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Hello, everyone, and welcome to UCB's Capital Markets Call to discuss the results of BE BOLD in psoriatic arthritis, which was presented on Saturday at the EULAR Conference in London. My name is Yvonne Naughton, and I lead the Investor Relations team here at UCB.

This call is intended for capital market participants only. For any other participants, we ask that you please now disconnect. This event is being recorded and is covered by the disclaimer and safe harbor statement as stated on Slide 2 of the presentation. Following this event, the presentation will be available for download on the Investor Relations section of our website.

Hosting our call today is UCB's Executive Vice President and Head of Patient Evidence, Emmanuel Caeymaex. Joining Emmanuel to present BE BOLD is Professor Iain McInnes, Vice Principal and Head of the College of Medical, Veterinary and Life Sciences at the University of Glasgow. We are also joined by Professor Joe Merola, expert in psoriatic disease and dermatologist and rheumatologist.

In conversation with Emmanuel, Joe will provide his perspective on prescribing practices and how he expects these to be impacted by BE BOLD data, after which Emmanuel will turn the call over to the operator for the Q&A. This call focuses on BE BOLD clinical data and perspectives on its impact on prescribing practices. We will not discuss any access, commercial or financial updates for BIMZELX. We are happy to take these questions at another time.

And with that, I'm happy to turn the call over now to Emmanuel.

Thank you, Yvonne, and welcome, everyone. Delighted to have you. Thanks for your interest in UCB and BIMZELX, a key growth driver for UCB. So I'm Head of Patient Impact, as Yvonne mentioned. Essentially, in other companies, this would be called development and global product strategy. And I'm delighted to introduce this call and maybe remind everybody that BIMZELX is now a product that is available worldwide in 5 different indications. 125,000 patients are benefiting from the drug. And over the years, we've accumulated about double that number in patient exposure.

So it really is a product, a brand that is making a big difference in rheumatology and dermatology practices. And it's approved in 5 indications. There's 4 in the make. So you're aware that we're testing BIMZELX in palmoplantar pustulosis, that is a Phase III study and also in 3 pediatric studies. So first of all, juvenile idiopathic arthritis; second, pediatric psoriasis; and then last but not least, hidradenitis suppurativa in children and adolescents. And so all of these programs are moving forward swiftly, and we look forward to providing you with further updates in the calls to come.

So if we move to the next slide, you will see, of course, that in psoriatic disease, we have been focused not only on demonstrating superiority versus what used to be the standards of care, adalimumab, ustekinumab and Cosentyx, but also are continuing to build on comparative evidence to inform clinical practice, designing studies with endpoints that essentially move the bar closer to what patients' expectations really are, but also closer to what physicians and payers look at in a contemporary setting. And the study BE BOLD was designed a few years ago, acknowledging that the use of IL-23 inhibitors, and risankizumab in particular, was set to increase in the space of psoriatic arthritis.

And so in psoriatic arthritis, nobody has ever really shown superiority on a joint endpoint at approved doses. And we saw the opportunity for BIMZELX to essentially be the first here to demonstrate superiority versus 1 of the 2 brands that really is growing the IL-23 class usage in psoriatic arthritis. And it's an important question because there isn't any comparative evidence. In fact, in psoriatic arthritis, there are very few, if any, trials at all that have shown superiority when it comes to the first symptom that people are looking at, which are joint symptoms.

We picked ACR50 because it's meaningful. So it's not just a measure of response. It's a measure of response that matters. And it was also the primary endpoint in our PsA program that we run in TNF in complete responders as well as in bio-naive patients. And so you will have seen from the abstracts that we've managed to show an 11 percentage point delta versus risankizumab in a manner that is highly statistically significant. And 11 points when compared with a response on that stringent endpoint of 38% or 40% up to 50% is actually quite clinically meaningful, I would think, and look forward to our speakers' commentary on that today.

So moving to the next slide. Thank you. So this is not just about how a patient does at 3 months, which really is when patients tend to be evaluated after initiation of a biologic. The point is that this is actually maintained over a year. And then as we've recently published over 3 years. And you will see that this ACR50 response in bio-naive patients and in TNF incomplete responders on a modified NRI, so stringent analysis exceeded 50% at a year. So now we're going to look with the BE BOLD data how that does over a 3-year period.

If we can just have the next click, please. Yes. Thank you. And so you will see that using the stringent measure of modified NRI, we still end up with more than 50% of patients achieving that stringent joint control goal in psoriatic arthritis at 3 years. And that really is testament to the staying power of BIMZELX, which is probably linked to the fact that it's a dual inhibitor of not just IL-17A, but also IL-17F, which is kind of the chronicity cytokine. And so it's great to know that the results that are obtained early for most patients stay over such a long period of time. Now of course, the question was how does BIMZELX do compared to the other newest entrants in the class, meaning the IL-23s and specifically risankizumab.

Next one. And so to help answer that question, I have the pleasure to hand over to Professor McInnes, who probably is no stranger to many of you. Over to you, Iain.

Thanks so much, Emmanuel. And if I could add my warm welcome, good morning, good afternoon, good evening, wherever you are listening. What a privilege it is to tell you a little bit about the BE BOLD study, and I do so on behalf of investigators and many learned friends and of course, colleagues in UCB who were pivotal in bringing this trial into reality.

The next slide will depict the various disclosures that I have. And if we move from that to the far more interesting conversation about what was the rationale? What was the background for comparing a p19 inhibitor with a dual 17A/F inhibitor. First of all, if you address your attention to the cartoon on the right-hand side of this slide, first of all, you'll see that there are numerous sources of IL-17A and IL-17F. These can come from the so-called adaptive arm of the immune system, adaptive lymphocytes, if you like, but also in the innate arm of the immune system. And because immunologists are creative imaginative beasts, we call them innate-like lymphocytes. So 2 different sources of downstream effector cytokines.

Now existing therapeutics prior to the introduction of bimekizumab were exquisitely specific for IL-17A, leaving the IL-17F member of that cytokine superfamily uninhibited, unimpeded, if you like. Now let's move to the left-hand side of the cartoon, and you'll see that upstream of the cells that are producing IL-17A and IL-17F, we have regulatory cytokines, of which IL-23 is probably the most important across a whole range of immune-mediated inflammatory diseases and certainly the psoriatic disease spectrum. But you'll notice that there is, therefore, a gap in the map here. There are cells that are capable of producing 17A and 17F which are probably not driven by IL-23, hence, the phrase that we've seen written in our literature, IL-23 independent 17A/F production.

Now this is all very well when immunologists draw the cartoons and we draw them with confidence. But of course, that needs to be tested in the human state. And that's where BE BOLD comes to the fore. Emmanuel mentioned there have been a number of head-to-head studies. The successful studies have been performed in cutaneous psoriasis. We've met with less success in the area of psoriatic arthritis. And when I think about it, really the most relevant study was EXCEED, where we compared secukinumab and adalimumab against the musculoskeletal outcome, and we did not get superiority in that study. Some of you may also be referring back to SPIRIT head-to-head, which is a head-to-head trial. But remember, in that trial, the outcome was a dual cutaneous and articular outcome. And here, we have a study, which I shall demonstrate momentarily sought to look at a specific joint focused endpoint.

So let's look at the trial design in the next slide, which will tell us a little bit about the inclusion criteria, adults, active PsA. And this is a clinical cohort that will be familiar to many clinicians in the field. And these were patients who previously either were biologic DMARD naive, treated with conventional synthetic DMARDs, of which methotrexate would be by far and away the most common in global practice or they had been intolerant to a maximum prior TNF inhibitor. This was an active comparator study, 1:1, bimekizumab or risankizumab, risankizumab, a p19 inhibitor. And what you should observe from the doses that are depicted here is that these are the licensed approved doses of these medicines.

You may be asking if you are new to our field, why is there 2 doses of bimekizumab. Well, that is predicated on a higher dose requirement for those patients who have moderate to severe psoriasis. But you'll notice that in our cohorts that represented in the order of 30 patients in either arm who had that severity of skin disease. And that's because a majority of patients in psoriatic arthritis clinics actually have less frequent severe skin disease, and this is something that Professor Merola and I can pick up in questions later on, just that juxtaposition of dealing with tissue domains. And then if you look at the bottom of the slide, you'll see that week 16 was our primary endpoint, and it was an arthritis-specific endpoint.

An ACR50, and of course, ACR50, there are 3 varieties of ACR. You can respond at the 20% level, 50% level or 70% level. And in years gone by, when Joe was still at school and I was a young clinician, well, an ACR50 was an undremt-of primary outcome. We used ACR20. But now the confidence in the field has grown over the last decade and really asking for primary outcomes that we believe will have clinical relevance, real resonance in the community. And that's amongst other reasons why ACR50 was chosen. And then the study after week 24, it concluded the treatment period and there was, as would be required, a safety follow-up period.

Now, I want to talk about the statistical analysis, which if you look at the next slide is depicted. And you'll see this was very common now in clinical trials, a hierarchical testing approach. And by this means we start with what's the most important outcome. And the first important outcome was is -- are these 2 drugs so similar to each other that they would be just non-inferior. So that was the first outcome. And thereafter, we asked a more provocative question, is one drug superior to the other when ACR50, a musculoskeletal outcome is the sole chosen outcome. Now thereafter, in the hierarchy, we moved on to the MDA, which is a composite measure capturing cutaneous well-being and articular outcomes. And thereafter, in the hierarchy, we moved to a combination of an ACR50 musculoskeletal outcome and PASI 100. PASI is a measure of cutaneous psoriatic disease activity. The 100 depicts clearance. And in the end, we would look at ACR50 at week 4.

Now the dark blue and light blue depict the fact that if you fail to move beyond a certain level of significance, everything else becomes nominal. That is when the statistical change stops. So let me tell you about the patients, next, please, Deanna. The baseline characteristics are as depicted here. This is a pretty typical clinical trial cohort that Dr. Merola and I have looked at many times together, maybe highlighting around 20% of the cohort had previously received a TNF inhibitor. And that as I've already indicated, only 10% of the cohorts had moderate to severe psoriasis. As to the rest of the characteristics, you can cast your eye down here, it's a pretty typical population of patients.

And in the next slide, we can have a look at what happened in the trial. So this is probably the most important slide of my presentation. On the left-hand side, you're looking at the primary outcome and in the blue, 49% of patients achieving an ACR50 at week 16 and in the red-pink, my daughter and I always disagree in color choices. So I hope we can all agree that red-pink is risankizumab, 38% of patients achieving the ACR50. And that's this 11% delta to which Emmanuel referred just a few minutes ago. And for what it's worth, this achieved statistical significance, and we'll talk about its clinical significance in just a short number of minutes.

Now on the right-hand side of this slide, you're seeing the time course of achievement of response. And what I would say the color code is the same all the way through for ease of viewing. You'll see that over time, there is a numerical difference achieved for the bimekizumab as opposed to risankizumab-treated patients. And you'll see that the lines would appear to separate as early as week 4. And in fact, the nominal hierarchical testing that achieved statistical significance.

So let's look at the next slide. Let's move through that hierarchy. And this is the minimal disease activity, which is a composite outcome, 7 different criteria, and you'll see that this was not met. And that, therefore, means that our formal statistical testing stops at the primary where we have clearly demonstrated superiority for the musculoskeletal outcome. But the MDA, is although numerically different, as an academic clinician, I have to say that the statistical test was not met, and therefore, we cannot confidently say they are different in the purity of trial design. There are some nominal p-values depicted in here about particularly in the early time points. We can reflect on this later on.

But one should remember that an MDA is 7 different measures, which all have to change and some of them actually need -- so you have no enthesitis beginning, no dactylitis beginning of your different domains of disease impact you differently as an individual, well, there are actually going to be really quite different potential outcomes for you in MDA. So this is not an entirely unexpected result.

So if we could move on now to the next slide, which shows you what happens when we combine the articular ACR50 with the cutaneous PASI 100 over time. The NRI stands for nonresponder imputation, put simply, if you don't respond, if your numbers are lost, if you've fallen out the study or the value is not recorded, we consider you a nonresponder. So that's a conservative analysis. And once again, you'll see that there is a numerical difference over time, particularly through week 16. And by the way, I should say that those responses appear sustained through week 24.

Looking at the next slide, you'll see now we focus on PASI 100. You'll notice we don't have ACR100 rheumatologists weep with envy when our dermatologists report PASI 100s, we don't have that facility yet in a disease representing unmet need, but how valuable to our patient population to have at least one domain of the disease potentially cleared. And once again, I would direct your attention particularly to the numerically higher responses and perhaps at those early stages, clear early separation in the achievement of clearance of cutaneous disease, and we'll talk about this. But that clearance has a huge impact. Those last few points in clearance, have a huge impact in the dermatology quality of life that patients can achieve. And remember, the patient has the whole disease, not just the joints. So although BE BOLD is about superiority in the joints, these other outcomes capture the totality of the human being who comes into our clinic.

And in the next slide, please. we're thinking a little bit about DAPSA, an articular measure. And these are -- this is DAPSA LDA (Low Disease Activity), REM (Remission), again, predicted and projected over time, the prediction being nonresponder imputation. And you'll see once again, clear numerical separation, which achieves nominal significance. But please, I do refer you back to hierarchical testing for absolute accuracy.

And finally, to safety, we report here safety for the BE BOLD study, and you'll see that there was no significant new signal of concern in this study. As expected and pretty much mechanism related, there is a higher frequency of candida associated infections in those patients receiving bimekizumab. This is something we've seen throughout the bimekizumab development program and is mechanism predictive. But I perhaps would urge you when thinking about the safety of different modes of action, particularly at this stage in their development cycle to refer also to large databases where we have extensive evidence of the tolerability, safety and challenges that we must look out for either with p19 inhibition or dual 17A/F inhibition.

Next slide, please. So in conclusion, ladies and gentlemen, the BE BOLD study is the first head-to-head trial that has shown superiority on a pure musculoskeletal outcome between different modes of action in the treatment of people with psoriatic arthritis. That outcome was achieved at week 16. We are, of course, looking at an ongoing basis, and we'll be discussing those data at a later time, but not today. We saw in the secondary outcomes because of the a priority statistical analysis program, only nominal values attributed to that, but there were a number of outcome measures, which appear to support the superiority of bimekizumab, at least at the clinical numerical level.

The safety profiles are acceptable and commensurate with what we have seen before in other studies. And we find these really rather interesting because this will help us in due course to guide our treatment decisions. And those treatment decisions are partly, I think, what I'm looking forward to hearing about momentarily from my good friend and very learned colleague Professor Merola.

So Emmanuel, let me hand back to you, and I further look forward to the conversation to come. Thank you very much for your attention.

Okay. Thank you. Thank you very much, Iain. And Professor Merola, welcome.

Thank you. Thank you.

Just got back from EULAR, I imagine, back in Texas.

Yes. Iain and I were just commenting on our pure fatigue and exhaustion. So hopefully, he's coherent post EULAR, but some of us may be less so. Anyhow, so...

Great. So perhaps to start, could you describe the type of patients that you typically treat in your practice? And acknowledging that obviously, you're one of the key researchers in the field of psoriasis and psoriatic arthritis.

Yes. And thank you for the invitation to be here. I'm quite pleased to be part of the program and chat a little bit with folks, hopefully give some insights. So I'll take a step back. I am a little bit of a unique bird in having the dermatology and rheumatology perspective, and I'm happy to try to walk that line and share a little bit of where perspectives align where they may align less so. I think for me, in my practice, I see a very broad range of patients with psoriatic disease. I'm in an academic setting. But -- so we certainly see folks who have predominant skin disease all the way through to early musculoskeletal symptoms to those who have multi-domain and difficult-to-treat disease that are being referred to me -- to us for complex management.

Maybe for level setting, if I may, Emmanuel, I'll just remind folks that when we think about psoriatic disease, psoriatic arthritis, we typically take this sort of domain-based approach. So we're thinking about patients with peripheral arthritis, enthesitis, dactylitis, potentially spine involvement, axial disease, nail disease, plaque psoriasis. And even there, we could sort of unpack subsets and subsets. So we're seeing all of those patients in there across the heterogeneity of disease and their involvement. And we see new starts to systemic therapy all the way through to, again, folks who have tried everything and they're sort of coming to us for what do we do now.

To answer your question, maybe, again, a little bit how do we think about our treatment and approach to treatment in this sort of a clinic setting. And I think it's very much about which of those domains of disease are involved because, again, every patient may have variable involvement, although many patients have more than one area of involvement. We try to align the treatment with comorbidities, whether it's to try to treat or at least align with comorbidities that they may have as part of psoriatic disease, of course, safety, tolerability. I think you saw the reassuring data from my colleague a moment ago from at least the BE BOLD study, but we can talk about that a little bit more in a global sense.

And then patient preference and then in the U.S., and I'm sure lots of other areas, we have to align with access. But for all of these reasons, I think we -- there's some complexity here, but we appreciate therapies where we know that we're sort of treating and firing on all cylinders, where we can treat across the full breadth of domains of disease where we have good safety, tolerability, we meet patient needs and align with their preferences very well.

And obviously, these comparative studies don't happen every year in psoriatic arthritis. So I was wondering how the BE BOLD study might influence your prescribing practice in your setting?

Yes, I'm happy to take that, too. I'm glad Iain already commented on this. So put my dermatology hat on for a moment that all of my rheumatology colleagues are so jealous of the plentiful head-to-head studies we have in psoriasis, and we have these beautiful network meta-analyses based on oodles of data. And here in PsA, we have had to date almost nothing, really, very, very little and Iain sort of outlined that. So I think it's incredibly important, and we're very grateful to UCB for having done. Albeit, pun intended, right, BE BOLD to put this study together. But it really is important for us. We have -- for many reasons, which hopefully, I'll cover.

I think if I'm honest, it does reinforce what I knew clinically. I mean if -- I don't think there was a deep surprise in the outcome of overarching efficacy here. And I'll tell you a little bit what I mean. But I think I had the data points in the past based on other items of differentiation, axial disease, inhibition of radiographic progression, right? There are other things that were not looked at in this study that have informed my opinion historically about the class and particularly in this population with psoriatic arthritis. I think for me, in addition to reinforcing what I believed clinically, which is important, we really need these kinds of high-quality data to inform our field. And these are the kinds of data that we look for when we're talking about treatment guidelines developing treatment guidelines in the U.S. and internationally. When we put NMAs together, these data weigh heavily because they're very high-quality data in a very well-controlled setting.

And so for me, it really jogs not only what I do reinforces what I believe I knew to be the case, but I think it will really help the field move forward and have conversations with my colleagues in a data-driven sort of manner.

Indeed, and we're glad to contribute to this comparative body of evidence in psoriatic arthritis and psoriatic disease in general. Now one of the questions is how clinically relevant is this 11 percentage point difference on the primary endpoint?

Yes. Similarly, Iain touched on this a bit, too. And we have a hard time, by the way, moving the bar in psoriatic arthritis. So we will take every edge and lead that we can get for our patients with psoriatic arthritis, again, a little bit distinguishing maybe from the skin arena where we've been able to really push the bar and we're talking about PASI 100. Iain alluded to that. I think it's an important time to take a step back and to ask a little bit also about how does time matter. I would say not only is it the delta that we saw, but it's the fact that it separates early and that, that's sustained out to week 24.

For many years, I think anyone in the field has heard quoted a very famous study that with a delay in diagnosis and delay in treatment of as little as 6 months, we saw very significant differences in patients with regard to damage, bone erosion, function, loss of function, quality of life impact. And that's been the case for decades. We've been talking about that. And it was even -- it sounds like a bit of marketing, but I think we have heard over and over again that time is bone, that time matters. And I think really this idea that patients want to be better sooner that we make decisions as clinicians in earlier -- increasingly earlier time points, I think, makes all of this data very relevant.

So yes, patient symptoms are going to be impacted by this in a relatively short amount of time. And I think the one thing we haven't had a chance to see, I know Iain and I will both be excited to continue to unpack this data and to see additional PRO data over time to help us unpack as well what this means for patients.

