Ipsen S.A. (IPN) Earnings Call Transcript & Summary

Hello, and welcome to Ipsen's conference call and webcast on Full Year 2024 Results. I'll now hand you over to David Loew, Ipsen's CEO.

Thank you, operator, and hello, everyone. I'm delighted to welcome you to our presentation this afternoon, which can also be found on ipsen.com. I want to use the time we have together to focus on the progress Ipsen delivered in 2024 and on the future opportunities and platforms for growth. Please turn to Slide 2. Please take note of our forward-looking statement, which outlines the routine risks and uncertainties contained within this presentation. Also, any of my commentary on growth will be based on constant exchange rates. Please turn to Slide 3. I'm going to take you through our brief presentation of our performance, followed by our CFO, Aymeric Le Chatelier, who will provide you an update on the financials and our Head of Research and Development, Christelle Huguet, who will focus on the progress and the key milestones of our pipeline. At the end of the presentation, all 3 of us will be participating in the question-and-answer session. Let's begin by looking at today's highlights. Please turn to Slide 4. I start focusing on the business. Please turn to Slide 5. Today's headlines illustrate how we are continuing to produce sustainable growth. In 2024, total sales grew by 9.9%, a result that is driven by the strong performance of our ex-Somatuline portfolio, which grew by 12.2% over the year. We also delivered a core operating margin of 32.6%. Since the beginning of the year, we have made strong progress with our pipeline, including a positive FDA decision for Onivyde in first-line pancreatic ductal adenocarcinoma in February, U.S. approval of Iqirvo in June, followed by the EMA's approval in September, along with Kayfanda approval in the European Union in Alagille syndrome. Looking ahead, 2025 promises to be another exciting year for our pipeline with 4 key milestones, including anticipated approval of Cabometyx in neuroendocrine tumors in the EU and the EU regulatory filing of tovorafenib, both in H1. In H2 2025, we anticipate a pivotal trial readout of Fidrisertib in FOP and excitingly, our first proof-of-concept data for our Long-Acting Neurotoxin or LANT in aesthetics. Christelle will cover those in more details. Lastly, our 2025 guidance includes total sales growth greater than 5% at constant exchange rates and the core operating margin greater than 30%. Aymeric will provide more details in his section. Please turn to Slide 6. Looking at our sales performance, Oncology has performed well this year, reflecting the growth of Cabometyx and ongoing Onivyde launch. Rare Disease continues to stand out, driven by the sustained success of Bylvay and the first-time contribution of Iqirvo. Neuroscience comprising Dysport delivered strong and consistent growth. I'll now turn to Oncology for more detail. Please turn to Slide 7. Starting with Somatuline, sales were up by 5.6% for the full year. Both Europe and the U.S. have experienced shortages of generic lanreotide, allowing us to see uplift in both Q4 and full year. Cabometyx sales were up 13.3% for the full year with increased volumes in both first and second-line renal cell carcinoma across all geographies. Decapeptyl sales were down by 1.1% as we experienced increased competition and pricing pressure in Europe and China. We anticipate that Decapeptyl will go back to growth in 2025. Tazverik sales rose by 24% despite the highly competitive environment in third-line indication in follicular lymphoma and supported