Roche Holding AG

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Thank you very much and hello to everyone wherever in the world you are. I'm really excited to share with you the results of 2024 for the Roche Group, because I believe this year has really been an excellent year for us. So let's look at the performance. So overall, group sales was at 7%. The base business, meaning excluding COVID-19, grew even with impressive 9%. Pharma, 9%, and diagnostics, 8%. We saw the last and final impact of COVID-19 sales in reduction in 2024, so there is no more impact going forward. The final impact was 1.1 billion, so exactly in line with the guidance that we gave at the beginning of the year. The LOE impact was 1 billion Swiss francs, so slightly better than the guidance we had given. To round out the very strong performance of the organization, Let's look at the third line here. Core operating profit growth plus 14%. Group core operating margin up 2.1 percentage points. Core EPS growth plus 12% if you exclude the tax effect, which we guided for, or plus 7% if you include it. Operating free cash flow up 34% at 21.2 billion Swiss francs. Certainly the number that Alan loves the most. Key milestones achieved in Q4, you see them on this list here. EU approval for the . We had positive readout for tritinamab, and also in the PRASI trial, we see a potential benefit in certain subpopulations with this disease. On the diagnostic side, it was a very busy quarter with the mass spectrometry launch, the 6,888 launch, and so on. And also on the deal side, we made good progress, introducing Poseida to our organization, allogeneic cortis, not only for oncology, but also in the autoimmune diseases and the DLL3 ADC deal in small cell lung cancer. 2025 will really be a significant year for us in terms of phase three readouts, but also in phase three enabling readouts. So movement from phase two and phase three, where we have up to seven animals Can you hear me? Yeah, now you can hear me. Okay, perfect. Sorry about that. Good. So now let's look at how we did versus the guidance. At the beginning of the year, we talked about mid-single digit sales growth for the year 2024. We definitely ended up at the upper end of this guidance at 7%. Also at the beginning of the year, we talked about mid-single digit core EPS growth, excluding impact from resolution of tax disputes in 2023. We raised that guidance in mid-year. And we've clearly exceeded this guidance with 12%. Again, if you include the impact, we are at 7%, which is in line with the sales growth. And we further increased the dividend. This means that we have increased the dividend for the 38th consecutive year. And as you will see at the end, we plan to do that also for the ninth consecutive year. Here you can see The slide that we always show, you can see that the rush group grew 7%. If you exclude COVID, we had a very strong growth of 9%. So again, very strong performance in the group. Now, this is one of the slides that I like very much. On the left-hand side, you see the group sales growth over the last couple of quarters and years. And then the right-hand side, you can see the growth if you exclude COVID-19. Clearly, we are one of the companies that had significant sales of COVID-19 between 2020 and 2022. In fact, around 19 billion Swiss francs. And we are also very proud of the contribution that we did at the time. But also, it means that as COVID-19 went away, and we always communicated that it would go away, we had in 2023 the situation that we had to compensate this loss. And we did so with significant base business growth, so excluding COVID-19. And this growth has been very strong over the last two years. You see 2023, 8%. If you take the average of 24, you're at 9% growth. And in fact, in the last three quarters, we reported 9% growth each quarter. I think this is a very strong performance from the organization. Now, let me quickly take you through this slide. A couple of highlights that I would like to make. First of all, we have now 17 medicines that have blockbuster status. Furthermore, in oncology, Pageta-Fesco conversion rate is now increasing to 46%. PolyV, U.S. patient share, first line DLVCL, now climbing to 29%, establishing itself to the new standard of care. It's also an opportunity to further build upon it with combinations with the CD20, CD3, by specifics that we have. Hemlibra, patient share in the U.S., EU, now reaching 42%. And we are now also looking forward to the phase three enabling readout of NXT 007, which is the next generation of Hemlibra. In neurology, Ocrevus subcutaneous, now with roughly 50% patient share being naive to Ocrevus. And the J-code is only to come in 1st of April. Eliminators with good launch momentum, and clearly Teresa will touch on that and on the promising two-year follow-up data from the phase three Embark study. Xola food allergy with continued strong uptake, now at more than 40,000 patients on treatment. mid-teens to be expected in terms of growth in 2025. But Biosmall pre-filled the range, now also approved in the EU, and is set to become the number one ophthalmology brand in 2025. In diagnostics, strong baselessness growth of 8%, as mentioned before. Now, let's take a brief look into the future. I can say that we have completed our strategic review, and we are really now in implementation throughout the organization. So we're set for the future. I would like to touch on the formation of our near-patient care organization in diagnostics. So in diagnostics, we have four customer areas, core lab, molecular lab, pathology lab, and near-patient care. In the first three, we're the number one globally. The area where we want to become number one is near patient care. And here we've done the acquisition of Lumira DX. And this has been covered quite a bit by Matt and myself in recent presentations. What's really special about this platform, it's a handheld platform. And on this technology, you can do multiple different technologies in terms of measurement, chemical chemistry, immunochemistry, coagulation, potentially molecular diagnostics. And it's room temperature. And it's really disruptive from a cost of goods position. AccuCheck CGM was launched last year. This will enter us into a very fast-growing, very large market. Covus