Roche Holding AG

Thank you very much. And hello and welcome. I'm looking forward to sharing the Q1 results together with my team with you today. In Q1, we had a very strong base business growth of 7% growth across both divisions. And overall group sales, including COVID, were at plus 2% constant exchange rates. The base business in both divisions, as said, was very strong, pharma at plus 7%, and diagnostics at plus 8%. The COVID-19 sales decreased by 0.7 billion, and with that, we have the COVID sales decline largely behind us, and we've had a LOE impact of 0.4 billion, and with that, both is very much in line with our guidance. This quarter, we have achieved a number of very important milestones. First, we received the U.S. approval for Xolia in food allergy as the first and only medicine in food allergy. And we already see an uptick in sales, and there's a lot of excitement in the medical community, and Teresa for sure will share more about that. Just last week, we received FDA approval for Alicenza in early stage in adjuvant setting for positive lung cancer. and very strong data here as well with a 76% reduction in the risk of recurrence of disease or death. We filed for U.S. accelerated approval for Invalicip in first line PIK3CA mutated HR-positive breast cancer, and we do expect approval later this year. In terms of key pharma readouts in Q1, we reported positive OS results for the Phase 3 Star Glow Study for column B in second line DLVCL. And we had very good data for the Phase 2 Cardia 2 results for Silvacerin in hypertension. And this was presented at ACC 2024, and Teresa will comment more on that. But this was on top of standard of care. In diagnostics, we've had U.S. regulatory approval for the first molecular screening assay for malaria for blood donations, so this is the first and only assay available to test malaria in blood donations. We've also received breakthrough device designation for the PTAL 217 ruling assay for Alzheimer's disease, and Matt will cover more of that as well. We have four remaining pivotal readouts this year, and importantly, we have 12 Phase III enabling readouts that will come this year, all of them addressing large opportunities, such as in Alzheimer's, Parkinson's, et cetera, and I will cover that in a later slide. Also, after discussing with regulatory agencies, we've made a decision to file the Phase III EMBARQ data for Elevitis in Degene Muscular Dystrophy. Finally, in diagnostics, we have a number of key launches ahead of us. This is a very important launch year for diagnostics, and Matt and the team will share more at the diagnostics investor event on May 22nd. As mentioned, Q1 base business sales growth was very strong, 7% for pharma, 8% for diagnostics, and 7% for the group. As mentioned, the headwinds from COVID are diminishing, this growth will shine through for the coming quarters. Here, you can see that our base business is really overcompensating both for the COVID-19 effect and the LOE effect. And you also see here that in first quarter, we still had a 8% effect on the currencies. Now, this is the base effect because The currency appreciation of the Swiss franc really happens after Q2 last year. And we should see, and Alan has a slide on that, a significant improvement here. Again, it's very hard to forecast currencies in a world with a lot of geopolitical tensions. But as it states today, in terms of currencies, we should see a significant improvement in the quarters to come. And as Alan will show the projection for the whole year at this stage is a minus 2% only. Now here you see the group sales over the last number of years. And you can see that in 23 and in 24, we've had high single digit growth in our base business. You see in the blue line, our total business, including COVID and for the coming quarters, you will see that the blue and the orange line will merge. and the blue line will go up to the orange line. Also, if you look on a divisional level, you can see that on a diagnostic side, we've delivered seven to 8% growth for quarter over quarter over the last number of years. And in Pharma, we really accelerated our business over the last year. So we do believe also that this will continue. On the pharma side, we continue to strengthen our pipeline, focusing on projects with high impact and with first-in-class and best-in-disease potential. In Q1, we terminated early-stage developments for five enemies based on clinical data, as well as prioritizing assets that deliver high value and high PTS. So if you look over the last three quarters, we've removed 20% of total enemies, really focusing our assets and our priorities and at the same time we thought in a number of assets from the outside with high PTS and high value in areas such as hypertension inflammatory bowel disease and also obesity and You can expect this kind of prioritization and partnering deals to continue over the course to come In addition to the pipeline prioritization and We're also working on opportunities to improve operational performance across the Rush Group. Now, let me highlight a couple of examples. Last month, we announced the divestment of our Vacaville biologics manufacturing facility in the US for $1.2 billion. And this divestment is a direct consequence of the ongoing efficiency gains for biologics manufacturing. We are also optimizing our geographical footprints here with facilities closer to the end markets, US, Europe, and Asia. In total, we now have 11 manufacturing sites with over 530,000 liters of biological manufacturing capacity online. And with that, we still have the largest manufacturing capacity in the industry. On this slide, you can see why we're doing this. On the x-axis, you see the time scale on the Y axis, the tighter that we get out of our cell lines. And what you can see here is that we have significant productivity improvements in our manufacturing. In total, we have about five times higher productivity. And with that, we don't need as many manufacturing sites as we've had in the past to produce even more products. In addition, we have a portfolio shift to smaller volumes because of higher potency enemies. So with that, we can optimize our manufacturing network going forward. In addition, we've also made other additional adjustments to improve operational performance. FMI moved from pharma to diagnostics, where we see a lot of opportunities in terms of leveraging synergies and also improving our operational cost position. We can combine the broadest portfolio that we have in the diagnostics industry to the benefit of FMI, and we can also leverage our next-generation sequencing capabilities across diagnostics and FMI. In addition, we've integrated point-of-care and diabetes care into one organization, into one business area called near-patient care. This allows us to take advantage of the fact that we have complementary patient and customer segments and also technologies. And we can then operate more impactfully as one organization and we can reinvest the savings into growth areas such as accelerating our CGM projects. Now moving to the future. We've launched 20 new medicines since the end of 2015. Now, 55% of our portfolio sales are from the new portfolio. With that, we have one of the youngest portfolios in the industry. You may wonder why it's only a 5% increase. You can see that Rona Brief dropped out. Without Rona Brief, the increase would be significantly higher and also a distance in Swiss francs. Just want to highlight that. We have two NME launches this year. One of them is Kravallamab. The other one is Navalisib. So we keep launching two NMEs per year. On this slide, what you can see is that the washout of COVID-19 is basically over. We have washed out 700 million in the first quarter alone. So it went out completely on the pharma side. and also on the diagnostic side, we'll continue to see some revenue, but basically the effect for the remaining of the year is in the range of only around 0.6 to 0.7% on the entire growth rate. So you can see the growth rate will no longer be materially affected when we go into the next quarters. And let me just say, we contributed significantly during this pandemic with sales almost 20 billion, and we washed out those sales without ever dropping into negative territory in terms of sales. Now, this will be the last time that I will show you this slide. On this slide, you will see what are the growth drivers beyond 2025. These are the enemies with significant potential, and also on the diagnostic side, these are only the launches of this year and next year where we have significant potential growth. And this slide, you will see it more often going forward, and we'll keep updating you on the different progresses that we've made in these enemies. And with these enemies, we really target the high disease burdens and areas with higher medical needs. So in this last quarter, we hosted a neurology IR call. where we highlighted new clinical data for phase one, phase two, which had been presented at the ADPD conference. There was new dose-finding data for Tritonimab, our anti-amyloid beta brain shuttle. Now, what you see is that within only a few months, the detection levels of the blocks, or the level of blocks are below detection level. So, you see a significant, very quick drop of plugs of these patients. And with all the data we know, we know that plug removal automatically has also a benefit. We also have shown the four-year open-label extension phase two data for PRASI in Parkinson's disease. We've also shown lately data in a conference from a phase two of a cardio two study of sebastarin And that's on top of standard of care where we see a significant benefit for these patients. Finally, on the diagnostic side, at the ATTD conference in March, we presented data on the AquaCheck SmartGuide CGM solution. So you can see we're nicely progressing on our pipeline, and I'll continue to give you more information on this. Now, let me just say that we still see very strong base business growth in our both divisions. COVID-19 sales decline is largely over. The rest of the year will not have any material effects. LOE is very much in line with our expectations. With that, we confirm our guidance in terms of mid-single digital growth. Also here on this slide, on the core EPS, we confirm our guidance as well as our intention to further increase the dividend interest ranks. With that, thank you very much from my side, and I hand over to Ella.