by share gains in epithelioid sarcoma. Onivyde sales grew 23.7% for full year and were driven by the U.S. that I will detail in the next slide. Please turn to Slide 8. Zooming in on Onivyde in the United States, where we continue to progress with our launch in first-line metastatic pancreatic carcinoma. Sales increased by 19.9% for the full year, and we continue seeing a steady climb of monthly sales. In addition, we achieved 32% growth in the top 25 accounts for the full year. However, it is important to note that changing prescribers' behavior in this challenging indication is taking time. Our key priority for 2025 remains expanding utilization from academic centers to community practices as we continue our efforts to educate health care providers. We're also generating additional data and have recently presented new results at ASCO GI showing improved overall survival of first-line Onivyde in NAPOLI Phase III versus real-world FOLFIRINOX in the U.S. Let's now turn to Rare Disease on Slide 9. Bylvay continues to grow nicely with annual sales of EUR 136 million. In the PFIC indication, growth has been driven by strong global demand and our market leadership. In the U.S., we continue seeing uptake in Alagille syndrome. For Sohonos, sales continue to struggle due to loss of patients to clinical trials in the label. This quarter, we had to make a decision to adjust our peak sales expectation, which Aymeric will discuss in more detail. Turning to Iqirvo. Sales reached 22 million with a continued uptake in the U.S. following first-line approval in June and positive early momentum in Europe. Let's zoom in on the launch on Slide 10. The launch continues with good momentum and in line with our expectations. In the U.S., we see a significant increase of monthly demand and over 85% of prior authorizations being approved for patients. We see our prescriber base continue to expand in a growing second-line market with the majority of Iqirvo patients being second-line naive, but also some switches. We also presented new data at AASLD last year, showing the long-term benefits of Iqirvo across biochemical efficacy, fibrosis, symptoms and safety. Notably, the data also showed an improvement in fatigue, which impacts over 80% of patients with PBC, which we think will be important data moving forward. In Europe, we launched Iqirvo in Germany and Austria and are already seeing strong patient uptake. In the U.K., we had simultaneous MHRA and NICE approvals in October, which is extremely rare given. U.K. patients immediately access to Iqirvo. Lastly, we have also initiated reimbursement processes across several additional European countries and rest of the world markets. Moving to Neuroscience. Let's turn to Slide 11. Dysport delivered another year of solid performance with sales growth of 9.2% for the full year. In aesthetics, sales grew by 8.3%, driven by continued expansion in most territories and market share gains in key countries such as the U.S. and Brazil despite some softening of the U.S. market. European markets remained resilient, delivering solid growth. However, fourth quarter sales were impacted by adverse shipment phasing in the Middle East and North America, while performance in other regions remained strong. On the therapeutic side, sales increased by 10.4% this year with robust momentum in the U.S. and Latin America. Market share gains in spasticity played a key role in driving growth across most markets. We look forward to another year of growth in 2025 for Dysport. That concludes the sales review. I'll now hand over to Aymeric. Please turn to Slide 12.

