very, very nice pickup of IQIRVO and also Bylvay. What we have done is we have split out Bylvay pediatric indication to a dedicated pediatric field force as of October. Now they're just being on the territory now. And that gives, of course, by the simple arithmetics, a bit more share of voice for the IQIRVO field force because they were also taking care of Bylvay there. So I think we are going to continue seeing a positive momentum on IQIRVO and Bylvay for the future.

Regarding your second question on the OCALIVA withdrawal and the split, I think, honestly, we're going to probably see a similar pickup of these OCALIVA patients in line with the market shares that we are seeing right now. I would say that the fatigue data has definitely helped us continuously seeing an acceleration as well on IQIRVO and being very competitive in the field here. So we're very pleased with the performance so far.

There are no further questions at this time. So I'll hand the call back to David for closing remarks.

Thank you very much, everybody, and have a good rest of your day. Bye-bye.

This concludes today's conference call. Thank you for participating. You may now disconnect. Speakers, please stand by.

Hello, everyone. I'm delighted to welcome you this afternoon to our H1 2025 results presentation, which can also be found on ipsen.com. I want to use the time we have together to focus on the progress Ipsen delivered in the first half of 2025 and on the future opportunities and platforms for growth.

Please turn to Slide 2. Please take note of our forward-looking statements, which outline the routine risks and uncertainties contained within this presentation. Also, all my comments on growth will be based on constant exchange rates.

Please turn to Slide 3. I'm going to take you through the presentation of our latest business update, followed by Christelle Huguet, Head of Research and Development, who will provide an R&D update, while our CFO, Aymeric Le Chatelier, will take you through the financials. At the end of the presentation, all 3 of us will be participating in the question-and-answer session. Let's begin by looking at today's highlights.

Please turn to Slide 5. Today's headlines illustrate how we are continuing to produce sustainable growth. Total sales grew by 11.4% in the first half of 2025, accompanied by a core operating margin of 36%. As you have seen, we announced last week the European Commission approval of Cabometyx in neuroendocrine tumors, an area where Ipsen has a strong legacy.

During this first half, we also made good progress with our pipeline, including the entry in Phase II of IPN10200, our long-acting neurotoxin AD in cervical dystonia. This milestone highlights the fourth study in the global long-acting neurotoxin development plan in therapeutic and aesthetic indications. Pipeline progress also came in form of the EMEA regulatory submission of tovorafenib for pediatric low-grade glioma earlier in the year.

In the second half, we anticipate a pivotal trial readout for Fidrisertib in FOP and excitingly, our first proof-of-concept data for our long-acting neurotoxin in aesthetics. Christelle will provide more details on these as well as on the development of elafibranor in PBC and PSC in her section. Lastly, based on the solid momentum and the strong performance of this first half, we are pleased to upgrade our full year guidance. We now expect total sales growth greater than 7% at constant exchange rates and the core operating margin greater than 32%. Aymeric will provide more details in his section.

Please turn to Slide 6. Our sales in H1 delivered a solid 11.4% growth, fueled by all 3 therapeutic areas with Q2 very much aligned with Q1 performance. Oncology has performed well with H1 sales growth of 6.4%. Rare Disease continued to have the most impressive performance driven by the sustained success of Iqirvo and the strong performance of Bylvay. Neuroscience with Dysport continued to deliver high single-digit growth.

I now turn to Oncology for more details. Please turn to Slide 7. Starting with Somatuline, sales were up by 14.1%. Both Europe and the U.S. continued to benefit from shortages of generic lanreotide. We do anticipate more lanreotide generic competition with potential entry in the second half of the year. Cabometyx sales were slightly down by 0.2% with solid performance in Europe from increased volumes, offset by shipment phasing and increased competition in the rest of the world. We're confident that Cabometyx should continue to grow its market share in the current indication in renal cell carcinoma and progressively launch in the neuroendocrine tumor indications. Decapeptyl sales were up by 0.5% as we experienced volume growth in Europe and China despite continued competition and some pricing pressure in some countries. Onivyde sales grew by 6.5% with moderate growth in the U.S., driven by the first-line metastatic pancreatic ductal adenocarcinoma. We recognize that it will take time to drive first-line differentiation and address some challenges around access to payers.

