H Lundbeck A/S B

Ladies and gentlemen, welcome to the Lombeck SA Financial Statements for the first six months of 2025 conference call. I'm Iruna, the course call operator. I'd like to remind you that all participants will be listening on remote and the conference is being recorded. The presentation will be followed by a Q&A session. You can register for questions at any time by pressing star and 1 on your telephone. For operator assistance, please press star and 0. The conference must not be recorded for publication or broadcast. At this time, it's my pleasure to hand over to Charles Van Zyl, President and CEO. Please go ahead, sir.

Good morning, everyone, and welcome to our first half results for 2025. And I want to, at the outset, also thank you for your flexibility to join the call at relatively short notice. Of course, we are very pleased with the good news we're delivering today to you. And it's, again, in my view, a very strong validation of our focused innovator strategy. So if we go to the next slide, please. So as part of our forward-looking statements and disclaimer, of course, what we discussed today is subject to change. Then if we could go to the next slide, please, just to orientate you to the agenda today. We will be, of course, I'm joined here by my leadership team who are really behind these results that we are showing to you today. We will be joined by our head of geographies, Tom Gibbs for the US and Michela for Europe International Operations. And our pipeline and portfolio view will be shared from you with Johan. our head of R&D, and of course Maria, who is our head of corporate and commercial strategy. And of course, the end will be concluded with Jörg giving us context around our financial results. So if you go to the next slide. So, of course, you know, the headline says it all. We are seeing a very strong momentum that is continuing over the quarters of our strategy. These strong results really also lead us now to an upgrade in our earnings today. And as I said from the outset, it is really a strong validation of our focused innovator strategy. And the strategy has really these three pillars, growth, innovation, and how we fund that journey going forward. On the growth side, again, this comes from really disciplined strategic execution of our key assets, our strategic assets across all our key geographies. And you can see that clearly in the revenue of 14% and our strategic brands at 21% growth. which make up 77% of our total portfolio. And standing out there would be VIEPTI at 56% and Rexalti at 28%. So really the efforts we have put in place over many quarters of sustaining that growth, investing in that growth in our commercial model is certainly showing us durable results across all our key strategic brands. When we think about innovation, again, what I would like to headline for you here is that we are seeing certainly an advance now in the pipeline. We have a mid-stage pipeline that is between five to six assets in the stage of phase two or three as we go into 2026, which are really important drivers of our strategy for the long-term sustainable growth strategy. of the company. And of course, we have a strong foundation in neuropsychiatry, but I will just highlight a few points on the scaling of our neuro specialty position. We're expanding our filing in Asia for VIEPTI, already starting in South Korea and others to follow in this quarter. We are also, of course, advancing anti-pay cap into phase two. And we have also today a discussion that will be led by Johan and Maria to highlight for you also our D1-D2 agonist in the space of Parkinson's and symptomatic treatments in Parkinson's. So that's building a very strong neuro-specialty position. We're also, of course, expanding into the neurorare space with high unmet need areas, there being Bexecastrin, as well as Amlenituk, with a lot of focus there on our clinical execution and enrollment of the phase three studies, while at the same time, we're starting to do early work on launch preparation for these assets. Now, the third component of the strategy is really our funding. And of course, here, again, I would say this is something we've consistently spoken to you about, but we also see with a capital reallocation potential that we can increase that based on what we know now to 1.3 to 1.5 billion by 2027. And these programs are really there to essentially fund either more innovation or more growth of the portfolio going forward. So with that, of course, it leads us to today's discussion around the guidance and that we have, of course, been able to upgrade the guidance today, both on revenue and adjusted EBITDA, based on what we've reported in our press release today. So this, again, confirms for us that we are in a solid position, strong fundamentals in place. And with that confidence, we feel we have really seen strong proof points of our focused innovator strategy going forward. So to talk more about the assets and the performance of the strategic portfolio, it's my pleasure to, of course, hand over to Tom Gibbs, our head of the U.S. operations. Over to you, Tom.

All right.

Thank you, Charles.