Yeah, thanks, Thomas. And thanks to everybody who has contributed, I think, to this great result in Q1. And we have made, I think, really significant progress. So let me dive into it right away. Another sales bridge was the same message here. I think when you look at the former side with the plus 2%, I think you see good growth in the U.S., Europe, international. Teresa will talk about it. You see a dip in Japan with Shugai, and this is really Rona Brief we had last year in constant rates, Rona Brief sales of 519 million. This is all here in Swiss francs in constant rates. So the other piece is coming from a price cut in Japan. So I think Theresa will shed some more light on this. Then the Dyer division, also here with the plus 2%, but also here is 194 million of sales losses due to the loss of COVID sales embedded. Without that, I think we know Pharma would have grown at 7%. Dyer would have grown at 8%. And when you look at the group in CR, plus 2% without the COVID sales impact, we would have been grown at 7%. You see the impact from currencies. I will come back to that later. Thomas made a couple of comments, and I will add a little bit more information to that one. And that leads you then to the development in Swiss francs at a minus 6%. So still quite a significant impact. And let me go back to the point about manufacturing in pharma and the sale of Vacaville. And I think Thomas has outlined the rationale why we have done that. But I think there's another element to it, and let me show you this. On the left-hand side, what you see on the slide is the sales development that we had between 2018 and 2023 in pharma. And you see cumulatively a plus 20%, which basically also highlights how well we have done given the patent cliff that we have mastered. On the other side, you see what we have lost in Avastin, Herceptin, and Rituxan, a minus 72%. So I think really the plus 20% is the point. When you then go to the right-hand side, you see the volume increase in that timeframe, which has been a plus 68%, so a significant increase on the volume side. And then I think you see the testimony to everything Thomas has said. I think certainly we have benefited from better efficiency in the production itself, but also, let's say, we came up with very good cost containment in our manufacturing network. And therefore, we could keep the cost of sales stable, so the cost of goods sold, including the period cost. So quite an achievement here. Let me add to this. It was not so simple as it looks like because we had to include new modalities as well. So I think quite some complexity here, very well mastered. By the way, certainly I think it fuels our ambition to defend the margin moving forward. Good. Exchange rates, exchange rates, exchange rates, exchange rates. Let me start on the left-hand side. Once again, the group growth in constant rates was plus 1.6%. That's the plus 2% that you've seen all the time. Right-hand side, you see the minus 6% when you look really at actuals in Swiss francs. And then you see the impacts. And the Swiss franc has strengthened, admittedly, against basically all the currencies that we're dealing with. It has really significantly strengthened against the RIMIMBI. That's an APAC, what you see. Do you see the U.S. dollar? And still, I can just mention it again and again. We have roughly 46% of our sales in U.S. dollar. So that's for us the dominating currency. And then you see Japan, where we got another hit. That certainly, I think, underlines where the Swiss franc is going. There is some hope at the horizon, and I will come to that. And here it is. Let me go through what Thomas has mentioned already. I think on the left-hand side, you see that these curves, that means the average year-to-date 2024 and the average year-to-date 2023, they're converging. for the U.S. dollar as well as for the euro. And that means the comparator gets better. So that's one element, which certainly helps us. You see on the right-hand side the model we're always running. And let me emphasize the fact that we keep all the currency rates at the end of March stable and then project what – the currency impact would be at the given timelines on this slide here. This is certainly highly speculative. I think what fuels our expectations that the currency impact might look a little bit better is certainly the fact that the comparative last year looks a little bit better. Everything else remains to be seen. But let's assume for a second our model is true and the currency rates stay where they They have been at the end of March. What would that mean for half year? You see a minus 5 percentage points on sales, a minus 7 percentage points on cooperating profit, and a minus 8 percentage points on core EPS. You see already on the sales, when you look really at the impact in the quarter itself, that the impact comes down quite significantly. And then when you look at full year, you see a minus 2 percentage points for sales, a minus 4 percentage points for all cooperating profit. and a minus 5 percentage point for core EPS. And you see really in Q4 and Q3, we would even see a positive impact given our assumption. As said, highly speculative, but I think fueled a bit by the comparator as well. Good. I think Thomas confirmed the outlook. Let me say, excluding the impact from the resolution of the tax disputes, the number has been in constant rates, 774 million Swiss francs, just to get that straight again. A little bit from a formal point of view, from reporting, we have a new customer area structure. In diagnostics, it affects pharma as well, as you can see. So what you see is we brought FMI into the diagnostics division, and in the diagnostics division, we brought it together with molecular lab. So in the diagnostics division, moving forward, you see my molecular lab, and that includes really the former molecular lab and FMI. And then you see really what happened on the diabetes care side. We brought point of care together with diabetes care, and this is now the organization new patients care and we will report and we'll certainly adjust the statements here also for previous year once we go through the upcoming quarters. Another reminder, we had that slide at the event. The restatements will be applied in 2024 as well. And this is nothing else that we move FMI from pharma to diagnostics. I think certainly no impact for the group, but certainly impacts for the divisions as well. And you see really the impact here as we had that slide already mentioned. Good. Upcoming IR events. I think while we're all excited about the Diagnostics Day, and I can assure you Matt is working on it and his team quite a bit, so that will be exciting. And then we have ASCO where we want to look really at the malignant hematology portfolio but also at solid tumors, so really a little bit of a comprehensive view on what we're doing in oncology. Ophthalmology will be exciting in Stockholm. We have a couple of new things here. And then the Pharma Day, big event because there will be an update on the group strategy as well as on the pharma strategy. And I think that's the perfect segue to hand over to Teresa.