Liat, we just recently announced the menu expansion into SDI, and we'll continue to build out the menu. But we have two more platforms in our pipeline. One is around blood gas, the other one around lab-like immunoassay performance, where we are going to continuously invest into the near-patient care segment, and we'll continue to build out that segment as we go into the next years. Now let's go to pharma. you've seen the very strong momentum that we have in our organization. And this is really due to the young portfolio that we have in terms of medicines. And you can see on the right-hand side that in the meantime, 56% of our pharma sales are coming from these new medicines. In fact, in 2024, we launched two new medicines. One is PSGuy and the other one is Itofbi. And I would definitely say ITOFBI is best in class, and we have very high hopes on ITOFBI. In 2025, we have a total of four potential enemies that with a positive phase three readout could lead to launches in 2026. We have a fifth one, which is Tirogolimab, but we didn't mention on here, because as we know, the hopes for Tirogolimab are lower. But there are still certain trials ongoing. Let's see how that runs out. But those are the four that we would like to highlight for 2025. What's also important is that we are one of the companies that has very little biosimilar exposure until the end of the decade. So we have less headwinds than many other companies have in our industry in this time period. Now let's look specifically at the pharma pipeline in 2025 and what we can expect. Here you see a list of a number of our key assets in our pipeline. In fact, we have more than seven NMEs with a peak sales potential of more than 3 billion and four with peak sales of 2 to 3 billion. We have six marketed products that each have trials ongoing with potential line extensions that could add another 1 to 2 billion each per asset. Now, 2025 will be a special year. because we have 12 key pivotal readouts, so approximately one per month. And we have four readouts that are linked to new enemies that could be launched in then 2026. And even more important, I would say, is that we are refilling our late stage pipeline. We have seven enemies that could enter into phase three. And that would be really, for us, a record. If I compare that to last 10 years or so, to bring seven additional NMEs into late stage would be really significant for us. Now, let me finalize with the 2025 guidance. And you can see that we expect LOE impact of about 1.2 billion Swiss francs, so slightly higher than what we saw in 2024. And we aim for group sales growth in mid-single digit sales range and core EPS growth in the high single digit range. And dividends, we aim to further increase in Swiss francs. Thank you very much. And with that, I hand over to Alan.

Yeah, thanks, Thomas. Hello from my side. Great to see everybody. I hope everybody's fine. Certainly what I also hope is that Teresa is getting better soon. Very pleased with the performance this year and would like to thank the whole team and everybody who has contributed. to that performance on one hand, and certainly everybody who has contributed to the well-being for patients. Good, let's get into it. And this is the overview. Sales, you see, plus 7%, 3% reported in Swiss francs. I'm sure Teresa and Matt will do quite a thing to explain the sales and dig deeper here. Underlying, as you heard from Thomas already, so without the COVID sales, plus 9%, quite impressive performance. And when you look at the cooperating profit with a higher momentum, plus 14%, I think very clearly good cost containment. And really, when you see the increases that we have in the cost lines well below the sales growth. Yeah, then we get to core net income and core EPS. And I would hit the two right away. Very clearly, what brought the dynamic down, the growth dynamic of these numbers are two elements. One is taxes. we have paid 1.1 billion more taxes than last year. Part of that is the tax impact or the resolution of tax disputes we had last year as a positive to 774 million. That certainly contributes to that increase. The other part is high interest charges, roughly 320 million or 400 million when you just look at interest that we had more. And that explains the core EPS growth of 7%. If you exclude the resolution of tax disputes from 2023, you go to a core EPS growth of plus 12%. IFRS net income down 19% in constant rates, minus 26% in Swiss francs. Two major impairments happened here where we certainly have to acknowledge that the expectations of these investments and assets didn't fulfill compared to what we had in mind when we bought these assets So we had to impair end of 2024. Yeah, and then the number I love most, Thomas is completely right, is the cash flow, 34% up, 28% in Swiss francs, 20.1 billion in constant rates as reported, and 21.2 billion in constant rates. That's really not a record number. I think once we had a higher one, yeah, but it's long ago, it's a fantastic number and certainly helps us to mitigate the debt increase and the interest charges. The free cash flow also on a high level, as you can see. So really money available to do further M&A, but also to pay the dividend. When you look at this group sales growth, and here you see the bridge, full year 2023 on the left-hand side and full year 2024 with 60.5 billion on the right-hand side. First, really, let's go through the divisions just to give you the broad overview. I think you see the database business has grown over a billion. COVID impact, a minus 552 million. Pharma growth above a 5 billion. Rona pre-sales impact from last year to 522. And then you see really the loss of exclusivity, which is roughly a billion with a minus 952. And then you see the currency impact, which brings The 7% sales growth in constant rates to a 3% interest rates. When you look at the P&L, as said, I think the cost discipline is obvious. I mentioned the sales. You see the other revenues with plus 215 million. This is, as you know, the line where we have the royalties in, where we have the profit shares in and all of this. Here, I would argue when Clexa profit share contributed to that number, and then Xole outside of the US, that caused an increase of a plus 215. When you look at cost of sales with