And hello, everyone. As Charles just mentioned, we're pleased with our commercial performance for the first half of 2025, which is headlined by 21% growth of our strategic brands. Please turn to the next slide and I'll first review the performance details for RIGSULTI. RIGSULTI continues to perform well and deliver consistent growths propelled by the continued strong progress within the AADAD segment in the U.S. Reported revenue in the U.S. increased 27% for the first half of 2025 versus prior year. Revenue growth in the U.S. was driven by strong underlying TRX demand delivering 23.3% growth during H1 2025 versus H1 2024. Resulting demand growth in the U.S. accelerated through the second quarter of 2025, recording record highs in market share, TRX, and NRX volume. This demand growth is attributable to continued improvement in execution across the marketing mix, including Salesforce execution across the alliance, optimized direct-to-consumer media mix, and market access programs. Growth in the U.S. was supplemented by continued strong demand growth in Europe and international operations, generating impressive growth of 30%, versus the same period last year. Looking forward, we expect Rizolti to be a key driver of growth for Lundbeck, and this is primarily driven by continued expansion of the AADAD franchise supported by solid growth of our base business in MBD. Now, let's take a moment to look deeper at our progress in AADAD. Next slide, please. Rigsalti AADAD volume is becoming increasingly important to the overall Rigsalti brand growth, and we expect this to continue through 2025 and beyond. AADAD monthly TRX volume has increased 550% versus baseline, and AADAD contribution to overall Rigsalti demand has grown to nearly 22%. This represents more than one out of every five prescriptions based upon our most recently available patient claims data for May 2025, and our expectation is that AADAD will account for approximately two out of every five TRXs at peak. Growth is being driven primarily by expansion of our HCP prescriber base, growing 438% since launch, to nearly 14,200 prescribers. Resulting AADAD market share of the total antipsychotic class has grown from 0.67 prelaunch to 3.99 share points, and this is based upon the most recent made claims data. I think importantly, we continue to see consistent growth on the non-AADAD side of the business achieving 15.4% growth when we compare May 2025 TRX monthly claims to May 2024. We believe this accelerated performance reflects the positive impact of the exclusive focus of our psychiatry sales team on RIGSULTI following the strategic decision to hand over full promotional responsibility of Trinfelix back to Takeda in 2024. The AADAD launch has really fueled 1,058% growth in the 65-plus segment across all indications. The 65-plus segment now contributes 32.4% or nearly one out of every three Regsolti TRX claims based upon the most recently available claims data. I believe this positive halo effect on the overall Regsolti 65-plus segment truly reflects the full value of the AADAD indication for this brand. The team is continuing to focus on the levers to even further accelerate growth for Rizzolti, and this is informed by our marginal return on investment quarterly analyses. As I shared with you last quarter, We are applying our dynamic resource allocation focus innovator principle to redirect a portion of our AADAD direct-to-consumer funds to expand our primary care footprint to drive greater breadth and depth of prescribing. The first wave of this expansion to our multi-specialty Salesforce team will take effect during 3Q 2025, And we expect to start seeing the impact of this expansion in the latter part of the fourth quarter. I'll now transition to VIEFTI. So next slide, please. VIEFTI delivered strong results during the first half of 2025. This performance has really been powered by continued strong growth in the U.S., and supported by robust adoption of VIEFI in our prioritized ex-US markets, including Canada, Italy, France, Spain, and Germany. VIEFI global net revenue for H1 2025 was 2.105 billion DKK, and this represents 56% growth over the same period last year. Net revenue for Vietti in the U.S. was 1.834 billion DKK, growing 54% over H1 2024. Importantly, we are beginning to see a meaningful contribution to global sales by ex-U.S. markets, with Vietti now available in 30 markets. Vietti growth in Canada and the major European markets exceeds the growth rate of the overall anti-CGRP market over the last 12 months, and we expect to see continued expanded usage of VIEPI across all ex-U.S. markets. Now, I want to focus a moment on the U.S. We continue to make purposeful investments in VIEPI through our disciplined capital allocation program that Yorg will speak to later. These investments focus on HCP engagement, patient activation, and patient support services to further enhance our specialty patient-centric commercial model. We believe our model is a competitive advantage in the marketplace because it enables our team to appropriately support the patient throughout their patient journey. We continue to see accelerating demand by driving depth and breadth of prescribing of IAPI and continued positive momentum in new patient starts supported by a high written-to-infusion conversion ratio and best-in-class patient persistency. Looking forward, we expect IAPI to continue to deliver strong growth in the U.S., driven primarily by new patient starts Based upon recent trends, we have confidence to raise our peak year sales projections in the U.S. from greater than $1 billion, which we communicated at the capital market event last year, to greater than $1.1 billion. Nicholas, over to you.

