Ipsen Sa S/Adr

Hello, everyone. I'm delighted to welcome you this afternoon to our H1 2025 results presentation, which can also be found on Ibsen.com. I want to use the time we have together to focus on the progress Ibsen delivered in the first half of 2025 and all the future opportunities and platforms for growth. Please turn to slide two. Please take note of our forward-looking statements, which outline the routine risks and uncertainties contained within this presentation. Also, All my comments on growth will be based on constant exchange rates. Please turn to slide three. I'm going to take you through the presentation of our latest business update, followed by Christelle Hügge, head of research and development, who will provide an R&D update, while our CFO, Aymeric Le Chatelier, will take you through the financials. At the end of the presentation, all three of us will be participating in the question and answer session. Let's begin by looking at today's highlight. Please turn to slide four. Turn to slide five. Today's headlines illustrate how we are continuing to produce sustainable growth. Total sales grew by 11.4% in the first half of 2025, accompanied by a core operating margin of 36%. As you have seen, we announced last week the European Commission approval of Covometics in neuroendocrine tumors, an area where Ipsen has a strong legacy. During this first half, we also made good progress with our pipeline, including the entry in phase two of IPN 10-200, our long-acting neurotoxin AD, in cervical dystonia. This milestone highlights the fourth study in the global long-acting neurotoxin development plan in therapeutic and aesthetic indications. Pipeline progress also came in form of the EMEA regulatory submission of tovorafenib for pediatric low-grade glioma earlier in the year. In the second half, we anticipate a pivotal trial readout for fitresertib in FOP and, excitingly, our first proof-of-concept data for our long-acting neurotoxin in aesthetics. Christelle will provide more details on these as well as on the development of elefribenor in PBC and PSC in her sections. Lastly, based on the solid momentum and the strong performance of this first half, we are pleased to upgrade our full year guidance. We now expect total sales growth greater than 7% at constant exchange rates and the core operating margin greater than 32%. Emmerich will provide more details in his section. Please turn to slide six. Our sales in H1 delivered a solid 11.4% growth fueled by all three therapeutic areas, with Q2 very much aligned with Q1 performance. Oncology has performed well with H1 cells growth of 6.4%. Rare disease continues to have the most impressive performance driven by the sustained success of iQurbo and the strong performance of Pilvay. Neuroscience with this work continues to deliver high single-digit growth. I now turn to oncology for more details. Please turn to slide seven. Starting with somatolin, sales were up by 14.1%. Both Europe and the U.S. continue to benefit from shortages of generic lanreotide. We do anticipate more lanreotide generic competition with potential entry in the second half of the year. Cobamethic sales were slightly down by 0.2%, with solid performance in Europe from increased volumes offset by shipment phasing and increased competition in the rest of the world. We're confident that carbometrics should continue to grow its market share in the current indication in real cell carcinoma and progressively launch in the neuroendocrine tumor indication. Decapestile cells were up by 0.5% as we experienced volume growth in Europe and China, despite continued competition and some pricing pressure in some countries. Oedipal cells grew by 6.5%, with moderate growth in the U.S., driven by the first-line metastatic pancreatic ductal adenocarcinoma. We recognize that it will take time to drive first-line differentiation and address some challenges around access to payers. Now, let's turn to rare disease. Please turn to slide eight. On the rare disease, BuildA continues to perform nicely, with H1 cells of 87 million growing by 53.7%, driven by strong demand in the U.S. and in Europe in both PCIC and Allergy Syndrome indications. We also had an increase in contribution from rest of the world with access and reimbursement now secured in 17 countries. Turning to Aquervo, the launch continues to track very well with sales reaching 59 million this semester. In Q2, we saw an acceleration in the U.S. with a 65% growth quarter over quarter, driven by an increasing uptake from new patients and switches from Ocaliva. Europe was also very strong with sales mainly from Germany and the UK and launches initiated in Spain and Italy in June. Moving to neuroscience, let's turn now to slide 9. This board delivered another solid performance with H1 sales growth of 9.7%. In aesthetics, sales grew by 17.5%, driven by continued expansion in most territories, including the US, Europe, and rest of the world, and by a strong performance from our partner, Galderma, who continues to gain market share in key countries and a solid growth in our Ipsen territories. On the therapeutic side, this work shows solid and consistent demand growth across all geographies. In the US, notably, we continue to gain market share in our specificity indications, with strong double-digit sales growth. Reported sales were, however, flat due to an adverse phasing of orders in Brazil. Supported by solid market growth in both indications and strong execution, we're confident that this sport should continue to deliver high single-digit sales growth in the short, mid, and long term. Now, I'd like to present the upcoming catalyst. Please turn to slide 10. In the second half of 2025, we are expecting updates in rare disease and neuroscience. Starting with rare disease, we should report the pivotal FALCON trial results for FITRESERTIP in FOP. Secondly, in neuroscience, we're expecting the proof-of-concept data rewrite for LAND in aesthetics. Looking ahead, 2026 is going to be a busy year for the pipeline, with several anticipated phase three data re-dives across all three therapeutic areas, including for Bilway, iQuerbo, Tasveric, as well as migraine trial re-dives for Dysport. With that, I'll now hand over to Christelle, who will provide more detail on our pipeline and those exciting milestones. Please turn to slide 11.