Now let's turn to Rare Disease. Please turn to Slide 8. On Rare Disease, Bylvay continues to perform nicely with H1 sales of EUR 87 million, growing by 53.7%, driven by strong demand in the U.S. and in Europe in both PFIC and Alagille Syndrome indications. We also had an increasing contribution from rest of world with access and reimbursement now secured in 17 countries.

Turning to Iqirvo. The launch continues to track very well with sales reaching EUR 59 million this semester. In Q2, we saw an acceleration in the U.S. with a 65% growth quarter-over-quarter, driven by an increasing uptake from new patients and switches from Ocaliva. Europe was also very strong with sales mainly from Germany and the U.K. and launches initiated in Spain and Italy in June.

Moving to Neuroscience. Let's turn now to Slide 9. Dysport delivered another solid performance with H1 sales growth of 9.7%. In aesthetics, sales grew by 17.5%, driven by continued expansion in most territories, including the U.S., Europe and Rest of World and by a strong performance from our partner, Galderma, who continued to gain market share in key countries and a solid growth in our Ipsen territories.

On the therapeutic side, Dysport showed solid and consistent demand growth across all geographies. In the U.S., notably, we continue to gain market share in our spasticity indications with strong double-digit sales growth. Reported sales were, however, flat due to an adverse phasing of orders in Brazil. Supported by solid market growth in both indications and strong execution, we're confident that Dysport should continue to deliver high single-digit sales growth in the short, mid and long-term.

Now I'd like to present the upcoming catalysts. Please turn to Slide 10. In the second half of 2025, we are expecting updates in Rare Disease and Neuroscience. Starting with Rare Disease, we should report the pivotal FALKON trial results for Fidrisertib in FOP. Secondly, in Neuroscience, we're expecting the proof-of-concept data readout for land in aesthetics. Looking ahead, 2026 is going to be a busy year for the pipeline with several anticipated Phase III data readouts across all 3 therapeutic areas, including for Bylvay, Iqirvo, Tazverik as well as migraine trial readouts for Dysport. With that, I'll now hand over to Christelle, who will provide more detail on our pipeline and those exciting milestones. Please turn to Slide 11.

Thank you, David. Good morning and good afternoon. Please turn to Slide 12. As David already mentioned, last week, we were delighted to receive the European Commission approval for Cabometyx in advanced pancreatic and extrapancreatic neuroendocrine tumors. This approval was based on the strong results of the CABINET study displayed here on the graph, which showed a significant improvement in median progression-free survival for patients treated with Cabometyx versus placebo. Working within the NET community for more than 35 years, we recognize that patients require multiple lines of therapy for this slow growing and chronic form of cancer. We are now focused on bringing this important treatment to patients.

Please turn to Slide 13 and our pipeline. We continue to have a strong and differentiated pipeline that has advanced in all 3 therapeutic areas in the first half of 2025. In Oncology, we have established a strong expertise in the MAP kinase pathway, starting with tovorafenib, a second-generation RAF inhibitor and the FIREFLY-2 Phase III study in untreated pediatric low-grade glioma patients. IPN01195 our newest third-generation RAF inhibitor has entered the clinic in April, alongside IPN01194, which selectively inhibits ERK also in the MAP kinase pathway.

Both IPN01194 and IPN01195 are being evaluated in a number of solid tumors. In Rare Disease, we continue to grow our rare liver portfolio, both in pediatric with Bylvay in biliary atresia and in adults, in PSC and PBC with Iqirvo. I will share more on the ELMWOOD study in a minute and also update you on the FALKON study in FOP.