a 5% increase, a minus 720 impact, I think the 5% is a major achievement because we had volume growth of 11%. When you look at pharma, 14%, diagnostics at 3% volume growth, I think that's a very respective outcome. I think for pharma, I can say 640 million increase. Here, half of that, basically half of that is triggered by a provision release we had in 2023. This is really the Rona pre-provision, as you know, that we released. I think that's a big explanation here. So they would have looked much better without that. Diagnostics, 80 million, with quite some volume as well. Then you go for R&D. R&D, modest growth rate with plus 1%. Very clearly, the reprioritization in the portfolio on the pharma side is going on and moving on. On the other hand, we have invested more on the cardiovascular side. And then you see really SG&A with plus 5%. Let me explain that. M&D plays a major role here in pharma, an increase of 319 million. Very justified, because when you look at the growth rates of the Buysmore, Kravis, Fesco, I think that's where we have to invest, and we did. And when you look at diagnostics, higher logistics costs of $90 million on the M&D side. And then there's an element of corporate. And you might ask yourself, OK, why is that coming? Well, one element is we centralized more in the company. So there were more costs coming from other units into SG&A. Diabetes care is one element that we integrated, just to mention an example here. That's roughly $100 million. And then the rest is informatics. In informatics, we have invested in artificial intelligence, ERP, and other technologies, which I think is very justified. When you look at other operating income and expenses, the minus 166 decline solely is driven by less gains on disposals compared to last year. Leads us to a cooperating profit of 20.8 billion with an increase of 14% compared to a sales growth in constant currencies of 7%. Well, you look at the margins, I think with such a performance, certainly the margins go up. And you see for the group in constant rates, 2.1 percentage points. Same applies to the pharma division with plus 2.1 percentage points. And diagnostics has gone with 1.3 percentage points. So really a great performance across the board. And you see both divisions improved their margins. When we go to the Cornet financial results, you see really an increase of 310 million reported. Major driver here is the interest expenses. As you know, the debt has risen. On top of that, we have changed a couple of mature bonds with other bonds that have higher interest charges, which is clear in the current environment. So I think that was the driver here. Equity securities with something small, that's our venture fund, small number. And then the net interest income is driven by the cash that we had on the balance sheet and that we just reinvested in a very cautious form. Good, the core tax rate. That's quite an interesting story. Let me start on the left-hand side here with the 11.9% in 2023, which was certainly a great outcome, very much driven by the 774 million positive tax impact. So you have to readjust for that. That's a minus 4.3 percentage points, brings us to 16.2% adjusted effective tax rate for 2023. When you compare that to the adjusted effective tax rate full year 2024 with 17.1%, I would argue, I think really very comparable to last year, major change here is the profit mix that comes in with different jurisdictions and different tax rates. What came into it on one hand is certainly the two pillar, the pillar two top up tax, the Swiss minimum tax, so to say. with plus 1 percentage point. And then we had a couple of resolution of tax disputes we cannot really budget for. It's very hard to foresee. That brought the tax rate down by minus 1.4 percentage point to 16.7%. I know everybody's eager to know what's going to happen in 2025. Guidance here is very clearly 19.5%. 18% for the, if you like, effective tax rate, and then 1.5 percentage points for the minimum tax. So we stick to that. Core EPS development. And that tells the story a little bit about the year. I think really you see on the left-hand side where we started with, you deduct the effect of the resolution of the tax disputes. You get to 18.02. And then you see operations is really that's the driver of the result in 2020. and 24 what worked against us less product disposals the minus 181 million that i've mentioned already you see the financial income and expense which has risen that's the minus 320 million and then you see the tax rate changed i've elaborated about already and that brings us to the 12 increase in core eps and you see it the driver is clear operations When you look at the non-core and the IFRS income, I start with the cooperating profit I've talked about with plus 14%, the outstanding performance that we have seen. You go to the IFRS net income line, you see the minus 19% in constant rates that I've mentioned already. And when you go through the lines, I see the global restructuring spans, very comparable what we had last year. I'd say, hey, that's a difference. Well, we have a positive effect in that line in 2024 coming from the Vacaville divestment of 240 million. Amortization of intangible assets, I would argue, pretty stable. And then you see the impairments of intangible assets, a decline of minus 3.4 billion, very clearly here as that driven by two major impairments that we have taken where the assets really didn't meet our expectations we had when we acquired them. And that really is the major driver. So goodwill impairment was 3.1 billion and 800 million additional impairments on the assets. M&A and alliance transactions, not much of a move here. And legal and environmental, I think in 2023, we had a positive impact because we released the provision for a court case. And I would argue in 2024, normal business. leads us to an IFRS operating profit of 13.4 billion. And then you see the total financial result and taxes when you put it together. So that's 1.4 billion more compared to 2023 in total, as I've said and outlined at the beginning already, leads us to an IFRS net income of 9.2 billion. Good. Yeah, I think this is not just the number, this is the slide I love the most when I look at 2024. and that's the cash generation. The cash generation has been