Thank you, David, and hello, everyone. I will now take you through more detail of our 2024 financial performance, our guidance for 2025 and lastly, our sustainability progress. Please turn to Slide 13. We delivered another set of very strong financial results this year across sales, COI and cash flow. Our total sales exceeded EUR 3.4 billion, growing by 9.9% at constant exchange rate as presented in detail by David. Our core operating income grew by 10.8% to EUR 1.1 billion, while our free cash flow increased by almost 9% to EUR 774 million. With that, we have a strong balance sheet, no debt, and we have EUR 2.3 billion of firepower available for external innovation based on 2x EBITDA. Let's take a closer look at those financials in the next slide. Please turn to Slide 14. Starting with the core P&L, the growth in total sales of 9.9% at constant exchange rate translated into 8.7% at current rates, given adverse currency movements from mainly emerging markets. Gross margin decrease was limited to 0.6 percentage points due to a one-off payment in 2023 received from our ex-U.S. partner for Onivyde. R&D costs increased by 10.9% and exceeded 20% of sales for the first time at 20.2%, driven mainly by the continuous investment in our internal pipeline across the 3 therapeutic areas and through our external innovation. SG&A costs increased only by 3.3% with the ratio to sales at 34.4% improving by 2.2 percentage points. This reflects our commercial investment to support the launches, especially in the U.S., but also the positive impact of our efficiency programs. As a result, our core operating income increased by 10.8% with a core operating margin at 32.6%, improving by 0.6 percentage points. Please turn to Slide 15. Turning now to the full P&L to net income. This quarter, we recognized an impairment loss of EUR 281 million before tax, almost entirely related to Sohonos, as David said, which is due to lower-than-anticipated patient uptake and revised sales. It's worth noting that we no longer expect Sohonos to exceed the EUR 100 million peak sales. As a consequence of that impairment, IFRS operating income and consolidated net profit decreased significantly versus 2023. At the same time, our core EPS continued, however, to grow double digit at 12.3%, in line with core operating income increase of 10.8%. The dividend for 2024 to be paid next week will increase from EUR 1.2 per share to EUR 1.4 per share as proposed by the Board. Please turn to Slide 16. Finally, on cash flow, we continue to generate strong free cash flow this year and have a very healthy balance sheet with a cash position of EUR 160 million at the end of December. Free cash flow increased by 8.9% to EUR 774 million, driven by EBITDA, growth in line with core operating income and sound management of working capital and CapEx. Net investment, including payments related to the external innovation transaction for a total of more than EUR 300 million, including 5 preclinical transactions and the licensing agreement with DayOne Pharmaceuticals (sic) [ Biopharmaceutical ], together with the milestone paid to Merrimack and Exelixis for Onivyde and Cabometyx for around EUR 400 million, partially offset by the proceeds from the sale of the priority review voucher and the disposal of Increlex. With a net cash position of EUR 160 million at the end of December and based on a maximum 2x net debt to EBITDA, we have now an available firepower of EUR 2.3 billion for external innovation. Let's now move to 2025 guidance. Please turn to Slide 17. In 2025, we expect another year of sales growth despite anticipated Somatuline generic erosion. For total sale, we expect growth of more than 5% at constant exchange rate. This year, we also anticipate a favorable impact of around 1% from currency. This guidance is based on an accelerated growth of our portfolio, excluding Somatuline, driven by the full year impact of the launches of Iqirvo, Onivyde and Bylvay. We assume that Somatuline will face an increased competition from loyalty generics in the U.S. and in Europe, including a progressive resupply from the current generic in the U.S. and in Europe during the first half of this year and the launch of an additional generic in Europe and in the U.S. likely in the second half of the year. On profitability, we expect a core operating margin greater than 30% of total sales, including additional R&D expenses from potential early and mid-stage external innovation opportunity. We will continue to generate efficiency in our cost base to invest into ongoing launches in the U.S. and in Europe to grow our pipeline and also to prepare for potential future launches. Please turn to Slide 18. Finally, let's look at our Ipsen sustainability commitments. In 2024, we made additional progress in our environment road map towards our 2019 sustainability goals, achieving a 45% reduction in Scopes 1 & 2 greenhouse gas emission and a 25% reduction in Scope 3. We also reached 99% of the electricity used across all our sites coming from renewable energy sources. Turning to the people component of our ESG strategy. We target gender balance within our global leadership team, which we have achieved with women representing more than 55% of our leadership team. This year, we are also pleased to share the recognition of our effort by key rating agencies. Ipsen achieved its highest score in the S&P Global ranking, placing Ipsen in the top decile of the pharmaceutical sector, our Sustainalytics risk rating further improved to 22.8 and MSCI rating maintained their level at A. With that, I will now hand over now to Christelle. Please turn to Slide 19.