In Neuroscience, we continue to evaluate the potential of our portfolio in both chronic and episodic migraine. We've also just shared that we have added a fourth Phase II trial in our program with CATALPA evaluating IPN10200 in cervical dystonia.

Please turn to Slide 14 for more details on the Rare Disease portfolio and starting with fibrodysplasia ossificans progressiva or FOP. FALKON is a Phase II registrational study evaluating the change in heterotopic ossification volume from baseline to 12 months and assessed by whole body CT scan. Importantly, Fidrisertib selectively inhibits the mutated form of ALK2 that is found to be a driver in FOP. We expect this data to read out in the second half of 2025.

Please turn to Slide 15. With an update now on the rare liver disease portfolio. First, starting with primary biliary cholangitis. At the recent EASL meeting, we shared late-breaking data from the Phase III ELATIVE study for Iqirvo in PBC. Additional analysis showed that at week 52 of treatment, 67% of patients treated with elafibranor, had a clinically meaningful improvement in fatigue compared with 31% of patients treated with placebo. Importantly, this effect was also shown to be independent of the reduction in pruritus. Alongside these data, we presented evidence from a comprehensive proteomic analysis that showed the PPAR-alpha activation is linked to the fatigue improvement in PBC.

Please turn to Slide 16. Moving into PSC. At EASL, we also shared the results of our Phase II ELMWOOD study, evaluating the safety and efficacy of elafibranor in primary sclerosing cholangitis, a rare liver disease that currently has no approved treatment options. In this study, elafibranor showed a favorable safety profile and demonstrated dose-dependent efficacy at 12 weeks versus placebo across a number of endpoints, in particular, significant improvement in liver biochemical parameters, including alkaline phosphatase shown on the graph on your left. In the center graph, stabilization of noninvasive markers, including enhanced liver fibrosis, ELF.

Of note, the changes in ELF are greater in patients with moderate-to-severe fibrosis at baseline. And finally, the graph on the right shows a significant improvement in pruritus, and this was observed using the Worst Itch NRS score at the 120-week dose. We are now engaging with regulatory agencies to decide on the next steps of our clinical development program for this indication.

Please turn to Slide 17. In Neuroscience, the next data readout is the LANTIC Phase II, a multistage dose escalation study, evaluating the safety and efficacy of IPN10200 in moderate-to-severe upper facial lines. The proof of concept is determined in the Stage 1, where we are evaluating IPN10200 in glabellar lines, and we expect these data in the second half of 2025. The Stage 2 of this study has already started and includes 4 head and lateral cancer lines.

We are excited to see these results coming from the Stage 1 in the coming months and a positive proof of concept will support a Phase III start. I would now like to hand over to Aymeric Le Chatelier for the details of our H1 financials. Turn to Slide 18, please.

Thank you, Christelle, and hello, everyone. I will now take you through the detail of our financial performance in the first half of this year as well as our guidance for 2025. Please turn to Slide 19. We delivered another set of strong financial results in the first half across sales, core operating income and cash flow. Our total sales of EUR 1.8 billion grew by 11.4% at constant exchange rates. Our core operating income grew by 21.9% to EUR 656 million, in line with our free cash flow, increasing also by 22% to EUR 483 million. Given this strong performance and our solid balance sheet with no debt, we now have at the end of June an updated firepower available for external innovation of EUR 3 billion. Let's go more in the detail of those financials in the following slides.

Please turn to Slide 20. Starting with the P&L to core operating income, the growth in total sales of 11.4% at constant exchange rate translated into 9.7% at current rates given the adverse currency movement, mainly from emerging markets. Gross margin increased by 2.1 percentage points, driven by a favorable product mix and higher other revenue from partners. R&D costs increased by 12.8% to reach a ratio of 20.1% of total sales, driven mainly by increased investment for Dysport in migraine, long-acting toxin in aesthetic and therapeutic and our early-stage oncology assets. SG&A costs increased by only 5.6% with a ratio to sales at 33.3%, improving by 1.3 percentage points, reflecting our commercial investment to support the launches, but also the impact of our efficiency programs.