And obviously, the kind of the details about the study, which not everybody may be aware, about -- so let me just say something around dosing, right? So in psoriatic arthritis, BIMZELX is dosed 160 milligrams every 4 weeks, right, from the very beginning of treatment onwards. Whereas in psoriasis, for the first 16 weeks, it's double that dose. Now as Professor McInnes mentioned, about 85% of patients were treated at the psoriatic arthritis dose, so the lower dose. So given that is the fact, to what extent were you surprised to see the level of skin clearance at that dose versus perhaps the dose that is usually used in psoriasis patients?

Right. Look, I think that the focus of this study, if I'm honest, was -- it's meant to be a PsA study, PsA endpoint. We also know -- I prefer to get my skin data from psoriasis studies. I can put my dermatology hat on for a moment because we know it's a different population. These patients have lower in the PsA study and no different in the BE BOLD study. They have low PASIs. They have -- the vast majority of these patients, I don't want to misquote, but I think only about 10%, 11% or so of the patients in this study actually had moderate to severe psoriasis, which is why such a small percentage received the dose you mentioned a moment ago, Emmanuel.

So I wouldn't -- I'll comment on the data here, but I think it's also -- I've derived my impression from -- of it being a highly effective skin drug, arguably one of the highest efficacy skin drugs we have based on the psoriasis data today. I think the fact that it is behaving as well as the psoriasis dosing of one of our other most highly effective skin drugs, I think, is very much reassuring. I reach for the full dose whenever possible in our patients with psoriasis. I think we always want to be best foot forward and with such a good therapeutic window here where we get such good safety and efficacy. I always lean into the higher dose where appropriate in a patient base where they tend to be higher weight, et cetera.

So I think the full dose really has provided some of the best data in the field. As an aside, I enjoy teaching, I have a lot of residents and fellows around me. One of the things I've told them is I like to quiz them on what the PASI 75 is in the psoriasis data for BIMZELX, and it's approaching 100%. It means that I can almost guarantee almost any patient that I see that they will improve. And here we are looking at PASI 90 and even PASI 100 data. So I think the -- to answer your question again, I think the half dose is impressive in what it can pull off. And for our patients with skin predominant disease, the full dose is really some of the most robust that we have in the field. So I would contextualize it around this being a PsA study.

Yes. Thank you. Exactly which it is. And you were presenting in front of a full room at EULAR in the last day. And apparently, there was a waiting line, which some of my colleagues described like a waiting line outside of the London Club on a Saturday morning. So it certainly attracted a lot of attention. So across efficacy or safety, was there anything else that you heard from colleagues or that you picked up in the convention center before or after the presentation of those results?

Yes. Well, first of all, I will acknowledge and own the pressure cooker there. It was packed indeed. There was a huge swath of people, as you mentioned, outside, all listening with earbuds. And so it makes -- it definitely raises one's blood pressure and heart rate to say the least, at the podium. But I think there was a lot of enthusiasm. I think it underscored to me, I have my bias, but I think it was one of the most important data drops at the meeting and people really were eager to see it. They stood around to the very end of the meeting in many cases to hear the data. So I think that speaks to the unmet need for these data and how people hopefully will be viewing them and we will take this back to their clinical practices ultimately.

Thank you. Thank you very much. So we'll stop the fireside chat here and give everybody on the line an opportunity to ask questions. And so I'm sure we have a system to identify who raise their hand first. And so let's see.

[Operator Instructions] Our first question comes from Stacy Ku at TD Cowen.

A wonderful presentation and fireside chat. So we have a few follow-up questions for Dr. Merola and Dr. McInnes first before a question to Emmanuel. First, Dr. Merola, following up on Emmanuel's question on EULAR and community response. As we think about the U.S., just maybe help us understand what percentage of rheumatologists view the IL-23 class as differentiated to IL-17 in joints? And how do you expect the study could change prescribing? So that's the first question.

And then the second, for both Dr. Merola and McInnes, as we think about the rheumatology angle, how do you expect other clinicians will balance the decision-making of BIMZELX versus other 17, obviously, excluding access? So that's our second question.

Our third is to Emmanuel. To the extent that you can comment, just help us understand as it relates to the U.S., what kind of potential payer dynamics we might see when it comes to the BE BOLD advantages? Is it more on the rebating side or more on the access side? Do you expect this is going to have ramifications as it relates to the rheumatologists' view on IL-17F? Just help us understand as both of these classes of physicians are treating the psoriatic arthritis patients.

I believe I'm kicking off, and I have to -- I'll try to repeat the question since we had a roll of questions. As I understood the question, it's about my U.S. colleagues. I think this is a globally relevant answer, but how my U.S. rheumatology colleagues view these 2 classes with regard to PsA. So look, I'll start first with our little microcosm because I can't speak to every community rheumatologist's view. But I think among the PsA expert community, I think we think of the IL-17 class in general and in particular, and the above IL-17A/F opportunity as really the go-to and I would even argue, best balance of efficacy, safety and tolerability for psoriatic arthritis.

I truly believe that because we have the experience to date, both in the clinic, but also the data, everything from what Iain shared earlier in SPIRIT head-to-head where we learned that IL-17 inhibition was as good as our gold standard TNF in joints, but far superior in skin, nails, et cetera, has borne out. I think that some of the gaps in data historically around radiographic progression, around axial disease, et cetera, I think has elevated the class around psoriatic disease, psoriatic arthritis. And I will say on balance that I think in recent time, not so much risankizumab, but guselkumab has shored up the value of IL-23 in psoriatic arthritis through a number of studies.

But I think that underscores why these data are so important that we have a head-to-head data as it relates directly to our patients with peripheral joint disease and using a joint focused clinically meaningful outcome like ACR50. So for me, this is very timely data to really solidify our impressions of IL-17, IL-17A/F adjacent to IL-23 inhibitors in PsA.

Yes. I'll maybe just add to that. I think there were 3 questions. I'll come in on that middle one, which is -- Emmanuel will be the master of where the marketplace lies and all of this. But it's a very interesting question as to whether clinicians in the field [indiscernible] all day and night about how cytokines work. And sadly for me as a clinician scientist, I suspect it's rather little. So let's think about what does guide clinical decision-making. And I'm just going to build a little on what Joe has said. Well, the first thing is recommendations and guidelines at the international and the national level. So we have guidance from ACR. We have guidance from EULAR, and we have guidance from GRAPPA. And it's always worth -- remember, there's the third group out there in terms of advising on therapeutic decision-making in psoriatic disease. And then I also want to pay due respect to other societies in the global stage, particularly in Asia, who, by and large, line up close to where EULAR and sometimes ACR lands.

So the first thing is that those recommendations and guidelines will be impacting in practice. And we will expect a little time for BE BOLD to get into those recommendations. We have to accept that. The flip side is that there were lots of people wanted to hear Dr. Merola talking Saturday at ACR -- at the EULAR Congress, and that's partly because he's a charismatic brilliant speaker and a really smart guy. But they were also there in addition to that because they wanted to know the answer.

So just to reemphasize, the question, I think, touched on the do clinicians see this as one general bundle Well, I think in the past, they possibly did. When I went out and talked to clinicians, they'll tell them about TNF inhibitors. They'll talk about oral inhibitors, think Janus kinases to some extent, maybe PDE4 apremilast. And I think they were taught to think -- we used to hear a lot about the IL-23, IL-17 axis. That's what was talked about. And the cutaneous psoriatic studies that Emmanuel alluded to earlier on have clearly shown that, that is not a fair, bland landscape that actually you can differentiate in head-to-head trials in the skin when you're comparing ixekizumab with a pure 17A inhibitor or for that matter, the TNF inhibitor or with ustekinumab p40 inhibitor.

BE BOLD tells us that if you then do a head-to-head for musculoskeletal, ACR50 being the primary as we've now well described today, that actually now differentiates in the musculoskeletal compartment. And I think that will be quite impactful. But can I say something and with due respect to our host UCB, we're not saying that risankizumab or the p19 inhibitors are not good drugs. So for Joe and I as clinicians who are balanced clinicians in the field, they're excellent drugs. That's why it's actually been -- that's probably why the MDA didn't differentiate in BE BOLD because actually risankizumab is a good anti-cutaneous psoriasis drug, and it also has proven efficacy and is in the marketplace because it's effective in people with psoriatic arthritis with musculoskeletal domain disease.

The point here is that bimekizumab may offer a bit more, and that was the clinical value that Joe and Emmanuel talked about just a few moments ago. And I think BE BOLD will add to the literature. It will build that momentum for thinking about distinct modes of action at distinct stages of clinical decision-making. I think the early impact will be the publicity and impact of BE BOLD both at EULAR and the subsequent publications. And then in due course, it will be felt as recommendations come through.

Thank you. Very good questions as usual. So in terms of payer dynamics, I would say that it depends a little bit on the payers. But as you know, they have clinical evaluation groups who put a lot of emphasis on the type of evidence we have just been producing. So randomized controlled studies, superiority, so you don't need to go through a common placebo response to derive the relative efficacy between different drugs. So it will really help those colleagues within the payer groups to defend the position that ultimately should support giving patients early choice and giving physicians choice across these various therapies.

Today, in the U.S. there's actually more use in new and switch patients of IL-23 inhibitors than of IL-17A inhibitors in psoriatic arthritis, right? So you can see that the community is heavily influenced by DTC, by access, by, of course, the quality of the data. And so it's important to -- for us to be able to illustrate that there actually is a difference when it comes to joints, and we've demonstrated that in a prospective manner. And the 17A/F class, which BIMZELX is the one and only that's approved, can thus benefit from this and really set itself apart from a class and in particular, the drug we compared against here that has been gaining substantial share over the last couple of years.

Now outside of the U.S., this will also help -- it will help us divorce BIMZELX from other molecules. And as you know, there's these practices to look across different classes of interleukins as price adjustments get made very much in a top-down fashion with limited space for negotiation for pharma companies. But this type of evidence really gives us a tool to ensure that the price revisions are limited and that we can argue based on clinical effectiveness since that is what is being valued and looked at. In the U.S., in terms of pricing, it's hard to kind of unravel what is pricing and what is positioning in the formulary. But clearly, those landmark studies like the one comparing BIMZELX with Cosentyx in psoriasis are the most important ones to either open up access or maintain access at a decent net price.

Our next question comes from Xian Deng at UBS.

So just one, please. I mean we've heard this number many times like roughly 1/3 of psoriasis patients actually have PsA. But just wondering how about the other way around, so how many actually PsA patients actually have skin problems? Do all of them have some degree of skin problems? And what I'm trying to understand is that to both professors, so just wondering what do you think is the best way to utilize the BE BOLD data here? Do you think this is better utilized to just to make BIMZELX sort of go-to in PsA? Or do you think you should also go to the top dermatologist colleague and have some sort of way of identifying psoriasis patients who are very likely to develop joint symptoms and then sort of utilize the data kind of push there? So yes.

Sure. Thank you for the question. I'm happy to start and Iain can correct me and/or keep me honest. But I will say that the vast majority of our patients with psoriatic arthritis have some form of skin disease, whether it be plaque disease, whether it be nail disease. That said, certainly, most do not have moderate to severe plaque psoriasis. But instead, as you see from the trials and real-world registries and data sets that it may be mild psoriasis in the context of psoriatic arthritis as previously defined. That's an evolving landscape as well, how we define mild psoriasis in terms of impact on disease and such. I won't -- I'll spare you the long-winded point about that.

But I think to your point about maybe the dermatologists and then maybe Iain or others want to comment more about the rheumatology view on this. I think many of my dermatology colleagues, to be honest, would say, first of all, they want to know that they are treating the joints when they're treating the skin. They like the reassurance that they're checking a box to that end. So they know that they're using a drug that is approved for psoriatic arthritis. Many of them do prefer to see that the reassurance that there is inhibition of radiographic progression so that they feel as though they're not missing a gap in some way. I've heard that from many of my colleagues. I think that that's real.

On the flip side, many of my -- again, derm colleagues would argue that the patients that they are seeing in their clinics are not necessarily, to be fair, the people or even most of the pivotal PsA trial patients in that they don't -- they aren't necessarily running to the dermatologists that they have 10 to 20 tender swollen joints, for example, they would say, instead, I'm seeing the patient with enthesitis or maybe a few joints or the achy patient who I'm concerned has PsA, but I'm not sure, or they seem to have early PsA. So yes, I do want to be balanced on that front because I think that this is practice informing for those seeing PsA. It should inform my derm colleagues who believe a patient in front of them might have PsA, especially that fits this profile.

But I do think there are different subpopulations of patients that you're alluding to, those with skin predominant disease, those with severe PsA, those with maybe more mild PsA, but severe skin disease. And I think we may think about them a little bit differently as well. But Iain, maybe you want to say something more intelligent or at least...

That's a highly unlikely eventuality, Joe. I will -- let me just be quite succinct and add a couple of things to Joe's excellent answer. Number one, there is a syndrome of psoriatic arthritis sine psoriasis. The history books tell us it's about 5% of patients. That number varies depending on where you are and what you are. And that was a group of people whose joints looked like PsA, but there was never any obvious or good evidence of the skin lesion. Now whether that's because the skin lesion was missed or never disclosed or transient, we don't know. And Joe is telling me that I don't -- I wouldn't recognize a psoriatic plaque if it was 10 centimeters in front of my nose as I think what Dr. Joe was saying there, but...

Not all, not all. But although I will go on record, Iain, I think a lot of those are missed to your point.

I agree.

One has to go looking and searching, but carry on, yes.

No, no, I agree completely. The second part of your question was about prevention -- that implicit in your question. And the answer is that, that is work in progress. And I do not think we yet have an evidence base that can support a strong argument for disease progression and trajectory interruption for any mode of action. And that is not what BE BOLD was about nor what the discussion today is about. Very good question, but that's not an evidence base that we can offer you at this time.

And thirdly, just developing very quickly Joe's comment. We now advise that clinicians treat the domains of psoriatic disease. And you'll hear I'm using that word quite psoriatic disease. It's a clinical collection of tissues that are involved. And I think what you heard from Joe was that we also advise clinicians to use the best evidence base for each domain of disease, which is why one would tend to go to the pure cutaneous psoriasis head-to-head trials to guide what's the best MOA for a skin dominant patient. And that's why BE BOLD is quite interesting because now we have a head-to-head where we can say, if I have a choice of MOAs and somebody with mainly musculoskeletal or musculoskeletal troublesome problematic disease, I can now say, well, here's evidence that this MOA may be better than that.

And I'll pause there, but that's domain-driven therapeutics and that is going to drive the treatment disease in the next 5 years and having this quality of evidence to guide one MOA versus another is really hugely helpful to us.

Our next question comes from Peter Verdult at BPN (sic) [ BNP ] Paribas.

Apologies. I'm in Munich at ADA. So apologies for any background. Peter Verdult at BNP. Just two. The minor one on the clarification is a backward-looking commercial question, Emmanuel, not forward-looking. But just I think rheum is around 20% of BIMZELX sales in '25. Could you just parse out of that what is psoriatic arthritis in 2025? And then my main question is for the doctors, both the doctors really. Could I just put you on the spot. I'm still not sure how you're using BIMZELX today, in ballpark what percentage of your psoriatic arthritis patients you're using BIMZELX in today and how that might change like to push you in terms -- on the back of the BE BOLD data, what sort of ballpark changes might we see if I take you as an example?

I'll just start with the question on within the rheumatology indications, psoriatic arthritis is by far the largest one. It's a bit different in the U.S. and in Europe, where it's a bit more balanced. But I would say globally, it's probably 3:1. Iain or...

Joe, do you want to...

I'm happy to start. I mean I -- it will seem biased to the call, but I will say honestly that I have every reason to use BIMZELX as a first-line agent in my PsA patients, and we certainly try to get it for our PsA patients whenever possible. I'm talking about new starts or folks who are not doing well on other agents, in particular, those who may be on TNF, IL-23 or even other IL-17A drugs who are not fully controlled. That said, I will say that payers don't always agree with me. I mean I sit in Dallas, Texas. I can't speak to every region of the country.

But by medical decision-making, I consider this a go-to drug. I know that I'm going to win the confidence of my patients early with these drugs. It gets them clear quickly. It makes them feel better quickly. That drives adherence. It makes us feel good doing what we do every day. And so I have no reason not to have it as a personal drug. That said, I will say that we will often get some pushback and have to back into other MOAs because of payer requests, not for clinical want. That's just the reality of my -- in my microcosm locally.

In the interest of time, I shall simply say that very similar arguments pertain in other country and payer regions. This is a compelling mode of action. The head-to-head data are helpful to clinicians in making decisions, but one has to remember that this is a multifactorial conversation, and it is very difficult to predict what one trial will do. Having said that, over time, as that percolates through into guidelines and recommendations and when payers take that on board, that's when we would hope to see the impact more obviously.

Our next question comes from Charles Pitman-King at Barclays.

Charles Pitman-King from Barclays. Two from me. Just briefly, a clarification on the treatment guidelines expectation. I'm just wondering when you would expect these treatment guidelines to account for the BE BOLD data and then how quickly you would expect that to be reflected in prescription uptake, noting obviously, you already previously received GRAPPA preferred first-line treatment. Just wondering when you would expect any change from that?

And then just secondly, my question relates to the longer-term durability of the delta. Obviously, Slide 13 showed a sustained delta to risankizumab on ACR50, but then we saw some catch-up on PASI100, Noting obviously the speed of onset advantage versus the candidiasis safety disadvantage, what are your thoughts on the potential for Skyrizi to catch up on the ACR50 endpoint on a longer duration for these chronic patients who need long-term treatment?

Yes. I may leave the second part for my colleague who presented the data, if that makes sense. To your first point, I'll just say, I don't think -- I think it's okay to share that both the GRAPPA guidelines are in progress for a refresh presently. And I believe these data likely would inform those, although I can't say for certain. The ACR guidelines are also due for a refresh this year and would not likely be out this year, but subsequently. So I'm hopeful that these data would inform those committees and there is a current refresh. I think that's the best I could certainly say on that front. I can't speak to EULAR, Iain may know. But these are -- this is the kind of data certainly that makes it to the SLRs and if not, hopefully, would be reviewed by committees because of the high-quality head-to-head nature of the data.

Yes. I would wish to speak for EULAR. They'll make their own decisions public in due course. I think the -- I would like to overemphasize though, the BE BOLD disclosure will influence practice from the word go. It will be in the mind of clinicians next week when they're facing that decision, which MOA do I go for within payer recommendations in the local area. The wider impact consolidating that in practice does tend to go with recommendations, and that influences the medium term of how different MOAs will play out.

Your second question, if I can very briefly deal with it. I showed you today that there continues to be, by and large, numerical separation. We will be disclosing in due course later in the year how the longer-term follow-up for the study plays out with one MOA against another, and that's because it takes time. And Paracelsus in the 1,400 said the physicians very friend in time is time and so too, this is our time. We just have to see how it plays out. But we did disclose data today up through week 24. And you see that, by and large, the lines are still numerically separate. That's a different conversation for a different day. Your remark around trade-off though for efficacy against safety, by and large, candidiasis is a very well managed and by and large, tolerated adverse event, which very rarely in clinical practice leads to cessation of therapy. And my judgment would be that it is unlikely that there will be a realistic trade-off for candidiasis against the use of this mode of action.

Our next question comes from Kerry Holford at Berenberg.

Two for me, please. We noted that the ACR50 results for patients on both arms of the BE BOLD study looks better than we had seen in the original pivotal trials for both of the drugs. Just curious to hear your views here from the physician perspective, any proposals as to why, whether the way in which outcomes have been measured assessed has differed at the time? And then my second question is on the topic of the secondary endpoint MDA. Professor McInnes, you touched on this briefly, but intrigued to hear your view as to why statistical significance wasn't achieved on that measure. And I guess given the complexity of using a composite score, which I think you said consists of 7 individual measures, was it the best secondary endpoint to use and how influential is that when it comes to the regular physician prescribing it?

You take the first piece, I'll deal with the second, Joe, how does that sound?