Thank you, Tom. Next slide, please. There we are. Let's start with taking a look at the Brentelix performance in the first half of 2025, where we overall saw a revenue growth of 3%, now to the tune of 2.39 billion DKK compared to last year, and where we also see several dynamics in play when we look at the regional performance. If we start with the US, there also, as Tom was saying before, we experienced a 6% decrease, which is aligned with our expectations due to our transfer to Takeda. This is a move, as Tom was alluding to, that while it reduces our revenue, it enhances our profitability. If we look at Europe and international operations, we saw a 7% increase, and again made up with different dynamics, where we have Europe achieving an impressive growth of 15%, largely driven by outstanding results in Spain, Switzerland, Italy and France, whereas international operations saw a 2% decrease compared to last year, which was affected by generic erosion across key international operations markets such as Canada. Looking ahead, we anticipate to see continued solid demand growth in both Europe and Japan. It is worth noting that we have extended our market exclusivity in Japan by two years, now lasting until 2031. In Canada, we expect ongoing competition from generics following their recent entry. And in the US, we expect to see a continued decline in revenue, but improved profitability in second half of 2025 due to the full impact of the transfer to Takeda. I'd like to just highlight Japan for a moment as well, where we continue to see the robust growth in demand with 15% year-over-year increase. And as I also mentioned last quarter, Trintelex holds the highest value market share in Japan at 23.6% in the MDD market. Next slide, please. When we turn to the Abilify franchise performance in the first half, we also see here a solid result with 10% overall growth, which has been driven by the two monthly formulation Abilify and Simtify. In the US, Abilify saw a growth of 8% compared to the first half of 2024, where the franchise also gained 1.1 percentage points in market share. Notably Abilify Simtify has continued its strong trajectory with 59% of patients converting from oral antipsychotics, other long-acting injectables or naive patients. We also saw a robust increase in TRX volume which is up 63% and with a conversion rate of 17% an even stronger conversion rate when we look at our NBRX conversion rate reaching over 21%. In Europe and international operations, the Abilify franchise delivered a strong 12% growth versus first half 2024, where we saw momentum in numerous markets supported by the additional rollout of Abilify, Symptify or the two monthly formulation, which is now launched in 20 countries. The uptake of Abilify, Symptify has been encouraging to watch with an average conversion rate of 14% and several markets already having surpassed 20% conversion with for example Spain at 32%. We also have research from Europe confirming that a significant portion of our new patients are coming from oral antipsychotics. Across several of our key markets, we see an overall growth of the Abilify LAI franchise volume market share at an average of two percentage points. Looking ahead, we anticipate continued strong uptake of Abilify two-monthly or Asymptify, while we expect to see generic approval in Europe in the second half of 2025. That concludes the business update. I'd now like to hand over to Johan and Maria to give an R&D portfolio update.

Thank you, Michaela, and thank you, Tom. It's great to see the momentum on our key brands across the markets. Let us turn to the pipeline highlights for the quarter. First, let me comment on programs within Neurology's specialty. For Eptinuzumab, the YPT brand, we have been very active last year in running additional supportive trials to expand its geographical reach and to further characterize its efficacy. Across the board, we have been seeing strong and consistent effects of the drug in migraine treatment. These data are being communicated at a steady pace. For example, the SUNRISE trial, which is part of our Asia Pivotal program, and the Phase 4 resolution trial in severe migraine with medication overuse headache, were presented at the American Headache Society and the European Academy of Neurology meetings in June. The data from those trials were very well received. Based on the positive outcome of the Sunrise trial, filings in Asia are progressing as planned, with South Korea already filed this month. Encouraging regulatory agency pre-meetings have also been held in China and Japan, and the submission preparations are progressing as planned, and filings are expected in the coming months. Continuing with the migraine portfolio, enrollment is progressing very well in the PROCEDE trial, a trial designed to establish dose response and enroll the administration information for the anti-PACUP antibody LU222. The first part of the trial constituted a subcontinuous administration dose ranging evaluation. This part has been concluded after scheduled interim assessment, and we have now an ongoing intravenous administration dose finding part. However, we have already been able to take a look at the outcome of the first part of the trial, the subcutaneous administration. This dataset is encouraging, showing dose dependency across readouts, and provide important information that, combined with the previous HOPE trial, allows building an informative PKPD model. The model will be further strengthened after obtaining the next dataset from the IV administration part. Consequently, by early spring next year, we expect to have comprehensive information on dosing regimen. Provided the last dataset comes out as expected, we will be able to design a robust pivotal program for initiation during H226. In neurology specialty, I also like to mention that we obtain interesting data in the early development portfolio on LU996, an innovative symptomatic Parkinson's disease treatment. Marie and I will describe this a little bit more in the coming slide. To build further on our newer air presence, we have currently two pivoter programs and one early development program. For alpha-synuclein antibody amlinitug in development from multiple system atrophy, we have a highly innovative pivoted trial ongoing for which we have systematically built critical regulatory support as well as obtained various orphan destinations from key authorities. In the now ongoing global mascot phase three trial, we have most sites activated and we are already seeing a very strong momentum in patient recruitment. Now turning to bexacathrin for developmental epileptic encephalopathies. In the program's two PIVOTER trials, Deep Sea and Deep Ocean, we are rolling out regulatory approvals, site activations, while recruitments were initiated. For the Deep Ocean trial, which is in Leno-Gastaut syndrome and other DEs, the rollout started somewhat later and trial approval has just been obtained in key geographies. I also like to mention the anti-acetase antibody LU-909, which is in early studies in patients. The program has received orphan drug designation in the US and Europe for the development in congenital adrenal hyperplasia. The Cushing disease part of the program is also starting to generate important patient data. Finally, note on the July 18 Psychopharmacologic Drug Advisory Committee discussion on Otsukas and Lundbeck's supplemental NDA for recombination treatment of brexbiprazole with sertraline and PTSD. Based on the data from one exploratory phase 2 trial and two pivotal trials with somewhat different outcomes, the outcome vote was 1 to 10 against that efficacy of brexbiprazole when initiated concurrently with sertraline has been established. the FDA has not indicated any decision date. Next slide please. Returning to VIEPTI, let us take a look at an interim data cut from the so-called INFUSE study, a real-world setting study in a hard-to-treat patient population. In this study, we were able to demonstrate improvements in disability and functionality in patients that have already been receiving other anti-CGRP treatments, for which they failed to obtain sufficient treatment response. On the left side, you can see the composition of the patients studied with an average of 2.7 anti-CGRP treatment failures. In the right graph, we have an example of the very strong data obtained with 42% of patients achieving 50% reduction in monthly headache days at six months following transition to YFT treatment. Overall, across the development program, we have seen strong clinical efficacy, which we now see translating into real-world effectiveness in these high disease burden patients. With this, I'd like to hand over to Maria to comment more about bexacathrin and amlinitug.