Thank you, Tom Salen. As both of you mentioned, in Q1, pharma sales reached 10.9 billion Swiss francs, growing by 2% at constant exchange rates, or 7%, excluding Ronapreve. All regions, excluding Japan, delivered strong growth. Sales in Japan were impacted by a base effect of 0.6 billion Swiss francs in Ronapreve sales, which occurred in Q1 of 2023, excluding Ronapreve. I think, as Alan mentioned, Japan declined at 6% in constant exchange rates, and that is primarily due to mandatory price cuts. As Thomas mentioned, there is no further wrong or pre-impact expected for pharma for the remainder of the year, so the COVID-19 effect is officially behind us. Overall, pharma volumes were up by 9%, and the price-mix impact was a negative 8%. Our young portfolio continues to deliver strong growth, led by our key brands, Babismo, Fezgo, Okavis, Polivi, and Hemlibra. Combined, these five products added a billion in additional sales in Q1 alone. So BISMO continues its excellent growth momentum, which is consistently beating market expectations, and Fesco has now become our second-strongest performer, thanks to its outstanding growth. Moving on to oncology, and starting with the solid tumor franchise, where total sales increased by 1% in Q1 to 3.9 billion Swiss francs. One key highlight here is certainly the completed, accelerated U.S. filing of inovalisib, as Thomas mentioned, in first-line PI3 kinase hormone-receptive positive breast cancer, where we reported a progression-free survival hazard ratio of 0.43 at San Antonio last December. We would now expect accelerated approval for this indication toward the end of the year, and EU filing is also expected later this year. I mentioned on the previous slide the strong momentum for FESGO, and you can see here that this is evident in the conversion rate, which has reached 41%. U.S. conversion is reaching 25%, which is just extraordinary when you think about the amount of patients who are now benefiting from this device. And hot off the presses, just last week on Friday, Alicenza achieved U.S. approval in adjuvant ALK-positive non-small cell lung cancer based on the very strong Phase III ALENA results that showed a disease-free survival hazard ratio of an outstanding 0.24, which unlocks an additional growth opportunity for ALENA. In terms of outlook, the Dicentric subcut PDUFA was set for the 15th of September, and we are expecting the Allicenza Alina EU approval in Q2. As Alan just mentioned, we will host an IR event at ASCO. That event will cover both our solid tumor and hematology TAs, and we'll focus in on our late-stage pipelines. So speaking of hematology, you can see that our hematology franchise achieved a strong Q1 growth of 12%, reaching $1.8 billion in sales. in Q1. Q1 hemp lever sales grew by 8%, which is driven by the EU, which had 17% growth in constant exchange rates, and international, which had a staggering 51% growth in constant exchange rates. U.S. sales were a bit down, about 1%, but that really primarily was driven by a buying pattern and a little bit of softer demand. Growth of the hematology franchise is also driven by the strong continued uptake of Polivi and first-line DLBCL in the U.S. and the EU5, with U.S. patient shares climbing to 23%. We're well-positioned to move into standard of care here. One more piece of positive news to cover is Columbia, which Thomas mentioned on his first slide. It's currently launched in third-line plus DLBCL, but we recently announced that the StarGlo Phase III and second-line DLBCL met its primary endpoint of overall survival. Those results will be submitted to global healthcare authorities and have been submitted for presentation at EHA as a late-breaking abstract. Of note, we also achieved Japan and China approval for Krivalumab and PNH, and those U.S. and EU approvals are expected later in the year. So on this slide, let me highlight a little bit further the additional investments that we're making in Hemlibra, particularly with regards to new convenience options to be launched later this year and into 2025. I think we all know that Hemlibra has established itself as a global standard of care in hemophilia A, with U.S. and EU market shares now exceeding 40%. Hemlibra's strong efficacy and safety profile across clinical trials has been confirmed by a substantial and continuously growing base of real-world evidence. We now have over 100 publications that really underscore the safety and efficacy of Hemlibra. In the real-world data that we see, about 80% of patients have zero bleeds, They have a very favorable safety profile. There is no risk of inhibitor development, and it's quite easy to use with more than 60% of patients already on every other week or every month dosing. This, by the way, includes pediatric patients who are now able to administer down to the age of seven with appropriate training. As a lifelong condition, we do know that convenience is highly important to hemophilia A patients. And today, 90% of our HemLabor patients are satisfied with our current convenience options. However, we continue to invest to find ways to offer additional convenience to those patients. And again, more options will be available later this year and in 2025. We just launched two new vial options and are introducing a new administration kit shortly. And in addition, we are developing additional administration options. So please stay tuned for those announcements at ISTH in June of this year. Moving on to neurology. Our neurology franchise achieved 2.2 billion Swiss francs in sales in Q1, representing a very strong 9% growth at constant exchange rates. Okravis grew strongly with 8% driven by all regions. I'm also very pleased to share with you that the U.S. PDUFA date for the Okravis every six months subcut has been set for the 12th of September. And RISD has now become the global leader for SMA and grew strongly by 7% in Q1, driven by the U.S. EU in Japan, which overcompensated for a 29% decline in international, which was solely caused by a delayed tender. We are also happy to announce that the EU filing of LLVDs and DMD, as Thomas mentioned, will begin this year, and we're looking forward to bringing this highly impactful therapy to EU patients. I am very pleased to report that the first ex-U.S. patient has already received LLVDs and UAE. And additional treatment starts are expected in the coming weeks. So very exciting for these boys and their families. In Q1, we also presented additional early trontinumab dose finding at ADPD. Again, Thomas mentioned this as well, with a 3.6 milligram dose, confirming the previously seen safety profile and rapid amyloid plaque clearance. There are multiple neurology news flow items for 2024 to watch out for, including the updated data for trontium, Alzheimer's disease, and prosy in PDE. The combination study of RISD with GIMP329 or antilatin, myostatin, and SMA is expected to have interim data in Q4. GIMP329, as you know, is also being explored in the context of obesity. And to this end, we are planning to initiate a phase one in healthy volunteers with obesity, and that FPI should occur in Q2. So switching gears and moving from neurology to immunology, total Q1 sales. And in the analogy, we're 1.4 billion Swiss francs. That represents a 3% decline in constant exchange rates. It's primarily driven by LOE impacts, particularly for metharituxin. Xolair clearly stands out here with very strong 10% growth at constant exchange rates. There's more good news on the horizon with Xolair for food allergy. We'll talk a little bit about that in a moment. But before we get there, let me mention one key upcoming news flow piece, and that is that the GAZAIBA Phase III study in lupus nephritis is expected towards the end of the year. And those data could be very, very promising for patients with this very severe form of lupus. So moving on to Zoller and food allergies. So this is the first medicine to reduce allergic reactions to multiple foods. And I think the results here, frankly, really speak for themselves. A significantly higher share of patients could consume the threshold dose of peanut, milk, egg, or cashew when treated with Zoller versus placebo. I think we truly believe that Zoller has the opportunity to redefine the way that food allergies are managed. The U.S. launch is just kicking off, and we can already see a very high excitement amongst patients and doctors, and we look forward to sharing more with you over the coming quarters. Our ophthalmology franchise reached $0.9 billion sales in Q1 with an impressive growth of 58% at constant exchange rates. Bovizmo remains our key driver, now reaching U.S. market shares of 25% in AMD and 18% in DME. That's up three percentage points versus the previous quarter. The U.S. RVO launch is showing strong momentum. We've already achieved 8% market share after only four months. Overall, the BISMO is continually increasing penetration into new patients, and I think just underscoring this, the expansion into new market segments is really exemplified by the fact that 15% of accounts not using the BISMO or using vobizomib have not used Lucentis previously. So you can really see that vobizomib was not only moving up earlier in the treatment paradigm, but it is moving in to physicians that have not had historic Lucentis experience. We have two key Q1 updates for vobizomib that I will cover in separate slides in just a moment. But before I do, let's cover quickly the outlook for 2024. So a couple important things to mention here. So SUSVMO, the U.S. commercial relaunch for SUSVMO and AMD is set for Q3 of this year, and the filing for DME and diabetic retinopathy is planned for the second half. And there are two Phase II readouts in second half for NMEs, which, if positive, could lead to Phase III initiations. That's the MICIBART, which is our IL-6 and DME, and then the ASO Factor B in geographic atrophy. Before I move on to the Vabizmo deep dive slides, let me also just reiterate that we do have another IR event at ASRS on July 23rd, and there we will present some long-term follow-up data for Vabizmo. So this slide looks at a network meta-analysis and a systemic literature review that was recently performed that shows Vabizmo improved anatomical results versus a Flivercept 8-milligram. These types of tools are validated to make comparisons across clinical trials, and this particular one by Lange et al. analyzed seven clinical trials, including pivotal trials of the BISMO, a Flibercept 2 milligram and a Flibercept 8 milligram, and AMD and DME. The combined studies cover more than 5,000 patients, and the key outcome of the analysis, as you can see on the right, is that the BISMO achieved greater CST reduction in both AMD and DME compared to a Flibercept high dose. and 2MIG during the loading phase at 12 weeks. This analysis adds to the growing body of evidence that Vobizmo's unique MOA leads to the superior anatomical outcomes and the drying of eyes. Supporting Vobizmo is the preferred choice for first-line treatment in AMD and DME. Speaking of that growing body of evidence, let me briefly highlight the rapidly growing body of real-world evidence for Vobizmo. Currently, more than 50,000 Vibismo patients have been analyzed across more than 10 real-world data publications. The combined insights from these real-world data studies clearly substantiate Vibismo's real-world treatment benefit. ARVO is taking place in just a few days, and you'll be able to see 36 abstracts covering real-world data on Vibismo. We continue to see that real-world clinical evidence is absolutely mirroring what we saw in our clinical trials. And, again, well-positioning Babizmo as standard of care. Moving on, I'm happy to highlight the positive phase 2 cardio 2 data results for Zolbiceron and hypertension. A single sub-Q dose of Zolbiceron showed clinically significant reduction in 24-hour systolic blood pressure at three months when added to three different standard of care regimens. You can see in the graph that this positive effect was seen in both mean ambulatory and office blood pressures. Furthermore, the positive effect on systolic blood pressure was persistent at six months, including at the maximum dose of omasartan. The results support the potential of twice-yearly dosing and the safety and tolerability of the profile continues to be very encouraging. And I'm proud to say that we recently just achieved FPI for our third Phase II study, CARDIA-3. The patient population here differs from CARDIA-2 in that the CARDIA-3 patients will be on two to four standards of care and are patients that are at a particularly high risk of CV events. The CARDIA-3 results will inform the upcoming Phase 3 cardiovascular trial study, which we hope to be able to share with you later this year. And last but not least, let's have a look at our 2024 key news flow. You can see we've added quite a few green check marks in Q1 for positive regulatory and clinical results, and I've covered the majority of them in previous slides. But let me highlight one additional piece of upcoming news flow that we are excited about. We expect to have phase one data for CT388. That's our lead asset in obesity from Carmont at half year in 2024 and aimed to present at USAT in September. This new data will cover cohorts 11 and 12, which is in patients without type 2 diabetes. And I'm looking forward to sharing this additional CT388 data as well as upcoming readouts on the other two assets, CT868 and the oral CT996 later this year. And with that, I will let Matt guide you through our diagnostics results.