As a consequence, our core operating income increased by 21.9% with the core operating margin standing at 36% of sales, an improvement of 3.6 percentage points.

Please turn to Slide 21. IFRS operating income and consolidated net profit increased both by more than 40%, thanks to lower restructuring and other operating expenses, lower financial expenses and despite impairment losses recognized for EUR 53 million in relation with discontinued early-stage assets as well as slightly higher income tax.

Please turn to Slide 22. Finally, on cash flow, we continue to generate strong free cash flow this year and have a strong balance sheet with a cash position of EUR 488 million at the end of June. Free cash flow increased by 22.8%, driven by EBITDA growth, sound management of capital expenditures and working capital. Net investment included payments related to regulatory and commercial milestones. With a net cash position of EUR 488 million at the end of June and based on a maximum 2x net debt to EBITDA, we have a firepower of EUR 3 billion available for external innovation.

Let's now move to 2025 guidance and turn to Slide 23. Based on this solid momentum in the first half of the year and that very strong performance, we are pleased to upgrade our full year 2025 guidance. First, we expect total sales to grow by more than 7% at constant exchange rate as compared to our previous guidance of sales growth above 5%. We assume also a negative impact of 2 points from currencies based on the latest exchange rate during the month of June. This guidance assumes, as indicated by David, a negative impact in H2 on Somatuline sales in the U.S. and in Europe with a progressive resupply from the current generic and a potential entry of additional generic.

On the other side, we expect an accelerated sales growth from the rest of the portfolio, driven by the significant ramp-up of Iqirvo in the U.S. and in Europe as well as the growth of Cabometyx. On the other hand, we anticipate now a core operating margin greater than 32% of total sales as compared to more than 30% in our previous initial guidance. It assumes, however, a lower level of profitability in the second half of the year, including additional R&D expenses from potential early or mid-stage external innovation opportunity, additional commercial investment to support our launches and a lower level of other revenue than in the first half of the year.

With all of that, I will now hand over back to David. Please turn to Slide 24.

Thank you, Aymeric. I will now move to the conclusion.

Please turn to Slide 25. We continue to deliver strong momentum and remain firmly on track to achieve our ambitions. I'd like to leave you with 3 key messages. First, we intend to continue growing our top line, fueled by the performance of our existing portfolio and launches. This consistent growth reflects our focus on execution and our ability to deliver across both commercial and medical fronts.

Second, we remain committed to continuing our R&D investments and growing our internal pipeline while investing to support our current and future commercial launches. Finally, we have a significant firepower to pursue external innovation. We remain disciplined but ambitious, and we are well positioned to seize the right opportunities to further strengthen our portfolio.

With that, please turn to Slide 26. This concludes our presentation, and we will now take your questions. Operator, over to you.

[Operator Instructions] Our first question comes from the line of Richard Vosser from JPMorgan.

Two questions, please. Just one on Somatuline. It seems like generics are always going to have supply issues. So at what point do you think we can think about a substantial residual tail to the business? Where might that be? How should we think about the outlook maybe beyond '25 for '26 and I suppose the profitability of the business during that period?

And then a second question on Iqirvo launch. Just obviously going very strongly, how should we think about that and the level of use maybe off-label in other indications that might come through going forward in the coming months?

Thanks a lot, Richard. On your first question, I mean, I have to say, first of all, we're very pleased with our performance on Somatuline, and it also shows that it is a very difficult to produce compound. So we have observed that Pharmathen is only coming back very slowly, delivering to Advanz in Europe and Cipla. So they're slightly increasing. And on Sun Pharma, which had the approval last year in October, we don't see them on the market. Now they are telling the market that they might come towards the second half in Europe. In the U.S., we have not heard anything. So it's correct that Somatuline is holding up very nicely, but we just want to be careful. Perhaps one day, they are going to figure out how to produce it, and we will see a somewhat accelerated erosion.