Thank you, Johan. Let's now transition from VIEPTI, which remains central to our neurospatiality business, to focus on two other critical assets in our late-stage pipeline. As we have emphasized before, expanding into neurorare diseases is a cornerstone of our strategy as a focused innovator. We are confident that our pipeline will solidify Lundbeck's leadership in this space across multiple dimensions. Bexicaserin and Amlenituk, both in Phase III trials, represent transformative opportunities. Together, these assets have the potential to redefine treatment paradigms for over 450,000 patients globally and contribute a combined peak sales potential exceeding US$3 billion, positioning Lundbeck for significant growth. Bexicaserin offers a compelling value proposition as a first-in-class treatment for developmental and epileptic encephalopathies, DEs, addressing all seizure types and causes. This broad applicability enables us to target a larger patient population compared to other treatments in this space. We anticipate that Bexicaserin's differentiated profile will resonate strongly with reimbursement agencies and payers by demonstrating meaningful improvements in both seizure and non-seizure outcomes. Additionally, this asset supports the expert community by advancing the operationalization of broad DE definitions, facilitating earlier patient identification and thus reducing healthcare burden. Onamlenituk, our monoclonal antibody, aims to be the first approved treatment for multiple systems atrophy, MSA, a devastating and currently untreatable condition. Based on input from movement disorder specialists, we believe this asset will deliver measurable value to healthcare systems. For treating physicians, Amlenituk represents the potential for the first disease-modifying therapy in MSA. For Lundbeck, this marks an important strategic entry into movement disorders, laying the groundwork for future assets such as our D1-D2 agonist program, which Johan and I will introduce on the next slide.

Thank you, Maria. As we're building momentum in our mid-stage pipeline, we're excited today to highlight further LU996, a program I have not talked much about in the past. We have been letting the molecules speak throughout phase 1 to enable and de-risk progression, including a series of smaller phase 1b Parkinson's disease studies. Naturally, we have since very long an excellent understanding of the pathophysiology of Parkinson's disease, where a key driver of overt progressive motor symptoms is new generation of basal ganglia dopamine neurons. Current treatments are associated with complications and better motor control on both D1 and D2 receptors are much needed. As you can see in the figure, LU-996 is an oral prodrug with excellent pharmacokinetic properties. 996 serves as a steady reservoir to a D1-D2 receptor-active metabolite, and thereby it can provide a much desired profile of continuous and stable dopamine receptor stimulation, which is translated to sustained motor activation, as in this case in the graph determined in an animal model. More importantly, in Parkinson's disease patients with motor fluctuations, we have seen an impactful effect on off-time as well as L-DOPA sparing effects after LU-996 administration in an open-label setting. With these findings, together with other positive attributes observed in Phase 1b, we consider the program ready to trigger the preparations for a decisive Phase 2 proof-of-concept trial, which we plan to have ongoing by early next year. With this, I'd like to hand over to Maria to outline its commercial potential and strategic fit.

