Roche Holding AG

Ladies and gentlemen, welcome to Roche's first quarter sales webinar 2025. My name is Henrik and I'm the technical operator for today's call. Kindly note that the webinar is being recorded. I'd like to inform you that all participants are in listen-only mode during the call. After the presentation, there will be a question and answer session. You're invited to send in questions for this throughout the entire session using the Q&A functionality of Zoom. In addition to that, you may also raise your virtual hand to address your questions verbally. for participants joining via phone, to raise your hand to star nine on your phone's star pad. When you then get selected to ask your questions, please follow the instructions from the phone and press star six to unmute yourself. One last remark, if you'd like to follow the presented slides on your end as well, please feel free to go to www.woosh.com slash investors to download the presentation. At this time, it's my pleasure to introduce you to Thomas Schieneker, CEO of Woosh Group. Mr. Schieneker, the stage is yours.

Thank you very much. And I'm happy to share our Q1 2025 sales with you today. Now, let's look at our performance. We had really a good start in 2025 with group sales growing 6%. And this was driven by pharma with, again, very strong sales growth of 8%. So you can see that we continue our very strong momentum on the pharma side. Diagnostics was flat, and this was due to healthcare pricing reforms in China. Matt will cover that. Again, this did not only impact us, it impacted the entire industry. And this is something that we had flagged also at the full year results presentation in January. The LOE impact was also in line with guidance. So now let's look at the key milestones in Q1. On the pharma regulatory side, we had EU approval of Columbia, plus GemOx in second line DLBCL. And this is based on the very strong phase three Starglow data. And it's the first and only bispecific with an EU approval in second line DLBCL. We also had the US approval of Sosfimo in DME, so the second indication, and DNKs in acute ischemic stroke. We have the filing in the US and in the EU, Vocociva in lupus nephritis, And this is based on the positive phase three regency data, which was presented at WCN and is also published in the New England Journal of Medicine. And we had the filing in the EU for Lunsumio in third line follicular lymphoma. We've had a number of positive phase three readouts. Let me highlight the Sanmo phase three readout from Lunsumio and Polyvi in second line, DLBCL. And we are now excited to move now our second bispecific into chemo-free combination with PolyV into early lines of treatment of DLVCL. More information on the positive outcome will be shared later in this year at a medical conference. We've also taken a number of phase three decisions. As we mentioned at the full year call, we said there are potentially seven NMEs that could move into phase three. which would be a record in terms of how many enemies we move into late stage. And these are all based on the bar criteria. In Q1, we did make two decisions to move two of them into the last stage of development, into phase three, based on the latest data. Trantinumab being one of them in Alzheimer's disease, the positive data was shared at 80 PD and phase three is expected to start later this year. And the second one is NXT-007 in hemophilia A. And the phase two data for this will be presented later in this year. We also had a very exciting business development deal, this collaboration with Seed and Pharma and Petrolintide, the leading long-acting amylin. And there will be more on this in a couple of slides from myself, but also Teresa will share more information on this. On the diagnostic side, we had menu expansion on the Cobas LIAT. So our point of care PCR system with lab-like performance with CT and G really building out our menu specifically here on STI. And we continue to place more of these systems in the market. Also very excitingly, we had the unveiling of a novel SPX sequencing technology. So sequencing by expansion. And I will also provide a little bit more context as well as Matt will provide more context And we shared real world and live experience of customers here at the HBT. We have significant new flow upcoming in 2025 for both pharma and diagnostics. And Therese and Matt will go into more granularity here. Clearly, there are a number of phase three readouts coming, including multiple NMEs that could lead to launches next year. across oncology with geradestrin, neurology with fenabrutinib, immunology, astagolamab, and ophthalmology with vermiculobar. Equally, we still have a number of phase three enabling readouts coming, which could enable us to move another five molecules into phase three, again, keeping to the bar criteria. Diagnostics is looking forward to several key launches still in 2025, including the Lexus P-Tau 181 and the high sensitive troponin T next generation assays. Now let's move on and let's take a closer look. We've had strong sales of 8% on the pharma side. So continuously very strong momentum. Diagnostic is flat. And I already mentioned that this was driven by healthcare pricing reforms in China, not only impacting us, but the entire industry. Now I used to have a favorite slide and I have a new favorite slide, which is this one. which really shows that over the last four quarters, we've had a significant growth of 8% across in our entire business. But if you go back until 23, we really had an underlying growth of 8% consistently. So we have consistently performed very strongly over the last two years and one quarter. And this is a strong pickup in our growth versus the 20 to 22 timeframe. Now, let me go to the key growth drivers. And I will start at the right top. Pachetta FESCO conversion is now at 47%. Both of our, on the hemophilia side or hematology side, both of our CD20, CD3 bispecifics are advancing now into second line DLBCL. And this is increasing our opportunity significantly. Column B, GemOx receiving EU approval and the positive phase three results from SunMall. NXT Series 07 moving into phase three, as already mentioned. On the neurology side, very importantly, Sonovo received the permanent J code granted on 1st of April. So we should definitely see a pickup here. As mentioned before, we do believe that the subcontainers version of Ocrevus will add two billion incremental sales. And right now the consensus is at about eight and a half billion. We feel very comfortable with that consensus. And the two billion incremental will obviously be, there will be more sales for the subcontainers version, but there will also be some switches. Evristi receiving U.S. approval for the tablet formulation and Xola still doing extremely well with now more than 50,000 patients on treatment. Well, Vaismo keeps expanding market share in all approved indications, and Teresa will talk about that as well. And she will also talk about the market contraction in the branded segment because of less funding for co-pay assistance foundations. But we keep seeing very strong momentum, as you can see here, with 17, or I think the bias was 18% growth. And we do believe that we can continue this kind of momentum going forward. Diagnostics, I've already mentioned as well. Now, the young portfolio continues to drive growth in the near to mid-term. If you look at the right-hand side, now the Young Portfolio accounts for 59% of our sales, up from 55% the year earlier. We have four pivotal NME readouts for the new NMEs. As I mentioned also before, astragalumab in COPD, vermicubart in UME, gerodestrin in breast cancer, and fenabrutinib in multiple sclerosis. And we do believe that this new portfolio will continue to drive growth at least until 2028. And we know that diagnostics will continue to contribute positively in terms of growth, especially with the new products. And all positive readouts that we should expect over the next years will then add to this growth. We don't have a cliff situation. And with that, we're at a more favorable starting position than many of our peers. Now, let me just highlight a couple of things on the recent announcement that we've made of our investment in the US. We have a strong legacy of partnership with 130 countries around the world. We basically have the full value chain present in most of our key markets, such as the US, in Europe with Germany, Switzerland, Japan, and China. It's always been our strategy to build out a fully value chain in each of these markets to be present where the patients are. And key parts of this legacy of investment is also our research and development and manufacturing footprint in the United States. Now, Tuesday's announcement to invest further 50 billion into R&D and PP&E in the US until the end of the decade, let me put that into a bit of context. This would be almost a doubling of our investment in the US over the next five years. compared to the previous 10 years where we invested 67 billion in R&D and PP&E. Let me also say, this does not mean that we change what we've said before in terms of CapEx availability between three to 4 billion annually. This is already included in any of these comments that we've made in the past. It also doesn't change what we've said in the past in terms of R&D spending. You can expect R&D to be flat this year, and that we keep very disciplined when it comes to our spending. Currently, we have 13 manufacturing and 15 R&D sites in the US across pharma and diagnostics, and we are planning to add two new sites. First is this announcement of investments, including the construction of a new R&D site in Boston. We've discussed this as a team that we have a very strong presence on the West Coast in terms of R&D, but we didn't have a presence on the East Coast. And so we strategically said we wanted to tap into the ecosystem in the Boston area, which is, I would say, next to San Diego and San Francisco, the third key ecosystem that we want to be present in. And that's why we've committed to make an investment here and also in collaboration with Harvard. And then there is also one new manufacturing site that we will establish in the U.S. where we've been in negotiations with different states in the U.S. We have not named the location yet, but we'll do that soon. And this is basically also for the manufacturing of peptides. So the incretins and also the amylin. And so both of our new sites will have a strong focus on CVRM peptides. Let me also highlight that we are probably in a much better position than most other companies in terms of our manufacturing capacity that already exists in the United States. Our drug substance capacity utilization is at 50%, which truly gives us a lot of flexibility to adjust our manufacturing volumes. And this is due to the fact that, and you can see it on the right hand side, that we've driven a five-fold productivity increase in terms of yields from our cell lines. So what that's enabled us to do is actually some of our medicines that we already produced in the US, we could increase the manufacturing in the US basically overnight of these medicines. And the only remaining medicine that we have to tackle when it comes to tariffs is one that's currently not being produced or produced in the US. And we already started the tech transfer of this medicine a number of weeks ago. Let me also highlight that When we acquired GenTech, not only did we keep manufacturing there, so we didn't move to Ireland, for example, we also kept our IP there. And with that, we've been a significant taxpayer in the U.S. Again, so I would just highlight here, we're probably in a better position than many others. Taken together, I do believe this sets a stage for next era of growth and innovation for us as a company to benefit patients in the U.S. and abroad. But also just want to reiterate, we'll also continue to invest in countries like China, where we're also expanding our manufacturing footprint. Now let's move to the outlook. And I want to highlight two areas. One is Roche sequencing, and the other one is our efforts around CVRM. And I know both Matt and Teresa will go into more details on this. At HPTV, we unveiled our novel sequencing solution, which combines our high throughput sensor module that we developed over the last years. And now comes the secret sauce. That's the SPX chemistry, the sequencing by expansion chemistry, which actually expands the DNA 50 times so that you get a better signal to noise ratio. With that, you increase the accuracy significantly and you increase the speed and throughput because you don't actually need to slow down This molecule, as it goes through the pore, it goes through very quick and you get a very clear and clean signal. With that, we have a very high accuracy, which is fit for clinical applications. We are extremely fast and we have a lot of throughput. And what also is unique is the flexibility. Because with technologies that are used today, you have to run a full plate to get the benefit of the price and cost. You don't have to do that with this technology. So we do believe that we are in a pretty good position here as well. Let me talk about our commitment to become a leader in CDRM. In IFAMA, we now have a broad portfolio of differentiated assets that address unmet needs in obesity, diabetes, and a number of adjacent indications. Let me just highlight there are probably more than 200 comorbidities that are linked to obesity. The GLP-1 GIP from the Comet acquisition, and also in Q1, we announced a collaboration with Sealand Pharma to develop petrolintide, a long-acting amyloid analog, and I know Teresa will go into that detail. Also, in Q1, we announced a plan to build a Boston Innovation Center in partnership with Harvard, and this will be focused on CVRM drug discovery and development. On the diagnostic side, again, let me highlight this. We are the global leader in this space. We know all of the key opinion leaders. We have the leading portfolio of cardiac and metabolic markers. We develop holistic solutions for the management of the diabetes and cardiac indications. And this includes CGM that offers unique smart algorithms and easy one-step application. But I know that both Matt and Teresa will cover more here. Let me just highlight here on the 2025 pipeline for pharma, the positive news flow and also the negative news flow. In green, you see the positive and in red, the negative. On the negative side, let me just highlight skyscraper 07 in ESCC, which missed its primary endpoint. But let me also highlight that when SkySix failed middle of last year, we stopped all of the teragulma studies that were still in progress and could be stopped as we mentioned at the time in this investor call. And we only let the ones run where it was not appropriate to stop these trials anymore. On Ocrevus high dose, which missed its primary endpoint. Again, I just want to say we're comfortable with the Ocrevus consensus where it is right now, which includes the 2 billion incremental sales. which are driven in the combination of a subcut and IV. And let me also say that we don't see a cliff situation also for Ocrevus beyond the end of the decade because of Ocrevus subcut and Ocrevus high concentration, which you see in green here as well. On the positive side, again, I just want to mention Trantinamab and NXT-007. moving into phase three, column V with the EU approval, non-sumio with a positive phase three readout in second line DLBCL, obesity for gym three to nine, where we are starting a phase two combination with incretins, and atopic dermatitis and MASH, two new indications for Tempkibard, DMD for Endspring, and the high concentration Ocarus that I mentioned. Let me just close by saying that we confirm the 2025 guidance. As you can see on this slide, sales growing mid single digit, core EPS growing high single digit and dividends to further increase. With that, thank you very much. And I hand over to Alan to take us through the finance slides.