Thank you, Aymeric. Good morning and good afternoon. Let me start by reminding you that Ipsen has built a strong research and development engine from preclinical research to clinical and late-stage development, including expert pharmaceutical development and regulatory submissions. And thus, we are well equipped to support a sustainable pipeline. Please turn to Slide 20. Here, you can see our well-balanced portfolio that continues to grow across the 3 therapeutic areas and phases of clinical development. IPN01194, which targets the MAP kinase pathway as an ERK inhibitor entered dose escalation following an IND filing in 2024. We expect another Phase I start in 2025 as well as a new IND filing as we continue to execute on our preclinical strategy. Both our Oncology and Rare Disease pipeline have a number of ongoing Phase II and Phase III trials with upcoming data readouts that I will highlight later. I want now to focus on the Neuroscience portfolio and our ongoing research in neurotoxin. We continue to advance our Phase III programs for Dysport in chronic and episodic migraine. And we have further expanded our Long-Acting Neurotoxin program with patients now dosed in the MERANTI study in migraine in addition to our ongoing Phase II in aesthetics and spasticity indications, which I would like to share more on. Please turn to Slide 21. Starting with our latest innovation in this field and our Long-Acting Neurotoxin AB. This is a fully recombinant toxin specifically engineered to bind to the receptors used by the botulinum toxin B and deliver the active light chain of the botulinum toxin A as illustrated in the image shown on the slide. This construct delivers both an increased receptor affinity and rapid cell internalization and leverages a higher receptor B density on neuron cells. We have demonstrated a longer duration of action of our LANT AB compared to currently purified available BoNT A in preclinical studies. We have also shown that the LANT AB engineered properties resulted in less tissue spread in preclinical models, indicative of a potential for a better therapeutic index for patients. We believe LANT AB has the potential to deliver better outcomes for patients with an increased duration of action, leading to a potential reduction in injection frequencies and a potential for enhanced tolerability. As previously mentioned, we continue to expand our clinical development of LANT AB with the addition of MERANTI, evaluating patients in both chronic and episodic migraine. Finally, the LANTIMA study is advancing well, and we expect proof-of concept for LANTIC in the second half of this year. Please move to Slide 22. Turning now to Oncology and our late-stage portfolio with tovorafenib for pediatric low-grade glioma, where there's a significant unmet medical need with no clear standard of care in second line. Tovorfenib specifically targets mutated form of BRAF in the MAP kinase pathway. The Ipsen team has built strong expertise in this pathway with IPN01194 in Phase I and other assets in this pathway in preclinical development. Pediatric low-grade gliomas are the most common tumor of the central nervous system in children and adolescents, accounting for about 30% to 40% of all tumors. While many patients with pLGG survive into adulthood, they face a severely reduced quality of life. We expect to file in Europe in the first half of 2025 based on the pivotal Phase II study, FIREFLY-1. The global Phase III FIREFLY-2 study remains ongoing, and we expect this program to be fully recruited in the second half of -- in the first half of 2026, evaluating tovorafenib in first-line setting. Please move to Slide 23. Supplementing our internal research, in 2024 alone, we added 6 new partnerships in Oncology and Neuroscience. The main focus was on expanding our early-stage pipeline and applying our translational expertise to shape their clinical development. We added some exciting new modalities with Sutro and Foreseen, highly selective antibody drug conjugates with high drug antibody ratio and with Marengo and Biomunex platforms T-cell engager, engaging distinct and specific T-cell subsets. Finally, not forgetting one late-stage asset, tovorafenib that we just reviewed. I look forward to providing updates on these programs as they progress through development. This leads me to turn to our upcoming milestone. Please move to Slide 24. Here, we show key data readouts and regulatory events for the next 2 years. In the first half of 2025 in Oncology, we are expecting a decision from the European authorities on Cabometyx in pancreatic and extrapancreatic neuroendocrine tumors. And we are submitting tovorafenib in Europe for relapsed/refractory pediatric low-grade glioma based on the pivotal Phase II FIREFLY-1 study results that gained an FDA accelerated approval last year. Later this year in Rare Disease, we have the readout of FALKON, our registrational Phase II study with Fidrisertib in fibrodysplasia ossificans progressiva, where we hope to bring an important new treatment option to adults and children over the age of 5 living with this debilitating ultra-rare bone disorder. In Neuroscience, an important readout is the LANTIC proof-of-concept for our LANT AB in aesthetic indication. 2026 will be a very busy year as well for the pipeline with several anticipated Phase III data readouts across all 3 therapeutic areas, and that includes Tazverik, Iqirvo and Bylvay as well as migraine trial readout for Dysport. I will now hand back to David to conclude this presentation. Please turn to Slide 25.