Thank you, Johan. Our D1-D2 agonist program represents a transformative opportunity to address a large underserved patient population with Parkinson's disease. With motor complications affecting an estimated 7 to 10 million patients globally despite treatment, this asset is uniquely positioned to meet a significant unmet medical need. As a first-in-class oral D1D2 agonist, the program is strategically positioned ahead of invasive treatment options, offering a non-invasive alternative that is both convenient and accessible for patients. Furthermore, the asset has the potential to be best in class in late stage PD, setting a new standard for treatment expectations in this critical stage of the disease. We expect the commercial competitiveness of this asset based on differentiated target product profile, which combines efficacy, safety and ease of use. Its oral route of administration presents an attractive value proposition for all stakeholders, from patients seeking less burdensome treatment options to healthcare providers aiming to improve adherence and outcomes and payers prioritizing cost-effective solutions. This program also represents a compelling global opportunity with significant market potential across key regions, unlocking substantial growth for Lundbeck. And now to take us through our financial results and outlook, I hand over to Jörg.

Thank you, Maria. I'm very pleased with the performance of the first half, but also with a strong outlook for the remainder of 2026. We are reporting a 21% growth in our strategic brands, with Q2 marking our fourth consecutive quarter of more than 20% of growth. This reflects strong operational performance supported by disciplined capital reallocation in line with our focused innovator strategy. But it even more underlines our ability to improve profitability while expanding and progressing our pipeline. Building on this strong H1 performance and the outlook for this year, we have raised our full year guidance. But let's move to the next slide for a closer look at our financials. Revenue reached 12.3 billion, growing at 15% at constant exchange rates, driven by continued strong performance across our strategic brands, which grew 21%. The adjusted gross margin was 88.6% and in line with the same period last year. Sales and distribution costs increased slightly by 1% to $3.8 billion, and this reflects continued investments in Biapti and Rexalt in the US, partially offset by redeployment of resources after the US Trintelix divestment. Administrative expenses decreased by 4% to $713 million, which is impacted by certain non-recurring items in the first half of 2024. Adjusting for this underlying costs increased mainly to inflation and continued investment in organizational development. R&D costs increased by 22%, reaching 2.3 billion mainly, driven by the continued progression of our Phase III programs for Bexie-Kasserine and Amlenetuk and a maturing mid-stage pipeline. Adjusted EBITDA grew by 24% at constant exchange rates, driven by the strong momentum in strategic brands and solid commercial execution, reinforcing Lundbeck's market leadership across key therapeutic areas. The adjusted EBITDA margin expanded to 34.4%, up 3.1 percentage points, reflecting strong cost leverage and continued disciplined capital reallocation. Next slide, please. EBIT increased by 43% to 3.3 billion, reflecting a combination of improved gross profit and lower sales and distribution and admin ratios, offset by the higher R&D investments. Net financials reached an expense of 554 million, mainly due to unfavourable currency effects, especially from the US dollar, and high interest costs related to the new debt obtained in connection with the acquisition of Longboard. Our effective tax rate was 22% and in line with expectations. Net profit increased by 19% to 2.1 billion, while adjusted net profit and EPS rose by 9%, reaching 2.9 billion, reflecting the strong EBIT development partially offset by higher financial expenses. Next slide, please. Cash flow from operations was in line with EBIT performance, reaching 2.3 billion offset by higher prepaid tax payments, reflecting the expected full-year income. Cash flow from investing activities was an outflow of 238 million, mainly related to investments in property, plant and equipment. And cash flow from financing activities was an outflow of 4 billion, mainly driven by the repayment of the loan facility used for the longboard acquisition and the dividend payment to shareholders in March 2025. Next slide, please. Over the course of this year, we have and will be making significant progress in our global capital reallocation program. We feel confident increasing our ambition level for this program, by raising the expected impact from this programme to 1.3 to 1.5 billion by 2027 from previously 1 to 1.3 billion. And we are estimating one-time costs of approximately 1.2 billion between 2025 to 2027. Our confidence rests on the proof points we have delivered so far. Our sources for redeployment stem from the higher Brentelix performance in Europe and international markets, the first adaptations in our commercial model by divesting the Trintelix brand back for the U.S., back to Takeda, and a number of operational effectiveness initiatives across our full value chain, such as a global spend assessment and optimization program called Procure for Growth. This freed up capital will be redirected to targeted investments for Biapti and Rexalti, the buildup of a sustainable pipeline, the continuous progress of our mid- to late-stage pipeline at the same time. This capital reallocation program is not about cost cutting for margin expansion, but placing our long-term assets for the best possible yield. Next slide, please. We communicated on August 13 an increase in our full-year revenue and adjusted EBITDA guidance at constant exchange rates, reflecting strong performance year-to-date and continued positive momentum. Revenue growth is now expected at 11% to 13%, from previously 8% to 11%, driven by the continued strong demand for Biapti and Rexalti and the delay of generic entry of Abilify maintainer in Europe in this year. Next slide, please. Adjusted EBITDA growth has been upgraded to 16 to 21 percent from previously 8 to 14 percent, reflecting not only the strong top line performance, but also the effective execution of our capital reallocation strategy and the precision of our expected R&D spend for 2025. And with that, I hand over back to Charles.