Yeah, thanks, Thomas. As everybody knows, a sales call today. I hope everybody's well. So my contribution will be brief today. Yeah, let me jump into the sales and what you see here, the reported sales in Swiss francs quarter one 2024 compared to quarter one 2025. So in total, a 7% increase. Let me start with the highlighted 6% in constant currencies. And you see we have different factors here. I think one element is really here on the diagnostic side. You see the China healthcare pricing reform that Thomas has mentioned already, which was a reduction for sales on diagnostics. On the other hand, excluding China, they've grown by roughly 5%, which I think is quite an achievement. So Matt will dive into this. And you see on the pharma side, I think really good underlying growth. Then as expected, the loss of exclusivity impact with a certain erosion in Q1, As you know, we expect more erosion for Actemra in the quarters to come. So still, we stick to our expectations that we're going to lose 1.2 billion in that segment over the year. You see, currency is a positive in Q1, you know, translating into Swiss francs. So to get to the plus 7%, and I will dig into that. But let me say, enjoy the moment. When you look really then at the exchange rate impact on the sales growth, and that is the 6% on the left-hand side in constant rates that you know already. It's now 6.4% as we added the decimal. And you see on the right-hand side in Swiss strength, the 7.2% growth. And then you see the currency fluctuations in between, and you see a major contributor to the performance has been the U.S. dollar, which has strengthened in that period. We all know what happened in April, and I will talk about that in the next slide, and here it is. Because, as you know, what we do is we keep all the currencies stable at the end of Q1 and then basically project them until the certain quarters, but also until the end of the year, and then measure the impact and announce that here. But let me say one thing. After end of March, as mentioned, I think we have seen a major volatility and a major weakening of the US dollar. And I will get to that. When you really look at full year 2025 impact, as of April 23rd, so really recently, and you assume all these currency rates remain stable until the end of 2025, we will have a currency impact at full year. on group sales of minus five percentage points. So quite significant. But as said, we're also not alone. I think other companies will be affected by this as well. I know it is of interest what that means for cooperating profit and for core EPS. So let me give you these projections, which are certainly highly speculative and very unlikely that they will really realize. But for cooperating profit full year, it would mean a minus seven percentage points and on core EPS, an impact of minus eight percentage points. So that's quite significant. As I've said, you see Q1, enjoy the moment, I think for the next quarters to come. I think if the currency stay where they are basically today, I think we will see a much worse in picture. Good, I think Thomas said everything about the guidance. I don't wanna just reiterate here that we confirmed the guidance. for 2025. And with that, happy to move over to Lisa.