Sure, sure. So I will say in any of these studies where we don't have a placebo anchor and we have 2 open treatment arms, we certainly see some upward drift. This is across many studies, and we can imagine the psychology of both the patient and assessor in these dynamics and in these studies. So indeed, I do think it's some of the best data, including for risankizumab that we've seen to that end. But we certainly do see this. We see this in these functionally open-label studies where everyone knows they are on active drug and such.

So a little bit it is what it is, and I think it's hard to unpack that any further, but it certainly is a known epidemiologic trend. And then Iain can comment on MDA. I just -- I think it's really an endpoint that's meant and has been used in placebo-controlled studies to be able to show a difference, but I'll leave that one to him.

Yes, there was a poster in the poster tour at EULAR Congress in London last week from OMERACT demonstrating that MDA does perform well when compared to placebo. It didn't consider the situation with active. It's a very astute question, if I may say. But if you could remember that this trial was powered to show a difference for musculoskeletal outcome. It was not to show a difference in a cutaneous outcome. So we wouldn't have necessarily predicted superiority to come through if some of the outcomes, which are contained in the MDA are cutaneous as they are. So in fact, the MDA is a state to which we aspire to get the patient.

It was -- I think it was a perfectly reasonable choice of endpoint in the statistical testing. One seeks, first of all, your primary subject of interest, in this case, musculoskeletal disease and then one seeks a state. Actually, I guess, UCB could have moved some of the outcomes around potentially to their own advantage, but they chose not to do that. The way the trial was designed was to say what is the difference in musculoskeletal outcome and does that then land in state. So I think actually the choice of hierarchical testing is pretty defendable. And just again, allows me to reemphasize the head-to-head comparison here, the unique element in BE BOLD is demonstrating the superiority in the musculoskeletal compartment.

MDA is really asking and addressing a different question. So although the question is astute and well taken, it's not really what the trial was all about.

This concludes today's Q&A session. I will now hand back to UCB for any closing remarks. Thank you.

So I'd just like to thank everybody for coming on the call today. And if anybody has any other questions, we can take them after the call. Thank you very much.

Welcome to the UCB Full Year 2025 Capital Markets Call. My name is Antje, and I'm doing Investor Relations at UCB.

Before I introduce you to the agenda and hand over to the speakers today, I have some remarks. This video is being recorded. You can find the presentation in our download center, if you dial in by the phone. The presentation and the following Q&A session are intended for institutional capital market participants only. If you're not, please disconnect now. This presentation and the following Q&A session are covered by the disclaimer and safe harbor statement as stated on Slide 2 of the slide deck. Kindly read this carefully.

With this, I'd like you to introduce you to our speakers today: Jean-Christophe Tellier, our CEO; Emmanuel Caeymaex, Head of Patient Evidence; Fiona du Monceau, our Chief Commercial Officer; Sandrine Dufour, our CFO; and this will then be followed by a Q&A session with all presenters.

Thank you. Jean-Christophe, over to you.

Thank you, Antje, and good morning, good afternoon, good evening, everyone, and thank you for joining our full year 2025 presentation. It is really with great pleasure that with my colleagues, we will share with you our results of what has been a very strong year.

Can we move to the next slide, please? Because, as you know, we are focusing on execution of our launches, and I think it's fair to say that 2025 has demonstrated our ability to continue to deliver strong growth based on our 5 growth drivers that we have, and thanks to them, they will allow us to enter and continue to build our decade of growth.

If I want you to keep just a few elements out of this slide, I will start on the top left part by just one number. Our net sales growth versus last year at constant trend has been at plus 35%. How we have been able to deliver this growth? It's in the arrow of the middle. And as you can see, our 5 growth drivers have reached EUR 3.3 billion, which is more than a double of the revenue that these products have delivered last year. Bimekizumab only delivered and achieved more than EUR 2.2 billion in 2025. So as you can see, a very strong growth that has been delivered in 2025, and Sandrine will be able to go further into the P&L.

But a few highlights maybe on my side about 2025. On top of this delivery of the growth and the growth drivers that we have, we have seen also some critical advancements in our pipeline, and that's the bottom line of the slide.

First, KYGEVVI. We achieved approval in the U.S., and we have a positive advice from the CHMP from Europe. As you know, KYGEVVI is active in an ultra-rare disease, TK2 deficiency. And it is the only -- first and only treatment that would be available for these children and family to save their life and help them to have a better life.

The second element in '25 was our bispecific. We have 2 of them in atopic dermatitis, donzakimig and galvokimig. Both of them have achieved positive endpoints -- the primary endpoint. But through a rigorous analysis, we have decided for the time now to focus on galvokimig and accelerate the development of these IL-13, IL-17 bispecific, not only in dermatology, but also into neurology. Then bepranemab, our anti-tau antibody in the Alzheimer's disease. We have a positive Phase II. We have -- we think we have very strong insight that will help us to guide to develop this product for these patients. And we have been pleased in February to receive a fast-track designation by the FDA.

And finally, in '25, we have also started the development of BIMZELX in rare disease, but quite debilitating, which is the palmoplantar pustulosis. '25 have seen also a decision, a very important and strategic decision for us, to make a significant investment in the U.S. with a total of $5 billion of direct and indirect investments into a mammalian manufacturing site to manufacture BIMZELX in the future from the U.S.

Next slide, please. So I think it's fair to say that the strong achievement that we have been able to realize in '25 guide us and promise us a bright and successful future for the decade of growth ahead. The first reason of that is that we are one of the few companies who will have a long periods of exclusivity before the next wave of loss of exclusivity. As you can see on the top, we will start in 2033 and the last one will be BIMZELX in 2037. This long period of exclusivity will give us the time and the space to really deliver on our growth.

The second element that can also explain our confidence in the future is the ability to continue to differentiate our portfolio. You remember that BIMZELX was the first product to be able to be launched with 3 clinical studies of superiority versus standard of care. As you know, we have started, a few years ago, one additional study in psoriatic arthritis, BE BOLD versus risankizumab. We were expecting this result in the second half of 2026, but we are pleased to share with you that thanks to a very strong and fast recruitment, we will be able to get the result earlier already in the first half of this year.

And we continue to grow our pipeline. We'll have this year one submission, 6 Phase II -- 6 Phase III, 5 Phase II, as you can see here. And because of a strong balance sheet and particularly our ability to reduce our debt, we now, of course, have the space and the capacity to think about inorganic growth to continue to fuel, expand and accelerate our growth future.

So thank you again for participating to this call. And with this, I would like to hand over to Emmanuel.

Thank you very much, Jean-Christophe, and hello, everyone. It's a real pleasure to be able to provide you with an update on our pipeline from this new vantage point for me as Head of Patient Evidence.

So let me take you through innovating with purpose and how we translate differentiated science in durable growth. Our engine is robust, and it's focused on immunology and neurology and their intersection. And today, I'll focus on galvokimig, FINTEPLA, our newly approved KYGEVVI after commenting on a few other key updates.

So on the next slide, you can see our mid- and late-stage pipeline that's driven to -- that's built to drive medium- and long-term growth to diversify risk and deliver innovation and breakthrough aimed at high unmet need populations.

And just for ease, I'll start at the top with the BE BOLD study, which Jean-Christophe just mentioned. So it is strategically important in the sense that there is an opportunity in psoriatic arthritis to raise the standard of care. And right now, the IL-17 A/F dual inhibition is not yet positioned as a first-line treatment and is not yet leading. Yet we believe, based on our Phase III results, that there is an opportunity to demonstrate superiority versus the IL-23 inhibitor, risankizumab, SKYRIZI. And so we've powered the study to be able to achieve this using a pretty assertive and stringent endpoint, which is the ACR50 at week 16.

And so provided this is successful, we'll have the opportunity to strengthen the positioning of BIMZELX across both rheumatology and dermatology, where many patients with concomitant psoriasis and psoriatic arthritis are treated. And as mentioned earlier, the results are expected within the first half of this year.

You also read that we started the palmoplantar pustulosis study. And this actually is a disease that is largely IL-17F driven, and this will be an opportunity for us to continue to establish the leadership of bimekizumab in the IL-17-mediated diseases.

Now for RYSTIGGO, rozanolixizumab, on the one hand, we have the MOG-antibody disease study readout in the second half of this year, and we're also very pleased to announce that we're starting a ocular myasthenia gravis Phase III study, recognizing the very good clinical performance of RYSTIGGO and the fact that most patients with generalized myasthenia gravis actually start with ocular symptoms, and so this is a logical thing to do to make sure that we enable symptoms to be tackled early and thereby prevent irreversible damage for patients with myasthenia gravis. So looking forward to starting this study within this year.

I'll briefly touch on FINTEPLA, fenfluramine, a little later. I just wanted to say a word also about bepranemab. So we've been working very proactively and constructively with regulatory agencies, starting with the U.S. FDA, who very recently gave us the fast-track designation for bepranemab in Alzheimer's disease. And so we're encouraged by the exchanges and the meaning of the data that we've been able to generate in our proof-of-concept study, in particular, in a subpopulation that was predefined. And again, that data was pretty convincing across biology and also across cognition and functional endpoints. So looking forward to more with bepranemab.

And then finally, galvokimig. So Jean-Christophe mentioned, we're starting 2 studies in respiratory diseases. And we have started the Phase IIb study in atopic dermatitis, and that's a 52-week study, which will report results by 2028.

Now if we move to the next slide, we can dive a little deeper into galvokimig. First, recognizing the fact that in atopic dermatitis, the results were pretty strong. And actually, this molecule was designed to tackle the heterogeneity of atopic dermatitis, delivered about 50% EC90 at week 12 and also very good pruritus data, each data. So the differentiated potential is there, which we will now test in this Phase IIb and really seek to define the optimal dosing.

Now what's new and what you haven't heard before is the foray that we're planning in COPD and in bronchiectasis, non-cystic fibrosis bronchiectasis. So COPD has a massive unmet need, as many of you know, it's very prevalent. It causes 3 million deaths per year. So the burden of disease is really very, very high. And it is entering a precision immunology decade. So in this sense, respiratory is trailing dermatology and rheumatology. But I think that the translation of biology is now happening. And with galvokimig, we have an agent that, through its combinatorial approach, really has the potential to addressing core mechanisms of disease in both COPD and non-cystic fibrosis bronchiectasis.

So in COPD, you're aware that some products were approved and the segment of patients that are so-called high eosinophils, they're served to an extent, but that's only about 30% of the population. And the other 70% really don't have an approved treatment or targeted treatment to go to today. And we do know that whilst the IL-13 inhibition is presenting a solution that other group probably needs a therapy that takes care of neutrophil-driven inflammation. And that is the concept we're going to test in quite a large study that is going to start this year.

Bronchiectasis is not as well known, but it's a disease which is chronic, is very debilitating, chronically diluted bronchi. With the advent of DPP1 inhibitors, there is a level of proof that addressing neutrophilic inflammation can have an impact, and we're talking about a 20% reduction in exacerbations in patients that have at least 2 exacerbations per year. So you see there's still a lot of headroom. And we do know that the pathobiology centers on neutrophilic inflammation, but also mucus dysfunction. And so that's offering validated targets for us and a target which by inhibiting both IL-13 and IL-17, we should be able to meet.

So we look forward to those 2 studies producing results. We certainly feel that the scientific rationale is very credible that in each case, one of the pathways is somewhat derisked and that the science underlying the second pathway in each disease is now well established. So together, this represents a very significant opportunity for galvokimig.

Now let's move forward to neurology and to FINTEPLA. So as you know, FINTEPLA has been really focused on developmental and epileptic encephalopathies. You learned last year that in CDD, which is an ultra-rare genetic DEE that FINTEPLA has had very nice results, which now will enable us to submit a file to the regulators for approval, hopefully rapid approval given the enormous unmet need here.

The news for today is that we're taking FINTEPLA into neurodevelopmental disorders and in particular, RETT Syndrome. So Rett syndrome is a disease with a profound unmet need. And the mechanism of action of FINTEPLA should be able to address that unmet need beyond the seizures. And so we're looking forward to initiating this Phase III, which is based on clinical observations and credible mechanistic hypothesis. We're looking forward to starting this in the next few months.

So FINTEPLA, with no generic until 2033, is representing quite a big opportunity for impacting patients, but also for UCB value creation.

So on to the next slide. And then to close KYGEVVI, where we just received FDA approval and CHMP nod. So KYGEVVI is the first and only approved treatment for adult and pediatric patients with TK2D deficiency. This is for patients that developed the disease age 12 or below. It is the first foray for UCB in ultra-rare diseases. It's a mitochondrial disease, and so we look forward to learning in this space and establishing capabilities.

So we're ready for an agile commercial launch that's planned in the first quarter of 2026 in the U.S. first. So as you see, the number of diagnosed patients worldwide today is probably around 1,500. So there's probably still some space to go to identify patients. However, many patients are already benefiting from KYGEVVI through our development program or in other ways. And so we look forward to expanding that over the next few months.

So with all of this, I hope that you're seeing that our development pipeline has gained momentum over the last year and with what is planned for this year. With COPD and bronchiectasis set for a biologics-driven decade and our programs stage for '26 to '28 catalysts, we're advancing differentiated mechanisms, disease-modifying ambition and value creation for the next few years.

And with that, it is my great pleasure to hand over to Fiona, who's just taken over as Chief Commercial Officer. Fiona, the floor is yours.

Thank you, Emmanuel, and I look forward to bringing KYGEVVI to patients. This is a unique drug with some survival benefit, which will really make a difference to these patients, but also to their families.

Good morning, good afternoon, good evening, everyone. As Emmanuel mentioned, we exchanged role 6 weeks ago, and so I'm delighted to share with you the performance of the team. I'm just back from the U.S., and I can tell you the teams are fired up to deliver on the 2026.

Next slide, please. So let's start with BIMZELX, our IL-17 A/F. It's been reaching more patients. It's fast, deep and durable action is really having a great impact on patients around the world. We've now been approved in more than 50 countries. We've been helping more than 116,000 patients. And as Jean-Christophe mentioned, reached net sales of above EUR 2.2 billion.

If we look at our dynamic patient share in the IL-17, we're around 30% for psoriasis, 20% for our rheumatology indications and 45% for HS. So from a net sales split perspective, that gives you about 53% in PSO, 28% in HS and 19% in rheumatology.

Now if we move to the right-hand side of the slide and look at our uptake in the U.S. compared to analogs, you can see that we're really leading the pack and look forward to continuing on that track. We are proud to say that we've increased our access coverage with 36 more million lives versus 2025 and so now have a coverage above 80% of the commercial lives.

And as I sort of think about these progressive diseases that really creates lasting damage, it's really important that patients get access to our drug as early as possible. If I may take sort of some metaphors, if you take PSA and you think about sort of sand in a gearbox, if you flush the sand away quickly, your car continues; if you delay at some point, your gearbox breaks.

Likewise, for HS and you think about sinkholes, if you fix it quickly, it's okay; if you wait too long, the whole street comes down. And for our HS patients, this is -- these are tunnels under the skin and lasting scars that you can never get back.

So let's move to the next slide. I know everyone is very interested in our performance on HS. So on the left-hand side, if we look at our performance in the U.S., we're now at a 32% market share. I think back in July when Emmanuel presented, we were at 25%, and we look forward to continuing to drive our Formula 1 forwards. And we've shared some of the market shares across some of our countries around the world.

Now we often get the question on what do we think the HS market is going to look like going forward? As you know, we're learning about this new market every day, and it's growing significantly. If we look at the number of patients back in October 2024 versus October 2025, we've seen a 24% increase in that space. And our estimates for between 2025 and '30 is that the market will continue to grow in the mid-teens CAGR and expect to reach around sort of $5 billion overall.

Now if we go to the next slide, let's talk about our rare portfolio. So first, our MG portfolio. We are at UCB, the first and only company offering a dual therapy portfolio. We have RYSTIGGO, the FcRn and ZILBRYSQ, our self-admin C5. Both of them are uniquely positioned. They're tailored to patient needs. You know that this is a population of patients that's very heterogeneous, and it's also called the Snowflake patients. We are supporting these patients with an excellent patient support program. They are now approved in 30-plus countries, have treated more than 3,700 patients and combined reach above EUR 0.5 billion in sales.

And then I will finish with FINTEPLA. With our strong heritage in epilepsy, FINTEPLA is it's now a foundational therapy in Dravet with about 20% market share in the U.S. and is gaining traction in LGS with 9% of the patients. Worldwide, we've now treated more than 14,000 patients and delivered sales above 420 million.

On that note, I'm going to hand over now to Sandrine, who will give you an overview of the overall portfolio as well as our disciplined execution and operational efficiency from a financial perspective. Thank you very much. Sandrine, the floor is yours.

Thank you, Fiona, and good morning, good afternoon. I'm pleased to present our '25 results and our '26 guidance.

We delivered strong top line growth. We have expanded margins meaningfully, all while continuing to invest behind our launches and pipeline. And that translated into a significant increase in profitability and clear operating leverage. And looking ahead, we remain focused on sustaining this momentum, driven by our 5 key growth drivers.

Let's start with 2025 net sales on the next page. The combined net sales of our 5 growth drivers more than doubled year-over-year, underscoring the strength of our portfolio. This performance was primarily driven by BIMZELX, with net sales more than tripled to EUR 2.2 billion, reflecting strong volume growth across all indications with particularly robust momentum in HS.

In the U.S., this was supported by a favorable payer mix with a high conversion to paid prescriptions and a meaningful proportion of unrebated scripts. And that momentum continued into the second half where we also saw a positive gross to net true-up versus H1, driven by a more favorable channel mix than what we had initially anticipated.

FINTEPLA continued its solid trajectory, delivering 26% year-on-year growth and reaching EUR 427 million in net sales, reflecting continued penetration across Dravet and Lennox-Gastaut indications. Within the GMT franchise, RYSTIGGO and ZILBRYSQ together generated more than EUR 270 million of incremental net sales over the year. And this was achieved in an increasingly competitive environment and reflects our differentiated assets in this space.

EVENITY also delivered strong growth with net sales up 33% in Europe to EUR 137 million. It's important to note that this figure represents only the direct European net sales. Our total economic exposure is significantly higher as reflected in the EUR 632 million net contribution from our partners in 2025, corresponding to 32% growth and which continues to be a meaningful contributor to profitability.

Beyond the 5 growth drivers, CIMZIA delivered net sales of EUR 1.95 billion, down 4%, flat at constant exchange rate. And despite being off patents, volumes grew by 4%, making CIMZIA the fastest-growing branded TNF across major markets. And this volume strength was more than offset by continued pricing pressure, particularly in the U.S. driven by the new IRA Medicare Part D legislation and including the growing impact of 340B.

BRIVIACT grew net sales by 11% to EUR 758 million with sustained growth across all regions. The product was approved in Japan in June 2024 and has reached loss of exclusivity in the U.S. this week and will achieve loss of exclusivity in Europe in August this year. And of course, this is reflected in our forward-looking assumptions.

Briefly on ESG in '25. We strengthened our environmental performance, improving our CDP climate change rating to A, and we were ranked An Industry Leader #2 in the Global Biotech by Sustainalytics. Our financial performance is underpinned by a consistent sustainability agenda, which we see as an important contributor to long-term value creation.

So let me now go to the financial performance and the profit drivers. And on the top of the page, let me start with revenue. So total revenues reached EUR 7.7 billion, up 26%, 29% at constant exchange rates. This was driven by net sales of close to EUR 7.4 billion, up 32% or 35% at constant exchange rate, reflecting strong underlying demand across our growth portfolio.

Turning to profitability. Adjusted gross profit reached EUR 6.1 billion, up 27% with the gross margin improving to 79.2%, driven primarily by a more favorable product mix from our 5 growth drivers. Operating expenses totaled EUR 3.7 billion, up a limited 5%, clearly demonstrating strong operating leverage. Marketing and selling expenses increased by 20% to EUR 2.5 billion, reflecting our continued investments behind the growth drivers, including deeper market expansion, new geographies and resource reallocation from mature to newer assets.

R&D expenses increased by 2% to EUR 1.8 billion, reflecting continued disciplined investment in the pipeline and early research, and as a result, R&D represented 24% of revenues. And finally, G&A expenses remained well controlled and decreased by 3%. Other operating income was a positive EUR 829 million, up EUR 265 million versus '24. The majority of this, EUR 632 million, came from the net contribution from our EVENITY partners, which grew by 32%.