outstanding. When you look at constant rates from 15.8 billion to 21.2 billion, reported on the right-hand side, 20.1 billion. I think really an outstanding number. And what excites me the most is, I think very as expected, operations drove that number, and you see that in the first green bar with 3.7 billion. But then we also worked on the net working capital. And you see net trade working capital, 1.3 billion, and I can say both divisions really brought that number home, so to say. This is really a fantastic outcome. And when you then look at other network and capital movements, I think that helped as well. Investments in intangible assets, that's what we want to do. So, we invested 600 million more here. So, overall, I think a fantastic achievement. When we look really at the cash flow margin, they jumped as well. And as I've said, I think both divisions contributed. Group debt, net debt development. So what does this cash flow generation mean for the net debt development? Let me first outline where we landed. End of December 2023, a minus 18.7 billion net debt. End of 24, a minus 17.3 billion. So really an improvement of 1.4 billion. So really, we overcompensated everything. So I think that's a great message. How did that work? I think the operating free cash flow, yeah, I've talked about it. In here, it's an investment in intangible assets of $1.5 billion. I think just to mention that. When you look at the non-operating free cash flow, taxes with $3.7 billion, treasury is $1.1 billion. And then you see certainly dividends and M&A, dividends paid $8 billion. M&A and transactions 3.1 billion. So you can argue, including the 1.5 billion for intangible assets, we have invested into M&A and intangible assets, which certainly drives the pipeline, 4.6 billion. Then you see a currency translation effect. As much as we love a strong US dollar in the P&L, it hits us in the balance sheet on the debt side, because 70% of our debt, and we have 34.7 billion gross debt on the balance sheet, 70% of that is in US dollars. And when the dollar strengthens, I think that number gets higher. And then you see a couple of other effects here. So that leads us to the 17.3 billion. Certainly very pleased with that as well, based on the strong cash flow that I've explained already. Good. With that, let's go quickly through the balance sheet. First time, we have more than 100 billion in assets in the balance sheet. And what you see is cash and marketable securities. Yes, we brought that up. We had a couple of bond emissions that helped us, and certainly 7.3 billion give you a lot of assurance that we can pay the dividend. Other current assets, I think very clearly slight decline. Why? Vacaville went away. I think that's 600 million. And inventories went down by 300 million, which I think is a great message. When the non-current assets slightly up, 4.8 billion here, very clearly deferred taxes played a role here. With the restructuring plans, I think the intangible assets impairments, all of that contributed to this, as well as the acquisitions that we have done. On the current liabilities, so we move to the right-hand side, accruals are the reason for the increase on the current liabilities, and the non-current liability is very clear, that's the gross debt. Gross debt increased from 29.2 billion to 34.7 billion, so by 5.5 billion, and that's reflected in that number. And you see overall the equity has increased by 2.9 billion. Good, with that, currency. Yeah, a little bit of a pain in the last two years. And when you look at 2024, you still see that on the left-hand side, this orange line is below the black line. And the black line is the average for 2023. And the orange line is the average for 2024. And whenever these lines are below, that's not a good impact for us. If you liked So you see on the right-hand side the results for the full year, a minus 4 percentage point impact on sales, a minus 6 percentage point impact on cooperating profit, and a minus 6 percentage point impact on core EPS. I think when you really look and you know we do that exercise, we assume really at the end that every currency rate stays the same during the year, and we project them for the full year, which is very, very hypothetical. But then we expect any impact for 2021. and 25, which is certainly encouraging. If we were looking at today, we even have a positive impact. But, well, we all know currencies are very, very volatile, but it looks like a better year compared to the last two. Now, a very formal slide, I know, and a little bit boring, but important to get to the right starting point for 2025. So let me start really with the core EPS as reported in 2024. of 18.8 Swiss francs. And what we have to, or what you have to adjust for, is the foreign exchange losses, which are so far not really reflected in that number, or not reflected in the number. So in the green bucket, what you see is an adjustment of 0.53 francs, 53 rappen. exchange rate effect. This is a result of dividing the 2024 currency losses of 291 million Swiss francs, as well as the 2024 losses on net monetary position in hyperinflationary economies of 163 million Swiss francs. This is shown in note four of our consolidated financial statements on page 62 of the finance report 2024. This number, net of taxes and non-controlling interest, by the number of diluted shares of 802 million. The 802 million shares you get in note 29 of the finance report, page 121. So when you do that exercise, you get to the 53. If you do that exercise, you might ask yourself, oh, this implies a pretty low tax rate for that impact when you do that. So you can do the math here. It would imply a tax rate of 6.4%. Let me take that topic right away because the one impact, the 163 million has no tax impact. So that's one element here. And the other piece is, yeah, the 291 has a tax impact, but in the holding. In the holding, we have certainly another tax rate compared to what we have in the group. So that leads you to the 53 rub and the adjustment here. So the starting figure for the outlook for 2025 is 19.33 Swiss francs per share. Good. With that, yeah, that's a bit formal, I know. With that, I think really nothing to say about the guidance Thomas gave that. And with that, it's my pleasure to hand over to Teresa.