Thank you, David. Good morning and good afternoon. Please turn to slide 12. As David already mentioned, last week we were delighted to receive the European Commission approval for cabometrics in advanced pancreatic and extra-pancreatic neuroendocrine tumors. This approval was based on the strong results of the cabinet study displayed here on the graph, which showed a significant improvement in medium progression-free survival for patients treated with cabometrics versus placebo. Working within the NET community for more than 35 years, we recognize that patients require multiple lines of therapy for this slow-growing and chronic form of cancer. We are now focused on bringing this important treatment to patients. Please turn to slide 13 and our pipeline. We continue to have a strong and differentiated pipeline that has advanced in all three therapeutic areas in the first half, of 2025. In oncology, we have established a strong expertise in the MAP kinase pathway, starting with pervoracinib, a second-generation RAS inhibitor, and the Firefly 2 Phase 3 study in untreated pediatric low-grade glioma patients. IPN 1195, our newest third-generation RAS inhibitor, has entered the clinic in April, alongside IPN1194, which selectively inhibits ERK, also in the MAP kinase pathway. Both IPN1194 and IPN1195 are being evaluated in a number of solid tumors. In rare disease, we continue to grow our rare liver portfolio, both in pediatric with BELVE, in biliary atresia, and in adult, In PSC and PBC with iCurvo, I will share more on the Elmwood study in a minute and also update you on the Fulton study in SOP. In neuroscience, we continue to evaluate the potential of our portfolio in both chronic and episodic migraine. We've also just shared that we have added a fourth phase to trial in our LANS program, with Catalpa, evaluating IPN10-200 in cervical dystonia. Please turn to slide 14 for more detail on the rare disease portfolio, and starting with Fibrodysplasia Ossificant Progressiva, or FOP. A FALCON is a Phase II registrational study evaluating the change in heterotopic ossification volume from baseline to 12 months. and assessed by a whole-body CT scan. Importantly, Fidricertib selectively inhibits the mutated form of ARC2 that is found to be a driver in FOP. We expect this data to read out in the second half of 2025. Please turn to slide 15. With an update now on the rare liver disease portfolio, first starting with primary biliary cholangitis, At the recent ESOL meeting, we shared late-breaking data from the Phase 3 L-active study for iCurve or MPBC. Additional analysis showed that at Week 52 of treatment, 67% of patients treated with L-afibrino had a clinically meaningful improvement in fatigue compared with 31% of patients treated with placebo. Importantly, this effect was also shown to be independent of the reduction in pruritus. Alongside these data, we presented evidence from a comprehensive proteomic analysis that showed the V-bar alpha activation is linked to the fatigue improvement in PBC. Please turn to slide 16. Moving to PSC. At ESOL, we also shared the results of our Phase II Elwood study, evaluating the safety and efficacy of elafibrinol in primary sclerosing cholangitis, a rare liver disease that currently has no approved treatment option. In this study, elafibrinol showed a favorable safety profile and demonstrated dose-dependent efficacy at 12 weeks versus placebo, across a number of endpoints. In particular, significant improvement in liver biochemical parameters, including alkaline phosphatase, shown on the graph on your left. In the center graph, stabilization of non-invasive markers, including enhanced liver fibrosis, ELF. Of note, the changes in ELF are greater in patients with moderate to severe fibrosis at baseline. And finally, the graph on the right shows a significant improvement in pruritus. And this was observed using the Worth HNRS score at the 128 dose. We are now engaging with regulatory agencies to decide on the next steps of our clinical development program for this indication. Please turn to slide 17. In neuroscience, the next data revealed is the LANTIC phase two, a multi-stage dose escalation study, evaluating the safety and efficacy of IPN 10-200 in moderate to severe upper facial lines. The proof of concept is determined in the stage one, where we are evaluating IPN 10-200 in glabella lines, and we expected this data in the second half of 2025. The stage two of this study has already started and includes forehead and lateral cancer line. We're excited to see these results coming from the stage one in the coming months, and the positive proof of concept will support a phase three start. I would now like to hand over to Aymeric Le Chatelier for the details of our H1 fundamentals. Turn to slide 18, please.