Okay, thank you, Alan. In Q1, pharma delivered 11.9 billion Swiss francs in sales with an 8% growth at constant exchange rates. You see the U.S., Europe, and international all delivered strong growth with 6%, 5%, and 18% respectively. And Japan is now returning to growth with a 3%, up 3% in Q1. Overall, pharma volumes were up by 13% in Q1. So let's kick things off with a look at the sales growth across the pharma portfolio. Please note that all absolute values in year-over-year growth rates are presented in Swiss francs at constant exchange rates. As Thomas mentioned, our young portfolio continues to deliver strong growth, led by the key brands, Fezgo, Vibizmo, Hemlibra, Polivri, OkraVist. Together, these added 700 million Swiss francs of new sales at constant exchange rates in Q1. For the first time, Fesco is our number one growth driver, and that's thanks to the very strong performance in our international region. So now let's take a closer look at our key therapeutic areas, starting with oncology. Oncology sales increased by 2% to 3.9 billion Swiss francs in Q1. This growth was primarily driven by the HER2 franchise. Fezgo continues to impress with incredibly strong 52% growth in Q1. The global conversion rate continues to climb. We're now at 47% across our 58 launched countries, with the growth in China accelerating noticeably following the NRDL listing earlier this year. Progetta conversion to Fezgo is ongoing, and we are looking forward to sharing the final affinity analysis, which is that 11-year follow-up at an upcoming conference this year. Katsaila continues to deliver good growth driven by uptake in the adjuvant setting. Switching gears over to Ticentric, sales in the first quarter remain stable. And as we mentioned at full year, we believe Ticentric is close to peak with limited to no growth going forward. The U.S. launch of Itofi is continuing as planned, and we are expecting EU approval later this year. Looking ahead through the end of 2025, we have two highly anticipated phase three readouts for Ghiridestrin with Ivera and Persevera expected in the second half. And additionally, we are looking forward to initiating our phase three trial of Diveracib, our KRAS inhibitor on top of standard of care and first line non-small cell. So now let's move on to hematology. Hematology growth remains strong starting the year with 14% growth, 2.1 billion Swiss francs in sales. And Libra showed strong growth momentum across all patient segments. As expected, the U.S. Q1 year-over-year sales were flat, and that follows the very strong growth we saw in Q4. We had 20% growth in Q4 in the U.S., and that was impacted by a buying pattern from one of our largest distributors. So we sort of expected this and signaled it as we head into, as we signaled it at full year. XUS, however, we saw very strong growth in Q1, with the international markets growing 72%. and the EU market's growing 7%, and basically all countries contributed across those regions. For a full year, we are confirming the ambition of mid-single-digit global sales growth for Hemlibra. There is also some exciting news on our next generation bispecific in hemophilia, NEXT-007, which I will cover in the coming slide. But for now, let's move on to our malignant hematology portfolio. Polivi first-line DLBCL continues to drive strong growth, and we've reached yet another milestone with more than 50,000 patients treated globally. U.S. first-line DLBCL patient share continues to climb. We're now at 31%, and we are looking forward to presenting the updated Phase 3 Polargo data and relapsing-remitting DLBCL at an upcoming medical conference at mid-year. Columbia and Lensumio are CD20, CD3 bispecifics. Launch performance is on track for both in their lead indications, third-line plus DLBCL for Columbia and third-line plus follicular for Lensumio. We expect to achieve the combined peak sales potential of 700 million Swiss francs in those initial indications, which are relatively small. I do want to highlight that both of these bispecifics are making good progress to move into earlier lines of treatment. and therefore bigger markets, specifically those first moves into second-line DLBCL. As Thomas mentioned, Columbia recently achieved EU approval based on Starglow, which demonstrated an OS benefit with a hazard ratio of 0.59, making it the first and only bispecific in the EU approved in second-line DLBCL. And in the U.S., we are still expecting FDA approval around mid-year. As mentioned before, we're also excited about the positive Phase 3 Sunmo data, for Lunsumio and Polivi in second line plus the LBCL, which offers patients another chemo fee treatment option. And we are looking forward to sharing that full data set with you in the near future. Staying with Lunsumio, there is quite the rich outlook in 2025 for hematology. We have the U.S. PDUFA, as Thomas mentioned, for the subcutaneous formulation of Lunsumio in third line of the follicular, and that is set for September 22nd. We are also expecting the phase three Celestimo readout in second-line follicular later this year as well. And then additionally, we are expecting phase three readouts for Vinclexta in first-line MDS and P.Sky in AHUS. So now, as promised, let's take a look at next 007. Certainly the key news here is that we are moving NEXT-007 into phase three trials. This is the next generation factor eight bispecific monoclonal antibody that we have in development with Chugai. Preclinical results indicate that it has the potential to achieve zero treated bleeds for hemophilia A patients without the need for additional factor eight treatment. We've mentioned before that NEXT-007 is 30 times more potent than Hemlibra. And we believe that this really could be a game changer for hemophilia patients. The aforementioned, so we are moving into phase threes. We are launching three phase three trials this year, including one head-to-head with Hemlibra. I think this gives you a very good sense of our excitement for next 007. And quite frankly, it really only makes sense to be including Hemlibra, which is the standard of care, as the comparator for any new trials in hemophilia A. All of these trials are expected to initiate in 2026, and we are also exploring device options. Phase 2 data for NX007 will be shared in an upcoming medical congress and as covered as part of the IR event on June 23rd. So up next, let's head over to our neurology franchise. Neurology continues to deliver strong growth of 10% at constant exchange rates, achieving 2.4 billion Swiss francs in sales. Okravis growth momentum remains strong at 6% globally. A lot has happened with Okravis in Q1, so let's delve a little bit deeper into the Q1 news flow. So as you know, the permanent J code for Okravis-Senovo, our sub-Q formulation, was granted on April 1st in the U.S. We believe that this will lead to an acceleration of U.S. uptake, particularly in the second half of the year. The early market response has been very positive, and we know that some practices were not only actively waiting for the permanent J-code, but we're also deciding against adding additional infusion shares in favor of starting on or switching patients over to Ocrevus-Zenovo. Importantly, based on internal patient claims data, we see that about 50% of Zenovo patient starts are naive to Ocrevus. So that continues to give us confidence that this new formulation will open up new patient populations to Ocrevus and not simply cannibalize existing share. Of course, in Q1, we also shared the negative Ocrevus high dose readout in RMS. And while disappointing, I think it is important to remember why we ran this trial. And the purpose of the high dose trial was really to understand if patients would experience greater efficacy with a higher dose of Ocrevus. And while this trial didn't meet its primary endpoint, the results clearly support Ocrevus standard dose as the optimal dose to slow disability progression. And this is actually great news for patients. So now that we have the answer to what is the optimal dose of Ocrevus, we are quickly moving forward with the development of a novel subcutaneous formulation that has a higher protein concentration, which will significantly reduce injection volume, which allows us to move into a more convenient on-body device with the goal of bringing Ocrevus closer to home. So more on this exciting development will be shared at a later stage, but we are moving with urgency into this next phase of the lifecycle for Okravis. In the meantime, Okravis franchise modeling remains largely unchanged. We predict the franchise to peak at the end of the decade and do not expect, as Thomas mentioned, an abrupt cliff situation due to Okravis subcut providing some level of protection to the franchise. For 2025, we continue to expect high single-digit global sales growth, and we continue to be comfortable with the Okravis consensus peak sales of $8.5 billion, including the $2 billion Swiss franc incremental sales opportunity for Okravis subcut. Moving on to Evrizdi, Evrizdi continues to deliver strong growth, and we expect the full-year growth rate to be at roughly the same level as the 18% that we achieved in Q1. The tablet formulation received its U.S. approval in February, which offers patients a simplified storage option, eliminating the need for cold chain and easing administration. EU approval is expected before mid-year for the tablet. The early launch momentum for Elevides and DMD continues to be strong in ex-U.S. and ex-EU countries, with 43 million in sales in Q1. We were profoundly saddened that a young man with Duchenne's passed away following treatment with LVDs, having suffered acute liver failure. Following this event, ongoing studies were put on temporary clinical hold by EU regulators. And as always, Roche and Serafta are focused on doing what is most important for patients, and patient safety is always our paramount concern. Based on the totality