Great. Thank you, Alan. So apologies for the mask. It is not a fashion statement. I am feeling a little bit under the weather, and so I want to make sure that I'm protecting my colleagues. But I am very pleased to share with you the 2024 results for pharma. So let's kick things off with a look at the sales performance. In 2024, pharma sales grew 8% at constant exchange rates to 46.2 billion, excluding Ronapreve. Sales grew 9%. All regions, excluding Japan, delivered strong growth, 9% in the U.S., 8% in Europe, and that extremely impressive 17% in international all at constant exchange rates. Excluding Ronapreve, Japan declined at just 2%, and that is primarily due to mandatory price cuts. And as Alan already mentioned, overall pharma volumes were up by 14%. Going into a little bit more detail, the core operating profit for firma increased by 13% versus an 8% sales increase with a margin of 47.7%. Going through the lines in a little bit more detail, you can see the cup grew ahead of sales, and this is really driven by cost discipline in both R&D and SG&A. Other revenue, as Alan mentioned, increased 16%. This was primarily driven by the increases in profit share income for the higher sales of Zoller outside the U.S. And as you mentioned, Van Clexta in the U.S. Cost of sales increased by 8% in line with sales growth and remains stable at around 18% as a percentage of sales. And again, this is including the base effect of that Rod and Pre provision released from last year, as well as that 14% volume increase. So I think overall really good performance on cost of sales. R&D. Costs increased only by 1%. This is about 24% of sales. And SG&A costs increased by 5% in pharma as a percentage of sales, though it decreased to around 15%. As Alan mentioned, this was due to increased investments, including marketing and distribution costs to support our ongoing launches, particularly of Abizmo, Sezgo, and Zolaire in food allergies. So I think, as Alan mentioned, money well spent. And then other operating income and expenses decreased by 25%, and that is solely due to lower gains on disposals of products. So Thomas and Alan shared with you their favorite slides. This one is mine. Our young portfolio continues to deliver strong growth, led by our key brands, the Baizmo, Fezgo, Okravis, Hemliver, Zolaire, Polivi, and Inbrisdi. Combined, these added 3.9 billion of new sales last year, which is really impressive. For the first time, Polivi has achieved blockbuster status, making it our 17th blockbuster of 2024 when you include Ben Klexta. So now let's take a deeper dive into our therapeutic areas, and let's start with oncology. Oncology sales increased by 3% to $15.8 billion in 2024. Let's start by highlighting some of the latest news flow for our most recently launched NME, Itobe. On Tuesday, we shared with you in the final analysis of Innova 120 that Itobe met the key secondary endpoint of OS benefit, and we are very much looking forward to sharing this data at future medical congresses and with regulators around the world. While the U.S. launch is ongoing, we expect EU approval in the first half of this year. With the HER2 franchise, we finished strong, had Silo delivering 7% growth, and Fezgo was 62% growth. Global conversion rate for Fezgo has climbed to 46% from 43% in Q3, and we would fully expect to exceed 50% in 2025. Moving on to Ticentric, in 2024, sales overall were stable. That's primarily driven by small cell and HCC. We do believe, as we have mentioned previously, that Ticentric is getting close to peak, and we expect sales growth to be in the zero to low single digit range going forward. Looking ahead at what's to come in 2025, I want to specifically call out the two highly anticipated phase three readouts for Ghirardestrin, Persevera in Q4 and Evara in Q2. And we are very much looking forward to sharing the outcomes of these potentially standard of care changing studies. So let's turn our attention to hematology. Hematology continues to deliver strong growth. We ended the year at $7.9 billion in sales with 15% growth. And let's start by looking at Hemlibra. In Q4, growth is strong across all regions and patient segments with good underlying market demand. We saw a very strong Q4 performance in the U.S., 20% at constant exchange rates, and that was driven by a large specialty pharmacy order, which is very similar to the pattern that we've seen in previous years. Going forward into 2025, we would expect a mid-single digit growth globally for Hemlibra. Staying with our hemophilia portfolio for the moment, as Thomas mentioned, we have the phase two readout of our next generation bispecific in hemophilia, NEXT-007, that is anticipated around mid-year. If positive, this would lead to the initiation of a phase three development program later in 2025. And as a reminder, we believe that NEXT-007, which is 30 times more potent than hemolibra, has the potential to receive zero treated bleeds without the need for additional factor VIII treatments. So this would really allow us once again to change the treatment paradigm for patients suffering from hemophilia A. Moving on to Polivi. In the U.S., first-line DLBCL patient shares keep on climbing. We're now at 29%. Polivi has been used in more than 42,000 patients globally. We also recently shared the five-year Polarix data indicating a positive trend in OS with the hazard ratio improving to 0.85 from 0.94 in the three-year data. which we believe will further support uptake. Columbia and Lensumio launches are progressing on track. For Lensumio, we completed US and EU filing of the subcutaneous formulation, which has all the benefits of the available IV formulation with the added ease of subcu. Looking ahead into 2025, there is quite a bit happening in hematology. We expect to move both Columbia and Lensumio into second-line DLBCL, much bigger opportunities. For Columbia, this means US-EU approval, based on the positive Starglow data with the Petufa set for July 20th. And for Linsumio, we're expecting that phase three Sunmo data in second-line DLBCL. For Linsumio, there are two additional events, the U.S. approval of the subcutaneous formulation in third-line follicular, which I just mentioned, and the phase three readout in second-line follicular. We're also expecting phase three readouts for Van Clexta in first-line MDS and P.S. Sky in AHUS. So lots to look forward to in hematology this year. Next up, let's talk a little bit more about our recent acquisition of