Thank you, Teresa. All right. Good morning. Good afternoon, everyone. It's my pleasure to present the Q1 results for Roche Diagnostics. So sales of 3.47 billion Swiss francs, the diagnostics division grew at 2% or 0.1 billion Swiss francs at constant exchange rate compared with Q1 of 2023. This growth was impacted by the washout of COVID-19 sales and total diagnostics revenue. Now, looking forward, we do not expect substantial COVID-19 revenue in 2024, and I would note that 2024 is the last year we expect meaningful impact of COVID-19 on year-over-year sales performance. Focusing on our base business sales, we see strong momentum with 8% growth for Q1 2024, excluding COVID-19. For full year 2024, we have guided for mid-to-high single-digit base business growth, and I would continue to reinforce our confidence in the performance of our base business. So with that, I'd like to take you through the sales by product category. So first, sales in our core lab business increased by 9%, with very strong momentum driven by immunodiagnostics at plus 10% and clinical chemistry at plus 8%. Molecular diagnostics had a decline of minus 3%, and this was due to lower COVID-19 PCR lab-based testing sales. However, excluding the COVID-19 test, Molecular Lab is growing at plus 6%. This is driven by strong growth in our blood screening business at plus 11% and in our virology-based business at plus 9%. Our new customer area near patient care, which you heard about from Alan and Thomas, had a decline of minus 20%. And this is mainly due to lower COVID-19 rapid antigen, which we had a large government order in Q1 last year, and decline of our blood glucose monitoring business due to the shift in the market to continuous glucose monitoring. This decline was partially offset by continued growth of our respiratory point-of-care molecular business, which grew 4%. and excluded COVID-19 testing, the decline of near-patient care was minus 2%. Sales in our pathology lab grew strongly at plus 19%, mainly driven by our advanced staining business and companion diagnostics. So looking across all regions, you still see the impact of COVID-19 on our regional sales. However, base business was very strong. Excluding the COVID-19 business, we see North America growing at plus 12%. In EMEA, the base business excluding COVID-19 grew at plus 4%. In APAC business, base business, excuse me, excluding COVID-19 grew at plus 4%. And in Latin America, sales excluding COVID-19 grew at plus 16%. So now I'd like to shift gears and talk a little bit about the growth of our installed base since Q1 2023. And overall, our installed base is the foundation for our future growth, and we saw very good development in the last year. Our overall serum work area platforms grew at plus 3%, but the main drivers were our new systems, the Cobos Pro and Pure, which grew at 77%. And this is represented of our overall performance in core lab, where we had the highest number of serum work area industry placements in our history. In molecular lab, the COBOS 5800, 6800, and 8800, which are automated systems for molecular diagnostics, grew at plus 20%. This was driven by sales of our low to mid-throughput platform, the COBOS 5800, and I would point out that we substantially grew our install base for automated molecular platforms, even coming off the end of the COVID-19 pandemic. I would also like to point out the good news, or excuse me, the good growth of COBOS LEAD, our molecular point-of-care system, which also grew at 6% in 2023, again, through the end of the COVID-19 pandemic. And our pathology lab, our main workhorse system, which is the Benchmark Ultra and the new Benchmark Ultra Plus grew at 10%, highlighting our future growth potential in advanced staining. And our HE600 system for primary staining grew at plus 12%. And I would also note that our digital pathology business is growing strongly as evidenced by the 29% growth of our DP200 and 600 installed base. This business will continue to grow and remain highly complementary to our overall pathology lab business. So now I would like to change gears again and talk about one of our upcoming launches that I'm very excited about, the AccuCheck Smart Guide, which represents our first entry into the continuous glucose monitoring, or CGM, market. This is a set of solutions comprising a real-time CGM sensor as well as digital tools to support and guide clinical decision-making, both for people with diabetes as well as physicians. We will augment the sensor with clinical algorithms to aid in a prospective two-hour glucose prediction as well as a nighttime hypoglycemic prediction. This addresses one of the key unmet medical needs of diabetics, which is the concern around hypoglycemic events during sleep. Additionally, we will provide software tools that enable sharing of patient data with physicians to enable better clinical decision-making and enhance their ability to provide clinical guidance to people living with diabetes. Our sensor is designed to be applied in a single one-step application with a sensor life of 14 days. As you heard, we publicly released the data generated for our regulatory submission at the ATTD conference in Florence in March of 2024. And we were really pleased with the data we released and also the response by physicians and key opinion leaders in attendance. So we're very much looking forward to the launch of this solution later this year. And with that, I will start to have an overview of our developments in infectious disease, which is another key topic for Roche Diagnostics, and specifically our focus on blood donor screening and highlight the launch of our CoBOS malaria solution. Malaria infection... is spread mainly via mosquitoes in regions with endemic presence of this pathogen. It can also be transmitted through blood transfusion, where it can cause serious complications and is potentially fatal. Screening with current ELISA-based tests may provide inconsistent sensitivity or specificity. Screening donors with a molecular test will provide higher certainty around the presence of this dangerous pathogen to better protect the world's blood supply. The CoBOS malaria test is designed to detect the five major species that cause human malaria infection to provide broad coverage and greater certainty of detection. The proprietary Roche tube allows for direct draw and usage on Roche fully automated CoBOS X800 systems for increased workflow efficiency. This assay is currently approved by the U.S. FDA and is under review in the EU for CE-IBDR approval. And so now turning to another area that's a key focus for the Roche group, which is neurology, I'd like to turn to our key developments in the diagnosis of Alzheimer's disease. So I'd like to walk you through our solutions by moving on the slide from left to right. We currently have our aid and diagnosis solutions available on the market. These are cerebral spinal fluid-based tests, which are both CEIBD and FDA-approved. These tests are used for aid in diagnosis and show concordance with amyloid PET for confirmatory diagnosis. While these tests represent an important step forward for the diagnosis of Alzheimer's disease, we recognize that it's important to continue to drive access to testing, and that is why the development of blood-based biomarkers is so important. If you move to the center box, what you'll see is we are currently developing our Alexis Amyloid Plasma Panel, which is a blood-based rule-out test for Alzheimer's, consisting of the biomarkers PTAL181 and APOE4. I would note that we are clinically validating these biomarkers in a real-world patient population in primary care. This test will enable a rule-out of Alzheimer's disease from a blood test, which is an important step forward. However, with a positive test result, confirmatory testing is still required. Now, consequently, we're developing a blood-based rule-in test for Alzheimer's, which you can see on the far right. This will be a critical part of improving the patient journey. It will consist of the PTAL 217 biomarker, which we are very happy to say just received breakthrough device designation from the FDA. This biomarker is able to provide a rule-in result and hence reduce the number of patients that need a final confirmatory diagnosis, which has the potential to really reduce the burden on healthcare systems worldwide. I would note that we are also clinically validating this biomarker in a real-world patient population, and I look forward to discussing our progress with you in future calls. I would really highlight, with all these solutions together, we're building a comprehensive portfolio to enable the diagnosis of Alzheimer's disease. So now I come to our key launches for 2024. As you heard, this is a big year for launches for diagnostics. In Q1, we achieved one of our key launches for the year, which was the malaria test, as we discussed. And I look forward to sharing the rest of the progress as we have subsequent calls in coming quarters. Now, lastly, as you heard from Alan, I would very much like to invite you to our Diagnostics Investor Day on May 22nd. It will be a hybrid event taking place in London and also virtually. With our leadership team, we have put together a very exciting agenda for you, and I'm looking forward to seeing you in person in London on May 22nd. You can register for this event on the Roche IR website. And with that, I'd like to pass it back to Thomas.