Thank you, Christelle. I will now move to the conclusion. Please turn to Slide 26. We show a strong momentum and are delivering on our 2027 objectives, and I want to leave you with 3 key messages. First, we're showing a continued top line growth based on our strong portfolio and delivered solid 2024 results. We aim to continue delivering excellence in execution across commercial and medical domains. This is key to grow our increasingly diversified, balanced and expanding business. We are also advancing our research and development pipeline at high momentum with multiple upcoming milestones, including several potential regulatory approvals this year and key data readouts as well as the completion of 6 pivotal trials by the end of 2026. We also continue relentless and diligent evaluation of external innovation opportunities to further strengthen our portfolio and have the firepower to do so. With that, please turn to Slide 27. This concludes our presentation, and Christelle, Aymeric and myself will now take your questions. Operator, over to you now.

[Operator Instructions] We will now take our first question. This is from the line of Xian Deng from UBS.

So yes, if I may just ask a broad question on Somatuline, please. Thank you for giving us a color on what you think about the generic entry. Just wondering, could you actually build on top of that to give us a color on what you expect in terms of the cadence of erosion pattern in 2025, please? And the kind of second question related to that is just wondering if you could give us some color on what have you seen so far in Europe as well as U.S. in terms of generic competition, please?

Thank you, Xian. On Somatuline, as you have seen to -- since about August, Cipla and Advance went into significant shortages. They are trying to correct that because it comes from the same supplier, which is Pharmathen, a company based in Greece, which is, by the way, also producing the generic octreotide. Our assumption is that the cadence of erosion is going to accelerate somewhat in comparison to historic levels because we also anticipate that Sun Pharma might be entering the market probably around half this year. They have received the approval in the decentralized procedure in Europe in October, but have not launched yet. So we have to see what's happening there. And then on Europe and U.S., I think -- on your second question, I think it links to my first remark, what was happening in the past. And so this is our current assumption, but we have to say it's relatively hard to have real visibility here. So our assumption, and this is why we have guided as we have guided, is that we are going to see a somewhat increased competition and a somewhat accelerated erosion for the future.

We'll now move to the next question. This is from John Priestner from JPMorgan.

It's John Priestner, JPMorgan. Just 2, if I may. So the 2025 core operating profit margin guidance of greater than 30% implies at least a 2.5 percentage point contraction versus what you reported for the H2 results. So can you maybe help us understand the drivers behind this margin contraction and in particular, really what lines are growing ahead of sales in terms of the costs? And maybe how we should be thinking about that in terms of the margin phasing for H1 '25 versus H2 '25? And then just on a second question on Dysport. How should we really be thinking about the shipment phasing that you saw in Q4? Was that just a pull forward of shipments into Q3, which you reported is quite strong? Or should we expect there to be a catch-up in Q1 '25? And has there been any catch-up so far this quarter? And any notable shipments?

Thank you, John. I'll let Aymeric answer those 2 questions.

Yes. So thank you, John, for the question. So your first question regarding the margin and maybe before getting into the half by half, overall reminding why we see that the margin is going to be lower this year as compared to 2024. As you've seen on our top line guidance, the first driver is clearly we see much more erosion from Somatuline in 2025. And I think David provided some detail just on the previous questions. And as you know, Somatuline will have a direct impact to our profitability. On top of that, we're going to continue to invest from a cost base in R&D, our guidance includes some potential early to mid-stage transaction that we envisage to complete in 2025. And this is including in our guidance as we did last year. On the SG&A, we'll continue to manage our cost base. We want to make sure that we invest both to support the ongoing launches, especially in the U.S., but also in Europe, but also that we are preparing for the future launches should the milestones be positive in the coming 2 years. And you've seen from Christelle that there's quite a number of exciting milestones. Regarding H1 to H2, yes, you should anticipate that the margin will be as it is always historically higher in H1 because there is cadence month of costs, which are always lower in H1. On top of that, all the deal we do will have more impact in R&D towards H2 and very importantly, because the cadence of generic impacting Somatuline, where we will have a much higher baseline in H2 will clearly impact the profitability. So we should expect that H2 will have a lower margin. Having said that, we should benefit also of the increasing contribution of the launch of our other than Somatuline products to maintain a good level of profitability in H2. So that's your first question. On the second question regarding Dysport, I just wanted to remind you that there is always a difference between -- especially, I think your question is really focused on the aesthetic sales where we had a 10% decline in Q4, while the therapeutic sales are quite well balanced quarter-by-quarter. So I think the inventory or shipment impact is mainly on the aesthetic and is primarily related to Galderma. As you remember, historically, we always have a lot of fluctuation between what are our ex-factory sales and the in-market demand from Galderma. I don't -- I think we had a very strong Q3 versus Galderma. We have a soft Q4 and Galderma will publish their quarter later on. This was the same since the beginning of the year. So you should be prepared for that type of fluctuation. Your question on does the underlying demand remain very strong. I think David was talking about some softness in the U.S. market, but it's a limited impact. So we continue to be very confident in the ability for Dysport in aesthetic and through our partner and also directly for Ipsen to continue with the robust growth in 2025.

The next question is from the line of Simon Baker, Redburn Atlantic.

Two, if I may, please. Firstly, on Iqirvo, which was a strong performance in the quarter. I wonder if you could just give us some color on how the launch is going in terms of what the typical patient and prescriber looks like at this, albeit early stage and how the competitive dynamics are evolving in the category given that Gilead has launched as well? And then secondly, on Onivyde in first-line pancreatic, could you give us an idea of where market share stands at the moment? And also how big the community setting opportunities that you alluded to in the slides?