Posida in its allogenic CAR-T portfolio. We've long believed that the Posida allocart T technology could potentially be best in class in malignant hematology. The early data in multiple myeloma suggests very strong clinical activity comparable to the auto BCMA CAR-Ts. Now with this acquisition, we're going to be moving quickly to bring this approach into MS and SLE as well with INDs already granted. And we're excited about the possibilities for patients represented by these programs And with the deal now closed, we'll be able to bring you more regular updates in the coming months. So with that, let's move on to our Neurology franchise. The Neurology franchise continues to deliver strong growth of 13% at constant exchange rates, achieving $9.3 billion in sales, starting with Okravis, the market leader in MS, and more specifically, Okravis-Synovo, a recently launched subcutaneous formulation. The launch is progressing as planned, and we continue to see very positive signals. In the U.S., more than 50% of Zenovo patients are naive to Ocrevus, and we see accounts that have not used Ocrevus IV in the past prescribe Zenovo. As we've said earlier, Ocrevus Zenovo expands the addressable market for Ocrevus, and it's not simply just about converting IP patients to subcutaneous. So far, we have more than 25,000 patients globally on Ocrevus Zenovo, and while we are waiting for a permanent J-code to be issued in April of this year, in the U.S., we would expect that that permanent J-code will lead to an acceleration of uptake in the U.S. And we remain quite confident in our 2 billion incremental sales projections for Zenovo. Looking at OkraVis as a whole, we closed the year with 9% growth. Q4 U.S. sales were negatively impacted by Hurricane Helene, which, as many of you know, disrupted IV supplies and therefore reduced IV administration capacity, as well as some modest year-end buying patterns. That having been said, the first few weeks of sales in 2025 have been quite strong, and we expect global sales growth to be in line with what you saw in 2024, so overall high single-digit growth. Evrisdy maintains its strong global position in SMA, achieving 18% growth in 2024, and we expect similar global growth rate in 2025. We are anticipating approval of the tablet formulation for Evrisdy later this year. The tablet simplifies storage, eliminates the need for cold chain, and increases the ease of administration, three great benefits for patients. If needed, that tablet can be dissolved in water. We are looking forward to bringing this innovation to patients and to further expand on the Avrisd-Best in disease profile. Elevides, the first gene therapy for DMD, has now been used to treat over 80 patients in the XUS-XEU region. Additionally, earlier this week, we shared positive top-line results from the two-year follow-up of the EMBARQ study, which will be shared with the EU regulators. And I will talk a little bit more on that in a minute. Last December, we also shared the top line results for the Phase IIb Padova study in Parkinson's. This as well, I'll cover in more detail in an upcoming slide. So another big outlook year in 2025 for neurology. In particular, this is going to be quite the year for MS. Ocrevus high dose data is expected and has the potential to be best in class, best in disease, setting a new standard care at MS. We also have the long-anticipated phase 3 readouts for fenobrutinib and RMS and PPMS, which we continue to believe has best-in-class potential based on the strong phase 2 data that we've seen. There are two phase 2 readouts for GIMM329 expected in 2025 in combination with Evrizdi in SMA and as monotherapy in FSHD. And last but certainly not least, we expect to share additional phase 1-2 data cuts for Trontiumebin Alzheimer's disease at ADP and CTAD. Gated upon these results, we are planning to move Tronte into phase three by the end of the year and with FPI to be achieved in the second half. So let's take a little bit of a closer look at the two-year embarked data for Elevitis, which we shared on Monday. The phase three embarked two-year data clearly reinforced a significant and sustained functional benefit for DMD patients. This benefit is seen across the primary and two key secondary functional endpoints of NSAA, time to rise, and the 10-meter walk-run. when compared to propensity-matched external cohort control. As you can see in the graph on the left, Elavides is favored in all three of these functional endpoints, and functional differences between patients treated with Elavides and the external control are getting larger between one year and two years after dosing. Additionally, pooled three-year data from the studies 101, 102, and cohort one of study 103 demonstrated consistent and durable clinically meaningful benefits compared to external control. Combined, we believe that this underscores the positive impact that LVDs can have for DMV patients, their families, and caregivers. We plan to present both data updates at MDA and share the embarked two-year data with regulators to support ongoing approval processes. Moving on to PRASI and Parkinson's. In December of last year, we shared that Padova missed the primary endpoint. However, a suggested possible benefit in patients with early-stage Parkinson's on L-DOPA treatment was observed. This was a pre-specified analysis, and these patients were accounted for 75% of the trial population. Further data evaluation is ongoing, and we're awaiting additional insights from the open-label extension. Together with regulators, next step for PASI will be determined later this year. To remind us all, we continue to see this as a high-risk, high-reward opportunity, but given the unmet need, we did feel like it was important to let this trial play out a little bit longer. So with that, let's move on to immunology. In 2024, our immunology franchise achieved 6.3 billion Swiss francs in sales and grew at 5% at constant exchange rates. The key growth driver here is certainly Zoller and its launch in food allergy. We are very pleased with the launch uptake, having reached the milestone of 40,000 patients on treatment. As I mentioned in Q3, we expect a year-over-year growth momentum in the mid-teens for 2025. Our second key growth driver here was Actemra. As we mentioned in Q3, the US and EU biosimilar launches continue to be slower than expected. We currently expect biosimilar erosion to pick up speed in the coming quarters, especially in second half of this