Thank you very much, Tim. And with that, we look forward to your questions.

So we have 45 minutes now for Q&A. And the first questions come from Richard Foster from JP Morgan. Richard, please.

Thanks for taking my questions. Two, please. Firstly, on to Century. Could you give us an idea of how much your sales are now of adjuvant lung and more about the impact you see from Contruda going forward? And a linked question, just thinking about small cell lung cancer. Astra has seen some positive data here. as well in limited stage small cell lung cancer. So how competitive is Astra there and how are they impacting your position in small cell lung cancer? And then second question, just on Vibismo, there's been a little bit of discussion about IOI in some of the medical journals around Vibismo. Could you talk about how that's being received by the market and whether you need to enhance the manufacturing process to clear that out or whether it's nothing at all? Thanks very much.

Great. Thank you. So, I'll start with Vibizmo. I mean, I think that the safety of Vibizmo is very well established, and I don't think there's anything that we are seeing that leads us to believe that changes are necessary at this point, because with any of our drugs, we monitor that closely, and I think at this point, we feel extremely confident in Vibizmo. When it comes to Ticentric, I mean, I think similar to sort of what we signaled in our last call, The sales for Decentric sort of globally will begin to stabilize as we see peak being reached in some of our key indications and competition heating up in other places. We will continue to see growth in other parts of the world that maybe offset more competitive impact in the U.S. I think adjuvant lung is clearly one of those places where we are seeing that competitive impact. As far as small cell goes, we continue to have a leadership position there, and I think we would anticipate holding on to that position for the foreseeable future.

Richard, did we answer all your questions?

Sorry, it muted again. Apologies. That's great. Thank you very much.

And we move on. And next one would be Emmanuel Papadakis from Deutsche Bank.

Thank you for taking the questions. Maybe a couple on Hemlibra, please. You hopefully mentioned over 60% on Q2 and Q4 week. If you'd give us a split, that would be very helpful. And then just talk a little bit about commercial momentum in the U.S. It seems to have stalled somewhat. In fact, you're actually down Q1 in the U.S. So talk to us a little bit about competitor impact, particularly interested in the impact from F&Z up to 12. And then the second question was on device improvements. It wasn't entirely clear. Are you referring to the two new vials and administration kit, or is there actually something else we're going to hear about, for example, a PEN? And if not, is a PEN... anywhere in development, and is there any potential to reduce the injection volume? I'm asking because we already have potential monthly competitors reading out with a low-volume pen device relatively shortly, so it would be interesting to hear your perspectives on the potential competitive risk that may represent. Thank you.

Sure. So while we have, I think we've disclosed that we have 60% of patients are already on that every other week or every four weeks. I don't think we've broken it down more finely than that, but I think that's still obviously the majority of patients In terms of competitive impact, and in particular the performance of the U.S., so the U.S. was down 1% in Q1. The majority of that was actually just a buying pattern issue with one of our larger specialty pharmacies. And that really was the biggest bolus. And I think we're not seeing anything that leads us to believe that momentum in the U.S. or that growth in the U.S. will stall significantly. We still expect to see single-digit growth in the U.S. this year for Hemlibra. In terms of the device improvements, so you are right, we have launched two additional vial configurations. We have a new administration kit coming later this year. And then in terms of additional convenience options, I would invite you to attend ISTH and learn more about what we have planned.

Emmanuel, did this answer all your questions or follow-on question?

I'll wait with bated breath until ISTH, so yes, thank you.

Yeah, unfortunately you have to. Okay, then we move on. Next one in the row would be Simon Baker from Redburn. Simon.

Thank you, Bruno. Thank you for taking my questions, everyone. Two, if I may, please. Firstly, going back, Thomas, to slide 11, the rationalization of the pipeline. You had a 20% growth reduction in NMEs, but you've added a few as well. So the actual net change is quite small. So I just wonder if you could give us an idea of what's changed in terms of the criteria for keeping products in the pipeline, adding them and removing them, because clearly something's changed there. And then secondly, on Ocrevus subcutaneous, thank you for giving us the PDUFA date there. I just wonder if you could give us an idea of how we should be thinking about the uptake of that and the potential both US and ex-US, please. Thanks so much.

Yeah, so let me answer the first question. You're right, the 20% reduction is gross. So net, it's not the same amount because we've also added things to partnering in M&A. Basically, we set a number of criteria in R&D, what molecule needs to have in terms of criteria in order to pass our bar to be in our portfolio. One of the things is that 80% of our pipeline needs to be either best in class or first in class or best in disease. But there are a number of criteria, value being one criteria, patient population, scientific evidence, et cetera. And based on that, we have prioritized our portfolio, meaning also that we put more effort and more speed behind molecules like trontinumab that have very good data, very high promise data. And so we try to enhance and accelerate our portfolios with that. You'll see that ongoing for the next one or two quarters, and then I think we'll be in a much more stable state, and we've really shaped our portfolio in the direction that we wanted to do.

Great. And when it comes to uptake on Ocrevus subcut, I would expect strong uptake on Ocrevus subcut. I mean, I think when you look at the clinical profile of Ocrevus, it continues to be the standard of care in MS treatment. The long-term safety and efficacy data are unparalleled. And so with the convenience of an every six-month, 10-minute, I would expect that we will both open up a significant amount of new patients in the U.S. as well as in the U. I mean, I think we've said repeatedly that we believe Ocrevus subcut is in and of itself a blockbuster opportunity, and I would see no reason to change that. I mean, I think it's likely to be upwards of the $2 billion range, actually. Okay.

Simon, any follow-on questions?

No, that's all very clear. Thank you very much.

Okay. And we move on. Next one would go to Matthew Weston from UBS.

Thank you very much. Two questions, if I can, please. The first on Hemlibra. Many of us on the call are looking forward to data from a competitor factor VIII pneumatic bispecific in the coming quarters. Teresa, I'd just be very interested as to how you see the market dynamics today. If there is another bispecific enters, do you think there is still plenty of patients who haven't yet moved from factor, and therefore a new entrant could drive incremental uptake in in the bispecific market, if I can put it that way, or do you think inevitably it becomes a market share fight and hence why we're all looking forward to your incremental information at ISTH? I'd love to understand how much of the market you still think is yet to switch that has the potential to switch. And then the second question on Inavalisib, you called it out as a key launch for 2024. PICRE was historically a very challenging medicine for patients never really met investors' expectations. You'll be launching in Avalisib while other competitors are launching TruCap. I'd love to understand how you think of the uptake of that medicine as to whether you think there's a very strong switch opportunity from PICRE or whether or not you think this really is about slow and steadily building the market as clinicians start to look for PI3K patients more.