And in addition, we continued our portfolio simplification strategy with the sale of an asset for EUR 315 million, and this was partially offset by EUR 111 million of one-off costs related to the resolution of contractual commitments linked to a noncore asset. Altogether, this resulted in adjusted EBITDA of EUR 2.6 billion, up 79% or 87% at constant exchange rates, driven by strong top line growth, improved gross margin and significant operating leverage.

EBITDA margin increased by 10 percentage points to 34%. And if we correct for the asset sale and the one-offs, adjusted EBITDA came in at EUR 2.4 billion, representing a 31.4% margin, which is in line with the guidance that we updated back in December.

Moving to profit. Group profit reached EUR 1.6 billion, up from EUR 1.1 billion in '24. Net financial expenses declined to EUR 126 million, driven by lower net debt. The effective tax rate was 14%, reflecting use of R&D incentives and deferred tax asset recognition despite a negative impact of Pillar 2, and it's in line with the underlying rate in '24 when adjusted for the China divestment.

Core EPS reached EUR 9.99, doubling year-on-year and closing another strong year for UCB. And finally, strong cash flow generation has allowed us to fully deleverage the balance sheet, giving us a strong and flexible platform to support future growth.

So moving to the next page. Let me now turn to our 2026 financial guidance. First, we have evolved our approach to constant exchange rate guidance to improve comparability and transparency. Our guidance also reflects current rules and regulations. It does not include any impact from potential MFN or tariff. We are, of course, closely monitoring the external environment.

So for revenues, we expect high single-digit to low double-digit growth at constant exchange rates. The underlying drivers remain the same 5 growth assets as in '25 with BIMZELX as the largest contributor, followed by RYSTIGGO, ZILBRYSQ, FINTEPLA and EVENITY.

On BIMZELX, we expect access expansion in the U.S. to come with a lower net price, which we anticipate will support strong volume growth. The overall revenue growth rate will also reflect the loss of exclusivity for BRIVIACT in the U.S. and Europe, to a lesser extent, impact LOE in Japan as well as a modest negative perimeter effect related to last year asset disposal. So overall, strong momentum from the growth portfolio, partially offset by expected headwinds from LOE and perimeter, and that's reflected in the revenue range.

Moving to EBITDA. we expect high single-digit to high-teens growth at constant exchange rate. And if we adjust the 2025 EBITDA for the product sales and the one-offs, so starting from a EUR 2.4 billion base in '25, we expect EBITDA growth at constant rate in the high-teens to high 20s, significantly outpacing revenue growth.

And there are 3 main drivers. First, continued improvement in adjusted gross margin driven by the evolving portfolio mix despite the impact of net price decrease. Second, regarding OpEx, marketing and sales and R&D expenses will continue to increase. Their contribution to margin expansion will be lower than the exceptional operating leverage that we have achieved in '25, and this reflects higher volume-linked variable costs in marketing and sales and our continued deliberate investments in innovation. We will maintain discipline and clear prioritization in the uncertain external environment that we operate in.

And last, EVENITY's contribution is expected to grow faster than the top line, supporting further margin expansion. While we will continue to actively manage and simplify the portfolio over the long term, we do not plan any established brand asset disposal this year. We expect the tax rate to increase to around 20%. And we have provided you, at the bottom of this page, with the sensitivity of the guidance to foreign exchange impact on both revenues and EBITDA lines.

So to conclude, overall, strong growth, accelerating profitability and a very solid financial position. So with that, let me thank you, and I'll now hand over to Jean-Christophe.

Thank you, Sandrine. And thank you, Fiona; thank you, Emmanuel, for this overview of our performance 2025 and sharing with you our guidance for '26.

And as Sandrine has just said, I think you would agree with us that with the strong performance that we have delivered in 2025 -- next slide, please. With the strong performance of 2025, we are confident that we will be able to continue to deliver a solid growth again for 2026 and pave the way for a successful long-term growth for UCB.

And this is based mainly on 3 components. The first one is the continuous focus on innovation that have guided us for the last years and will continue. This focus on innovation give us a possibility to build a portfolio of differentiated assets that creates very differentiated value for patients who need this asset to have the life that they want to live.

Two. Rigor and discipline in execution, the ability to be resilient, to be agile, to get the resource where we feel the highest return in order to deliver strong performance and efficiency.

And three. By creating an environment, a culture for everyone to be at their best and be purpose-led in such a way that we deliver the maximum value on the long term for all stakeholders, including, of course, the patient and shareholders.

So with this in mind, we would like to move now to the Q&A, but allow me maybe a personal message before handing over to Antje for managing the Q&A. Because today, it's quite a special day for us at UCB and maybe also for you as it will be the last full year results that Antje will have the chance to be with us, and we have the chance to be with Antje. As Antje has decided, after 27 years at UCB, to enjoy life outside of corporation, which I think it's fair for her to let her benefiting from that.

Antje, you know, has been the voice and the face of UCB for all of us and all of you. Her dedication, our energy, our engagement and commitment to serve our shareholders and all of you have really been an anchor of UCB successes in the past. And for me, as CEO, since my very first day here, I always have had, with Antje, a very good and solid sparring partner who have been able to build and strengthen the reputation of the company and help me all along.

So Antje, thank you very much. Antje will pass the baton to Yvonne Naughton, who will take the position as of May 1 and have just joined us. So we'll have a few months of handing over. And so, of course, we are very pleased to celebrate and welcome Yvonne, but at the same time, we are a little bit sad to let you go, Antje.

So with that, I hand it over to you to reorchestrate the Q&A again for us. Thank you.

Okay. Thank you so much. That's indeed a very emotional moment. I'm thankful for everything. I think we live together through so many different situations. I enjoyed it fully, even though it might sound strange, but that was good and bad. And yes, it's time that I'm going private. I'm going to do all the things I haven't done yet from now into what's next, seeing the full potential.

And I will definitely miss you, this company and it's -- especially its people, my colleagues are fantastic and has been my life and my family. I'm here, as you say, until end of April, so we will have an opportunity to connect in the remaining weeks and also introduce Yvonne to you, who is already with us here. And yes, for those who see us in London next week, that's for sure where you're going to meet us.

Okay. Thank you. So going back to business, we will now start the Q&A session. [Operator Instructions]. The question session will be handled by our operator today, Kjell. You can also e-mail your question to me under [email protected], and I will ask your question on your behalf. Kjell, operator, please explain how to ask a question.

[Operator Instructions]. Our first question comes from Peter Verdult from BNP Paribas.

Peter Verdult, BNP. I'm going to break with 20 years of traditional protocol because I, myself, never thank or congratulate management on public conference calls, but I will make an exception on this one and say, Antje, personally and on behalf of many people on the line, thank you for your service and professionalism. It's been great fun, and good luck with your next chapter.

Now back to business, 2 questions. Firstly, just on R&D and then secondly, on capital allocation. Just on R&D, clinical trial risk in immunology and inflammation. We've seen the pharma industry generate mixed data for OX40 in AD, MoonLake missed in HS, we've seen mixed data in COPD for IL-33. And some industry CEOs are claiming it's now harder to do clinical trials in I&I, citing difficulty recruiting biologically naive patients, moderate to severe patients and dealing with a higher placebo response rate.

So maybe anyone or Emmanuel, does UCB agree with this premise? And can you remind us what UCB does to ensure clinical trial success and how much of that clinical trial is done in-house versus CROs? So sorry, a bit of a big picture question, but I think it's important when you think about galvo and the promise of that asset.

And then more quickly, JC or Sandrine, your net cash found there's no interest in buybacks, and I assume your dividend policy is unlikely to change materially. So is the message on be still about platforms and modalities and early stage pipeline efforts? Or are you now signaling that you're broadening your scope in terms of considering inorganic growth opportunities that might add revenues nearer term?

Yes, Peter, thank you very much for your question. And we see this, although there is variability across diseases. So in certain cases, the endpoints, the duration to achieve the endpoints and the availability of patients that are moderate or severe is not as much of an issue. But clearly, the trend has been more noise. And so the way we deal with this is, first of all, we're more prudent and careful around the design of the study.

We're very careful around endpoint and time selection. We're deploying more people, site managers to ensure that execution is tighter and that the education of the various sites around the world provides a level of homogeneity. We also tend to allow for size -- not to be too conservative on the sizing of the samples, just recognizing that there could be more noise.

And finally, in terms of CROs, we've gradually taken in more roles. But at the same time, we do acknowledge that in new areas, often CROs have a lot of experience that we can learn from. And so we are very open in collaborating with those teams to make sure that we do not repeat mistakes or that we learn from prior experience.

Thank you.

Thank you, Peter, for your second question. So you're right. I mean, our strength in our balance sheet and the fact that we have now reduced and have no debt creates a lot of space in a sense for being able to consider investment in inorganic growth for the future. As you know, because we have our loss of exclusivity will not be before 2033 for the first one and until 2037, there is also -- we have also the time to think about it.

I used to say, and I think I've said that with you last year, that it was years of execution of launches, and we didn't want to create a potential risk to disrupt the organization by making integrations or acquisitions that will require local resources. Of course, after now several years of execution of the launches, we start to be in a phase where we can have some time to dedicate to potentially addition to our pipeline. But the focus will be most likely on early clinical or clinical area -- assets and area where we have capabilities.

And these questions of integration and complexity of integration will be, of course, also very much scrutinized. So yes, we always have been looking. We are now a little bit more intentional on that with the objective to strengthen our capabilities, thinking about the long-term growth and be careful about not disrupting the execution of the launches.

Our next question comes from Stacy Ku from Cowen.

At the risk of becoming emotional, many thanks to Antje for her key support in our coverage of UCB. Very excited for you, and we'll miss you.

So first, back to the Q&A. When we think about the revenue guidance range, the low end does suggest BIMZELX is in line with consensus and the high end of the range seemingly driven by BIMZELX outperformance. So I would love to hear your views. And specifically, how we should think about the bio-naive HS patient segment as it relates to access and reimbursement? Curious to get your thoughts on whether it will be different this year, as we think about upside?

Second question is whether or not you all would be willing to provide additional details around donzakimig prioritization? Does it relate to the emerging atopic dermatitis competitive landscape, your ability to think about donzakimig as a broader I&I platform? Just any additional details would be very much appreciated.

Stacy, thank you. I'm happy to start with the donzakimig question. So indeed, as you mentioned, the atopic dermatitis field is quite competitive. And when we look at this from a portfolio point of view, we saw a big opportunity to double down on galvokimig based on the data we have in hand. In terms of the biology of donzakimig, the combination of IL-13 and IL-22 inhibition probably is having a more narrow potential in terms of disease areas where this can make a big difference based on today's understanding of biology across autoimmune disorders. So indeed, those 2 things come to play. Now eventually, we'll release the data, and it's an asset which we believe can have value. However, from a portfolio point of view, it wasn't prioritized at this point.

Right. And Stacy, your question on HS comparing the bio naive and the access and the reimbursement. I think it's fair to remind that in 2025, we clearly benefited from a strong access from HS patients even in areas where there was no access coverage of formulary where there was a clear efforts from both physicians and patients to get access to the drug, and that, of course, translated into a full price.

We do not expect this to repeat in '26 clearly because we have expanded access and formulary. And so what we expect to see that there will be a coverage, which will be a mix of what we have, i.e., double-step edit, single-step edit and first line, and that expanded access will certainly trigger a stronger volume growth.

A quick follow-up then, Sandrine or Fiona. For HS, is the vast majority -- and this is obviously for the U.S., is the vast majority of coverage remaining at single-step edit access?

Yes. So 2 out of 3 of the PBMs is at single-step edits. I would add also that, as you know, I mean, this is a market that's expanding along sort of 3 axes. One, for the moment, the diagnosis is extremely long. It's above 7.3 years. And so we're working on accelerating that so that patients get treatments quicker to biologics in general.

Second, if you look at sort of the knowledge of the HCPs and then the number of HCPs willing to treat HS is expanding. And then there's a whole component around sort of patient activation. And this is a disease that comes with a lot of stigma; a lot of shame, unfortunately; and helping those patients come out and ask for better treatment. Currently, if you look at sort of the split bio-naive versus not, we're at roughly sort of 40-60.

Our next question is from Naresh Chouhan from Intron Health.

Both on BIMZELX, please. Just on the rheum indications. Now, the BE BOLD readouts we've seen come forward six months-or-so, have you assumed any acceleration in the rheum indications in H2 in your guidance? Obviously, your MSLs will be able to talk to the data, even if your reps can't. So just trying to get a feel for any potential upside, either included or not getting included in guidance?

And secondly, just a bit more details on HS. Something, Fiona, you didn't mention was stay time, and duration or persistence for patients on NHS. Obviously, for Humira and Cosentyx, we see very short stay time. Just trying to get a feel for what you're seeing in the real world? I know you've got 3-year data out there, but in the real world, what are you seeing in terms of stay time on BIMZELX? And in your $5 billion market size estimate, are you assuming increases in stay time?

Thank you for the question. So on the rheumatology indications, so we are expecting to accelerate in our rheumatology indication. We have a strong belief that the IL-17A and F plays a difference for these indications, particularly in the joints. And as I -- sort of I was mentioning earlier, the earlier you treat sort of with a strong medication, the more you prevent lasting damage, but once it has taken place, it's difficult to reverse. I would also say that you have a non-negligible portion of your psoriasis patients who do go on to develop psoriatic arthritis. And so we also expect sort of to have a spillover effect there.

On your second question around sort of HS. Yes, we look forward to taking advantage of the duration of some of the other therapies that we see on our sides. We do see a longer persistence in for HS, and there is a slight difference between bio-naive and previous -- and switch. But all in all, we're -- we have a good persistence there.

And then your last question around sort of the $5 billion, I think it's -- I mean, as I mentioned, it's a combination of seeing sort of this disease being more and more recognized both by HCPs, but also, by your generalists who are gonna refer much quicker to dermatology. It's about sort of patients being more active and feeling less stigmatized and sort of pushed to the side, and an acceleration on your diagnosis times.

Thank you.

Our next question comes from Richard Vosser from JPMorgan.

One question please, on BIMZELX as well. I think, Sandrine, you mentioned a gross-to-net adjustment in the second half. I wondered if you could quantify that and maybe just give us a little bit more detail in the gross-to-net development from the second half of 2025 and into the first half of 2026, just to give us some color there as you increase the coverage?

And then second question, just on bepranemab. Very good news getting a fast-track designation, but this is still a pretty high-risk area relative to others in development, so just wondering about the thoughts around partnership here to share the risk of further development around that product.

Yes, so on the impact, indeed, so I said that in the second half of '25, we had a crew up of gross-to-net from H1 to H2, and it represents around 5% of our total BIMZELX, just to give you a sense. And then, you know, on the evolution from '25 to '26, we still benefited in the second half of '25 from this large proportion of unrebated scripts, and logically, as we are expanding the access, that will come with full price moving to net price, which are very in line with the ranking of the access coverage, so depending on the indications and depending on the payers, as you know, we have a mix of double-step edit, single-step edit, and first line, and so that's how it should evolve from '25 to '26.

And Peter, thank you for your question on bepranemab. So indeed, we share your view in terms of the risk that comes with Alzheimer's disease programs. So at this point, we're open to various ways to mitigate that risk. So far, we've been really focused on unlocking and addressing critical path questions of CMC and regulatory nature, and now that this has progressed well, we are looking at this de-risking, which is both an asset and a portfolio consideration.

Our next question is from Xian Deng from UBS.

First of all, thank you for all the interactions and all your help, Antje, and wish you all the best.

To my question, so just wondering in terms of HS, so just wondering -- thank you very much for the color in terms of the 40-60 split between bio-naive and refractory patients. But just wondering going forward, where do you expect as a main source of growth? So do you still have big bolus of patients that hasn't had either bime or Cosentyx, or is it more from switch from Cosentyx or even just naive patients, you're kind of -- all patients who are not seeking active treatment at the moment?

Kind of linking to that so just wondering, when you mentioned the mid-teens CAGR for the HS market, linking to this question as well, so just wondering, do you expect this to be relatively linear or more back-end loaded, as you probably have to educate the physicians and everything? So that's kind of a, sorry, long first question.

Second one, on galvokimig. So on ct.gov, it still says the primary endpoint is 16 weeks, but now you're saying you're doing blinded dosing to 52 weeks with top-line data in 2028. So just wondering would you be able to -- is ct.gov simply not updated or would you be able to potentially have a look in the middle and start Phase III before 2028?

Thank you for the question on BIMZELX. I would say, I mean, it's a combination, and it's gonna happen, of course, over time. So first, it's about gaining market share in the IL-17 and moving that whole class sort of earlier moving from moderate to severe to moderate and as closely as possible in the pathway.

Two is accelerating that diagnostic, so moving it from sort of 7.3 down to significantly lower. Three, expanding the number of physicians who are ready to treat HS, and then in parallel, of course, activating patients. So that's going to happen over the next sort of five years in a staggered way.

Emmanuel, I'll hand over for galvokimig.

Yes. Thank you. And thanks for your question indeed.

So the study is blinded for the entire 52 weeks, we would want to ensure that not to jeopardize the study integrity. It's a study where it's both a learned study and a dose-ranging study, right? We certainly want to make sure we get the full value of this investment. It's designed to inform us to take the best possible step in an area which is quite competitive, but also quite complex from a heterogeneity point of view. So with this, we're not going to move earlier, as per your question.

Our next question is from Rajan Sharma from Goldman Sachs.

I've got a couple. Sorry, another one just on BIMZELX then and price. I'd just be interested to understand when you expect to reach a steady state on net price in the U.S.? Is 2026 sort of a step-change in the trajectory? And then within 2026 specifically, do you expect price to compress through the course of the year? I'm just wondering if any of that positive effect that was -- that you mentioned in the second half of '25 holds true into the beginning of 2026.

And then second question was actually just on pipeline. So I noticed that you had the ocular myasthenia gravis phase III. As it happens, one of your competitors shared their phase III data this morning. They showed a 2-point improvement on the primary endpoint. Do you expect to show a similar level of efficacy, or is there room for improvement, and do you expect to use the same endpoint?

So maybe first to answer your question on BIMZELX and the net price. As Sandrine was mentioning, I mean, versus last year, we'll have much less unrebated scripts or full price, as we've sort of negotiated more and more the access across our different indications. There is still more potentially to come, where we evaluate, of course, every decision sort of meticulously from a finance perspective on increasing access versus -- and increasing volume versus rebates. What we can tell you for the moment is, we've just increased by EUR 36 million, and we'll continue to evaluate that as opportunities and negotiations progress.

Thank you for your question on ocular MG. So I'll get back to you -- or our team will get back to you as to the endpoint. I'm aware of the news this morning, but I haven't gone into the details yet. What I can say is that from a generalized myasthenia gravis experience point of view, two things have become clear over the last years. Firstly, that anti-FcRNs really are used early, and therefore, going into ocular MG, where most of the patients start with eye symptoms, makes a lot of sense for the medium and long term.

And second, we know from clinical practice that not only does RYSTIGGO provides a pretty robust efficacy that stays over time, but we also see that the cycle times are not too variable, relative. We believe that there's something with this medicine that will translate to ocular MG, and again, we'll get back to you as to what we can share in terms of the details of the study.

Our next question comes from Charles Pitman-King from Barclays.

I'd just like to also pass my thanks to Antje for all her help over the time covering the company.

I think two questions on BIMZELX from me as well to maintain the theme. Firstly, just within the psoriasis indication, one of the things we've seen in some of our prescription data is that it appears BIMZELX has started to lose share versus other novel biologic peers over 4Q 2025, particularly against some of the IL-23s, so I was wondering if you could just provide a bit more commentary on if whether or not that's a trend you're seeing and what really explains it, and what your -- specifically, therefore, what your strategy is for trying to regain that share going forward to support your broad expansion of the BIMZELX sales?