Thank you, Juergen, and thanks to the leadership team for the presentation. Before we open for questions, let me just make a few closing remarks. So if we can go to the next slide, please. So again, what you see today and what you've heard from us is really the results are reflecting a very disciplined strategic execution of our strategy. The company Lundbeck is in a position that is stronger than we were one year ago. You see that we're investing. We're investing in growth and innovation without compromising profitability. You see a pipeline that is evolving with five to six mid to late stage assets in 2026 that start to answer our long-term sustainable growth question. And we see a very disciplined capital allocation, reallocation based on clear strategic choices that we've made. So based on that, we see really these strong results, strong momentum in our strategy that led us to increase our guidance today. So with that, I would now pause and we invite you for questions.

Ladies and gentlemen, we'll now begin the question and answer session. Anyone who wishes to ask a question may press star and one on their telephone. You will hear a tone to confirm that you have entered the queue. If you wish to remove yourself from the question queue, you may press star and two. Anyone who has a question may press star and one at this time. First question from the phone comes from Mark Goodman with Larrick Partners. Please go ahead.

Hi, good morning. This is Basma on for Mark Goodman. Thank you for taking our question. We have a question about Bexie Castron and the K-12 enrollment and clinical trials, five initiations. You mentioned it was slower to get approval for deep sea trial. Did you understand that correctly? And if so, could you provide more color why this is the case? Also, did you have any recent regulatory interactions either within the U.S. or outside of the U.S. regarding the 50 program? And if so, did you sense any change in the alignment on the clinical trial design and regulatory path forward? Thank you. That's it for us.

Good. Thank you for that question. Johan, do you mind?

Thanks for that question. So as you may recall, the deep sea and the deep ocean trials are studying different populations, and the timing and the preparation of them were not 100% aligned. So one was rolling out a little earlier than the other one. The deep sea was ahead. The deep sea is in Dravidian syndrome, which is an area where we think actually we may be a little more challenged with enrollment because there are a lot of trial activities going on in that space. But it was actually the deep ocean that we rolled out later that has been a little bit more struggling with regulatory approvals. throughout the world. These things take a little time to discuss and we hit the summer period. But now we have gone through this and we are actually opening up the trial across our major geographies. But that is a very recent event. Regulatory interactions have generally been very good. There's not been any comments or big questions. Of course, the population is new if you come with DE, so you need a little bit of education around that. The DE is, of course, the one that has been mostly recognized in the U.S., so that needs a lot of cultivation with other regulators. But there has been no major change in the design or rather no change in the designs. It's more the conversation about what may the data lead to in terms of populations that can get on a label eventually. So we are not concerned about the design of the trials. Obviously, it's a competitive space and that's what we're watching out for.

Thank you. Thank you.

Thank you.

The next question from the phone comes from the line of Xian Deng with UBS. Please go ahead.

Hi. Thank you for taking my questions. Two, if I may. So the first one is on Rook Salty PTSD at-home. So, I mean, the vote was, you know, very much against frontline usage, but when I look at the commentary, so actually many of the panel members actually said they are quite happy to use in patients that you know, that do not respond well to sertraline off-label. So, of course, you can't promote off-label uses, but just wondering, you know, what are your thoughts on that, you know, hypothesis that many of the panel member actually brought? And also, just wondering, what is the general, as a payer, dynamic in terms of off-label usage in psychiatry, you know, experience? Like, do they generally quite happy to cover that, or is that quite challenging? So, that's the first question, please. And the second one, I guess, is more for Thomas. So, of course, you raised top-line three-year guidance, but then the Q2 results is actually quite in line with consensus. I mean, we thought you had a beat, but then the VFD kind of broadly in line with consensus. You touched on some of the, you know, lead indicators and, you know, patient activation and things like that, but just wondering, you know, could you give us a bit more color on the, you know, you know, the key KPIs, the leading lead indicators, especially on VFT, that drives the big confidence in the second half, especially because we don't really have TRX for that. Yeah, thank you very much.

Good. Thank you, Jian, for your questions. Johan, do you mind commenting on PTSD.com? And then I will hand it to Tom to talk about off-label use in the payer environment in the U.S.