of data, however, we do remain confident in the efficacy and safety profile of LVDs, And we are not changing forecast guidance at this time, and we will work with EU regulators to minimize any potential delays to the program. Trontinumab in Alzheimer's, we presented the more mature phase one, two data set at ADPD and more on that on the next slide. But importantly, we have made the decision to move Tronte into phase three and look forward to initiating that trial later this year. On the outlook for neuro, we expect a steady new slow through the end of the year. The phase three readouts for fenobrutinib in RMS and PPMS are expected at the end of the year. And there are two phase two readouts for GIM329 expected in 2025, one in combination with Evrizdi and SMA, and one is monotherapy in FSHD. But before we leave neuro, let's take a closer look at the two molecules we highlighted at the recent ADPD conference, Tronti and Prosnizumab. Starting with Tronte, as we mentioned, we presented updated data from our Phase 1-2 brain shuttle trial of Tronte and Alzheimer's, and you can see that that rapid and deep amyloid clearance continued to be achieved at different doses. Importantly, 81% of patients on the 3.6 mg per kg dose achieved amyloid PET negativity within just 28 weeks. At the same time, in the safety and tolerability profile remained very favorable. ARIA-E and ARIA-H rates were below 5%. across the 114 patients treated in parts one and two. Based on these very positive results, we've decided to move Tronte forward into phase three with the trial start planned for later this year, and we would expect final readout of that phase three trial in 2028. So now let's briefly move on to Parkinson's. At ADDP, we presented the phase two B Padova data Despite missing the primary endpoint, the results show a delay of confirmed motor progression in PD, especially in L-DOPA-treated patients. We are waiting for additional data from the ongoing label extension, and with the benefit of that additional data and in close alignment with regulators, next steps for PRASI will be decided around mid-year. Just to remind everyone, we continue to see PRASI as a high-risk, high-reward opportunity. So now let's continue on to immunology. Our immunology franchise achieved 1.6 billion Swiss francs in sales and grew 8% at constant exchange rates. This growth was primarily driven by Xolair and its strong launch trajectory in food allergy. Xolair's benefit in food allergy was further confirmed by positive updated data from Outmatch, which showed that Xolair is more effective and has fewer side effects than oral immunotherapy for treating food allergy. For the full year, we expect growth in the mid-teens for Zoller. And as a reminder, we don't expect any biosimilar launches in 2025. Actemr saw a minor decline of 1% due to biosimilar impact. U.S. biosimilar launches continue to be slower than we expected, while EU biosimilar penetration is increasing as planned. And we anticipate that the overall biosimilar impact will accelerate in the second half of this year. And as Alan mentioned, we are confirming that 1.2 biosimilar impact for the full year. across the portfolio. More on Gaziva on the next slide, but let me just mention here that the positive Regency results were recently published in the NEJM. Our TL1A program had quite the busy start to the year. First and foremost, we have finally received our INN just last week, and so we are now officially known as a fifth gabard. We also started trials in three indications, all of them achieving FPI in Q1, phase three in Crohn's disease, a phase two in atopic dermatitis, and a phase one in MASH. Further indications are currently being evaluated. Afimki is one of our internal fast-track molecules where we work across all levels of the organization to ensure development at speed. And this is a direct outcome of our R&D excellence work, and Afimki is one of the programs where you can really see the impact of that. Considering the outlook for the rest of the year in immunology, we have phase three trials for gaziva and SLE and astagolamab and COPD expected to read out. And for ASTI, as a reminder, we continue to see this as a high-risk, high-reward opportunity. Now let's take a closer look at gaziva in lupus. We shared the positive regency results at the WCN conference in February. Gaziva demonstrated a superiority over the standard of care with a clear benefit in complete renal response. Safety was in line with the very well-characterized profile of Gaziva with no new safety signals, and the U.S. PDUFA has been set for October, and EU filing has been completed. Phase 3 readouts for additional indications are expected in 2025, Allegory and SLE, and Insure and INS. And then, obviously, the MN trial is ongoing. Moving on to ophthalmology. Ophthalmology grew by 17% in Q1, achieving 1.1 billion Swiss francs in sales. But Bison is now the most prescribed treatment in AMD in the U.S. Market shares in the U.S. continue to expand with AMD now at 33%. That's up 3%, DME up 2%, and RVO up 3%. This is also true for ex-U.S. launch countries, where we continue to see market share increases across all indications. Additionally, the share of treatment-naive patients starting Vivizimo in the U.S. is now approaching 60%, and I think this further confirms Vivizimo's positioning as a first-line treatment. As Thomas mentioned, at the same time, U.S. sales were impacted by a contraction of the U.S.-branded market, and this is primarily caused by funding shortfalls from the co-pay assistance foundations. This dynamic in the U.S. is likely to persist, and the overall impact of that constriction will likely take several quarters to wash out. Outside the U.S., we see very strong uptake. EU conversion to the recently launched PFS is rapidly increasing. It's already at greater than 70% in all the markets where it's available, and the China launch accelerated markedly after achieving NRDA listing in January for all three indications. Taken all together, we still expect roughly 20% sales growth globally for Vibismo this year, but we do have to caveat that there is a difficult to predict development, or it is sort of difficult to predict how the U.S. branded market will develop in the coming months. Some good news for SysVima, U.S. approval in DME was achieved, and EU filing for AMD is expected later this year. And similarly, we expect data for our IL-6, the Mickey Bart in UME, later in 2025. Wrapping up our tour of the therapeutic areas with a quick look into our CVRM franchise. Like Thomas, I am very excited about our recently announced collaboration with Zeeland to partner on petrolentide and obesity. Together with Zeeland, we believe that monotherapy petrolentide has the potential to become a foundational therapy in weight management with improved tolerability and a mode of action differentiated from GLP-1s. as amylins work by increasing that feeling of satiation, while GLPs work by reducing hunger. Petrolentide's favorable physiochemical properties will allow for easier co-formulation and co-administration with other peptides. So thus, in addition to just exploring as a monotherapy, we are also exploring different combination opportunities, starting with a fixed-dose combination of petrolentide and CT388. Our belief in the best of class potential is also based on the strong phase one results shown here. Placebo-adjusted weight loss of up to 6.9% was achieved at 16 weeks, and at the same time, safety and tolerability were quite favorable, with the vast majority of treatment emerging adverse events reported as mild. A phase two in obesity without type 2 diabetes is currently ongoing. Now, the Zeeland collaboration very nicely complements our existing obesity and diabetes portfolio. And we see great potential for monotherapies and combinations to address the various unmet needs in obesity, diabetes, and the linked comorbidities. And we're making very good progress with multiple molecules expected to advance in 2025. It is quite a list. The interim data for CT388 in obesity will become available this year and will inform our Phase 3 GO decision in the second half. I did want to reiterate what we shared at half year, that we only plan to share the final phase two results for this study, which are expected in early 2026. We will, however, announce a phase three decision once it is taken. Data for CT868 phase two in type one diabetes with overweight and obesity is also expected this year. Our phase two trial for CT996, our oral, will also begin this year. as will our Phase 1 for CT173 or PYY in obesity and the Phase 2 trial for GIMP329 plus a GLP-1 in obesity. For 2026, as I mentioned, we expect the CT388 plus petrolentide Phase 2 study to be initiated. As Thomas mentioned earlier, Roche is committed to becoming a leader in CVRM, and the scope and speed at which we are expanding and developing our portfolio I think really underscore this. And so to close my section, let's look at the key news flow side. So we've added quite a number of check marks since we last showed you this slide at the full year presentation. I won't go through them in detail since we covered most already. So just a quick run through. Columbia received EU approval in second line DLBCL. Gaziva completed U.S. and EU filing in lupus nephritis. SysVimo achieved U.S. approval in DME. Lensumio with positive phase three results in second line DLBCL. NEXT-007 and hemophilia A and tonchinimab and Alzheimer's are both moving into phase three. And as Thomas mentioned, TNKs achieved U.S. approval in acute ischemic stroke. Of course, we also had to add a red cross for the Ocrevost high-dose study and RMS with the Gavat trial and PPMS still ongoing. But of course, our hopes for a positive trial in that indication are diminished somewhat with the result that we saw with Musette. So now that is all for me, and I have the pleasure of passing it over to Matt to cover diagnostics.