And then secondly, just in terms of competition, I mean, one of the other things we've seen very recently is that MoonLake has announced that they have been -- they've received a positive confirmation from the regulator that they can file using one of their Phase III and their Phase II data, with the potential that any of their label -- any label would therefore include numerically superior efficacy results, so I'm just wondering how you're feeling about the competitive dynamics from sonelokimab across HS and psoriatic arthritis, given their Phase II positive data?

Yes, let me answer your question. So maybe there -- I mean, on the first one, so you'll see that we, over the last two weeks, we've had, 2 consecutive weeks with over 7.2. I think it's important to realize that January and a bit February has been sort of a -- there's been a lot of noise in the system for all products because of snow days, four days a week, and the general noise that you have in January as the new year kicks off. I think we -- you'll see that we've continued to grow from an IL-17 -- within the IL-17 class. And we look forward to having BE BOLD that reboots and gives us even more energy to continue to compete in the psoriasis area.

If I take MoonLake, I would say, well, first, we are the only one on the market with significant data over all our head-to-heads and over the duration, if you include not only launch, but also all the clinical data that we've accumulated. They have shown some efficacy. It's been mixed results, and that information and that data will need to be included should they be able to get an approval. So I think you can't go in thinking that you can cherry-pick data. The FDA will expect to have the full package.

And let's see how they do that and what happens there. But yes, want to reinforce that by the time they come on the market, we will have been there, we will have proven how effective our drug is, and our data is consistent not only within our indications but across each of the indications.

Our next question comes from Sarita Kapila from Morgan Stanley.

Just on BIMZELX and coming back to HS, apologies. Could you comment on the market share evolution versus Cosentyx? Has this now stabilized? And how should we think about the broader HS market in terms of growth expectations this year? And are you to be confident that you can continue to meaningfully outgrow the market this year based on current scripts?

And then the second one is on the change at the FDA with a single pivotal trial sufficing for approval. How might this influence dapirolizumab for SLE? Is there a chance for an earlier approval based on the current one positive trial?

So let me start with BIMZELX, and Emmanuel, let me know if you take dapi or not?

So first on BIMZELX, HS, I think you've seen the graph that I showed earlier, where we see sort of good progression with currently around 32% market share within the IL-17. Previously, back in July, Emmanuel shared data with you that was around the 25%. We have the better drug. The F component in the IL-17 really does make a huge difference to these patients, so it's our mission, both for the teams out in the field as well as us in the head office, to make sure that these patients are treated adequately with the best treatment option.

I was speaking a few weeks ago with a patient who was in a clinical trial, who was on the placebo part, and he shared with me sort of the scars just from that simple 6 months period, and those are scars that never go away. So I think it's not only important, but it's our duty to make sure that we continue to progress this year in the IL-17 and lead the pack there. And I think from a sort of market growth perspective, as we mentioned, it's gonna continue to grow in the mid-teens. Between the effort of us and other players in the field, we are seeing that market continue to progress.

Emmanuel, do you wanna cover dapi?

Yes, for sure. Thank you for your question. Indeed, we did approach the FDA with that question. However, it won't apply to dapimab yet. I think there's some intricacies around the secondary endpoints in the first phase III study as well as the phase II study, which makes that package not quite reach the level that would be acceptable today for going with a single Phase III study. Obviously, if we see more opportunities to cut the time, we'll seize them. For now, we're busy recruiting rapidly in the second Phase III study.

Our next question comes from Charlie Haywood from Bank of America.

Charlie here with Bank of America. I have 2, please. First one, I'll keep it simple. BIMZELX '26 consensus is around EUR 3.1 billion, which I think if you annualize your second half sales, gets you to within 10% of that number, so How comfortable are you with consensus?

And secondly, I think by my maths, your second half U.S.-based sales are around EUR 400 million. Given in second half, you had 2/3 of the big PBMs covered, which is likely the majority of volumes. Can you just help quantify of that EUR 400 million number, the absolute pricing benefit, sort of uplift you could have seen in second half that could reverse, as those patients become rebated?

Yes, I can take this. I don't think we comment on consensus per asset. We typically don't do that. But overall, I think we provided the guidance. We -- '26 for BIMZELX is going to be a combination of strong volume growth and evolution of the net price. I wanted to call out the fact that in the second half of 2025, we had a bit of this true-up that you need to factor in when you look at how H1 and H2 dynamic comes in '26. And at this point, this is how we want to support and help you on the projection.

Our next question comes from Luisa Hector from Berenberg.

Of course, thank you to Antje. I just have a couple of questions. Could you comment on the U.S. formulary position in immunology in terms of any trend you are seeing towards basically parity access for all drugs and this leading to a bit of a shift to competition more in the doctor's office? Just wondered -- we heard it from a competitor. Just wondered if you're also sensing that trend.

And then interested in your comment that CIMZIA are still seeing volume growth, and I just wondered is that across all markets? And are you, on the whole, expecting that TNF volumes will be stable to slightly growing in the future? Just thinking of that as a sort of a pool of patients switching to newer therapies, but overall, should we anticipate TNF stable to growing over the coming years?

Thank you for your question on the U.S. formularies. No, so I wouldn't say that we've currently sort of seen everyone going to parity. I mean we still have sort of the double-step, single-step or first line or excluded in sort of the packages that -- yes, and how the formularies are set up for the moment in the U.S.

On your question on CIMZIA, so we continue to see increase in growth for CIMZIA. I would say it's standing out from the TNF lot in general. So there's very different dynamics for the rest of the TNFs. And I do think it's really because of the uniqueness of CIMZIA and how it's PEgylated formulation and the impact it has on particular patient populations.

Thank you.

Our final question is from [ Rudy Lee ].

Congrats on a strong year. Also want to add my congrats to Antje for your new journey. I have two questions. First is regarding BIMZELX. For psoriasis and for the rheumatology indication, how should we think about the penetration or market share in the total biologic market beyond just IL-17? And how should we think about the gross-to-net in the longer term?

Second question is for FINTEPLA. I'm just curious about your current thoughts on the gene therapy competitor programs, including the ASO and AAV gene therapy for Duchenne syndrome. Apparently, at the same time, you know, there are a couple [indiscernible] drug, in late-stage trials. How would these new products potentially, I mean, change the market dynamics in the coming years?

So maybe let me start with the gross-to-net. I mean, I think Sandrine has sort of mentioned it as well. So one -- I mean, we will see a difference between last year where we had quite a few scripts, medical exception at full price. Now you will see a net price or gross-to-net more in line with where our access coverage is, whether it's first-line, single-step or double-step edit as well taking into account, of course, that the dosages across the different indications and loading doses are different.

Your question around FINTEPLA -- sorry, I'm just going back to my notes linked to the question that you asked. So your question around FINTEPLA and potentially future competition. Well, first, in general, usually competition increases the market and is a good thing for both patients and for us. I would say what we are seeing with FINTEPLA is really a strong impact.

From an efficacy perspective, we've just, as Emmanuel mentioned, shared the outcome of the Phase III data for CDD, which reinforces not only the impact that we have on seizure, but also on the non-seizure outcomes and we hope to sort of further increase our data package and improving the efficacy and the benefits of that drug with our Rett syndrome indications. So I think that by the time that they come on the market, the wealth of data and the proven real-world evidence will support FINTEPLA as a strong option.

Thank you.

So that was the final question for today. Thank you so much. Thanks to Jean-Christophe, Fiona, Sandrine and Emmanuel, of course, of my screen here. Thanks to the audience, you have been very patient with us. We went definitely well above the hour. And yes, thank you all for everything. I enjoyed every moment, and I wish you all the best.

For every question that is open for any future interactions, you know where to find us. We are here, and we are going there to continue to serve you as good as we can. Thank you.

Welcome to day 3 at the JPMorgan Healthcare Conference. I'm Richard Vosser, European pharma analyst at JPMorgan, and it's my great pleasure to introduce the UCB CEO, Jean-Christophe Tellier to you.

Just before I hand over to Jean-Christophe for his presentation, I'd just remind you that if you have a question, please take up your hand and wait for a microphone or you can put your questions on the portal, and I'll ask them for you.

With that, Jean-Christophe, welcome to the conference.

Thank you, Richard. Good morning, everyone, and thank you for joining me this morning for the UCB presentation. It's always a pleasure to be in front of you and share with you some updates about the company. And give you the confidence that you need to get with the progress that we are making and the future and the perspective of the company. So thank you for being here.

If there is only one message that I would like you -- it's not the disclaimer, by the way. If I have only one message that I want to get -- to leave you with today is the fact that we are in a position of strength and the level of performance that have been able to deliver for the last couple of years is the best possible introduction to the decade of growth that we have ahead of us. And so the strength that we have today is built on a lot of different pillars that I would like to highlight with you in the next few slides.

So of course, the first element that you should be confident with is the fact that this decade of growth has been built on a very solid and strong foundation. We have a company of almost 1 century of history. We will celebrate our century in 2028. So it's getting closer. And the foundation of the company has been a family which have always, have believed in the future and in innovation. And these strong foundations on innovations and sustainability and success have been executed towards today. Two pillars.

One is immunology and the second is neurology. And is today translating in these five growth drivers that you have on the right-hand side of the slide. And of course, the first one that you think of when you think about UCB today, is BIMZELX with the five indications of the product that we have been able to launch a few years ago. But it's not just BIMZELX. You see here the other products, general myasthenia gravis in Dravet, Lennox-Gastaut, fragility fracture that you have here. Five growth driver is the first pillar of the growth and the first reason of this decade of growth ahead of us.

The second element -- sorry, I should mention another thing on this slide. The second pillar of growth that you get -- you have to think of when you think about UCB is the fact that we have a huge visibility ahead of us. The green dots that you see on the right part of the slide, almost outside of the slide, actually, it's the delay versus between now and the loss of exclusivity.

So BIMZELX, for example, the loss of exclusivity will be in 2037. So with this five growth driver, we have ahead of us a huge period between 2033 and 2037 before we will have to face the next round of loss of exclusivity. So strength with the growth driver, strength with the visibility that we have ahead of us. The strength that we have today is also the results of a strategy that has been executed with agility and resilience. And it's also something that illustrates UCB and has been illustrating UCB for a while.

So if you think about the first element, which is the innovation piece, we always have invested more than our peer in R&D. And this level of investment for the last years, at least the last decade, have created the strength that we have today.

The second element is we are continuously investing in areas and in geographies that support innovation. And in the current environment, and particularly here in the U.S., we have decided last June to expand our manufacturing capacity and building a state-of-the-art mammalian factory in the U.S., which remain -- which will be an investment of $5 billion for a company our size. It's quite a significant investment. But it's also an illustration of the growth that we have ahead of us and the ability that we will have to produce more regionally and to be closer to where the innovation is.

And then last but not least, invest in our own research is, of course, very important. But it's not everything. I don't think there is any company today, which is able to grow long term without a combination of organic and inorganic growth. And the other pillar of strength that we have today, it's our strong balance sheet. And the strategic flexibility that we have already today to invest in potential inorganic growth in order to strengthen, accelerate and give us even more solidity in the future.

So if you think about that for us, we will, of course, start with early stage with research, strengthening our discovery engine because with five growth engines right now, we have enough on our plate and we don't want to add additional element now. I cannot resist to the pleasure of spending a little bit of time on this slide, right? Because when you look at the strength of UCB, it's the ability to deliver results, which, of course, is the most important one to give confidence in the future.

And this is not the result of the growth over the last 10 years, actually. It's just '25 versus '24. And so you can see 24% of growth, and you can see 700 basis points of improvement of EBITDA. And being here for the last 12 years, I have heard a lot of time skepticism when we put the guidance to say we will reach more than 30% by '25 of EBITDA, there have been some questions about how you will get there. And now it looks like 31% is quite conservative. But frankly, I like to be in this position on making sure that we can deliver what we have promised and show confidence in the future.

So when we look at the strategy in action, I would like now to zoom a bit on a few elements. The first one, it looks maybe general, but it's the reality of the company, and it's the reality of who we are today. The focus on innovations, the ability to invest in research and science is the heart of the company because we always believed that if we are able and as long we are able to translate science into differentiated candidates, we can deliver additional value for people suffering from chronic disease.

And the way to do that is on the paper quite simple, not that easy to execute. But the first thing is first is better understanding of biology. If you understand better the human biology, if you really put connections between the patient and the science, then you can extract from this knowledge an ability to formulate differentiated hypothesis, scientific hypothesis that then you can translate into different candidates.

And if you are able to execute on these science, develop faster with a higher probability of success, which we have been able to demonstrate with BIMZELX, for example, and execute commercially, which we are demonstrating today then you completed the circle from innovations to results that should give you confidence in our future.

The last product of the portfolio is Kygevvi. So Kygevvi, it's a product which is the first and only treatment today, just got approved in the U.S. It's a rare disease. It's even an ultra-rare disease for kids suffering from TK2d deficiency. And this is really a very severe disease for the kids, the only treatment available. So it's not a big patient population, but it's here also a good illustration of what patients value means and what unique differentiations can create.

The second element of the pipeline that I would like to illustrate is galvokimig. So galvokimig is an illustration of a multispecific antibody targeting different pathways. So it's a natural evolution, if you think about science. It's a natural evolution of how we can evolve and how we can progress in the treatment of auto-immune disease. By nature, autoimmune disease is not just the result of a dysfunctioning of one pathway. It's a multiple complex consequences of man functioning of the immune system.

And so after targeting one interleukin in certain disease, it looks natural to try to combine different target together and having one monoclonal antibody and ability to target different interleukin. So with galvokimig, we have the combination of IL-13 and an IL-17A and IL-17F. And by doing so, we hope that we will be able to provide additional clinical value for patients suffering from atopic dermatitis in the first disease that we have evaluated the drug here.

If I move now just to give one example in neurology after covering -- after having covered immunology. Alzheimer's disease, it's a very complex disease, of course, and it's not an easy one. I think -- we think that with bepranemab, we have something quite unique there. The first time that we have been able to demonstrate clinically, some improvements in patients suffering for Alzheimer's disease with an anti-tau treatment. And we think we have a good option there because we have been able to demonstrate with human cells that we were targeting the right epitope that can translate an anti-tau into clinical positive outcome.

So as you can see from a pipeline standpoint, I just highlighted three components. I could have added dapirolizumab for lupus that we have with our partner, Amgen, which is in the second Phase III now, and it's also a huge unmet patients need, right? So you can see multispecific dapi in lupus, beep in Alzheimer, Kygevvi in rare disease, you can see that we have already in the phase of preparations of the future of the company.

So pipeline is one. Execution is the final -- is also another one, right? And you can see here what has been very specific for us, and we have not been used to that before. On the launch of BIMZELX is the speed by which we have been able to complement the first launch of one indications in one country by a launch globally in multiple indications. So in less than 2 years, we have been able to reach 50 countries, 5 indications. And we have still some to come with pediatric studies and with PPP that we have started to develop. And that's how it translates into results, right.

More than 100,000 patients have been treated already today with BIMZELX in just 2 years of treatment in most of the countries where we have been able to launch. We have no additional elements there, no signal, things are doing very well and the feedback of the patients, the physicians on the product have been amazing, which is translated in the graph below, where you see the dark green in terms of patient acquisition, which is above competition. And once again, I think with the level of competition that we are facing, I think it's pretty remarkable there. .

And for '26, we are happy, and we have published that yesterday in the press release, we are happy to add 36 millions of life covered. And so we will be able -- which is an increase of 25% versus '25, which means that now we are able to cover already 80% less than 3 years after the launch of a product in such a competitive market, we are already covered 80% of the commercial lives.

But as I said, the growth drivers are not just about BIMZELX. We have also other products that drive the growth of the product -- of the company for the next 10 years. And all of them illustrate very unique specificity and outcome for patients. EVENITY is still today the only anti-sclerosin with able to build back bone at a moment where you need it, which is able to translate into 50% reduction of fragility fracture.

And what means life expectancy going up if you are not able to get the bone and the quality of the bone that goes with it. RYSTIGGO and ZILBRYSQ are two portfolio brands that we have in general myasthenia gravis. RYSTIGGO is the only one that have the indications broader between [ Muzkalanti ACH ] and ZILBRYSQ is an anti-C5 on a daily indication and daily prescriptions and dosing, which is a very important one for younger patients who want to stay active and to control the disease all over the year.

And last but not least, FINTEPLA in Dravet and Lennox-Gastaut. So you see a full portfolio who will drive the growth and behind the pipeline. So the last thing that I wanted to share with you is really to leave you with this message, UCB is a company today which is very uniquely positioned in the industry today in terms of ability to enter into a negative growth, visibility with a very limited number of products with a loss of exclusivity in the next 10 years. Plus the evolutions and the investments in innovation that translate into a solid pipeline and an ability to execute both from research to development and to commercial executions that fully provide the results that we want to see from research to the patients.

Thank you very much for your attention. Thank you for your confidence. And with that, Richard, I hand over for the question. Thank you.

[Operator Instructions] Maybe I'll kick off. Jean-Christophe, you highlighted that the incremental patients and lives covered on BIMZELX that you've been able to achieve, that presumably comes with elements of increased rebates to the payers. How should we think about that -- the balance of that as we go forward for the growth of the brand in the U.S.?

Yes. No, Richard, it's a great question, of course. And it's a fine line. Finding the right balance of how much you want to cover patients and get access to the patient versus the gross to net that you leave on the table. So two elements that I would like to illustrate on that.

The first one is we have never considered price as a way to capture new patients. We wanted to be at the level of the market. We wanted to make sure that we follow the rules of the market and we provide the best access that we can. But we didn't want to push the rebates to a level that can stimulate even further competition on price. Why?

Because we have the differentiation, and we have the outlook. Don't forget, we have already published three comparative study versus standard of care where we have demonstrated superiority. And these have been really instrumental to make sure that all of the three major PBMs include us since the beginning in their formulary. And so we are very happy that just at the first year already, we had already a very solid coverage.

And these positive coverage gives us an additional opportunities to switch patients from our bridge program, which was ability for the patients to get access to the drug, but didn't create any revenue for us and shift the patients faster to commercial coverage, which have helped us in '25 to increase and to get a good level of revenue.

So yes, EUR 36 million of additional life covered in '26 translate, of course, into a less medical exception and less patients who pay full price and an additional more pressure on the net price. But once again, we had already the contract, we had already the coverage. We have no exception in the PBMs and for the major indications.

And then we will be able to expand that now, which means that after 3 years, we can be very confident that if a patient need our drugs and if the physicians want to prescribe the drug, it will be able for the patients to get the drug. And you know how important it is, and particularly in this market, where sometimes the time between getting the prescriptions to being able to actually benefit for the treatment, it's sometimes weeks and even months.

So it was important to get this volume in order to make sure that the environment was not creating additional hurdle if the willingness to prescribe is here, but doing that with a minimum impact on the net price, is something that we wanted to achieve. And I think we have a very good balance now.

One of the indications that boosted the growth in '25 was HS. And that was a relatively new market. So how has been the ability? And what's the ability to go going forward for you to sort of expand that market with -- there is another IL-17 as well?

Yes, absolutely. I mean HS is a new market. It's a new indication. And it's a market where it's not so easy to treat patients. And you just need to keep in mind two things on HS. First is patients suffering from HS, very often, we are very disappointed by the treatment they have been able to get so far.

And because of the disappointments, the patients have left the classical secret of treatment or connection with the health care system. And many of them actually are out of the system, treated from time to time with antibiotic or with a surgery, but are not connected completely with the dermatologic environment. So we have to bring them back and we have to educate them also and to let them know that there are new solutions available for them that will help them to treat their patients.

So HS growth is there. It will be there for the long term. Epidemiology said that basically 1% of the populations may suffer from HS. We are far from having these patients connected to the system being diagnosed, average time between early symptoms at diagnosis is more than 7 years. We need to reduce that, and we need to treat patients earlier and earlier in order for them to benefit. But the benefit of the treatment and particularly BIMZELX is real.

I just want to give you one illustration of that. In our Phase III clinical trial in HS, the patient was all severe at the beginning of the study. None of them describe their state as mild or moderate. At the end of the study, more than 50% of the patients consider that they had a mild disease expression. So you can see the impact from the drug on the disease. So I'm very confident that we can leverage the differentiations and the power of dual inhibition of the IL-17A and IL-17F for these patient populations.