Thank you, Christelle, and hello, everyone. I will now take you through the detail of our financial performance in the first half of this year, as well as our guidance for 2025. Please turn to slide 19. We deliver another set of strong financial results in the first half across sales, co-operating income and cash flow. Our total sales over 1.8 billion grew by 11.4% at constant exchange rate. Our co-operating income grew by 21.9% to €656 million in line with our free cash flow, increasing also by 22% to €483 million. Given this strong performance and our solid balance sheet with no debt, we now have at the end of June an updated firepower available for external innovation of €3 billion. Let's go more in the detail of those financials in the following slide. Please turn to slide 20. Starting with the P&L to core operating income, the growth in total sales of 11.4% at consortium exchange rates translated into 9.7% at current rates given the adverse currency movement, mainly from emerging markets. Growth margin increased by 2.1 percentage points, driven by a favorable product miss and higher other revenue from partners. R&D costs increased by 12.8% to reach a ratio of 20.1% of total sales, driven mainly by increased investment for D-SPOT in migraine, long-acting toxin in aesthetic and therapeutic, and our early-stage oncology assets. SG&A costs increased by only 5.6%, with a ratio to sales at 33.3%, improving by 1.3 percentage points, reflecting our commercial investment to support the launches, but also the impact of our efficiency programs. As a consequence, our co-operating income increased by 21.9% with a co-operating margin standing at 36% of sales, an improvement of 3.6 percentage points. Please turn to slide 21. IFRS operating income and consolidated net profit increased both by more than 40%, thanks to lower restructuring and other operating expenses, lower financial expenses, and despite implement losses recognized for €53 million in relation with discontinued early-stage assets, as well as slightly higher income tax. Please turn to slide 22. Finally, on cash flow, we continue to generate strong free cash flow this year and have a strong balance sheet with a cash position of 488 million euros at the end of June. Free cash flow increased by 22.8%, driven by EBITDA growth, sound management of capital expenditures and working capital. Net investment included payment related to regulatory and commercial milestones. With the net cash position increasing, of 400 million and 88 million at the end of June, and based on a maximum two times net debt to EBITDA, we have a firepower of 3 billion euros available for external innovation. Let's now move to 2025 guidance and turn to slide 23. Based on this solid momentum in the first half of the year and that very strong performance, we are pleased to upgrade our full year 2025 guidance. First, we expect total sales to grow by more than 7% at constant exchange rates, as compared to our previous guidance of sales growth above 5%. We assume also a negative impact of 2 points from currencies, based on the latest exchange rates during the month of June. This guidance assumes, as indicated by David, a negative impact in H2 on somatidine sales in the U.S. and in Europe with a progressive resupply from the current generic and a potential entry of an additional generic. On the other side, we expect an accelerated sales growth from the rest of the portfolio, driven by the significant drop-off of iCurvo in the U.S. and in Europe, as well as the growth of Cabometrics. On the other hand, we anticipate now a co-operating margin greater than 32% of total sales as compared to more than 30% in our previous initial guidance. It assumes, however, a lower level of profitability in the second half of the year, including additional R&D expenses from potential early or mid-stage external innovation opportunities, additional commercial investment to support our launches, and a lower level of other revenue than in the first half of the year. With all of that, I will now hand over back to David. Please turn to slide 24.