Yeah, I mean, I think there's a combination of both things going on there within Abilisib, to be honest. I mean, these data, as you saw, were just stunning. I mean, the initial trial population showed an incredibly impressive response and a very good safety profile. And we continue to generate evidence in combinations other than just with Palbo. So I would expect that in breast cancer alone, this could be a $2 billion opportunity or $2 billion opportunity over time. So I think we are just really confident in what we've seen with our initial data and would think that we would both see naive patients coming on as well as patients who have been previously treated with a drug in this space. And certainly additional testing will help. As soon as people are looking for it, they will find more of these patients. In terms of the sort of dynamics of the overall hemophilia market, I mean, I think there are still a large number of patients who remain on factor for various reasons. We certainly believe that Hem Libra is very appropriate for a large number of those sort of mild and moderate patients who, for whatever reason, choose to remain on factor. And the profile of Hem Libra, you know, 80% of patients not experiencing bleeds, the well-characterized safety profile, the zero risk of inhibitors, I mean, these are all things that make hemolibri, I think, if you're going to switch to a prophylactic treatment, it will continue, I believe, to be the standard of care and the treatment of choice for these patients. And, yeah, I mean, I think there are still more patients on factor who could benefit from these prophylactic treatments. And hopefully similar to what we saw with anti-CD20s and MS, it just means that more patients will move to high-efficacy therapies. And certainly I think that positions hemolibra extremely well.

And maybe just let me add on enamelisib. The reason why enamelisib is so well tolerated is because it's so selective for the mutated version of PIK3CA. And with that, we believe not only will patients switch, and this will be the predominantly used medicine, but it will actually expand the market. Because one of the key problems with medicines in this space is that it's not so well tolerated. So we see both opportunities.

And I think it's also fair to say the competitor that you mentioned, we actually haven't seen their data yet. So we should probably wait to see their data before we start assigning the market share because time labor is going to be hard to unseat.

Matthew, any additional questions? Okay. Then we move on, and the next one in the row would be Louisa from Bonebook. Louisa.

Thank you very much for taking my questions. On Columbia, could you say any more about the potential for the Starglow data and how that might impact the sales and any other comments that you have on the launch? I know the sales are still small now, but obviously in the later lines. So just an update on Columbia. And going back to the pipeline prioritization and reshaping, As you get to the end of this, and obviously we've seen some deals in recent months, but were there any other notable areas or modalities missing as you reviewed the pipeline? Thank you.

Thomas, do you want to start with pipeline, and then I can come back on Columbia?

Sure, I can do that. We are constantly looking at opportunities, both for partnering and acquisitions. You know, I think when you look at our slides showing where our focus areas in terms of disease areas are, you can imagine that these are the five disease areas that we're really focusing on. And, yeah, we are open to do more deals. But what has to happen is that the science convinces us and also that the financials convince us. And then we'll continue to also bring in assets. We're looking at assets that have – you know, data to prove that it's a high PTS opportunity and also where we believe it's a high value opportunity.

And in terms of Columbia, Lisa, you're absolutely right. The initial indications for both Columbia and Lunsumio in third line, those represent a relatively small opportunity, a couple hundred million combined. When you get into second line, though, you are looking probably upwards of a $200 billion opportunity overall. So we are really looking at Starglow and then subsequently at the Sunmo data, which will become later this year, as very significant possibilities for market share expansion for both Columbia and Lunsumio. And then obviously, when we start getting into the first lines, those opportunities get even larger.

So 2 billion opportunity second line and obviously even bigger opportunity if you go to the first line.

Luisa, any additional questions?

That's great. Thanks, Bruno.

And the next one would be Sachin from Bank of America.

Hi there, thanks for my question. This is Sachin Jain, Bank of America. A couple, please. Firstly, on the VC asset, thank you for the color on the data coming ESD, but one of you just provided just a bit of clarification on those cohorts 11 and 12 you mentioned. What titration have you used in those? The reason for the question is should we see better safety in this data than the data at ESD last year where I think it was 30% vomiting? Could you also confirm it would be the 12 to 24 week data we see? And where are you with just finalizing your titration arrangement with this asset? Secondly, I guess a question for Thomas based on Alan's comments. The September R&D day has been framed as a big strategy update in both Group and Pharma. The annual event is usually more educational. So just want to check, you know, if we empty any big fireworks we should potentially see. And then my last question, just a quick check. For BISMO, obviously, you've referenced continues to beat consensus expectations. Any change in trajectory for that asset since the high-dose J-code competitor earlier? Sorry. Thank you.

Yeah. So, in terms of Paramount, I'm actually not sure that we're disclosing our dose titration at this time. So, more to come when those data are released later this year. I think we still have every internal confidence that this is a best in disease asset and one that will demonstrate safety and efficacy that is very much in keeping with sort of the second generation of obesity assets. you know, sort of in that Viking-like range. I mean, I think this is what we would be expecting out of CT388 when we see that data. And, unfortunately, we don't have too much longer to wait. In terms of the BISMO and impact from the J-code for high dose, no, actually, we haven't seen any impact of that at this time.

Yeah, and to your question around the FAMA day, We are working very hard in the organization to really set us up well in terms of pipeline, also in terms of operational performance. So there are a lot of things ongoing right now in the organization and also working on clarity on strategy, both for pharma and for the group. And there's a lot of things that are rolling out in the organization. But as you understand, we want to roll it out in the organization first before we inform more on the public side. And that will then happen in September. So there's a lot going on. September will be kind of more the external communications.

And maybe a subject here to add from my side on the Karmot assets. I think we have been saying that we will have data for all three assets in the clinic. And CT388, that's where we will talk about cohort 11 and 12 at EADS. But there is a second conference where we could have additional data presented. And yes, to confirm, we have the 12 and the 24-week data in-house in the second half. So we'll see at what occasion we will share them.

Did we answer all your questions? That's perfect. Thank you, Bruno.

Okay. Then we move on. Andrew Baum from Citi. Andrew?

Oh, sorry. Andrew, you can talk now. Yeah, very good. Could you just highlight or talk about the BioNTech mRNA, adjuvant pancreatic cancer program that you have running. You have a phase two in a drug with a very unfortunate short time to recurrence. Could you talk whether this data is filable, and if so, when you anticipate receiving the phase three data? And then second, you have rights to two cell therapies from Poseida, which are allo, non-lentiviral transduced cell therapies, which obviously have cost and potential safety advantages. I know you have rights in the oncology setting. Could you confirm that you also have rights in the autoimmune setting and whether you intend to, or how quickly, I should say, do you intend to initiate trials within the autoimmune space? Thank you.

So, Andrew, you were asking questions that are sort of before your time. So I think we all have a great degree of interest in what allogenic heart T could do in settings outside of oncology. But we're not in a position to discuss that externally at this time. So more to come most likely by far of a day on that. And the Phase 3 data, given that that's a partner program, I'm actually not sure what we're disclosing there. I don't know. Maybe Thomas or Bruno, if you might be able to help here.

Maybe just to jump in, I think we just started the Phase 2, fourth quarter of last year, but I think we have not yet disclosed the timeline and when this will read out.

But can you confirm you can file on the Phase 2 data? Because that's my understanding. Okay.

I think we have not confirmed or been outspoken about whether we believe there's a possibility to file on these data. Thank you. Andrew, this was all from your side?

Yes, many thanks.

Then the next question would come from Tim Anderson from Wolf Research.