Thank you, Simon. So on Iqirvo, our launch is going according to our expectations. We see in terms of patient profile that the large majority is coming from de novo second-line patients. Of course, also some switches are happening now from Ocaliva because you have seen the FDA tightening of the label. In terms of the prescribers, we see very good feedback from our prescriber base. Of course, now Gilead is also in the market. It's a competitor not to be underestimated, but I mean, we have been successful also in other settings where we have had large companies being established there. So we will have to see over the next quarters. We have, in fact, increased our field force size now as of January. And I was also very pleased to -- that we have reported at the AASLD, the data on fatigue, which is affecting 80% of patients with PBC. And I think that's an important data point going forward. To your second question on the performance of Onivyde. So we see 32% of the large academic centers now using Onivyde, and we see continued growth. Of course, it's going to take time. The sales increase that we are seeing is basically exclusively coming from the first-line setting. In terms of the academic versus community size, it's about 50-50 in terms of patient pool.

Next question is from the line of Sachin Jain from Bank of America.

[Technical Difficulty] So firstly, on the margins [Technical Difficulty].

Sachin, sorry, we cannot hear you. You come across completely scrambled.

Is that any better?

Yes, now it's better. Yes. Thank you.

Apologies for that. So just 2 follow-on questions. So on the margin commentary, Aymeric, is the 2H margin a proxy for how we should think about '26? I understand that 2H is typically lower in the R&D commentary, but it will be the first half that we see the full-to-maximum impact. So any color on how we think about that going forward? And then secondly, just a follow-on to Iqirvo. Obviously, the launch is going well, but any commentary relative to consensus forecast as they sit for '25 and '26?

Okay. So margin, Aymeric, do you want to take that?

Yes. So Sachin, thank you for the follow-up questions. I'm not going to give the guidance by half. I think your number is very low. So we are not anticipating that. Clearly, there will be some phasing of cost, and this will depend on how many deals we're going to do when during the year. But remember that we are expecting also, and this is maybe some of your second question about the Iqirvo or the other product that's going to contribute more and more quarter-by-quarter and the baseline, especially for Iqirvo is pretty low. So we anticipate that there will be a difference of margin between the 2. But the second half is going to be still a good level of margin. Remember that the guidance is to be above 30%. So we're not saying it will be at 30%, and remember that our midterm outlook for margin is really to be at least at 32% by 2027. So we are pretty consistent that we're going to be able to overcome the erosion of Somatuline that we see accelerating this year and which will continue to accelerate in the coming years.

Regarding your second question, Sachin, on Iqirvo and the consensus comment, '25 and '26, I mean, as you know, we are not commenting on consensus figures. What I can say is that we see a growing market. We anticipate that the market is going to expand further because there is also trials ongoing in the below 1.67 segment. So we are not changing our peak guidance that we have given for the drug, but I really can't comment on the consensus figures because we have never done this, and we are not going to do it.

We'll take our next question. This is from the line of Florent Cespedes from Bernstein.

Two quick ones, please. First, a follow-up question on Dysport. If you could give us a little bit more color on the subsegments where maybe you see some opportunities and on some other segments, if there is any challenges and how you believe you will boost this business with the long-acting products you have currently under development with trial readout this year? That's my first question. Second question is more about M&A. As Aymeric said, you no longer have any debt with a quite significant firepower. Could you maybe give us a little bit more color on how you see some opportunities and if you see more opportunities these days because you have in our guidance already only costs for the rest of the year following some potential acquisitions?

Thank you, Florent. On your first question regarding Dysport and the opportunities in which segments and the Long-Acting Neurotoxin. As you might have seen on our slide that Christelle presented on the Long-Acting Neurotoxin, we are developing the long-acting in the Aesthetic segment, but also in the Therapeutic segment. And we have started the Phase II trials already in upper limb spasticity as well as in migraine, but we can take, obviously, that drug into many, many other indications where in the past, perhaps we have been underexploited with Dysport. We are catching up on the migraine part. But the long-acting can really open up also many other indications that we are actively screening right now. So clearly, the profile of the drug is to have a truly Longer-Acting Neurotoxin. We have tried like other companies to change the formulations, but what we have seen in the preclinic is that doesn't really do the trick to significantly push the duration of action. So this is why we have done this recombinantly engineered botulinum A and B because there are more receptors on the neurons also on BoNT B. So the integration into the neurons is happening better. And what we have seen on the early data so far, but we are waiting for the puck is that indeed, we are getting a very different profile. So we are pleased with that. And we think this could, if it works well, and we have to wait for the data, but if it works well and it's confirmed, they could open up really significantly a market because patients experience is going to be totally different because they have to get much less injections. And for the health care system, it's also advantageous because actually the patient needs to go back much less frequently to see the physician. So that's an opportunity. On M&A, I will hand over to Aymeric.