That's all I can say because we're not inside the production buildings of these companies, and it's hard to say how well they are doing on eventually ramping up. So I would assume that there is going to be a tail in the future even because of those reasons that it's so hard to produce. On Iqirvo, we are, as you said, on a really nice trajectory. We are off to a great launch in the U.S., but also outside of the U.S. We have had outside of the U.S., a substantial advance versus Gilead. And we have also seen the withdrawal of Ocaliva in Europe. So that has accelerated things for sure. And we have been able to capture a lot of switch patients as well.

And we're only about to launch now in other large markets. We just got the reimbursement in June in Italy and also in Spain. So we are ramping up there. So things are going very well. In terms of off-label use, PSC, I guess, you would allude to because we have shown results in May at the EASL conference, which look very promising, and we are going to discuss these results with the FDA and potential way forward in PSC.

But I can't really comment on off-label. As you know, we are not promoting it, obviously. We can only have scientific exchanges through our MSLs when we get questions. But so far, so good. I mean there is a lot of enthusiasm on Iqirvo. And we also have shown new fatigue data. We analyzed the data with proteomics. And we believe the PPAR-alpha effect is actually linked to this fatigue effect, which is totally independent from pruritus. So that's also encouraging data. So I'm very positive on Iqirvo, I have to say. Thanks a lot for your question.

next, we have Xian Deng from UBS.

And just 2, please. The first one on Cabometyx. Now you've got the NET approval in Europe. So just wondering how should we think about the cadence in the second half? Roughly when are you thinking to launch? Can you actually launch immediately given this is actually a drug that's already on market, so we should expect already uptick from Q3 or this is more going to be back-end loaded? So that's the first question.

And second one on Dysport, please. Just wondering what's the latest underlying trends in aesthetics that you've been seeing? Have you seen any softness in the U.S. from macroeconomics and anything else?

Thank you for your questions. On Cabometyx, obviously, we're very enthusiastic now launching into neuroendocrine tumor. This is an area that we know very well, obviously, because we have had a very long legacy with Somatuline in this. We know the KOLs very well. We can launch in Germany, as you know, immediately because you can launch when you have the approval in Europe in Germany. And then for the other markets, we will have also some payer discussions. And it sometimes takes up to 12 months with payers in Europe outside of Germany to actually get the reimbursement, and then we're going to be ready to launch there as well.

On Dysport, your question on the trend in Ax, we don't really see a softening in the U.S. We see that our partner, Galderma is doing an excellent job in the U.S., gaining market share, but also outside of the U.S. gaining market share. And we see a similar trend in the territories that we have in aesthetics, where we also see a nice growth. So as I said, on this part, we expect short, mid, long-term, really nice growth in aesthetics, but also in therapeutics. So next question, please.

next, we have Victor Floch from BNP.

Maybe first on Iqirvo. I was wondering if you could comment on the potential next step in PSC. And I guess it's mainly tied to the Iqirvo IP situation. So -- if so, what are your options to meaningfully extend Iqirvo LOE? And if you can do it, what would be the other indication you would be looking at?

And my second question on the LANTIC readout later this year. Any chance you could remind us what data you are expecting to share in the second part of the year? So I can understand it's going to be limited to the Stage 1. And so can you confirm that out of those Stage 1 data, it will be enough to have a clear view on the asset duration of action?

Okay. Thank you, Victor. On Iqirvo regarding next steps on PSC, as I said, I mean, we have presented the data, which was very encouraging, not just on ALP, but also on the fibrosis, which is what you want to see in PSC. So we are going to have a discussion with FDA in terms of potential trial design. On IP, as you know, we have orphan drug designation, but there is also method of use patents. So if you would, for example, get an approval in PSC and since this is a different dose, it's 120 milligram, we could also get another orphan drug protection there. And so this is what we are right now discussing.

Regarding the LANTIC data, I will ask Christelle to comment.