Thanks very much, Teresa. So good morning, good afternoon, everyone. It's my pleasure to present the Q1 2025 Diagnostics Division sales results. As you heard already from Alan and Thomas, with sales of 3.5 billion Swiss francs, the Diagnostics Division sales were stable versus Q1 2024. And this was really driven by the healthcare pricing reforms and volume-based procurement in China and As Alan mentioned, excluding China, the growth of the business was plus 5%. So let me walk you through that on a customer area level. So sales in our core lab decreased at minus one. Now, this is really impacted by the reimbursement reductions in the VBP in China. This resulted in a decrease of immunodiagnostics by 3%, which was partially offset by 4% growth of our clinical chemistry business. Excluding China, core lab grew at 8%. Now, sales in our molecular lab increased at plus 2%, and this is due to strong growth in our blood screening segment at plus 6%. But this was offset by a minus 5% in our infectious disease business. Now, this infectious disease decline was driven by a decrease in our HIV business in Africa. This is a result of the USAID funding pause for testing. Now, excluding this effect, molecular lab grew at plus 6%. And we are optimistic that the USAID pause will end and that this business will resume. We will keep you updated in the coming quarters. Now, sales in our near-patient care business decreased at minus 5%. Now, this is mainly driven by the decline of our blood glucose monitoring business at minus 7 due to the market shift to continuous glucose monitoring. And this was partially offset by a healthy plus 6% growth of our molecular point-of-care LIAT business. We'll talk about the STI approval for CT and G later. And I would note that we are confident that our CGM solution and Cobos Lumira will drive growth of our near patient care business in the future. As I've said at the full year, we don't expect material contribution from CGM in 2025, but our manufacturing scale up is going as planned and our launches are going as planned and look forward to updating you on that in future calls. So now switching to the regional view, I'll take you through the business performance by geography. In North America, we saw strong growth of plus 7%. In EMEA, the business grew at plus 4%. In LATAM, we saw strong growth at plus 11%. And in APAC, we saw a decline of minus 15%. And as previously mentioned, sales growth in Q1 was impacted by the healthcare pricing reform and VVP in China. As a result of this, the sales in China declined by 23%. Now, we expect this effect to continue over the course of 2025. And since this is primarily due to the price decrease, there's obviously a corresponding impact on the profitability of this business. I would call out that we're implementing operational excellence and cost discipline measures to offset this. And I would also call out that we had a strong quarter in terms of instrument placements in China and that China is still a critical market for us and we remain the market leader. And our ambition, again, for the division for this year is to grow by low to mid single digits. And now I'd like to talk, you know, to the engine of our growth for the future is really our instrument placements. And here in the full year of 2024, we saw strong growth across all of our customer areas versus 2023. And let me point out a few areas of growth by customer area. So in the core lab, this is our Cobos Pro, which is our high throughput serum work area. And our CoBus Pure, which is our mid-throughput serum work area, placements grew by 65%. In our molecular lab, placements of our fully automated CoBus 5800, 6800, and 8800 systems for low to high-throughput testing and molecular diagnostics grew at plus 22%. And I would call out here that we've seen continuous growth of these platforms, even through the pandemic into the endemic phase, which really shows that they are the standard for automated molecular diagnostics testing in the clinical laboratory. Moving to pathology lab, we saw placements of our benchmark ultra and ultra plus have combined growth of plus 10%. In digital pathology, our DP200 and DP600 grew by 36%. And I would call it, we got the primary diagnosis claims for these last year, which is going to accelerate our position in digital pathology. And our primary staining business, the HE600 placements grew at plus 4%. Now in near patient care, Placements of our co-boss Liat, our lab equivalent PCR solution, grew at plus 7%. And I look forward to updating you in the future on some of the growth of our newer platforms in the next year. But lastly, we also saw strong growth of pre-analytics and connectivity by 12% and our Navify lab operations with good growth of plus 16%. So now I'd like to come to some of those new launches that you heard Thomas mention. And start with our Cobos mass spec solution, which got a C mark at the end of 2024. So with this launch, we plan to establish and shape the IVD market for automated, simplified, end-to-end mass spectrometry testing. This will drive market expansion and a transition from a segment dominated by lab-developed tests to one with mass spec as a part of the routine core laboratory environment. I'm pleased to report that we've had significant progress since launch with a number of placements throughout Europe. We also achieved sea launch for our system and steroid assays on track and vitamin D assays in February 2025. And we delivered some of the key installations already this year. And I'm pleased to share that the initial sites reported a very fast installation time and positive system performance in terms of uptime and serviceability. I would call that we are on track to launch approximately 40 assays in the first wave throughout 2025, which will cover the vast majority of routine testing for mass spec, and a second wave will come in the following years. So now going back to some of that innovation that you heard Thomas mention about our sequencing solution, which is the really exciting unveiling we had at the AGBT conference. And what really makes this solution so exciting is, as you heard, the marriage of the Genia technology with the Stratos SBX technology. And the Genia technology is a nanopore technology, which is complementary metal oxide semiconductor. It allows for extremely high resolution nanopore signal to noise ratio. And you combine that with the Stratos SBX technology, which is a surrogate polymer encoding what's called an expandomer. As you saw from Thomas' slide, it's 50 times larger than a native nucleotide and also enables really high signal-to-noise ratio. Combining these together, they're going to get high throughput, unprecedented throughput, high accuracy, and high flexibility, which you don't have in standard next-generation sequencing. And so the NGS market, which is valued at $6.4 billion, is projected to grow at around 9% per year over the next three years. And the clinical segment will experience strong double-digit growth, driven by applications like therapy selection and minimal residual disease monitoring and oncology. Our Roche XBX technology has the potential to really be transformational. And you see here on this slide, some of the data presented at AGBT from the Broad Institute. Now here, the Broad Institute demonstrated the high speed potential of the technology, completing the entire sequencing workflow from library preparation through a whole genome sequence analysis with variant calling in under seven hours with the SBX FAST workflow. And I would call out, as you heard from the founder of Stratos Genomics, Mark Koukouris, at the AGBT webinar, that this was not even an optimized protocol, and we're hopeful that we can even improve this in the future. I would emphasize that this data showed a level of accuracy that could lend itself well to clinical applications, as demonstrated by the strong Q and F1 scores. This workflow could be practice-changing in clinical environments, where a fast genome is important for decision-making such as the NICU. And third, as you heard me say before, this sequencing chemistry enables batch flexibility and makes it cost-effective to run small batches. We demonstrated flexibility in read length with one workflow operating the classic short read range and the other having the potential for longer reads to improve coverage. The unveiling of our XPEX technology showcases our commitment and the capability to deliver innovations that could transform the sequencing field. So now moving to our near patient care business, I'd like to speak about our Liat CTNG for which we received FDA clearance with CLIA waiver in January of 2025. So the molecular STI market is valued at about 1 billion Swiss francs in 2023. There's over 2 million STI infections for chlamydia and gonorrhea in the United States. and affects over 200 million people yearly worldwide. With the Cobas Liat CT&G, we'll offer the first FDA-cleared, CLIA-waived molecular diagnostics point-of-care solution for CT&G and expand Roche's menu of lab-equivalent PCR solutions for rapid and accurate diagnosis at the point of care. With this launch, we can leverage our installed base of over 13,500 Liat analyzers, to drive access to our point-of-care molecular menu. And so now, following Teresa, I'll provide a report on our key launches for the diagnostics division. So the 14 launches shown here, we achieved two in Q1, the LES, CT, and G, as I just covered, and our chest pain algorithm, which helps triage in the emergency room for suspected myocardial infarction. We are making good progress towards the other launches, which are on track. and I look forward to providing further updates in the future. Last but not least, I'm also pleased to invite you to our Diagnostics Day on May 27th, a hybrid event in London and also online. Here we have a prepared and exciting agenda, and we'll further discuss our forthcoming rose sequencing solution, as well as our pipeline and portfolio highlights across our customer areas. And with that, I will pass it over to Bruno, and thank you very much for your attention.