Thanks. Yeah, I have a few things I can comment on, but obviously what is known is quite public, those that listen in to it. But I can summarize a little bit what went on there and then I can comment a little bit by the sort of vote, but also the sentiment at the meeting. I think it was a really good outcome to start with. I think it was a solid discussion. The discussion centered around is the previous Phase 2 trial, which explored four different dose regimens. Is that a supportive trial or not? And I think we made good arguments that it should be considered, but that was one of the concerns, what was really the testing hierarchy and how solid was this predefined in terms of the combination treatment. And then obviously we have two trials. that is very strong, very positive, very clear data, and one that didn't show any separation from placebo, although placebo in that case was stronger. And traditionally in psychiatry, you like to see two pivoted trials replicated. And that was the conundrum for the committee. And quite frankly, it's been for us as well. And that's why I think most of the panel members and FDA, they see very positively on this. Remember, it's 23 years ago, any approval was in this space with paroxetine and sertraline. So it's a high medical need as well. So I think this is an interesting sentiment because we have good data. but not what you'd regularly like to see for an approval in this space.

Thank you, Johan. Tom, do you want to comment on payer environment, off-label use, and then maybe also bridge to the question around the leading indicators for VIEPT and Rexalti?

Sure. Thank you for the question, Jane. And I think that you accurately reflected our approach from a an ethics and compliance standpoint. We only promote our products within indications, and that is our focus in terms of driving growth. As you said, physicians do have the opportunity to prescribe the medication based upon their clinical experience as well as the broad clinical data that supports the overall clinical value proposition of the product. From a payer standpoint, there's For the most part, if you look at Rizalti, Rizalti enjoys very good payer access on the commercial side as well as the Medicare side as well. For example, in Medicare, Rizalti is available 96% of Part D plans and 100% of traditional Medicare. As it relates to the utilization management from a payer standpoint, it really does not get managed at the indication level, it's more at the molecule level. And any sort of prior authorizations that are associated with Rigsalti are related to utilization of a generic first before you go to Rigsalti rather than any specific indication. And then secondly, when we think about the leading indicators for our brands, I think one of the important things to remember is when I look at the brand, I look at what the underlying brand fundamentals are. I look at things such as depth and breadth of prescribing, looking at new patient starts, and I think those are good indicators in terms of what the future trajectory of the product and brand is. With VIEFI in particular, there's a couple of things that we look at that give us confidence as relates to the trajectory of the brand. The VIEFTI Infusion Network, as I shared with you, provides us perfect data, if you will, on the patients who are going through the VIEFTI Infusion Network. We're able to look at what the number of prescriptions coming in, the written conversion ratio, the utilization of of 100 milligrams versus 300 milligrams. We're able to look at what the persistency is, and we're getting these data on a regular basis. I think the areas where I'm most pleased with is looking at how VIEFTI is being used related to line of therapy. We're seeing Vajewski move up line of therapy in some cases. We're also looking at persistency, and quite frankly, when we look at our cohort from last quarter to this quarter, seeing a fit going up for a 12-month This is the best 12-month persistency that I've seen in my 29-year career in CNS. So this is, I think, reflective of the overall benefits that patients are seeing as well as the confidence that HCPs have in prescribing VIEPTI. And I think lastly, when we look at VIEPTI, it's from a market access standpoint. If we look two years ago, the number of commercial plans that supported VIEFTI in terms of one or fewer steps from an anti-CGRP was 60%. Now that number is up to 82%. And if we look at what the reasons are for seeing greater prescribing of VIEFTI, there's elements saying that the market access has improved and that they're seeing that the patient experience is highly improved. There's a high satisfaction of patient experience related to their patient journey, specifically through the VIEPT infusion network.

Good.

Thank you.

We can go to the next question.

The next question from the phone comes from Michael Novod with Notre Dame. Please go ahead.

Thank you very much. Question to Abilify LAI. I was just wondering when you look at the conversion rates happening in the US and also outside the US, should we consider this franchise a growth franchise going forward despite sort of generic erosion of the one month formulation? But as soon as you get past that, then is it a growth franchise or is it more sort of a flattish franchise? And then also to the VIEFT infusion study, super interesting. Does that mean that you will also move more sort of aggressively to try to address patient needs for those who've been sort of starting on an oral anti-CGRP and then try to expand VIEFT's role in that area? Because I guess a lot of patients will be coming off the orals at some point in time.

Good. So thank you, Michael, for your question. Let's go to Abilify LAI. And I think let me start with maybe some comments from Michaela on that topic.