Thank you. Victor. So yes, indeed, we're reading out the Stage 1 of our LANTIC study that looks at the safety and efficacy in glabellar line. And this study has a design that includes a follow-up of both our primary and secondary endpoints out to 6 and 9 months. We're very excited to see that data coming, but it's too early to comment on the outcome of the study. But you have the design that gives you an idea of what we're really looking for a differentiation at a longer duration of action that we've built in our study.

Next, we have Charles Kings from Barclays.

Two focusing just on your Neurology portfolio. Firstly, a quick one on Dysport and the therapeutic. Wondering if you could just quantify that phasing impact from Brazil on your therapeutic results. I'm just wondering if that should unwind over 2H '25 to kind of bring you back in line with that high single-digit flat top line growth you're targeting?

And then secondly, as far as the kind of long-acting neurotoxin strategy, can you give us a quick update on what the latest is as far as the arbitration with Galderma is? And then thinking maybe just a bit more holistically, what is the kind of long-term goal here? Assuming you're successful with the arbitration, do you see value in trying to produce your own distribution network for the aesthetic indications? Or would you try and continue to leverage Galderma's distribution network? And what are the associated investments that would be required to do that? And just a kind of connection to the investment on LANT, like can you give us any breakdown of the impact of higher R&D costs in 2H as to why you're expecting a step down in that EBIT margin for the full year guide?

Okay. Thank you, Charles. Regarding Dysport phasing Brazil, I'll let Aymeric elaborate.

Yes. So thank you for the questions. I think we are very pleased with the performance that we have in therapeutic, as you know, across the board, including the performance in the U.S. in spasticity, the performance also in Europe. I think the performance was impacted by some shipment phasing that we have with the Ministry of Health in Brazil. We're not going to provide the quantification exactly, but we expect that to stabilize by the end of the year. And I think that overall, in therapeutic, we expect Dysport to continue this high single-digit growth.

And then on the question on the LANT arbitration, we are expecting that the arbitration should read out probably towards the end of the year. So we just have to be patient and then see what the arbitration is going to say. So I can't really elaborate on longer-term aesthetics, et cetera, or partnering aspects because we first need to see the arbitration naive and then see where we take it from there. Thanks a lot, Charles. Operator, next question.

Next, we have Simon Baker from Rothschild & Co. Redburn.

I'll try and squeeze 3 in, if I may. Firstly, on Bylvay, I wonder if you could give us some idea of the split of revenues between indications. And then for Iqirvo, could you remind us how you see the relative size of opportunities in PBC and PSC. As you said, there is no currently approved treatment for PSC. You're probably 3 or 4 months ahead of Mirum in PSC. So I just wonder if -- how confident you are that you can be first to market and to give us some sort of idea of what would be a reasonable time line to get to market.

And then the final question was, you mentioned the U.S. share gains for Dysport. I wonder if you could give us a little bit more color on exactly what's behind that and where those are occurring.

Okay. Thank you, Simon. On Bylvay, we're not guiding on split of sales, et cetera, for competitive reasons, obviously. But what I can say is that since we launched in PFIC first and Mirum launched in Alagille first, both companies are a bit more dominant in these 2 indications. We are now launching Kayfanda and in Alagille in the U.S. So we are gaining market share in the U.S., but also we will start to see the effect of the Kayfanda launch ex U.S. in the coming months and years. So Bylvay is on a really good track. We are going to reinforce also in the U.S. our infield strength to further push the product because we think the product has a really nice potential, and we can penetrate even more with some more share of voice.

On Iqirvo, regarding your question on the size of PBC and PSC. So the PBC market in second line is roughly 40,000 patients. In PSC, the first-line indication because you need to now compare first line, that will be the first product to be used in PSC because there is no other product, you have also 40,000 patients. So the 2 market sizes are actually fairly similar. Now I didn't quite capture your logic on Mirum developing in PSC because that's not at all the same mechanism of action. We don't see that Mirum would have an effect on fibrosis, which -- or long-term outcome, which is really what you need to look for, not just pruritus. We do assume that Iqirvo also has a pruritus effect, which you have seen in the Phase II data. But much more importantly, in PSC, you want to see an effect on the fibrosis on the long-term impact on your liver.