Thanks, Matt. And just quickly to summarize here, Matt already mentioned the next upcoming IR event will be the live diagnostics event in London again. And then, as mentioned already by Teresa, in June, on June 23rd, we will have a hematology update, basically covering all the data for malignant and non-malignant hematology, which are presented at the summer conferences. So including ASCO, IHA, ICML, and then also ISTHT. That's the first time when we will show the clinical data for 007, which were the basis of the decision taken now to move the molecule into phase three. And with that, I think we are ready to open the Q&A session. The first one in the row is Sachin Jain from Bank of America. Sachin, please.

Can you hear me?

Yes, we can hear you.

All right, thanks. Two questions, please. So first, I'm going to kick off with Vibisma, if I may. So, Teresa, if you just comment to how you see U.S. sequential growth from here, should we expect continued sequential decline through the year, given comments for several quarters to wash out? And if that's the case, to get to the 20 percent global growth that you're sort of roughly guiding to, is the bulk of that coming from ex-U.S. where we have lower visibility? And then the second is a big picture one you'd expect, Thomas, on sort of US policy. You commented on the wires that tariffs you thought were absorbable. What assumptions within that have you made given the wide variety of scenarios? And then on your US manufacturing R&D commitment, you and others have made commitment for the US in recent months. Is there an expectation that this commitment from the industry can reduce or influence tariff proposals from the administration or just sort of what's the big picture intent? Thank you.

You can go ahead with the baseline. Sure.

So starting with Fabizmo, so basically the dynamic that's happening in the U.S., we all know that within the U.S. retinal space, there has always been a very large sort of unbranded market dominated by Avastin. Over the course of the last couple of years, what we've seen is a decline in that portion of the market and more patients funneling into the branded therapies. With the early closure of the co-pay assistance fund or the CAF, We are now seeing the unbranded market, and in particular the Avastin share, continue to grow while the branded market constricts. Within that branded market, however, Vibismo is growing in every indication that we have. And so we will continue to see growth in the U.S., It may just be at a lower rate since the overall branded market has shrunk, if that makes sense. But we will definitely continue to see our share of that branded market continue to grow. We do also anticipate significant growth outside the U.S. as new countries come online and as the pre-filled syringe continues to enter into new markets. So overall, we think it is a story of growth everywhere in the world. And that dynamic in the U.S. will likely just take a little time to wash out.

Good. Yeah. Sergeant, thanks for that excellent question. What I can say is that we've looked at a very wide range of different scenarios. And I think we cannot go through all of the scenarios today, although I'm sure that everyone would like to. But we've put in mitigation measures to mitigate against these different scenarios. What I can say already is if we look at the first half of the year and also in Q2, we will not see much of an effect from the tariffs. One reason is that we've shifted inventories and that should mitigate a significant impact already this year. And the other part is we already started to increase manufacturing of a number of medicines in the United States. So we are very actively working on mitigating all of these topics. And we also in our budget are making sure that we can absorb potential tariffs throughout the year. So we're really working hard on all of those different topics. Regarding our engagement with the U.S. government, I can just say that we are in exchange with the U.S. government. We are in exchange with the U.S. government through the Industry Association. but also with other governments like the EU and certain EU member states. And I don't want to disclose all of those conversations at this stage, but I can just tell you that we're on the case.

Okay. Then we move on. Next questions would come from Matthew Weston, UBS.

Thank you, Bruno. Can you hear me?

Yes, we can hear you.

Perfect. It's just one question from me, please. And it's for Teresa. It's a follow-up to Sachin on the BISMO. So you made clear the success that the BISMO has as the market leader in AMD in the US. But I just want to dig into this charitable foundation issue. So the previous Optha market leader was a leading donor in the charitable access foundation market. Now that you're a leader, shouldn't we expect that Roche steps up its contributions to the charitable foundations? And if not, why not, Teresa? Is it potentially linked to the DOJ's continued investigation into charitable donations? Or it seems that after the recent court win and appeal win, that looks like it's broadly resolved.

So, Matt, as I'm sure you can appreciate, all charitable foundation giving is done through our foundations. which is completely separate, and it would be inappropriate for me to comment on how they do their giving. So unfortunately, I really can't answer your question.

Okay, understood. Can I just quickly follow up? Your answer to Sachin's question suggested that you felt that the cash market was just winding down. But can I just check that there's no structural reason why we should assume that CAF from everybody's donations should wind down? It's simply the moment the charitable foundations are short of money.

At the moment, the charitable foundations seem to be without money.

But to say that, I mean, that will be just a rebasing of the market and just will take a couple of quarters to wash out.

OK, thank you.

But overall, I mean, the growth rates you saw in Q1 with 18% is roundabout what we expect for the full year.

Understood. Many thanks for the detail.

Okay. Then let's move on. Next one is Emily Field from Barclays.

Hi, thanks for taking the question. Maybe one on NXT 007. What dosing intervals will you be targeting in the Phase 3 studies? And then for the comparator study versus Factor VIII, will you be using a long-acting Factor VIII as the comparator? And then... Going back to obesity, on CT996, I was wondering if you could make any comments on the back of the high-level oriflaglomeron data that we saw last week, you know, if you're able to comment on any structural differences between the two molecules and if that is sort of the framing of targeting what you think you could achieve with CT996 in a pivotal study. Thank you. Great.

So with regards to the next 007 study, trial design, both in terms of dosing and in terms of which factor we would use. Those are both great questions, which when we have the phase three trial design, I will be able to answer for you. But right now, it would be premature. In regards to your question around the Lilly molecule and our CT996, that structure has not yet been disclosed. And I think as we've sort of repeatedly said, reducing everything down to just structure sometimes is a little bit overly simplistic. One molecule or one atom here and there can really, really make a big difference. And so I think we are very confident in the data that we've seen thus far with our oral molecule, and we are looking forward to advancing it in other trials. And at this point, we've seen just phase one data, just to be clear.

Emily, did this answer your questions?

Yes, thank you.

OK, next questions come from Justin Smith from Bernstein.

Yeah, thanks very much. Just one from me. Sorry if I'm being slow. On Vibismo, are you basically saying that the global area under the curve of the drug is the same or it's just going to come down?

So the overall size of the U.S. So if you think about the U.S. market as a pie, the size of the pie will likely remain the same. The amount of that pie that goes to the unbranded options is likely to get a bit bigger. So the slice that's left for the branded market, we would expect Vibismo to continue to take share. And so. I just want to continue to underline, we do believe that the BISMO will continue to grow. And as Thomas mentioned, the same level of growth that we saw in Q1 is the level of growth that we're hopeful to see throughout the rest of the year.

And again, this is just now a base effect for a couple of quarters, and then it will wash out and we will see continued growth like we've seen now in the first quarter. We'll continue to see growth going on in the BISMO.

Thank you. So just very quickly, so I get that. And then so in terms of ability of XUS to pick up any slack? Does that help as well?

I mean, remember XUS, we still have a number of markets that aren't yet approved or reimbursed, and we're still in the midst of launching the pre-filled syringe XUS. So there is actually a tremendous amount of opportunity that remains. And we're still in very early days in very big markets like China, which just launched in January with NRDL coverage for all three indications. So there is still a tremendous amount of room for Babaismo.

There's a significant amount of growth left in the bicycle. Exactly. Thank you.

Okay. Next questions go to James Quigley from Goldman Sachs.

Great, thank you for taking my questions. I've got two on some of the upcoming news flow for the second half of this year. So firstly on gerodestrin. Again, I know this isn't necessarily the best indicator, but primary completion dates listed on clinicaltrials.gov for Persevera and Avera have now slipped into 2026. So you've already confirmed 25 readouts, but is there any risk of slipping into 2026? Also similarly on the CERD space, we've seen some data from Astra, Lilly and Pfizer. So just wondering what your take is on this, particularly with continued success in the ESR1 mutation population. And then what are your thoughts on the commercial opportunity? And secondly, on fenobrutinib, we spoke to some care wells recently that suggested that in terms of Abajo's apparent overperformance in recent phase three trials relative to the original phase three program, patient population was the biggest. biggest change there. So from what you've seen, is there anything sort of different or novel for your trials versus what we've seen for the other two competitor trials in their populations? And when you're planning the studies, to what extent did you assume an uplift in efficacy for a budget? Thank you.

And I'm sorry, James, could you repeat the first part of your second question? I didn't catch it.