year. We had previously shared with you the exciting news of positive phase three data for gaziva and lupus nephritis, a program you all know that I'm very fond of. We look forward to presenting the full data set at the World Nephrology Congress in February. Our IR team is also preparing a call in parallel, and that data has now been submitted to the US and EU regulators, and we would expect approval decisions later this year. Going to our immunology outlook and staying with GIVIVA for the moment, we expect phase three data from our allegory trial and SLE later this year. Astegolamab and COPD is also expected to read out later this year. And there are multiple upcoming developments in our anti-TL1A portfolio, which I will talk about now. So I am very excited to share the progress that we've seen with our TL1A program recently. As you know, TL1A is a highly validated pathway that's important in a number of disease areas. We previously shared that our phase three in UC is ongoing and enrolling rapidly, and that our phase three in Crohn's is expecting SPI this quarter. It's safe to say that we're moving at pace with our IBD trials, but as you know, we are not stopping there. We did share at JPM that we are initiating a phase 2B trial in atopic dermatitis and a phase 1B trial in MASH and Q1 with additional indications under consideration. We've also added an anti-P40 TL1A bispecific to our pipeline, and that phase 2 and IBD will initiate later this year. Now moving on to ophthalmology. So in ophthalmology, sales reached 4 billion Swiss francs last year with an impressive growth rate of 44% at constant exchange rates. This franchise is led by Bovizna, which continues to expand its U.S. market share across all three indications. Before we get started, I did just want to call out that after our last IR call, we were informed by the third-party vendor that provides our market share numbers of a restatement of the Q3 U.S. market shares. We believe that this was related to stockouts of other products included in the market definition, primarily aliquot and avastin. To account for this, the Q3 values were restated to improve accuracy. Because of this change, you can't directly compare the Q values here, the Q4 values here to the ones that we shared at Q3. If you do compare the restated Q3 values to the Q4 of abysmal market shares, we expanded in each of its three indications by roughly three percentage points. We expect that you'll once again be able to see the expanding market shares when comparing Q1 2025 to the Q4 24 values you see here. We remain confident that Babizmo is well on its way to becoming a new standard of care. Our share of naive patients within the new-to-brand patient segment remains greater than 50%, indicating very strong preference of ophthalmologists to use Babizmo in the frontline setting. Performance in the U.S. in Q4 was impacted by the significant channel filling we saw immediately after the launch of pre-filled syringe. So we saw a little bit of a spend-down in Q4, but we are seeing a strong trajectory for Babizmo in our January sales to date. Staying on the topic of our next generation pre-filled syringe, we achieved EU approval in Q4. U.S. conversion rates continue to climb to above 85%, clearly indicating that HCPs are very eager to use the simplified administration option. Regarding the 2025 outlook, we expect to see continued strong growth and further market share expansion. And as I said, we remain confident that the BISMO is well on its way to being the new standard of care. Moving on to SysVimo, our AMD commercial relaunch in the US is on track with roughly 100 implants completed in 2024. As a reminder, in this stage of the launch, it's all about getting new ophthalmologists exposure to SysVimo and trained on how to perform the implant and refill exchange procedures. This is very much a story of going slow to ultimately go fast. For 2025, we aim for a few thousand implanted eyes. Also in 2025, we expect to complete the EU filing in AMD. And lastly, our new NME, the Mickey Bart, which could become the first IL-6 in ophthalmology, is expected to have pivotal results in UME later this year. And finally, before I get to our 2024 and 2025 news flow, I wanted to take a quick look at how our pipeline reshaping is progressing. Complementing on what you saw from Thomas earlier, I'd like to highlight our continued efforts to strengthen the pharma pipeline. You can see the different additions and removals over time, and there are two recent additions in Q4 that I just want to call out. the Allogenic Part T that we added as part of the Poseidon acquisition, and the ADC DLL3 in small cell, which was added to our pipeline via a deal within events. All in all, we brought in 10 assets via high value partnerships since Q2, 2023. And at the same time, our internal R&D engines, P-RED, G-REN, and Chugai delivered 14 new NMEs. Next, I want to quickly show you the final 2024 news flow. You know this slide well from all of our quarterly results last year. There were three final updates in Q4, which you are aware of. The tiragolumab and first-line PD-L1 positive non-small cell was negative. As previously mentioned, the readout for PRAZI and then trontinumab NAD had positive interim data cut, which we did present at CTAD. And so with that, let's take a look at what we can expect in 2025. As mentioned by Thomas, we expect 12 key phase three readouts this year. And this includes four NMEs, but also importantly, seven phase three enabling readouts. So let me just quickly highlight some of the key phase three readouts. We have the Ghirardestrin program in first-line and second-line HR-positive metastatic breast cancer. We have Lansimio plus Polivi in second-line DLBCL. We have Ocrevus high-dose in RMS and PPMS, Phenobrutinib in RMS and PPMS, Astagolamab in COBD, and Vimikibart in UME. In addition, we also have multiple phase three enabling readouts, including NEXT007 in hemophilia A, Tranti in AD, GIM 329 and SMA and FSHD, Zalbiceron and uncontrolled hypertension, CT868 and type 1 diabetes with obesity, and CT996 and obesity with type 2 diabetes. As you can see, it is going to be quite a busy year, and I'm looking forward to sharing the news flow with you as updates come in. I am also pleased to say that as we get to the end of January, we already have our first green tick, and that is for the Linsumio sub-Q filing in Europe. And now I will hand it over to Matt to guide you through our diagnostic results.