And the growth in this indication is just at the starting point, because we will bring more patients to consultation. We will shorten the time of the diagnostic. And because of that, patients will be better treated and so there will be much more motivation to follow the treatments and to continue to be adherent to the treatment.

Today, we have already 3 years of exposure to the product in our open-label extension more than 80% -- 86% of the patients who have been controlled at the beginning, continue to be controlled after 3 years. So we are very confident that despite the severity of the disease, despite the complexity of the treatment, BIMZELX is a huge potential tool in the toolbox of the physicians to provide to the patient the relief that they need.

I think in the excitement on HS last year, we sometimes forget that psoriasis is a very, very large market and still growing today with biologic penetration and PSA too. So maybe you could give us some color on how BIMZELX is performing there and what the opportunity set you see.

Yes. I mentioned in the slide that you have noticed that what was very different from UCB for UCB with BIMZELX was the ability to launch in many markets at the same time, almost and in many indications. So we have five indications now. And as you mentioned, HS is just one of them, which creates a lot of excitement because there is not a lot of solution.

And so you can feel and see the growth for the future. But the other indications are also very much present. Psoriasis, basic arthritis, ankylosing spondylitis and non-radiographic-axSpA. We are present in all of these indications, and we are doing well, and we are growing in all of these indications. There is one element that I would like to highlight here maybe. It's the psoriatic arthritis.

I mentioned already the growth opportunity with the additional coverage and access in the U.S. I have not mentioned the other elements in '26, which is our head-to-head study versus IL-23 in psoriatic arthritis. We will expect results in this study in the second half of this year. And our expectation is that we will be able to demonstrate superiority versus IL-23 in psoriatic arthritis. It will be the first time that we can demonstrate superiority versus this product and this class.

The reason why we have chosen psoriatic arthritis, is because we feel that the pathways of 17A and 17-F, is very important in psoriatic arthritis. Actually, it was the reason why initially we had the hypothesis that targeting both interleukin will create more patient value because of the high level of Interline in the joint of patients suffering from psoriatic arthritis.

So of course, if we are able to demonstrate that we have superior 2023, you can imagine that we can have an additional growth there. But we feel also that the growth will not be just for psoriatic arthritis, but also for psoriasis. Because one patient out of three today is suffering from psoriasis will have psoriatic arthritis one day. The problem is you don't know who, which patients will have and which will not have.

And so if it was you and if you suffer from psoriasis and you don't know if you may be, subject to have psoriatic arthritis in the near future, it's probably better to choose immediately in psoriasis to be treated with the product, which offer the best coverage for your skin and you're joined at the same time.

So as you said, Richard, HS is the most recent indication but we have others and in particular, the ability to provide other and further element of differentiation in this case, psoriatic arthritis versus IL-23 will help us also to grow in other indications such as psoriasis.

And I think you snuck on the slide, PPP as well. What's the opportunity there? And what could we see?

Well, from a clinical standpoint, the PPP opportunity is a very important one. If you think of a disease where basically you cannot walk and you cannot hold anything in your hands because you have trouble on both palmoplantar. It's another illustration that sometimes quantitative percentage of skin touch with the disease doesn't mean a lot. Because if you look at palmoplantar -- palmoplantar pustulosis, it's basically probably 5% of your skin.

But this 5% are so critical that you cannot leave a normal life, right? So it's a rare disease. It's not a strong patient -- a big patient population, but it's a very damaging disease and it's a disease that create when you suffer from it, which creates a huge impact on your quality of life, on your inability to have a normal life to go to work and to -- and just to walk and just hold and do the normal things of the daily life.

So it's a quite damaging disease. We've started the study right now. And so far, there is no treatment available. So even if it's a small patient population, it's a nice and it's a very important addition to what we currently have.

Maybe we can pivot to the pipeline. You highlighted on the slide, galvokimig, which we've seen strong data in AD. You also have donzacamig, as well potentially with data coming up with your results. How should we think about the early positioning of those two products in AD? And you have a large R&D budget, but do you have -- how do you think about progressing both those agents?

I think it's a very fair question. As I said in the presentation, I do feel that multispecific antibodies in autoimmune disease, in particular, it's a big part of future treatment for these patients. And the reason is the diversity and the complexity of autoimmune disease and immunology in particular.

If you think about all of these disease, you don't just allocate or dedicate one disease to one pathway. It's much more complex than that. It's not an anomaly of one pathway that create the disease. It's much more complex than that. So it seems natural if you feel and if you understand better the biology of autoimmunity and the fact that the system does not recognize itself and stimulate antibody towards targets, which are normally your own targets, you can think that multispecificity and addressing different targets at the same time is the way to go moving forward for autoimmune disease. So -- so that's the point number one.

The point number two is it's, of course, very natural for UCB to dedicate time and resource for this potential evolution because with our centers in Slough, in particular, we are very strong in our ability to engineer antibodies, right, and to make sure that we get the best possible antibody to address the target. I think EVENITY is one illustration of that. BIMZELX is another illustration of that, right?

It's not just that you need to identify the target to potentially translate that into a strong medicine. You need to engineer an antibody that create the affinity and creates the ability to interact with the system. So multispecific, I think, will be not only just for one disease, but for a lot of different autoimmune disease will be a way to go.

Now having said that, once again, it's not necessarily that by combining two that you treat only one disease. So we have with galvokimig and donzacamig. We have first -- the first clinical study has been done in atopic dermatitis. It doesn't mean that the two drugs will be developed in this indication. Indications have been chosen because of the ability to execute the potential utility and knowledge of the targets and the potential differentiation.

And I think what you have seen with galvo first set of data, demonstrate this ability that there is still an unmet medical lead, and there is still value for differentiation and value for the patient.

In a nutshell, we have here another illustration of what we have been able to do with BIMZELX. The target was well known. The IL-17 role in psoriasis was well known. But the combination of A plus F was not done and was able to be translated into added value for the patient. It's what we aim with this bispecific is delivering more than what is currently available by just targeting one pathway.

Galvo is 13 plus 17A and F. So here, the objective is to get the synergies of the interleukin on inflammation. Donzacamig is 13 plus 22. And here, it's a different type of combination. It's the classical inflammation on one side. And on the other side is the ability to target the skin and making sure that we can restore the skin barrier, which is such an important element of the morbidity in the case of atopic dermatitis, for example.

But to complete the answer to your question, for the time being, we are looking at the data in this indication, we are evaluating the strength of the data that we have and the potential other indication where these different type of combinations may create the best possible value for the patient.

And then we will evaluate the ability to execute, the speed by which we can get at the level of unmet patients need before deciding which indication for which patients and for which assets.

And you mentioned bepranemab as well, the anti-tau. Different sort of risk profile, I would say, in Alzheimer's. So how do you think about managing that risk in terms of that asset. We've seen some Phase II data with some signals there. When you're allocating capital between the things, how do you think about it?

So on the capital allocation question, I think, even when you focus on innovation, you need to profile your allocation of resources in a way that maximize the long term of the company. So based on that, it will not be reasonable to dedicate 100% of your budget of research on identification of new targets and potentially translating that into new mechanism because new mechanism, it's great. It's high risk, high reward.

But I feel -- we feel that you should dedicate a certain amount of your portfolio on this type of assets, but not all. So 25%, 30% is fair, but certainly not 80% or 90% would put the company at too much risk. This is what we have with bepranemab. With bepranemab, we wanted to leverage our knowledge of biology by identifications of new target and anti-tau. There is no anti-tau in the market today for Alzheimer's disease.

At the very early stage, we were able to reproduce what other anti-tau could have done and try to connect that with the epitope where we feel there was the highest probability of success to translate the binding of the antibody on the target to a clinical outcome.

So we are not surprised to see how the other anti-tau results unfold because we knew that we are not binding at the right position in the right place, right? And we have confirmation of that in the Phase II, because in the Phase II, we have been able to have some signals, and we think we have a signal in the Phase II, where we can see improvement for the patient.

Now for the next phase, we need two things. We need to define, what is the population which will at best improve or increase the probability of success and the magnitude of the outcome? And two, we need to define at what stage of the disease we have a higher likelihood of delivering this?

So there is an element of patient profile and an element of timing of the disease, but it's still a very high risk. And so as you know, when you have a high risk in your portfolio like that, basically, you can also think about partnering because partnering is a way to either develop capabilities where you don't.

Get the scale that you don't have or share the risks that you don't want to do by yourself because by sharing the risk, it gives you space to do other things. So this is what we are exploring today.

Maybe one last pipeline question in this area. Dapimab, you had a full successful Phase III trial with your partner, Biogen. How is the next Phase III, you need another Phase III, I think, to get to market? How is that going?

Yes, we needed, and we had a lot of discussion with the FDA on this topic, and the outcome was we needed a second phase III, and I guess the reason was we needed sufficient patient exposure to get an ability to evaluate, particularly the safety of the drug on sufficient scale for the FDA to be comfortable to have a regulatory pathway.

So this is what we are doing. I think if you ask me, I think that in the future, real-world evidence would be able to cover what is needed to be covered right now, but we are not yet there in this phase. So we are still in the phase of doing another Phase III with our partner, Biogen.

We are very optimistic and positive because once again, we have done one already, and we know the results, what the result is. So we are quite confident that we will be able to confirm in the second Phase III.

And the first Phase III doesn't have a signal of a safety element, which you may remember. But was sometimes the case with an anti-CD40 ligand so -- with another CD40 ligand. So there is -- so far, we are in a very good position. We need to do the second Phase III. We are doing the second Phase III.

We are very bullish on the product because we feel that with the results we have been able to achieve with the first Phase III, there is a huge unmet patient need there also. And the market in lupus, I don't feel have got the development that was needed and a lot of patients are not really treated at the level of quality which is required for them.

So they are expecting something else. I think the market will grow when we will be able to put on the market a product that can help the patients. And suddenly, the market size will grow. I don't think that the current solutions available in the market are sufficient to accelerate the market growth and help the market to mature. I think, dapimab will be a product that will do that. And so we are really looking forward to the launch of this product.

We've talked through a number of late-stage pipeline assets in mid-stage or pretty late, actually, with galvo and donza as well. What you highlighted on the slides the long LOE time to 37%, 35% for some of the assets. So what do you think you need to allocate capital outside of your R&D budget outside of the late stage? Are you thinking -- what are you thinking about the growth and preparing for that longer-term period?

So first thing first, for a company like UCB, if you want to be successful for the long term, the only way to do it in my perspective, is to be able to have a discovery engine, which is at the best of the heart and the best of the industry.

So focusing on research. Focusing on the ability to better understand human biology. I mean, I mentioned that in the slide, but it's really the heart of UCB. And as long as we are doing that the right way, the rest is possible. If you don't have this, you may have best for the rest, but it's more difficult.

So in terms of capital allocation, think about that in the near future that we're continuously looking at how we need to be connected to science to the evolution of the pipeline and the platforms in the environment to make sure that we can integrate, collaborate partner in order to build an engine that increase the probability of success, of better understanding human biology and translate that into scientific hypothesis.

So it starts with AI, but it start also with immune reset for immunology, better understanding neurodegeneration, better understanding blood brain barrier. So all of these components, if you look at the evaluation and the evolution of the science, you can feel and see that science is booming right now. And it will be very unreasonable to stay and to stick just on what we are doing now and hoping that we will continue to provide innovation for the future. So the first thing is a discovery engine and continue to build the state-of-the-art leveraging what the science and the environment is creating today.

Two, as I said, growth in the long term, it's organic and inorganic. In our five growth drivers today, we have organic product that we have discovered and we have all products that we have acquired. Acquisition for commercial products have been in the past, focusing on strengthening the pillars that we had in the therapeutic area that we had because we didn't want to increase our OpEx. Our P&L by additional new therapeutic areas.

But with the growth drivers that we have today, adding a commercial asset now will be too early, right? So we have time. And so for the short term, it's probably more early stage that you need to think about us from capital allocation, so research, platform, early stage. And then moving forward, we will get closer to the end of this decade, we will probably looking at what's next.

But as I said, we have a very strong balance sheet. We have a strong financial situation. So we have everything in our hands to be able to leverage these resource allocations and capital allocations in the best possible way. We have never been in this situation at least for many years. And so now we are already in a very good place there.

Any questions from the room? Then I think we're probably at the end of our time. Thank you very much for the chat. Thanks, everyone.

Good afternoon, good morning, good evening. Welcome to the UCB Half Year 2025 Capital Market Call. My name is Antje, I'm the Head of Investor Relations at UCB.

Before I introduce you to the agenda and hand over to the speakers today, I'd like to make some remarks. This presentation and the following Q&A session are intended for institutional capital market participants. If you're not, please disconnect now. This video conference is being recorded. You can find the presentation in our download center on our website in the Investor Relations section, of course, if you dial in by phone. And this presentation and the following Q&A session are covered by the disclaimer and safe harbor statement as stated on the Slide 2 of the slide deck. Please kindly read and respect this carefully.

With this, I'd like to introduce you to our speakers today, our CEO, Jean-Christophe Tellier; Fiona du Monceau, Head of Patient Evidence; Emmanuel Caeymaex, Chief Commercial Officer; and of course, CFO, Sandrine Dufour. And then we're going to have a Q&A session with our speakers.

With this, Jean-Christophe, over to you.

Thank you, Antje. And from my side also, good morning, good evening, good afternoon, everyone, and thank you for joining the call. It's a pleasure to have you here and to share with you what have been pretty extraordinary first half of the year for UCB in 2025. So we are happy to share with you the strong results of this first half of the year, which are supported by an unprecedented growth, which illustrates the focus on the strategy based on innovation and delivery.

So on this slide, you can see on the left-hand side, a summary of what this strategy means this patient value strategy. It means for us that we try to better connect the patient to science, thanks to a better understanding of pathway biology and then we connect this science to a solution and engineer a solution, thanks to our technical platform. And this leads us to get differentiated products that we are better than others able to validate the data with our 86% of successful rate of Phase III. And thanks to that, we can deliver this differentiated solution to the different markets where we have a significant impact.

Last year, when I described the half year results, if you may remember, we presented a growth of plus [ 13% ], and it was at that time, the start of the decade proof of growth. The best way to continue to engage into this decade of growth is to accelerate the growth, of course. And you can see here that we have moved up from 13% last year at this period of the year to a plus 26%. Sandrine, Emmanuel will comment in more details the financial -- the detailed number. But just to give you one number, our 5 growth drivers have realized this first half of the year more than 2.5 twice the revenue of last year, which is very promising. And of course, we have also had a strong delivery on the pipeline of which Fiona will comment.

Next slide, please. So as I told you, this unprecedented growth is the consequences of the strategy, but it's also for us an ability to continue to invest in our future. Invest in our future first by an investment in the pipeline. You see here our engagements already to 4 additional indication for BIMZELX and 2 for FINTEPLA. Engagements and investments in the future based also on expanding our manufacturing footprint with the recent announcement that we shared with you on U.S. greenfield investment for $2 billion of direct investment and up to 5 billion of economical impact.

And also, of course, we are investing in our capabilities in order to provide the complete and as much as possible accelerated service to the patients that we serve. And it's to access, and we are pleased to have expanded our access, and you can see the result of this expansion of the access with the numbers of patients of BIMZELX compared to [indiscernible]. So yes, definitely, a first half of the year that illustrates the strategy, the good execution of the strategy and the impact that we have on the marketplace.

And with that, I would like to thank you, and I will hand it over to Fiona.

Thank you very much, Jean-Christophe. Good morning, good afternoon, good evening. I'm delighted to give you an update on the progress of our pipeline. And I hope you'll see that UCB really committed on investing in differentiated innovation that truly makes a difference to patients and that fuels the future growth of UCB.

Let me show you on the next slide how we're delivering on that innovation and continuously enriching our pipeline. Let's start with the news for 2025. So first, doxecitine and doxribtimine or [ DXM ], to make it simple. This is a treatment for TK2 deficiency disorder an ultra-rare mitochondrial disease. So where the muscles are not getting enough energy, which means that it's difficult to walk, to eat, to drink to brief. We shown a above 90% survival rates. And as you know, we submitted in the U.S. and in Europe, and we expect by end of the year.

Next, Fenfluramine or FINTEPLA. We've recently received excellent results for our Phase III trial in CDKL5 deficiency disorder. This is the third developmental and epileptic encephalopathies where FINTEPLA yet again shows great results. And as an investigator was sharing recently, it's extremely gratified to see the impact of the reduction in seizure. Then bepranemab, our anti-tau antibody. We all have someone close to us in our family or friends families that are suffering from Alzheimer's disease. As you know, we've had some encouraging results in our Phase IIa in a predefined subpopulation. We're engaging with authorities and defining our next steps.

Now let's move to the middle, where we have our multi-specific antibodies with galvokimig first and some of you will have seen a redacted mandatory submission that we had on the EU clinical trial of registry, where we've shown some great results. But please stay tuned, you'll have the full story at the EADV in September in Paris, and we are moving to a Phase IIb. Donzakimig, IL-15, IL-22, is progressing as planned, and we will have the results by the end of the year. And then most recently, as we've shared with you, glovadalen, our small molecule for Parkinson's disease, where we've had some positive Phase IIa and are assessing the next steps.

All programs for 2026 and beyond are progressing as planned. So now let me pause and focus on BIMZELX. I will first provide you an update with our ongoing pediatric studies and then share with you the exciting news about the new indication we're pursuing. Palmoplantar pustulosis or PPP with our [ BC ] in Phase III global trial. So on the next slide, as you know, at UCB, we're committed to every patient. We've got numerous pediatric studies ongoing but today, I will focus on the 3 central ones, BIMZELX.

So first, [ upsorisis ] study, this is a head-to-head. And it's important to note that 1 out of 3 patients psoriasis patients are under the age of 18. Next, [ Hindradenitis Superativa ], or HS. Again, here, 1 out of 3 patients are under the age of 18. And in addition to that, a lot of patients to whom I've talked to have their first symptoms during their puberty but unfortunately, it takes many years before they're then finally diagnosed. With the increased awareness of the disease, and the availability of treatments like BIMZELX, we hope to really close that gap. And finally, [ in idiopathic ] arthritis study. All 3 of these studies are enrolling as we speak.

And now on the next slide for the exciting news, our commitment to palmoplantar pustulosis. As you can see in the top 3 images and hear from the name, this is a chronic skin disease that impacts the palms and the soles. As you can see from the pictures, you've got pustules that cover the hands and the feet. These are extremely painful, itchy and prone to cracking. As speaking with a patient last week, and he shared that it was a little bit like having 100 paper cuts on your hands and in your feet. So you can imagine how painful that must be and how many simple tasks that we do every day are extremely difficult. They're carrying your shopping bags, greeting someone, walking around. Unfortunately, we lack approved treatments in Europe and in the U.S. and there are no established standards of care, and we hope to change that.

In a small study, [ Professor Pacira ] has shown that 17 out of his 21 patients have achieved complete skin clearance and this quite rapidly within 1 to 4 months. So we really [indiscernible] show the strong results BIMZELX has had across multiple indications with the fast, deep and doable impact.

I hope you can see that at UCB, we're committed to making a difference to patients with truly differentiated products and that we're looking to fuel that future pipeline. On that note, I'm going to hand over to Emmanuel, he will share with you the exciting impact that he's having in the markets.

Thank you, Fiona, and hello, everyone. Delighted to be with you today. As you know, UCB has been launching many medicines, and so we've had a particularly high intensity of launches over the last [ 2 ] years and a launch is a process. It's not a single moment in time.

So today, it's my delight to update you as to the results of the many launches both products and indications that have taken place. And obviously, as Chief Commercial Officer, it's my responsibility to ensure that those [indiscernible] are successful. So let's have a quick look at this. We'll focus most of the time on BIMZELX because I hear that, that is where you probably have the highest interest and number of questions.