Thank you. A few questions on Robismo again. What percent of VEGF treatment-naive patients are you capturing now? Periodically you've given those updates in the past. And then in as much as you've looked at it, there was a Department of Justice lawsuit against Regeneron on their reimbursement practices for ILEA related to credit card fees. I don't believe Rush does that. I'm wondering if you have a point of view on that and how that tilts things in their favor or does not. And then just last question, you talk about Blizmo becoming standard of care and it's a better product. So can I interpret that to mean you think eventually Blizmo actually overtakes ILEA in terms of market share?

So, I believe that patients who want to have the best opportunity to have a good outcome with their disease ought to be on vavizmo. And eventually, I would think that that would mean more patients would end up on vavizmo than on Fluricept. To answer your question about the DOJ lawsuit, obviously we wouldn't comment on ongoing litigation against another company, but I can tell you that that does not represent the practices that we follow here. And I'm sorry, Tim, I missed your first question. Oh, 40%. More than 40% of our patients are currently naïve.

So maybe to add, Tim, I think we have seen an EVE patient share continuously increasing. A year ago, Q1, 23, I think we stood at just over 10%, and now we are above 40%. Exactly right. Tim, any additional questions?

Well, I guess I'll just follow up on that first one. So you said you're not seeing an impact from the J-code that high-dose IVA has. We're only really three weeks downstream of that. So, if we look three months or six months downstream, do you think that will have, you know, is that kind of a material event? Do you think it will accelerate the uptake for a high-dose hyaluronidine employee who buys Muxbox?

Yeah, I mean, as of right now, with the approval of high-dose and the coming of the J-code, we're just not seeing that impact. Again, I think many physicians are making a very reasoned and rational clinical choice about where they believe they can get the best clinical outcome for their patients. And if you look at the data, that would suggest that they choose Vopizemol.

Thank you. Bless you. Okay, then we move on. The next one in the row is Steve Scala from Cowan.

Thank you. Two questions. First on Trantinamab, would you clarify whether or not tau reductions were observed in the phase 1-2 trial, and will phase 3 studies select for or stratify patients based on their tau level? So that's the first question. Second question is that Roche has previously stated that eccentric sub-Q will be largely protective of the franchise. I'm curious how to interpret the words largely protective. Could sub-Q be 50% of total current tex-centric sales if the IV declines, or is that too optimistic and not what you're implying? Thank you.

So I think when we say largely protective, I think what we mean is that patients who are currently on tex-centric IV would potentially switch to tex-centric subcut. And when you look at sort of tex-centric subcut alone, I think we're assuming a couple additional sort of 100 millions in sales that would come above and on top of the IV that's there, right? So patients who would normally have gone on IV will go on subcut, or IV patients would switch to subcut. But patients who would join or take Decentra just because there's a subcut is really in that couple hundred millions range. Steve, does that make sense?

Yep, but you can still hear me. Okay, great.

And then in terms of tronc... Oh, sorry, go ahead.

But it sounds like the subcu could be... A couple hundred or a couple billion Swiss franc, right? I mean, it could be a huge drug.

A couple hundred million.

And this is when we talk about, we talked about, Steve, 200 additional, a million in additional sales. In additional sales, exactly. Of course, they're switching ongoing on the line from IV to subcutaneous, and therefore, you know, G-centric will be a one-bit plus product.

But it was also said that current patients can switch to the sub-Q, so that's a big number. Cool.

Correct, but it wouldn't be additive. So if you make 100 Swiss francs today, you might have some of that IB business will switch to subcut, but you'll only get a little bit more on top of the 100, if that makes sense. I just want to make sure we're being clear that we don't see it as a big upside for Tocentric overall. Okay. And in terms of Tronte and Tao, I don't think that we have disclosed the design of any future studies at this juncture. Bruno, can you confirm, have we talked about tau in the?

No, I think we haven't. If it comes to study design, future study design, we have not yet been talking about any details, you know, patient selection, patient screening, comparator arms, which we can think about. But I think the question was also, Steve, whether we have been looking at tau reduction. And sure, I think we look at a whole variety of biomarkers, and we'll also see whether there's an impact on tau. I got this question right, Steve. Yes. Thank you. Any additional questions?

No. Good. Thank you.

Then we would move on with Richard Parks from EMP.

Hi. Thanks, Bruno. Thanks for taking the questions. So firstly, big picture one for Thomas. Just wondering what the response of the R&D organisation has been in terms of morale to your efforts to improve focus and prioritisation. Obviously, it's involved kind of tightening up a budget and termination of programmes. wondering how it's impacted retention and recruitment of people and how the organisation's responding to that effort. And then on CT380, I just wanted to push your views again on the potential of the drug as a single agent. I know you've talked about I hope to deliver 20% to 25% plus weight loss, which would make it very competitive. But we've got Novo's Cagrasema coming later this year, and you're likely to be a late entrant. So just do you see that as a stepping stone to then develop your combinations or how material an opportunity to see this as a single agent? And importantly, can you talk about manufacturing capacity and how quickly you can ramp that up? Because obviously it's been a big investment that other companies have had to make there.

Thanks for the question on generally R&D organization. Let me also highlight that over the last months, we've really worked on the end-to-end R&D process within Roche. So there's more work ongoing than just portfolio prioritization. We have also worked on setting up our pharma development organization in a better way. So there are a number of things that are ongoing. In terms of the reaction in the R&D organization, I think everyone wants to deliver more with the money that we have. And so I think there's a lot of buy-in in the organization that this is the right time to do these things. But I think the feedback has been very positive that this is the right direction that we have to go.

Great. And in terms of CT388, I mean, I think we do believe that from a monotherapy perspective, it would have best disease activity. But certainly, we're very interested in additional combinations, whether that's with our anti-myostatin, which we've talked quite a bit about. But there's also possibilities in combination with other CV, metabolic, renal, ophthalmology. I mean, obesity comes with so many comorbidities. the potential combinations with other drugs in our pipeline are quite significant. And so I think these are also things that we're teasing out as we're putting together what the life cycle for CT38A and the follow-on molecules could potentially be. So I think we have a – we believe we have a significant opportunity here because of the monotherapy benefit that will be provided here. in combination to help address additional comorbidities that many of these patients suffer from. In terms of manufacturing, certainly today, as Thomas mentioned at the beginning of the presentation, we have one of the largest pharmaceutical manufacturing footprint in the industry and are very keenly thinking about how we will manufacture and bring these drugs to market, both as a monotherapy as well as a fixed-dose combination. So, Much more to come, but this is certainly something that's top of mind for us.

Thank you.

Richard, does this answer all your questions?

Yes, great. Thank you.

Okay. Then the next one is Emily from Barclays. Emily Fields.

Hi. Thanks for taking my questions. I'll ask two. First one, a little bit of deceleration on Okravis in the U.S. and EU in the quarter. I was just wondering if you could run any color around that. And I know you'll have the subcut launch later in the year, but are you expecting double-digit growth globally for the full year for Ocrevus? And then on Cribelumab, I was just wondering if you could characterize the commercial opportunity in the U.S. and PMH, you know, given that there are also recent launches of drugs like Febhalta and also Voideva. Thank you.

Yeah, sure. So let me start with Crovus. So, you know, PNH is just sort of the entry ticket for a C5 complement drug. So we're actually not expecting really significant sales in any part of the world with Crovolumab and PNH. We believe the real benefit of this drug and where we believe we could see really material sales are in things like sickle cell disease, which are earlier in the life cycle in the pipeline. So more to come on this drug, but I think clearly – clearly the opportunity in P&H, we believe, is going to be relatively modest. When it comes to Okravis, we do continue to believe that we will see growth with Okravis globally. You know, there's a little bit of buying pattern sometimes that happens in Q1, but the overall anti-CD20 class continues to grow, and Okravis, as the market share leader here, continues to get a disproportionate share of new patient starts. We continue to see great retention on Okravis. and patients being very satisfied with their therapy. So, yeah, I would continue to have a lot of confidence in the growth of Ocaris going forward.