I mean, M&A, first, as you see, we have a firepower of EUR 2.3 billion today. We are not including in our guidance anything related to late stage. It doesn't mean that we're not interested to do deals both early mid and also later stage. You've seen what we did in 2024. And I think that we are looking at the same type of opportunity, continue on early mid, which are including in our guidance, but also be able to take any opportunity in the later stage or commercial assets and using the majority of that firepower for this type of transactions.

Next question is from the line of Shan Hama from Jefferies.

Just 2 for me, please. So AbbVie had pretty negative commentary on...

Shan, can you get closer to the mic, please? We can hardly hear you.

Yes. Can you hear me?

It's a bit better.

So sorry, I was saying AbbVie had pretty negative commentary on the 2024 call regarding the aesthetics market in the U.S. And it seems as though Galderma and by extension, Ipsen has been somewhat immune to this. Could you give us some more insight as to why this is and perhaps the expectations for the U.S. market going forward? And then secondly, what are your expectations for Iqirvo's growth trajectory this year? And how should we be thinking about this in terms of the competitive dynamics with Livdelzi?

Sorry, can you repeat your second question regarding Livdelzi because you jumped from aesthetics market to Livdelzi. And what was your question on Livdelzi?

Yes, sorry. So what are your expectations for Iqirvo's growth trajectory this year? And how should that compare to Gilead's Livdelzi?

Okay. So on your first question, AbbVie has commented quite significantly on the softening of the U.S. market. However, we actually think it's mixed this story on the AbbVie performance because what we are observing is a slight softening on the U.S. market, yet our partner in the U.S., Galderma is gaining market share. So I think there are 2 different underlying dynamics, and it's not all the softening of the U.S. market. In fact, our forecast is that the trajectory of the longer term on the aesthetic market is going to continue to grow because there are still many customers starting to get into aesthetic treatments. So that trend, we believe, is going to continue, albeit perhaps not at the exact same speed as it was in the last, let's say, 5 years because there was a bit of a zoom effect, if you want. But it's going to continue to have attractive growth. Of course, there are some newcomers into the setting as well. But I think those 2 dynamics are still making that market very attractive in the long term. Then on your question on growth trajectory, Livdelzi, I think that's a question you need to ask to Gilead. I can only say we are sticking to the guidance on the peak sales that we have given you in the past. And we are pleased with the uptake that we are seeing right now. As I said, we have also presented new data at AASLD, so more to come. Thank you, Shan.

Next question is from the line of Richard Parkes from BNP Paribas.

Apologies if there's some repetition because I dropped off briefly. So I might be asking something someone's already asked. I'm just wondering from the proof-of-concept study in aesthetics this year, what visibility you'll get on the LANT profile and how that might inform pivotal studies and what other work you might need to do? And then also just remind us of what the situation is with Galderma in terms of that program and when you might be in a position to make a decision on future aesthetics plans in terms of pivotal development? And then just on the margin discussion, are you able to give us a view on a midterm R&D where you expect to see that as a percentage of sales? You reached 20% this year. I don't know whether your inclusion of additional transactions means we should see another step-up from that 20%? Or are you just thinking about that growing kind of in line with sales?

So I will let Christelle answer to your first question on the proof-of-concept on the LANT. I will take the second one on Galderma and also perhaps your question on arbitration, what is the link here and what's going to happen then on LANT in aesthetics. And then also the third one on the margin and the midterm R&D is going to be answered by Aymeric. So over to you, Christelle.

Thank you, David. Thank you for the question. So this is a very important readout for us. Our LANT AB recombinant toxin is in proof-of-concept study. What we can expect from this readout is proof of efficacy, the safety profile and truly the long-acting nature that we have already seen in preclinical studies. These data coming later on this year will inform our Phase III strategy. But we will have, for the first time in the clinic, the demonstration of the properties we have engineered in this LANT AB toxin. Thank you for the question.