Yeah, thanks for the question, Michael. So first of all, of course, as we see the rollout of Abilify, Simplify, where, as I said, we're very pleased with seeing the uptake and the conversion rates, and we still have not seen the generics enter in Europe, and therefore it is a growth case currently. But when we do look ahead and we expect to see that generic entry sometime later this year, then of course we do not expect that Asymptify can outgrow the one monthly, but we do expect that we will be able to hold our ground at least in the coming period. So it will of course all depend on the erosion curves and how fast it goes, but so far we're at least pleased to see how well Asymptify is grabbing the market also in the US.

Good. Thank you, Michaela. On the topic of treatment and earlier treatment in VIEPT, maybe Tom, do you want to comment on your experience in the U.S.?

Sure. I think one of the areas of focus for the U.S. as relates to continuing to drive greater and greater uptake of VIEPT has been moving VIEPT up the treatment paradigm. If we look traditionally, we have done a a terrific job in terms of establishing Vietti as a market leader in the later lines of therapy. And one of the areas that we believe was important was to be able to generate clinical data, real-world evidence to be able to demonstrate the benefit of using Vietti earlier in lines of therapy. And I think that's how Johan described the design of the IMFUSE study. I believe the that we're seeing of the INFUSE study are very encouraging and very supportive of the clinical value proposition of VIEFTI and the response that we saw at the American Headache Society from thought leaders did support the use of VIEFTI earlier and earlier in the treatment paradigm. You know, my view is that we, our ambition is to be the first switch after a trial of an anti-CGRP. And when we say first switch, that includes either orals or sub-Qs, and we're seeing progress in terms of achieving that ambition.

Great. Thank you very much.

The next question comes from with PNB Paribas. Please go ahead.

Hi there. Thank you for taking my question, Ms. Kirstie, from PNB Paribas. First one on R&D expense. You've previously indicated that you expect similar levels of investment in R&D over 26 and 2027 as your late stage pipeline progresses. Can we take the adjustment today to the kind of lower end of your previous guidance that efficiencies can continue to be made in future years? Or would you call this kind of adjustment today a more 2025 specific effect just related to kind of increased clarity as you go through the year and phasing of costs? And then the second question on the D1, D2 agonist progressing into phase two. Thank you for the additional colour in the prepared remarks. I was just wondering if you could maybe elaborate on some of the signals that you saw in phase one that has given you, in the Open Label trial, that has given you confidence to take this forward to phase two and what you believe kind of is needed to show in terms of clinical differentiation versus standard of care to progress this further, especially in light of kind of the mixed updates from the D1 agonists from UCB and Lilly recently. Thank you.

Great. Thank you, Kirstie. So let's outlook for R&D. Jörg, would you mind?

I'd be happy to take that. I think let's look at R&D first of all. We originally guided for this year 5 to a 5.2 billion, and we're now saying around 5. So it's basically not a not a delay in any kind of program. It's still a significant increase, not only versus what we spent 24, but also what we spent in the first half of this year. So we don't see a delay, and I would consider that more to be a timing effect. I think on your question regarding the outlook, we've always communicated that we see a corridor of around 20 to 25% of sales as the R&D corridor that we will travel through. And I think The benefit of the capital reallocation program is that when we now increased a little bit our ambition that we are potentially even able to, you can say, best into that target structure a little bit earlier than previously anticipated.

Good, thank you. Johan, D1, D2 agonist?

Just to add on Jörg's comment on the R&D experiences, we also finished up a few trials and you consolidate the costs at the end and you realize that you spent a little less so that those are positive things that come through when you wrap up activities. On the D1, D2 agonist, we are progressing and we're going to reveal more of the design and where we're aiming for. We have spent quite a time in early development, very early development with a couple of patient populations to really hone in where we like to place this drug. For the moment, we are not going to talk so much about it, but you got some idea that we are working on people that are really hard to treat here. The clinical differentiation is really on several parameters if you look generally the field and that's what we're looking at you have two things on time and off time and then you have how bad your on time is and those are the parameters we're working on we will present what we've seen in the open label phase one in coming meetings but if you just look at simple things like off time it's strong enough for us to think that this is clearly differentiated

Maria, do you want to comment on how we see the positioning?

Just to supplement what Johan just said and I mentioned before, we see this drug as a potential to delay or an alternative to invasive treatments. So these are, as you know, I mean, invasive, of course, burdensome to the health care system, both from a capacity point of view, but also from an expenditure point of view. So you can clearly see that the clinical value is matched also by value to health care systems.

Great. Thank you, Maria. Good. Are there any other questions?

There are no more questions, sir.

Good. Thank you. Then again, I would like to conclude the call today. Thank you very much for joining us. And we look forward to interacting with you again in the future. Thank you.