Any additional questions?

No, that was great. Thank you.

Okay. Then we move on to Mark Purcell from Moem Stemming.

Yeah, thank you very much for taking my questions. It's Marcel from Morgan Stanley. I have two. The first one's just a general question in terms of OPEX and supply investment, following up from the last question on that. But when you sort of think about getting into obesity and immunology and hypertension, sort of three areas where, I guess, apart from metrolizumab, you haven't been in the near history, how should we think about the investments going to be made both in these large primary care and specialty care focused trials, sort of building out fill forces, the supply chain was just mentioned, but it'd be interesting to try and understand what the gating factors are for what could be very significant investments into these three areas. And the second question is on PASI for PD as well as the GMY myostatin asset for SMA. Could you help us understand the potential to move these two assets from phase two to filing? You know, what would you have to potentially see? Have you had discussions with your regulators in terms of accelerated filing for these two assets? Thank you. Great.

So with GIM 329, so as I think it was mentioned on the slide, that is currently being studied in combination with Evrisdy. In patients with SMA, assuming we see positive data there, there is a potential that that data could be filable. So, obviously, we'll need to see the data, but it is possible that you could move relatively quickly there to an approval with a combination. The mono data for obesity, obviously, the phase one is just initiating, and we would have to see – we would have to begin conversations with regulators once we see some data there. In terms of PRAZE, I think, again, we will get data later this year that will inform whether or not we move into Phase 3 with Parkinson's. And once we have that, we'll be able to give you a better sense of what we believe the registrational pathway for that ought to be. Love your question about how we would commercialize Zalbisara and the Karmat assets and the TL1A. So certainly when we purchased these assets, we looked at a fully burdened cost structure, right? So we know that the clinical trials here are large. As Thomas has mentioned, a lot of the pipeline costs. calling that we've done has been done to create room for these assets so that we can do the trials that they deserve in order to get the labels that they'll need to be competitive. When it comes to a commercialization front, we obviously considered what it would cost to do all of the DTC and the primary care-like sales forces that would be required. If the same kind of marketing that was necessary in the past will be necessary later in the decade, And I think what we believe is that a different kind of commercialization structure will become more the norm as we get to the later part of the decade. There is just no appetite from physicians, from healthcare systems, to continue to have the kind of commercialization footprint that most pharma has been operating with over time. I think what we've seen as we've changed our own commercialization structure is that you can market your products extremely effectively and in a very different cost structure. So while we are prepared to do it, if we believe that it is necessary and that is what it is going to take in order to maximize the assets, we also believe that there may be a third way forward, and that is what we intend to explore over the coming months and years. I do just want to sort of reiterate that we know that commercialization in these areas begins now, and that is something that we are fully prepared to do and are commencing immediately to ensure that we are ready to be competitive when these drugs come to market.

Maybe let me add a couple of points here as well. First, we will continue to protect our margin. So nothing we're going to do is going to dilute our margin. Second, as Theresa has mentioned, when we do M&A, we look in the entire P&L. So that's already included in our plans. And third, you know, when we look under the hoods, there's still a number of opportunities to improve our operational efficiencies, and we're tackling those as we speak.

Mark, any additional questions, comments?

No, that's very clear. I was going to ask about how much room is being created and if there's going to be the kind of incremental pressure on margins. But I think, Thomas, you've answered that pretty clearly in terms of you do not expect the operating margin within pharma to decline between now and 2030. No.

All of our plans are predicated on stable margins going forward.

Great. Thank you.

And we go on with Peter Welford from Jefferies. Peter. All right.

Hi, thank you. I've got just two questions left. Firstly, just on going back to Hem Libra again, I'm curious, as again, obviously we're all looking to, as everyone said, to the potential competitive data. I'm curious, given what you've said, you highlighted that the real world data has got 80% zero exclusive bleeds. But I think on the label, you've got lower percentages than that. So just curious whether you see the potential here and the festive threat to come from a potentially, I guess, superior percentage on zero-treated bleeds, or whether given all the effort that you're talking about, convenience and the new vials and pens that we may see at IPH, whether it's more the administration and the injection site paying attention that you're focusing on as a way you think potentially a competitor could differentiate. And then just secondly, on the portfolio rationalization, I guess relative to prior quarters, we've seen a decrease in the number of discontinued, if you want to call it that, or deprioritized assets. And I think, Thomas, you sort of suggested at the last call we're going to see, you know, continuing over the next few quarters, there's more assets being deprioritized. Again, is the number, you know, the five that we see this quarter, is that representative now of perhaps a shift in the phase now for the rationalisation and sort of pruning, if you like, to a new stage where now we're looking at how you best invest the money and sort of more internal changes? Or is it just phasing? And actually, you know, we shouldn't anticipate that in any way that the five projects is a slowdown. In fact, further rationalisation is going to happen during the course of the year. Thank you.

Let me just answer the second question first. There are a number of programs that have been stopped that will only show up in Q2. So this process is ongoing, and that's why I mentioned you'll see it in the slide, I would say, for the next one or two quarters, and then we should be, again, back to normal situation. Again, we're still looking at opportunities to bring in other assets, and as I mentioned before, we have a strong focus on really bringing in first-in-class, best-in-disease assets with a lot of potential to drive also sales in the future.

Yep. And talking about first-in-class best-in-disease assets, Hemlibra perfectly exemplifies that. So, I mean, Hemlibra is the standard of care in hemophilia A. We have a tremendous amount of real-world data, which equates to real-world experience. We have a very high level of patient satisfaction on Hemlibra. And I think the efficacy data, the safety data, the lived experience of physicians and patients who treat and are treated with Hemlibra, 80% of patients not experiencing please, 90% of patients being very pleased with the convenience options that already exist with Hemlibra even before improvements are made. The zero risk of inhibitors. All of these things are things that are going to make it very difficult to ultimately unseat Hemlibra. And so, you know, I think we can talk theoretically about what options might be necessary in order to make inroads, but I think, A, we don't have data yet. Let's see the data. The data that is being generated by new maids is not going head-to-head against Hemlibra. It's going head-to-head against inhibitors. So, you know, we're not even really going to see an apples-to-apples comparison. I just – I truly believe that what we have with Hemlibra is going to be very difficult to really practically unseat in the market as the standard of care. We all know that experience counts for a lot with physicians and patients, and the experience with Hemlibra has just been overwhelmingly positive.

Peter, any additional questions?

Sorry, just to follow up on that, given what you've just said about very difficult to unseat Hemleber as the standard of care, is Roche still keen on developing NXT? And how do you see NXT therefore potentially falling within that?

Yeah, that's a great question. And looking at NXT, NXT will have to provide an additional efficacy benefit over Hemlibra. And I think we feel pretty strongly as we've been thinking about designing the clinical development program for that drug, what it would need to demonstrate to suggest that it would be able to sort of compete successfully against Hemlibra. And I think an additional efficacy benefit an additional efficacy signal is going to need to be seen. It's going to need to be just as safe. It's going to need to be just as convenient. I mean, the bar is high. And I think we consider that even when we look at our own internal portfolio and what we might choose to invest in going forward in terms of next generation assets.

Thank you.

So I think then we come to the final question. I think Emmanuel Papadakis is back. Emmanuel, you get the final one. Oh, no, he just dropped out. So I think then we are basically done with the call today. And I hand back to Thomas for a final remark.

Yeah, thanks very much. And also thanks for your interest. Just to close out, let me just reiterate that we have strong base business growth and that for the coming quarters, we'll see the headwinds diminishing. And we've worked substantially on our pipeline, and you will continue to see that we will do a lot to progress our pipeline and to build really a leading pipeline in the industry. Thank you very much.