So that's my second question. We spoke to some KOLs recently who said that in terms of Obagio's apparent overperformance in the current phase three or in the phase three trial for your competitors versus its own phase three program, the key change there was patient population. So is there anything different in your patient population versus what we've seen for tolbutinib and or ibuprofenib?

So I'm still not sure I totally understand what your second question is. The first one's fairly easy. The gear-destined trials are event-driven trials. It is possible that we may see slippage just because they are event-driven. And as soon as we have concrete information, we will certainly share that. And we continue to believe that our CERD is materially differentiated from a structural standpoint from the other CERDs out there. And so While I think the additional data from other trials is certainly informative, it's not definitive. And I think that would probably be the way that we would look at it. So you're talking about fenabrutinib. Okay, got it. So the question, the second question was fenabrutinib and did we see anything different in our phase three patient population?

Yeah, so infenobrutinib, Obagio has done better than people thought, right? So that seems to be the reason as to why tolobrutinib and evobrutinib weren't successful. And KOL, as we spoke to, said that's because of the patient population. So have you adjusted for that patient population in your trial? What were you expecting in terms of the Obagio efficacy when you originally planned the trials as well?

Got it. So I would say that based on the phase two data that we have seen from phenobrutinib, based on the fact that it is a materially different BTK from the other BTKs that are out there, it's non-covalent. We believe preclinically that it's more potent, that it's more selective. We've seen very strong phase two data with phenobrutinib, you know, virtually, you know, we are quite confident that we have a molecule that is very different from the other molecules that are out there. So from a patient population, I'm not entirely sure that there's anything materially different in the patient populations that we're looking at. But I think we do believe that we just frankly have a better BTK and one that we were able to bring forward into phase three is at what we believe to be the most appropriate dose. And I think that's the other thing that has potentially impacted some other trials is they just weren't able to get to the level of dosing that they needed. We believe we've gotten to the level of dose that we need. But obviously, you know, the trial is still ongoing, so we haven't been able to formally look at the baseline characteristics for all the patient populations. But, you know, there wasn't anything in how we structured the trials that we think would be materially different.

Got it. Thank you. Yeah, maybe, James, I can quickly add here. Your first question was this referring to gerodespirant timelines?

Yes.

So there's no change there. Just to confirm, they both will read out in 25 with eVira expected to come in before Pesavira, and you would have these, we expect these data still to come in, you know, from mid-year towards second half, one after the other. And the other question on the Obachio, I think, you know, this was widely debated, I think, once the competitor data were out and several KOLs communicated on it. I think due to the changes in the treatment paradigm in the meantime, you can expect these effects. But it's not that we would have known the extent up front and would have, you know, fundamentally differently designed our studies or selected the patients.

Great. Thank you.

I think the dose is a very important point in terms of the ability to go to a higher dose.

Yeah. Okay. When we move on to the next one is Kerry Holford from Bloomberg. Kerry.

Thank you, Bruno. A couple of questions for me on obesity, please. So CT388, in the context of what is now your interest in a triple approach with sealants, amylin, Can I ask you to remain committed to pursuing the dual agonist alone? So can we anticipate a phase restart for 388 next year? And then secondly, in the context of your incremental U.S. investment, I wonder if you would be willing to tell us approximately how much of the $50 billion will be allocated to obesity? And can you confirm whether you ultimately plan to manufacture 100% of the RASH obesity assets in-house or indeed whether you do intend to use CMOs for API and fill finish. Thank you.

So the CT388, we certainly do remain committed and that phase three will actually start most likely this year. We are anticipating the phase three go decision for the CT388 phase three this year.

Thomas, do you want to take the... Yeah, just wanted to say around the 50 billion R&D investment So, around 80% of that is, or close to 80% is actually R&D investment in the United States. The remainder is CapEx investment. And this includes all the different sites investments that we highlighted in the press release.

And then your plans with manufacturing of obesity assets going forwards?

So in the transition, as we are working in different phases through development, we will also work with CMOs, but this gives us enough time to build up our manufacturing plans, which we will announce very soon. And let me just highlight again what I said during my presentation, just to be clear and to be very sure that everyone gets this message. This investment that we're making in the United States is included in all of the messages we have made in the past in terms of our annual spend on CapEx. So there is no change of any of the messages that we've made in the past. We believe we have enough space in our CapEx because we've put a lot into manufacturing over the last decades in our network. So we have enough space in our CapEx to make those investments. And the same goes for R&D. When we talk about R&D investments, flat this year and very disciplined in the future years.

Got it. Thank you very much.

Okay. Then we have next in the row Sarita Kapila from Morgan Stanley. Sarita.

Hello, thanks for taking my question. So just on the Zealand amylin, how are you viewing the upcoming competition from Lilly's amylin where we get data in phase two data, sorry, in Q3? And then also be interested to get your thoughts on the Gubra molecule and why you passed on it given 8% weight loss posted at week six and the much smaller upfront contribution from AbbVie. And then just a follow-up question on 007, please. If the phase threes are initiating in 26, how soon can we expect it to be on market? So are you targeting before the Hemlibra patent expiry in 2030? And do you expect NXT to expand on the current Hemlibra peak sales opportunity where I believe consensus is touching 5 billion? Thank you.

So start from the back and move up. So 007 phase threes, I think when we have the announcement on the phase three trial designs and starts, we'll be able to tell you when we expect those trials will read out. We are obviously, as we would with any molecule that we believe has this kind of transformative potential, we will be moving as quickly as possible to bring this to patients. And so it would be premature to comment at this point exactly when it will come into market and what our plans would be. But we do believe that this could potentially expand the number of patients that are on prophylactic treatment just based on what we believe it may be able to do from a clinical standpoint. From the Zeeland perspective, I mean, certainly we would expect the amylin space, as every space in this market is, to be competitive. That having been said, we think that the data that we've seen from the Zeeland molecule has the potential to be best in class and certainly to be first into the market. And we don't yet have data from the follow-on compounds. And so I think we're extremely excited about the opportunity in front of us. And again, this is going to be a competitive space, but we feel like this molecule is well positioned to compete. I don't know, Thomas, do you want to take the?

Yeah, just I would like to just add that when we screened the market for potential partnering opportunities, We obviously looked at all partnering opportunities, and we saw this one as the best and first choice for us in terms of partnership because of it showing the best data versus the other available potential ambulance that we could partner with.

Yeah, the combined ability, too, here.

And the combined ability and safety, exactly.

And Sarita, let me also here quickly add, the patent expiry for Hemlibra is actually not scheduled for 2030, but it's beyond 2030. That's the guidance we have previously given.

Okay, thank you.

Yeah, okay. Then we move on to Simon Baker from Redburn.

Thank you, Bruno. Good afternoon, everyone. Two questions, if I may, please. Just going back to... to Vibismo. Your comment, Theresa, about being comfortable with sales expectations in light of a larger slice of smaller pie would imply that you have reduced expectations for the competition in that category. Is that indeed the case, that you simply see that Vibismo market share is likely to be higher than previously thought? And then secondly, for you, Thomas, going back to the question on CapEx, you indicated that the the total level of CapEx is the same. The total level of OpEx is the same. The amount being spent in the US is higher than before. I'm assuming that wasn't in the budget. So definitionally, you'll end up with a happy US government because more money is being spent in the US. Therefore, there will be less money spent ex-US. I just wonder if. Am I thinking about that the right way? And where is less money going to be spent going forward? And are there any political implications for doing that? Thanks so much.

The last question first. So if you look, for example, at our manufacturing network, we've completely modernized our manufacturing network over the last decade. If you look at our R&D network, for example, in Switzerland, if you've been here recently, it's completely modernized. So a lot of the investments that we had in other areas, we can now also redirect. And it was very clear if we want to enter the peptides manufacturing with Incretin and Amelin, we also have to build out manufacturing. So this was part of our budgets when we made the acquisition. The same goes for CGM. In terms of CGM manufacturing, that was also part of our business plan. So these are all investments that we've made, and we've decided to make those investments in the U.S. also because it's the biggest market in terms of obesity medicines, but also in terms of CGM. So I think it's just a very logical step in terms of the investments that we wanted to make.