So if we look at BIMZELX in the first half on the next slide, you will see that we have broadened and deepened the reach of the product globally. We now are touching 82,000 patients as we speak, in 50 different countries. And the sales amounted to EUR 800 million over the first half of the year. But of course, it is a significant increase to both first half last year and second half last year. And that's been driven by, I would say, predominantly 2 factors: the first one is the very successful launch of the new indications, in particular, [indiscernible] [ Supertea ], now amounting to 21% of our first half sales, but also the rheumatology indications which launched a little earlier and for which the international and European contribution really starts counting. Psoriasis field themselves grew by a factor of about almost 2.5. So successful broadening as well of our psoriasis business.

The second factor relates to a fast and extensive conversion to paid scripts in the U.S. And this was always an important variable last year. And I'm delighted to say that in the first half of this year, we've seen a continuous improvement month after month to rates that are really very, very competitive and are getting the latest benchmarks. And what underpins that is, first of all, the fact that BIMZELX is widely available on formularies in the U.S. as Jean-Christophe mentioned for greater than 70% of commercial lives with many lives in single step or better. But also 9 out 10 Medicaid patients and more than 6 out of 10 Medicare patients have access to BIMZELX in the U.S. And that is not just in psoriasis, but also in the indications that were approved between September and November last year by the U.S. FDA.

The other reason that underpins this is the fact that our patient onboarding and support programs really have performed in a superb way and the bridge and the specialty pharmacy metrics look very, very good, which means that typically, patients move quite quickly from bridge to paid. And we've been quite effective in ensuring that this continues to happen as our indication expansion took place. And so with that, the April dynamic market share in psoriasis topped 35% in the IL-17 segment. We are very proud about that, and we're also very proud about the fact that we're already at 20% dynamic market share in rheumatology. And remember, it's just after 6 months of commercial launch in the U.S. What we're seeing is that BIMZELX is being adopted at a very high rate by the top 1,000 or [ 100 ] rheumatologists and dermatologists in the U.S. and clearly, at a faster rate than what's been seen before with [ R17 ] inhibitors.

In addition, our DTC efforts are paying off and currently, we are beating the launch benchmarks by 2x in terms of our ability to generate incremental patients on the brand. Now in Europe, we are reporting what you would call TRx data here or patient share data. And so what we're seeing with this 21% psoriasis share within IL-17 is that as planned over a period of time of several years, the TRx for patient share is catching up with the dynamic share. And remember, the dynamic share was around 35% in Europe in IL-17 and so that 21% over time will move to that higher dynamic number. And likewise, if we look at the total biologics and oral markets, that share currently stands at 5% and is also set to increase, particularly as the persistence data that we continue to collect, both in Europe and the U.S. are really look very promising for BIMZELX and psoriasis. And I think we'll see the same or in fact, we do early days in the rheumatology indications.

So then moving to the next slide. We'll focus on hybrid and [ IT operative ] because, of course, of all the indications it's the one that probably has represented the largest difference compared to your and our expectations for the first half of this year. And on the left panel, you can see a depiction of a campaign that we have put together really with patients anchored in patient insights to try to sensitize dermatologists to their lived experience and experience of payment suffering, an experience of feeling stigmatized of isolation of shame and loss of dignity. And these campaigns won the most awards at the European first half of [ BM Society ] meeting in London across any industry [ Michel ] and marketing campaigns because it's really enables people to not only learn something, but it really changes someone's perspective and leads to different action.

And we've seen with this, for example, that together with this campaign and the tools that we've put out to dermatologists, we've been able to increase diagnostic confidence by 40% in HS. And our goal is also to reduce the time to diagnosis, which currently stands at 10.3 years in Europe and at least that in the U.S. as well.

So UCB is positioning itself as the company in [ HydroSport ], and I believe that dermatologists looking at various surveys, including many that you are fielding clearly perceive BIMZELX as the best-in-disease product in HS. And so one we can see it translated in the dynamic patient shares in the biologic market, which essentially is [ balumumab ] and [ HUMIRA ], [ secukinumab ] and BIMZELX. And you can see here after 4 months of commercial launch, BIMZELX was achieving 26%. And if I look at the last point estimate, we're probably around 40% now in the U.S. In Germany, we're at similar kind of numbers and in Japan, where there's just 2 products approved, [ adalimumab ] and BIMZELX, we stand at 65%. So it's very promising. And I believe that we have a strong chance to lead and to capture that position in the near term which is even more important as the field is due to grow very significantly.

And on the next slide, you see that we have about 1 million patients diagnosed in the world, most of them in the markets you see depicted here. And many of those patients, in fact, the majority are patients that would need a systemic treatment and a biologic in particular, given the severity of the disease, but also the value of treating early to prevent surgery and scars as well as the tremendous psychological anxiety, et cetera, that comes with this disease. We would see that about half of that eligible population is likely to be treated with a biologic within the next many years. So you take those left-hand side numbers, you multiply them by 30%, and that should give you a sense of where the market is heading. So in our estimation, and you just look here at the 5 large European markets, U.S. and Japan, we see a sustained CAGR and at least 175,000 patients on systemic biologic treatment or others by the end of the decade.

So with this, let's have a look at some of our other launch brands. And you will see on the next slide that UCB has progressed very significantly in our capability to launch successfully in rare neurologic conditions. And first and foremost, in generalized [ myasthenia gravis ] RYSTIGGO and ZILBRYSQ contributed to more than -- to about EUR 240 million sales in this first half and FINTEPLA, more than EUR 200 million sales as well. I remind you that UCB is uniquely positioned in [ myasthenia gravis ] with a unique and differentiated portfolio of targeted medicine that will enable us to meet the diverse needs of patients, but also the evolution in the treatment dynamics, which are quite different from region to region where in the U.S., there's a clear preference for the [ anti-FcRn ] mode of action. I would say it's probably 70-30 now in terms of new patients whereas in the world, it's almost perfectly balanced between anti-FcRn and complement C5 inhibitors.

If we look at FINTEPLA we now have more than 11,000 patients benefiting from the treatment. We started in [ Dravet ] syndrome, where FINTEPLA is a foundational treatment. Our market share in the U.S. is 19%. In [ Lenox Casto ], which is a more recent addition, and we're actually lacking targeted treatments. FINTEPLA has increased to 8% share, our sales increased by about 30%, both in the U.S. and worldwide as we significantly expanded access for FINTEPLA around the world.

And so with that, I hope that you have understood a few reasons for the great results that we've just presented. And I'm going to ask Sandrine, who will take us through some more details into the financials.

Thank you, Emmanuel. Thank you, and thank you for these exceptional product launches that are driving our strong financial performance in the first half. So good morning, good afternoon, everyone. We first go through the drivers of the strong first half performance, and then I'll take you through what it means for the year with an upgraded guidance.

And so starting on next page with net sales. Net sales were EUR 3.32 billion in the first half, 26% growth, clearly boosted by BIMZELX performance, but also a very nice double- to triple-digit growth for the other recently launched assets as well as BRIVIACT.

Starting with BIMZELX. Net sales quadrupled to close to EUR 800 million with strong volume growth in all regions, all indications and outperformance of HS indications as well as effectiveness of access strategy in the U.S. translating in higher percentage of paid scripts. So Emmanuel also commented on FINTEPLA and RYSTIGGO and ZILBRYSQ performance and combined the 3 assets delivered close to EUR 200 million of net sales growth. EVENITY, net sales grew by 36% in Europe to EUR 63 million and as you know, Europe is now profitable, and it is adding to the EUR 282 million net contribution from our partners, which is booked in the other operating income, we see this in a minute when we comment on the next slide. And BRIVIACT, BRIVIACT continues to nicely grow by 15% and increased net sales to EUR 377 million.

Last, CIMZIA. I'd like to highlight a few drivers on the first half performance of CIMZIA. CIMZIA remains the fastest growing branded TNF in all major markets and global volume grew by 7%. And part of this 7% volume growth demonstrates the brand resilience with CIMZIA differentiated clinical profile, whether it's in women of child-bearing needs or with the high rheumatic fatter. And part of this 7% as well is the result of some anticipated buying pattern in the U.S. that we expect will normalize and will not repeat in the second half.

And in this first half as well, there were some favorable channel mix effects that should not repeat in the balance of the year. While on the other hand, we continue to see pricing pressure with the impact of [ IRA Part D ] redesign and the rising trend of 340B. So overall, that's why we saw only a modest decrease of 2% at constant rate in the first half.

Now at the bottom of the page, you can see the progress in our sustainability journey as we continue to be rated in the ESG top leaders in our history. CDP, which is the Carbon Disclosure project, awarded UCB a level [ A-score ] on supplier engagement assessment, which demonstrates the efforts we do to manage the reduction of our Scope 3 CO2 emission impact. And also UCB was recognized by [ Time and Statista ] as one of the world's most sustainable companies, and the company maintained the #1 position of the biotech sector by Sustainalytics.

So let's now look on the next page to the full P&L. All in all, the first half was a very good illustration of the meaningful margin expansion equation that we've been explaining for a while, with robust net sales growth leading to improved gross margin performance and operating leverage. And revenues achieved EUR 3.487 billion, a 25% increase, which is very close to the growth of the net sales that I have just commented. Adjusted gross profit was EUR 2.8 billion, a growth of [ 28% ] and adjusted gross margin improved by 2 percentage points from 77% to 79%. And the main driver of this margin expansion was the improved product mix as the key growth drivers come with a higher individual margin.

Operating expenses totaled EUR 1.845 billion, it's a 15% increase which is now lower than net sales growth. And starting with marketing and selling expenses, they grew by 23% to EUR 1.165 billion reflecting the continued investments behind the global launches, but also [indiscernible] fee for service expenses in the U.S. And this fee for services they are, for example, paid to the [ PBM ] or to the specialty pharmacies, they are directly linked to gross sales, and they will continue to expand as the franchises grow. The R&D expenses, they grew by 9% to EUR 860 million, reflecting the continued investment in the clinical pipeline in the earlier stage research activities and also digital initiatives where we are advancing the digitalization of research and development activities, and the R&D ratio reached 25% in the first half after 28% last year.

We had lower G&A. They decreased by 7%, and [indiscernible] last year, the accounting effect of [ DLTI ] and the one-off implementation costs of our new growth organization model did not reoccur. And the other operating income increased by 18% and this is largely driven by the net contribution of EVENITY, which went up by 24% to EUR 282 million. So all of this leads to an adjusted EBITDA of more than EUR 1 billion, EUR 1.033 billion to be precise, which went up significantly by 58% as a result of the strong revenue growth, the improved gross margin and the operating leverage. And the EBITDA margin increased by close to 700 basis points, reaching 29.6% and compared to a 23% in the first half of 2024.

So moving to profit. Profit of the group amounted to EUR 475 million, more than doubling with us EUR 208 of last year. And the average effective tax rate was 20% compared to 16% in June 2024. The increase in tax rate is mainly driven by the strong business performance, the tax impact of an internal reorganization and also the international minimum tax. And all of these effects are partially offset by the continued use of the R&D incentives. Finally, core EPS, EUR 3.53 per share, compared to EUR 2.09 last year, it's a growth of 69%.

So in summary, the first half of file highlights our commitment to delivering robust financial performance, driven by exceptional product launches, while we continue to invest in innovation. And on the basis of this strong first half, we feel confident to upgrade our guidance for the year. And so if we move to the next page, we increased our revenue guidance to at least EUR 7 billion for the full year, our EBITDA margin to at least 30% and our core EPS to at least EUR 7.25. On revenue, overall, we expect the key growth drivers will continue with the strong momentum for the second half. On BIMZELX, we do expect to see continued strong volume growth and the effectiveness of access in the U.S., observing that the conversion to the paid scripts has already achieved a high level in the first half.

And maybe a few additional elements to highlight for the convenience of your modeling the second half of the year. On CIMZIA, as mentioned, some favorable elements supporting the first half performance will not repeat in the second half, and price erosion is expected to continue. [indiscernible] the currency impact, particularly U.S. dollar depreciation is expected to be a stronger headwind in the second half versus the first half. So if the average July rates were to prevail for the remainder of 2025, we would expect the full year currency impact to be a negative 3 percentage points on net sales for the full year. And while the net sales are exposed, we are not expecting any major negative impact on EBITDA on the year. On this year, as a reminder, the hedging policy is to hedge most of the cash flow 1 year in advance, and therefore, EBITDA is mostly protected in 2025.

And maybe a last comment, a reminder that you can see on the left part of the chart of the fact that 2024 included EUR 427 million that we're flagging on the left part to help the like-for-like comparison, and that includes the sum of the proceed of the 2 established brands that we did last year. That includes the [ Minasin ] termination impact and the sales of the 2 established brand and the site China neurology and allergy portfolio, and the majority of this was on the second half of 2024. So reflecting all these elements, we are confident to move up the revenue guidance to at least EUR 7 billion compared to a range of EUR 6.5 billion to EUR 6.7 billion previously guided.

Now if I move to the EBITDA margin, we expect to deliver at least 30% EBITDA margin, same key drivers as in the first half, continued gross margin improvement, thanks to the mix of the portfolio and operating leverage supporting the margin expansion. Marketing and sales will continue to increase. R&D expense should be relatively stable in absolute and decreasing as a percentage of revenues. EVENITY will maintain its growth trajectory and consistent with our approach in the prior years will continue to effectively manage the tail ends of our portfolio. And with this, core [indiscernible] is expected to be at least EUR 7.25 with financial expenses slightly lower than '24 and a tax rate of around 20%, consistent with the first half.

And as I mentioned in February, there are no impact reflecting this guidance of potential tariffs that could be imposed on export goods to the U.S. We do not yet have full visibility on the scope of the various agreements nor do we have the outcome of Section 232. We've taken proactive steps to ensure sufficient inventories in place in the U.S. to meet patient needs over the coming months. Therefore, we do not anticipate a material impact on the 2025 results if and when tariffs would be effective.

So this concludes the financial part of the presentation. And with this, let me thank you and hand over to Jean-Christophe.

Thank you, Sandrine. Thank you, Emmanuel. Thank you, Fiona, for these additional explanation that go deeper into our first half result. Next slide, please.

So I hope that with this global overview, you will be able to share with us the confidence that we have in the future based on unprecedented growth that we are delivering today. I think the focus on innovation, the differentiation of our portfolio, ability to invest into the pipeline give us the best possible way to enter into this decade piece of growth that we have started to share with you last year. This decade of growth, despite the uncertainty of the environment, we'll be able to guide us towards more ability to offer to patients suffering from chronic disease, the life that they want to live and provide to shareholders, employees, the best possible return and to protect the planet.

So with that, I would like to thank you again for your attention, and we'll hand over to the Q&A now.

Thank you, Jean-Christophe. We will now start the Q&A session, which will be handled by our operator today. [Operator Instructions]. You can also e-mail your question to me under [email protected], and I will ask the question on your behalf to the presenters.

Operator, kindly explain how to ask the question, please. Thank you.

Thank you, Antje. Ladies and gentlemen, we will now begin our Q&A session. [Operator Instructions] Our first question is from Stacy Ku from TD Cowen.

Okay. Hopefully, you all can hear me all right. Congratulations on a really impressive half for BIMZELX and some really solid [ POC ] for galvokimig. So 2 questions, first, maybe, Emmanuel, could you provide some updated thoughts on near-term HS adoption? Your 80,000 biologic-treated estimates look to be somewhat conservative versus Novartis' epidemiological expectations for biologics -- patients on biologics this year. And if you can't go into that type of detail, maybe just help us understand where the commercial team is most focused in terms of HS adoption? Is it competitive dynamics within IL-17, expanding patient size? Or is it really simply just making sure the commercial team is prepared to handle the access and service the HS patient volume.

And then the second question is maybe for Sandrine. The total revenue guidance suggests -- or Emmanuel. The total revenue guidance to suggest BIMZELX sales will remain second half weighted with some good momentum. So maybe talk about the pushes and pulls there? Thoughts on net pricing into the second half, what nuances we should consider? Just help us understand that dynamic. And congrats again.

Thank you, Stacy. So in terms of the dynamics to HS adoption, the first thing I'd say is that a large contribution of the numbers you've seen there come from the U.S. So the U.S. HS market has been developing very fast. This being said, over the last 6 to 9 months, we've observed that the main dynamic was a substitution of [indiscernible] by the [indiscernible] agents, Cosentyx and ANF BIMZELX.

So in terms of future growth, I would say that the jury is still out and that the IL-17 companies over the next year or 2, we'll need to move investments towards market expansion as we are more than midway towards this replacement of the TNF mode of action by IL-17.

The commercial teams are still very much focused on ensuring that BIMZELX is understood. That it leads efficacy is well understood and that the experience of physicians and patients is optimal. And we're seeing the surveys that we conduct, that we now have achieved very good scores across all those metrics. We also see that the adoption by dermatologists has been quite broad with about 4,000 prescribers in the U.S. for HS. And so from here, we can really look to continue to expand our share within the patients that are diagnosed and treated. And as we look into the next year or 2, look at strategies that will aim to expand the market. But for now, that is still too early as our dynamic share isn't yet dominant.

Then in terms of the dynamics for the second half of the year, well, as you know, all those treatments are [indiscernible] treatments. The persistent traits with BIMZELX are very high, relatively, which means that we naturally will see a continued expansion in all the diseases for which the product is indicated. And to that, you will add the fact that access is expanding outside of the U.S. for the various new indications. So there's still a little bit of a flywheel effect to the rollout of the various indications internationally that will contribute in addition to the market share gains and to the additional patients.

In terms of pricing, out of U.S., I would say pricing will be stable. And within the U.S., typically pricing is agreed on an annual basis. So I'm not forecasting huge changes when it comes to pricing. We already have gained a lot in terms of the paid scripts ratio. So there may be some incremental gains left for us this year. But I think that we're probably getting closer to [ decreasing ] marginal gain here even though we, of course, pursue that. So I hope that this helps you to understand where BIMZELX will go in the second half of the year, Stacy.

Our next question is from Charles Pitman from Barclays.

Charles Pitman from Barclays. Two more on BIMZELX. Just to dig a little bit more into that pricing dynamic, please, Emmanuel my understanding based on gross to net conversations at the beginning of the year is that the split of HS patients between those on the bridging program and they will progress to reimbursement at a less price level. And over time, when you renegotiate access with formularies, they will then shift to a negotiated rebate level.

So just thinking about as [indiscernible] has start to see conversations with reimbursers and insurers for [indiscernible] coverage, how should we think about pricing between [indiscernible] and that full on formulary cover for next year? Could that generate some negative pricing pressure and should that be more than offset by the rising volumes as you highlight given the significant prescription uptake? So just some more thoughts around that would be really helpful.

And then just secondly, on the future of the HS market. I was wondering if we could just get some comments around how you think about clinical differentiation potential on a placebo-adjusted high score 75 and high score 50, that would make you think that BIMZELX couldn't face -- could, in fact, face some competition from novel therapeutics.

Charles, thank you very much. To your first question, the simple answer is yes. So indeed, with expanding access usually comes an extended rebate rate on average. We fully model them, but of course, the growth in patient numbers will clearly we'll clearly outnumber that I mean it's a very typical dynamic. In the first half, we actually did open access for BIMZELX with 2 of the big 3 PBMs and some of their downstreams in single step edited position, meaning a patient having failed on either Humira or Cosentyx would be able to get BIMZELX [indiscernible].

So now in terms of bridge dynamics, I would say that many HS patients in the early days were patients that have suffered for a while, had tried 2 treatments. And so pretty quickly, they access to BIMZELX if not in a covered manner on a medical exception manner and which also explains the attractive gross to net rate or the net sales associated with HS as you saw that as a proportion of total sales for BIMZELX, really driven by the U.

S. You had a second question, Charles?

Hopefully, he's telling me. Yes, just in terms of kind of thinking about future differentiation versus be heard would mark clinical differentiation in your view?

Look, I'm not going to speculate about what results might be in the future. What I can tell you is, from what I've seen so far, I haven't really seen something that if you properly adjust it per phase statistical analysis plan looks very different. So again, let's see how the upcoming agents report on their Phase III studies. But certainly, there's nothing that I see in the data that have been shared so far that looks significantly different or in my opinion, that would even enable to power a superiority study, for example.