So that's going to, of course, take a bit of time, such a trial. We are going to discuss endpoints with FDA to look at exactly how we would structure that trial. And then we will come back to provide you more details. So it's a bit too early to answer this question on the time line.

Regarding Dysport at the U.S. market share, what is behind, I would say you should really ask Galderma, of course, if you want to have the details. But what I can say is that I think they have done an excellent execution on the launch of Dysport and Dysport has a very strong perception in the market. So they are gaining market share.

Next, we have Shan Hama from Jefferies.

Two from me, please. If I could just push you a little bit on that arbitration. So if the resolution isn't favorable to Ipsen, do you think there's scope to renegotiate with Galderma for better financials? And then secondly, what's your outlook on Onivyde for the rest of the year and even into 2026 because it looks like uptake is strained a little bit. Is this because of the physician preference for the original and cheaper regimen? Or is it something else that is important for us to note?

Thank you, Shan. On the arbitration, I really can't comment. As you know, whenever you are in a legal situation, you don't want to speculate on whatever could come out. So I will have to park this for really after the arbitration readout, which should come anyway fairly soon. And then on your second question on Onivyde and regarding the longer term. So as I said, we recognize that this is a bit of a slower penetration. There is, I would say, a bit of habits with modified FOLFIRINOX, especially in the academic centers. We have been presenting recently real-world effectiveness data, which look very good and actually very strong. We're also going to start doing more trials in the office space because we want to make sure that we show that also this drug can be used very well in the office space. Of course, this is going to take a bit of time.

And we're also negotiating with payers to take away the hurdles that some of the payers have put in place. We have already had one smaller payer, which has lifted this. We are still negotiating with other payers. So it's going to take time to see the growth. So we think it's a bit of a slower growth over time.

Thank you for your question.

Next, we have Florent Cespedes from Bernstein.

Two, please. First, on M&A. As your firepower is improving over time, could you maybe elaborate a bit on your strategy? Is there the time to be or maybe a bit more ambitious or to look for maybe bigger targets or you stick to your historical strategy?

And my second question is maybe a follow-up on the LANTIC trial. Just to figure out, could you maybe give a little bit more color about the time frame because still you have the Stage 2 and the Stage 3. Do you have to understand that it will be further the Stage 2 and then Stage 3, the same patients? Or is there anything that could be running in parallel? Any color on the time frame would be great.

Thank you, Florent. Regarding M&A, I mean, as you rightly outlined, we have a very significant firepower now. Regarding our ambitions, we will always look for the best science. And then we will make up our mind how we are going to split that firepower. Having said that, we want to continue doing deals over the full spectrum of preclinical, early clinical, late-stage clinical, but also on market. And so it gives us optionality, obviously, when you have more firepower on what you can do and how many deals you can do. So that's actually quite a nice situation to be in. So we are, of course, very actively screening for really nice scientific data of companies. And then you will hear more once we have sign -- won acquisitions or we have done licensing deals. On LANTIC, I will hand over to Christelle regarding the design.

Thank you, Florent, for your question. So indeed, you are right, it's a 3-stage study. The Stage 1, our proof-of-concept readout is in glabellar line and a positive proof-of-concept from that stage will support a Phase III start. While in parallel, the Stage 2 is running in forehead line and lateral cancer line or other lines of the phase. And that Phase II will be followed by Stage 3, where we will study the full upper facial line, glabellar line, forehead line and lateral cancer line. But just to be very specific again, the proof-of-concept in glabellar line will support a Phase III start in glabellar line. The others will come in parallel.

I see no further questions at this time. I will now turn the conference back to David Loew, CEO, for closing remarks.

Thank you, everybody, for attending, and I hope you have a nice summer break. Thank you.