And, you know, the simple answer to your question is I would just reiterate what I've been saying now for a number of years, which is I do believe that Vibismo is the new standard of care in retinal disease. We are steadily increasing our market share in every indication. We continue to grow our first-line share. The pre-filled syringe has extremely high adoption in the U.S., is growing in adoption in those markets where it's launched. this is the drug on the market to beat. And so I just fundamentally do believe that we will be taking share from others in that branded space.

Right. Thanks so much. Okay. Then we have Richard Fosser from JP Morgan. Richard.

Thanks, Bruno. A couple of questions, please. Firstly, on Progetto and Fesco, I wondered if you could give us an idea of the share of the two products between metastatic and adjuvant and whether the switching of Fezgo is greater in adjuvant or in metastatic or very similar. And secondly, on Progetta as well, biosimilars were highlighted in the annual report as coming in 26. Could you give a bit more colour on the timing and whether we could anticipate that being pushed out? Xolair was, I'm just trying to ascertain that. And then finally, one question on 996. We saw adenoglycol from Pfizer having liver enzymes and being discontinued. Could you just talk about how you're thinking about that in relation to 996? Thanks.

Sure. So for your first question, I don't believe that we've broken down Progetta penetration by line of therapy. So I don't have that information. Um, in terms of biosimilars, we expect that the biosimilar exposure for, uh, Progetta is going to be relatively limited right now. We only see one that has the opportunity to come in, um, at around the time that it would be eligible to do so. Um, so, you know, we, we don't think that they're likely to enter the market until sort of the end of 2027 or later. So right now it's not a threat that we're, we're super worried about for Progetta. Um, But we'll obviously continue to keep an eye on it and keep you informed. In terms of 996, you know, obviously our number one concern with any new molecule is patient safety. And so we are, with all of our molecules, we pay very, very close attention to the potential risks. And liver risk is certainly one of them. Right now there isn't anything that's necessarily giving us undue pause here. but it is clearly something that we will continue to monitor as we would with any of our molecules.

Yeah, and let me just add that there is no bison expected in the midterm for FESCO. Very important.

Yes, that is true.

And maybe here to add one thing, Richard, I think in terms of the split you asked about adjuvant versus metastatic, the only number we once mentioned is it's a roughly 60-40 split over the entire franchise, but we have not specified whether there is a big deviation there. now between Pagetta or Fesco in the universe to late setting.

Splendid. Thanks all. Very kind.

Thank you. Okay. Then next one in row is Peter Fiddled.

Yeah, thanks, Verena. Pete Bedold, BNP Paribas. Two questions for Teresa, please. Teresa, I'm going to be sort of positive on one and perhaps a little bit negative and cynical on the other. Forgive me. But starting on a positive note, just on Fenerbrut, conventional wisdom out there is that the trial won't work. because you're seeing two competitive failures. Now, we've had hypotheses already put on the call as to why that may be, but the one that we get from KOLs is that, you know, basically T1 triglyceride reduction was just, you know, that efficacy weighing for your competitors. So can you remind me, sorry to be gnarly, can you just comment whether the suppression you've seen with phenobrutinib is sustained beyond the early cuts of data? And just whether you're cautiously optimistic or optimistically cautious about beating Revis in PPMS? So that's the sort of positive spin question. And then just being a little bit cynical on 007. In your pre-prepared mark, you talked about 30 times more potency. That sounds very much like the Novo pitch on Hem Libre. And to be fair, you've got to admit, you've been talking down the debauches of Minet versus Hem Libre over the last few years with those sort of arguments. I just want to better understand where 007 differentiation is coming from. Is it just that, or are there other things that you didn't mention in your pre-prepared marks? Thanks. Thanks.

Yeah, no, I think, so let's start with 007. I mean, I think fundamentally 007, yes, we believe that it is more potent, but it also has the recycling and sweeping technology built into it. And so, I mean, it is just fundamentally a next generation molecule. I don't know how much we've actually disclosed on the actual composition of that molecule. Bruno maybe can remind me. But it is just fundamentally a different molecule from Hemlibra. So this isn't just, I think, a little bit better than, I think this is a different than.

Right. I think, Pete, what you should read into the announcement is also if you made the comment, you know, that we would benchmark versus Hemlibra. So I think this was missing with competitor studies. And I think that's the ultimate test to really see whether we can establish a new standard of care.

Absolutely. I mean, I think we've been very clear that we believe that Hemlibra is the gold standard for treatment in hemophilia. And we are putting our money, as we always do, where our mouth is in these trials and running our next generation up against the current standard of care. And we love nothing more than beating ourselves. So we're excited for that possibility.

That's something we can discuss in more detail at the June 23rd meeting.

And then in terms of phenobrutinib, I mean, again, just to reiterate, I think we just fundamentally believe that we have a different molecule than the other BTKs that are out there. It is a different composition. It's a different structure. It's more potent. It's more selective. It's non-covalent. And we have, I think, more phase two data than most of our other competitors have had. And I'm just referencing here, we have longer term 48 week open label extension data that really shows that we're able to suppress disease activity. So the open label extensions here will go out to 96 weeks. We'll get that later this year. And so I think we we do believe that we have something different on our hands and the phase two data is playing that out. And again, when we get that 96 week open label extension data, hopefully that will be another piece of the puzzle. But, you know, this is really one area where I don't think you can compare our molecule to someone else's molecules because they just are different.

And Therese, just three parts, just PPMAS, I mean, are you cautiously optimistic or optimistically cautious you could be a crevice?

Uh, I think I'm cautiously optimistic. Um, and Okravis really is the standard of care for these patients. So if, if it beats Okravis, I think we really know we have something. Um, and that having been said, orals comprise 30% of the MS market. And so, you know, there is a very good spot for phenobrutinib, um, even if we don't see superiority to Oprevus. Understanding it's a slightly different population.

Thanks.

Okay. Then we move on. David Evans from Kepler. David.

Thanks very much, Bruno. So yes, two questions, please. One on petrolenside and one on brain shuttle. So on petrolenside, in your slides, you referred to looking for high quality weight loss. I was just wondering how convinced or confident are you that amylin can be differentiated on less muscle loss and more fat loss? How much of the rationale was that for you going into amylin? And then is that in practical terms, how amylin you think can really differentiate? And then on brain shuttle, well, we've seen amazing proof of concept data from Trontinumab so far, but where are you on that? on your brain shuttle CD20 in MS. Might we see data on that anytime soon? And are there any other brain shuttle projects in the way that we should know about? Thanks.

Yeah. So as you mentioned, we do have the brain shuttle anti-CD20 in very early R&D. I don't believe we've disclosed when that first data set will come out, but it's likely not to be for some time. That's relatively early stage. And we are certainly looking at the brain shuttle technology in other diseases where we believe crossing the blood lane barrier is going to make sense to do so. So clearly a technology that has really proven itself in AD, and we will be bringing forward other opportunities to look at that in other diseases. In terms of parenteral lymphoid, the amylin class does work fundamentally differently, obviously, than the incretins do. And so it is I think very likely that we could see a different kind of weight loss with patients on these drugs. And clearly the data are early days, but the clinical hypothesis is solid. And so I think we're very hopeful that this could be a fundamentally different kind of weight loss than what you saw with GLP-GLP1s.

Thanks very much. David, did this answer your questions or any follow-ups?

Yeah, perfect. Yeah. Thanks very much.

Okay. I think with that, we are at the end of today's call. I will hand back to Thomas for a final remark. Thomas, please.

Yeah. Thank you very much, Bruno. And thank you very much to this team. I really appreciate everything that you're doing every day. And to all of you also, thank you very much for your interest. I can just say we are implementing our strategy that we have rolled out last year. with a lot of discipline and also with a lot of speed, taking out costs out of the system where possible and shifting it into new areas, staying very cost disciplined. We are focusing on our pipeline and we also focusing on commercial execution. And I can only say we will deliver.