On your second question, Richard, regarding the Galderma collaboration and what is the impact then going to be on the Long-Acting Neurotoxin in aesthetics. As you know, we have given notice to Galderma that we are terminating the research and development collaboration on this. They have a different view and they took us through arbitration. That process is ongoing, and we believe the arbitration is probably going to rule towards the end of the year. So we can tell you more by that point. So for the moment, I can't give more comments as this is ongoing. And so I hand over to Aymeric regarding the margin and the midterm R&D spend.

Yes. So Richard, regarding your question on the R&D, as we said at the Capital Market Day in December 2023, our objective is to be at least at the 20% of sales in R&D, which means that, yes, this is the beginning this year. You should not expect that ratio to grow very significantly, maybe depending on the timing and phasing, a couple of points maximum. This will be a combination of our existing pipeline, but remember that we have quite a number of Phase III that will read out this year and even more in 2026. So that will reduce our existing pipeline. And this will be complemented with all our external innovation strategy, adding more early mid-stage assets, which will make these investments. And that's part of our commitment to exceed 32% margin by 2027.

Could I take one further question, if that's all right. I just wondered if you could discuss the reasons for the Sohonos downgrade and how that impacts your expectations for Fidrisertib?

So maybe first, I can talk about Sohonos impairment, and then I will let David answer maybe on Fidrisertib. Sohonos is purely that we don't reach the expected peak sales. You remember, we are talking about EUR 100 million that was our peak sales expectation. Today, unfortunately, and you've seen the quarterly numbers on Sohonos, we are not there. Most of the patients are mostly on clinical trials and the risk benefit of the drug is not proven here in the U.S., and we have very limited access outside the U.S. So by revising our peak sales, we have to take this accounting impairment under IFRS, which explains the EUR 280 million loss that we booked in our 2024 financial accounts. We're going to continue to be in the FOP market. And maybe, David, you want to elaborate on Fidrisertib?

Yes. Fidrisertib has a different mechanism of action. You remember, Sohonos had a futility analysis and the premature growth platelet closures, so got a pretty restricted label. That is not going to be the case on Fidrisertib. So we are waiting for the readout. That trial has included much younger patients as of the age of 5. So it is going to have a different profile and should not have the, let's say, the side effects that Sohonos has shown. So of course, now we have to be patient and wait for the data, and we are looking forward to the unblinding.

Next question is from the line of Laura Hindley from Morgan Stanley.

Laura Hindley from Morgan Stanley. A couple, one on Decapeptyl, please. What is giving you the confidence that this drug will return to growth in 2025? And is this based on trends that you're seeing in a particular region? And then one follow-up on the Long-Acting Neurotoxin. Thank you for running through all that detail, super helpful. But with that proof-of-concept readout we're getting in H2, can we expect to get a clear indication of the duration of action, for example, 6 months or 9 months? And will we get a read on the improved tolerability that you referenced earlier?

Thank you, Laura. On Decapeptyl, what gives me the confidence is that, in fact, in '24, we have seen volume growth in both in China and in Europe. And so you get from time to time price negotiations that you have to take. And so you will then, or you should then see again, growth, for example, for Western Europe. In China, the dynamic was slightly different. We had some Chinese competitors coming in with a 1-month formulation. We are launching now the 3- and 6- months formulation, so changing the dynamics of the market and those competitors don't have a 3- to 6-months formulation. So we think we can come back to growth over 2025 and also a longer term. On LANT, perhaps I pass the question to Christelle regarding the duration of action, 6 or 9 months, what will we see from the POC and what is also going to be the data we will have on tolerability?

Thank you, Aymeric (sic) [ David ], and thank you for the question. So our proof-of-concept is designed and powered to measure a longer duration of action. So we will have this readout later on, and that includes the 6-months endpoint. And on tolerability, you will remember that we have included higher doses in this proof-of-concept because we've already seen sign of really good tolerability. So we eagerly await the unblinding of that study, and we should have all of the data we need to shape our Phase III development program later on this year, and I look forward to sharing that data at a later date.

Thank you, Christelle. I think that's our last question, and this concludes our conference. Thank you very much for attending, and back over to you, operator.

Thank you very much. This concludes today's conference call. Thank you for participating, and you may now disconnect.