Our next question is from Peter Verdult from BNP Exane.

Happy to do this, thank you so much. So just asking a question to Sandrine. UCB will stay innovation focused, but BIMZELX is set to have a powerful effect on the P&L. Current EBITDA margin guidance of more than 30% is [ Silian's ] context. Why will it not be more than [ 40% ] of in the longer term?

Second question is about the galvokimig data. So I think it's going to Fiona. The doctors are excited, interested in UCB's thoughts and dosing intervals being planned in the Phase IIb. Thank you.

So the at least 30% is the guidance for this year '25. And as you know, we're not providing a long-term guidance, a long-term margin guidance. And on the long term, I agree that there are levers to continue to increase EBITDA margin with top line growth with the operating leverage. I think we've said in the past, the long-term ambition is to achieve the comparable profitability levels. But I don't want to give a new guidance on the next 3 or 5 years.

I also want to call out that we indeed will maintain our strong commitment to the R&D and to the innovation. Thanks.

Thank you, Peter, for the question. And thank you for sharing with us that the physicians you talk to are excited about our data. We too are quite excited about the data and we will be sharing more in September at the EADV conference in Paris. Too early to share details on dosing of [indiscernible] but please do stay tuned, and you'll have more information very soon. Thank you.

Our next question is from Xian Deng from UBS.

Two, please. The first one is to Emmanuel, just wondering I mean think about the overall level of rebate for BIMZELX, [indiscernible], the long-term average for this sort of category is about 50%, 5-0. Do you think it's fair to say that we are probably -- for BIMZELX is only halfway there, given only psoriasis as strong line [indiscernible] is still kind of upcoming and then this -- whatever level of the rebate rise probably relatively stable for the rest of the year until you actually go into next year's negotiation. So that's the first question.

And then the second one, also to Emmanuel please. Just wondering what do you think -- how should we think about the BIMZELX HS dynamics for the rest of the year? If we think about Cosentyx this time last year, they had a big initial bolus of patients that had no treatment options for a very long period of time that have gone to Cosentyx. And then have you already seen some of them start to switch to BIMZELX? Or do you expect the majority of the bolus to actually come in the second half? That's also why we should also expect even more accelerated HS adoption in the second half?

Thank you, Xian. And in terms of the levels of rebates, I would say that we're in line with industry averages. But there's different components to rebates, right? There's the actual rebates to PBMs. But then there's also the statutory rebates in [indiscernible], which together probably more or less of the size of what goes into 340B. And so one really needs to think about BIMZELX across those various channels. I agree with you that for the second half of the year, it's likely to be relatively stable as we largely have stable contracts for this year. Of course, we will try to improve incrementally here and there with custom plans.

And then in terms of HS dynamics, currently, we have almost 4 out of 10 patients that are [indiscernible] bio-naive, meaning they haven't had biologic treatment over the last year or 2. The second source of business for us is indeed switches from Cosentyx and the rest is switches from other products. Now if you look at the number of patients that have been approved and along Cosentyx, there's still probably a big bolus of patients there that's over time. will be candidates for BIMZELX. And so I would foresee that dynamic to continue to be strong in the second half of the year.

Our next question is from Rajan Sharma from Goldman Sachs.

Just on the tariff piece. So Sandrine kind of heard your comments there that there's uncertainty that still exists but you have inventory in place for 2025. At what point might you start thinking about building inventory to insulate yourself against potential tariffs in 2026?

And then one question just on galvokimig, although not specifically on galvokimig, I know you don't want to say too much ahead of the data presentation, but it would just be helpful to understand your view of the atopic dermatitis treatment market. Where are the areas of unmet need? Do you think patients need more efficacious products, safer products or potentially less frequently dosed products?

I can take the first one on the tariffs. What I said is that we have indeed moved the inventory in the U.S. for the coming months, I have not given further time lines and we continue to produce and we'll see, but it's a pace that needs to be in control. We need to think as well on the shelf life and the supply chain overall organization. So certainly, we are preparing ourselves, looking at what we can do. But for sure that what's missing is really the visibility on how things will unfold and hopefully, we should have this in the next weeks also.

Thank you for your question on the atopic dermatitis field. I think as you know, there's -- there remains a significant unmet need for these patients. As you've seen from our reducted data. We've shown some significant improvement in [ EASI75 ] as well as impressive differentiation in the [ EASI1900 ]. So what we're truly looking for is ensuring that we are bringing something that makes [indiscernible] to patients and to their lives. So something fast durable and that has a deep impact. Thank you.

Our next question is from [ Sofia Grabill Neeson ] from JPMorgan.

So you've seen encouraging data from [indiscernible] we're waiting results from donzakimig. Given the competitive landscape in atopic derm at either one or both of these assets under consideration for a partnership? And then just in terms of opportunity for BIMZELX and BP, I think competitors have cited this as a potential EUR 3 billion to EUR 4 billion market by the end of the next decade. Is this aligned with your view of how you think of the opportunity?

I mean we've got great data with [ Gallacher ]. We're willing to see the later end of the year donzakimig. They are different multi specific antibodies with different properties. And we -- once we have the data of both, we will look at them independently on where we can maximize the different assets. Thank you.

Yes, on the PPP opportunity, I think that's probably an optimistic view. It is possible, but I think it's [indiscernible] little early to call these kind of numbers. The point being, today, no treatments are approved. What is being used off label is not particularly effective. So there is a potential for that to happen. And PPP in certain cases, presents on its own and in certain other cases, presents with psoriasis or psoriatic arthritis. So it's a different entity that is associated with comorbidities. The reason we are very confident about BIMZELX's impact here is, first of all, the data that Fiona referred to that were published in [ Geman ] dermatology.

And then second, really the proof that [ IL-17F ] plays a role in PPP as a disease. And so therefore, we really see this as an opportunity within PPP itself, but also in a broader way to really cement BIMZELX leadership in [indiscernible] diseases. And so part of the value we ascribed through that as well.

Our next question is from Kerry Holford from Berenberg.

Thank you and Kerry asked me her question as she is connecting from the [ hervication ] place. So the first question is on BIMZELX in HS, I think it's going to Emmanuel. There's positive progress with this indication that which has surprised you in the market. Novartis clearly lost share to you but has talked about fighting back by focusing on the better efficacy seen with more frequent dosing of [indiscernible]. Meanwhile, [ Moon Lake Phase III ] data readout is coming. What are your expectations for BIMZELX market positioning in HS in the context of the competitive environment?

Second question is for Sandrine. It's about the full year '25 margin guidance. Adjusted EBITDA margin guidance for at least 30%, you almost hit that level in H1. Are you being conservative with your H2 outlook? If strong momentum continues, as you expect for the top line, continuing the positive mix shift, why not more optimistic on H2 margins? Thank you.

Thank you, Kerry, for those questions. So I'm not going to comment on Novartis' commercial stage but let me remind you that BIMZELX [indiscernible] IL-17A and IL-17F inhibitor. And so bumping up the dose typically means that a patient may not be deriving for benefit from a single mode of action, meaning IL-17 inhibition. And we've seen also in U.S. real data that those patients that get escalated also are those patients that are likely to discontinue. So I'm confident that, over time, many patients will switch over to BIMZELX, which combines a very selective and potent 17A inhibition with the inhibition of 17F, which has been shown to be very present in HS lesions. And probably underpins some of the clinical results that we've observed in our mid- and late-stage studies.

Then in terms of market position for new entrants. Look, I think this is -- it's not unprecedented, right? We've had 5 anti-TNFs. We've had a few [indiscernible] in autoimmune disorders. So there will be a place, we welcome competition. 17A and F drill inhibition is a great mode of action. HS is a heterogenous disease, very much so, which means that there is going to be a space for different modes of actions as well. And the art will be to find which mode of action works best for what patient. In the meantime, we are accruing a lot of real-world experience, a lot of real-world data. And I think we'll be in a very strong position by the time new entrants come to help serve patients in the HS space.

Yes. And so on the full year margin, EBITDA margin is expected to be better in the second half versus the first half, despite the fact that we will spend more in marketing and sales in the first half and more in R&D than the first half. And as you know, we are still in this early phase of many launches, we see good traction on the return of our investments so we feel that there are opportunities to further invest behind the brands to maximize the trajectory, and we will do so.

And on top of that, you need to factor what I've explained on the dynamic of the net sales in the second half with a mechanical lower growth in the second half versus the first half in the net sales with the one-off not repeating and the FX. So all of that, that's why we say at least 30% for the full year.

Our next question is from [ Naresh Tusan ] from [ IntralHealth ].

Just firstly, again, going back to BIMZELX and net price please. We estimate that price fell by 15% in H1 '25 versus H2 '24. Obviously, we'll expect in '26, you to try and get more access which I would imagine would require more rebates. There should really -- and there's obviously lots of competition. So should we be breaking in double-digit price cuts on an annual basis over the medium term? That's the first question.

And then secondly, can you just give us a bit more color around sales and marketing cost growth? I'm just trying to get a feel of leverage into '26, please. I would imagine that in the U.S., you're -- there's minimal incremental growth given you fully invested in launches and [ PTCs ] underway. And you're now launching 50 countries ex U.S. So just some color around what the drivers of sales and marketing growth would be. Thank you.

Thank you, Naresh. I'm going to be a bit cryptic on net price. There's there's a lot that comes to see to get from gross to net prices. I think directionally, you are right, in particular in the U.S. we would expect some erosion over time. I'm not sure I would go double digit for several years. But of course, in the near term, it is likely to happen even though we continue to try and ensure that as many patients are possible as possible are actually on paid for scripts. And the script count itself, it is something that also has its books and takes since we work with an internal bridge with specialty pharmacy. And so I appreciate that those calculations are not necessarily easy.

I would also remind you that for now, we're still very much in launch period and accruing a lot of new patients who in some diseases like psoriasis and [indiscernible] go through induction doses. So meaning the number of syringes and sometimes even the number of prescriptions per patient tend to be higher closer to an indication launch as the proportion of new patients are higher.

Sandrine, perhaps I'll hand over to you in terms of a general comment on sales and marketing cost growth.

So well, as you know, we'll give more color on the various elements of the OpEx when we guide for next year in February. But directionally, for sure, at some point, we don't expect to see it has higher growth on the key components of marketing and selling expense except what I really wanted to call out, which you need to see, which is what we -- the fee for service expenses, which are booked in the marketing and selling expenses and apply in the U.S. these fees, they are based and a percentage of the gross sales, not the net sales across -- the volume in a way. So it means that there's a portion of the marketing and sales, which is increasing very significantly that you need to have in mind. And of course, if we were to exclude that, you would see a better operating leverage with the marketing and sales expenses.

Our next question is from Charlie Haywood from [ RECH ].

Charlie Haywood, Bank of America. Big picture question on MFN. To the extent you can comment, obviously, how are conversations progressing here? And do you have any sense of the potential channel that could be a focus or the likely extent of any demonstration projects? And within that, are there -- are you discussing any specific product price discounts or our DTC sales a potential future strategy?

And then second question, BIMZELX, I'll try my luck here. You noted at full year '24, you're comfortable with BIMZELX cons of EUR 1.3 billion to EUR 1.4 billion for 2025. And it sounds like BIMZELX has driven the majority of sales guide upgrade of EUR 400 million at the midpoint. So would it be reasonable to think you're comfortable with higher sales of around EUR 1.7 billion to EUR 1.8 billion for full year '25?

Thank you, Charlie. So on MFN, I'll give you a few comments. I'll also invite Jean-Christophe to add some color. So of course, UCB is preparing for potential interactions with [ HHS, CMS ] and representatives of the administration. I think it's a little bit of a moving target. And so right now, what I can say is that as everybody else, we are looking at opportunities for direct-to-patient platforms and which parts of our portfolio might actually be relevant here. We actually do have a small targeted offering already with 2 of our antipolitics which are subject to generic competition. So this is not completely new for us.

In terms of demonstration projects, obviously, Medicare B, perhaps D and potentially Medicaid could be candidates. So there, we haven't heard much but are preparing as well to engage if and when needed. But the bigger picture is that whilst we recognize that there needs to be a fair sharing of the investments and the risks that come with generating new medicines we are also of the opinion that in the U.S., a lot of the reasons why patient prices and out-of-pocket prices are high, which is really driving voting sentiment. Is the fact that there's a lot of intermediaries and 340B shops that capture about half of the values being generated. And so we very much would like to ensure that this gets addressed. And if we can be a part of this alongside other industry players, then that is something we will consider.

Now in terms of BIMZELX and/or simple arithmetics, it's hard to disagree. I'm not going to commit to a number. It kind of makes sense the top line, so I'll just keep it at that from now, Charles.

Thank you, Emmanuel. And from my side, I don't have anything to add to what Emmanuel have said. The only maybe additional comment that I would add on these notions of pricing is effectively that it's the patient experience at the pharmacy that lead to today a lot of younger and frustration there. And I think it's also fair to say that different countries needs to make sure that the support of innovation, which is so important as there is a high level of a medical need that remains that there is this support to innovation in the various country that can support it.

Our next question is from [ Michael Lui ] from Jefferies.

Thanks for the opportunity. The first one is for Fiona on [indiscernible]. Now that you have decided to go into a Phase IIb in atopic dermatitis. Can you talk to subgroup or target profile? And the second question is, again, to Emmanuel. Can you talk to the source of U.S. patients TNF alpha versus Cosentyx?

Thank you, Michael, for the question. As you know, we've -- for the moment, we've done a Phase IIa, which is still limited in numbers. So too early for us to provide you more details on subgroups. But overall, the efficacy was really great, as you've seen. Thank you very much.

Yes. And thank you for your question with -- I assume pertains to our source of business for [indiscernible]. So in the United States, [indiscernible] Cosentyx is actually a larger source of business now than TNF. And that's changed probably around the end of the first quarter. In the rest of the world, anti-TNF is still the first source of business.

Our next question is from Emmanuel Papadakis from Deutsche Bank.

Just a couple of follow-ups, please. Maybe one on tariffs. You've alluded to the persisting uncertainty but let's assume that 15% is the minimum impact. Could you talk a little bit about what headwind that creates for you in 2026 and indeed beyond until you're able to either bring CMO or indeed to a new U.S. facilities in mind?

And I'm not sure if you've actually ever clarified exactly how much CapEx you're planning to invest in the U.S. You obviously mentioned the EUR 5 billion of economic impact. But if you could talk a little bit about the magnitude of CapEx and the time frame for investing that. Is that going to be particularly [indiscernible] over 1 or 2 years or spread out, for example? And then maybe -- and it's perhaps a related question, a bit more color on the internal tax reorganization would be helpful. The rationale for that and talk to us about tax outlook over the coming years, it seems to be a fairly material step change in your tax situation.

Right. So on tariff, I will not expand further because you cannot just say 15% in there. So many different underlying assumption. Now it could apply or not apply, whether it's at the drug substance, the country of origin, et cetera. So I think it's not useful to speculate there. And once we have visibility, we'll make more comments.

On CapEx, the certainly, the investment in the U.S. is something that is greenfield, as we say. So it will take time for us by the time we identify the location and put this at work CapEx will be spread over time. However, overall, we expect our CapEx to increase. We are in a period of growth, and we want to be able to support the growth over the long term. We are also strategically reinforcing the resilience of our supply chain and definitely for those the past level, you should expect to see growth of our CapEx. Part of the reason is the U.S. investment, but overall, the other investment that we are doing to support the resilience of the supply chain for the long term growth of the company, but also for the pipeline, which is coming.

And last, on your question on tax, it's part of a usual level of company to constantly look at what makes sense from that point of view. And that's why we went through a reorganization. And if you think of where we are, I think we've always said that long term, the tax rate would be around 20%. So we are now getting very close to the long-term range we have in mind. So that's the 20% that we talk about in an environment where we will continue to use the R&D incentives but also have to manage the overall international environment with the minimum tax rate that hit in many different countries.

Our next question is from [ Kia Ding ] from Redburn.

I have one question related to BIMZELX. So today, you announced the initiation of a Phase III trial for BIMZELX in PPP. Given BIMZELX has a differentiated mechanism of action. So do you think there is room for potential indication expansion for BIMZELX in the future?

Not 100% sure I understood your question. So we are going ahead with the palmoplantar pustulosis where we believe the BIMZELX can bring a significant difference including based on sort of the small numbers that [ Professor Patron ] in France has seen. We are constantly looking at how we maximize each one of our assets and what additional indication as well as balancing sort of that pipeline in markets with new indications, late stage in an earlier stage and we'll keep you posted as we bring more.

But beyond PPP, do you have any other potential indications that you think BIMZELX can expand into?

As mentioned, we're constantly looking at additional opportunities. Today, we announced the PPP for BIMZELX and RETT for FINTEPLA. And we constantly assess new opportunities and balance the needs between our end market and newer once.

Our next question is from Jacob Mekhael from KBC.

I just had one on how you look at the potential impact on ZILBRYSQ from Astra's once weekly subcu C5 inhibitor, which recently met its Phase III end point?

Should I take that one Emmanuel or you want to thank take it?

Why don't you start and [indiscernible].

So one, it's important to know that it's a very heterogeneous disease. So there's different needs for different types of patients. I think you'll see that ZILBRYSQ has demonstrated significant improvement versus placebo by week 12, and that sustained over 120 weeks. And many of those patients, up to 61% also see steroid reduction, which, as you know, has a significant benefit for patients. So we believe that we've got a product that's really making a difference of patients that is easy to use and convenient.

Emmanuel, anything else you want to add?

You're right. I mean -- and ZILBRYSQ it's a macrocyclic peptide, right? So it's very fast, and it has a fantastic lasting power. And so the question will be, and we'll look at the data to see whether it's format will produce similar clinical efficacy data. So that's something I'll be looking out for.

Your next question is from Maxime Stranart from ING.

Thank you. This is for Sandrine. He's asking for the phasing of the EUR 2 billion CapEx program for, I think, you mean the plant in the United States, over '25 to 2030? And second question is the market potential and the R&D costs attached for the new potential indications of BIMZELX? Thank you.

Right. So as I said on the investment in the U.S., it's going to be spread over time. So I'm not aware that we've given spread of our CapEx per program in the past, and we will not start this, but '25 would be minimal. That's as we are more in the study phase, and it will ramp up as of next year. So but it's something that takes time to build.

And I don't think we give either the cost per program on R&D, I'm not sure if that was the question. So I will not go further.

Our last question is from Xian Deng from UBS.

So just a very sort of quick one, in terms of longer term both BIMZELX and general space. So now we've seen actually a quite interesting oral molecule [indiscernible] from J&J. That's actually for the first time, actually demonstrated at least some sort of early-stage biologic type of efficacy. I mean, of course, that's still nowhere near BIMZELX level, but just wondering, in the very longer term, potentially, we will see a wave of actually biologics like oral options on the market when you think about the long-term position of BIMZELX versus potentially efficacious oral?

Yes. So as you point out, those oral products are associated with a different level of clinical efficacy. So it is possible that these products could take share in the segments that are currently occupied by oral therapies in psoriasis and elsewhere. I mean, many -- what I'm hearing from physicians is that when somebody has already been on a treatment every 4 weeks or every 8 weeks or even every 12 weeks, moving to something that potentially is not as efficacious and needs to be taken on a very regular basis, even once a day, it's not really a big plus.

However, for incident patients with mild-to-moderate disease. It could be an option that will find its place as other oral treatments have in the past. So we'll continue to keep an eye on those developments, and react accordingly. But I think for now, BIMZELX amongst oral biologics is probably one of those that is going to be exposed to these kind of potential new entrants.

If I may add just a patient perspective, with HS, the scarring is dramatic and delaying treatments or delaying really effective treatments that has a lasting impact. So speed and efficacy is really important for these patients and getting the treatments as early as possible is really important.

Thank you. This concludes the Q&A session. I will now hand back to Antje Witte.

Thank you so much indeed. I think the plenty participants, your very engaged questions and thanks to the -- to our speakers.

This now concludes the first half '25 call. Have a wonderful break, if you go for a break. And do please reach out to us to the UCB Investor Relations team for any more questions or any more help. Thank you, and goodbye.