So, good morning, good afternoon, everyone. It is my pleasure to present the full year 2024 Diagnostics Division financial results. So, as you heard from Alan and from Thomas, our diagnostic sales grew 4% at constant exchange rate and our base business grew at plus 8%. Now, the increase was mainly driven by our strong base business growth of 8%, but the As you previously heard, this is the last time we will discuss COVID-19 sales separately from base, as this disease has transitioned to an endemic state. And so now I'll walk you through the results by our different customer areas. So first, sales in our core lab increased at plus 8%, with strong momentum driven by immunodiagnostics, which grew at plus 9%, and clinical chemistry, which grew at plus 8%. Molecular diagnostics had an increase of plus 4%, There's a strong growth in our virology-based business, which grew 10%, as well as our donor screening blood screening business, which grew at plus 17%. Now, this was, again, offset by lower COVID-19 PCR lab-based testing sales, and excluding those, molecular lab grew at plus 8%. Our new customer area, which you heard about earlier, near-patient care had a decline of minus 17%, and this is mainly due to lower COVID-19 rapid antigen testing, as well as the steady decline of our blood glucose monitoring business at minus four due to the market shift to continuous glucose monitoring. Our point of care business grew at plus, our base point of care business grew at plus 6%, and this is really driven by our point of care molecular diagnostics business. Excluding COVID-19 sales, near patient care declined minus 1%. Not to be outdone, Our pathology lab grew at plus 17%. This was mainly driven by our advanced staining business, which grew at plus 12%, as well as companion diagnostics, which grew at plus 41%. So now I'd like to shift gears and walk through the sales results across the different regions. So first, excluded COVID-19 business, we see strong base business growth across North America, EMEA, and LATAM. And in North America, the base business excluding COVID grew at plus 8%. In EMEA, the base business excluding COVID-19 grew at plus 6%. In LATAM, the base business excluding COVID-19 grew at plus 23%. Now in APAC, the base business growth excluding COVID-19 grew at plus 3%. And sales growth in Q4 was impacted by volume-based procurement and reimbursement reduction for immunoassay in China. while our consistent ambition for the diagnostics business is to grow at mid to high single digits. As a result of the headwinds from VBP and the reimbursement reductions in China, our ambition for 2025 is to grow the business by low to mid single digits, which would be a one-year dip with a return to our consistent ambition in the years beyond. I would also call out that China is still a critical market for us, and we continue to be the market leader. So now let me walk you through the diagnostics divisional P&L line by line. So core operating profit on sales of 14.3 billion Swiss francs increased by 12% at constant exchange rate versus 2023. Cost of sales increased by 1%. Now this is driven by favorable product mix, really due to lower sales of COVID-19 rapid antigen tests. R&D costs increased at plus 2%, mainly driven by the integration of Lumira DX, as well as investments in some of our upcoming late-stage launches, such as sequencing, mass spec, and continuous glucose monitoring. SG&A increased at plus 3%, driven by those high distribution costs you heard from Alan, as well as increased sales volume and the commercial costs associated with the preparation of these upcoming launches. This resulted in core operating profit of 2.4 billion Swiss francs, with a margin of 16.8% at reported currency. So now I'd really like to talk about some of the exciting innovation that we launched in 2024, specifically starting with our core lab and our mass spec system. So I'm very pleased to announce that we successfully received the CE mark for our CoBOS mass spec system, along with the wave one steroid assays. The current mass spec market, which is valued at 3 billion Swiss francs is predominantly composed of lab developed tests that require specially trained technicians special laboratory arrangements. And with this launch, we intend to establish and shape the IVD market for automated, simplified, end-to-end mass spectrometry testing and drive a market expansion. Our ambition is to reach a billion Swiss francs in sales by the end of the decade. And this year, we will launch over 40 new assays in our first wave, which will cover the vast majority of routine mass spec testing. And a second wave of tests will follow in the coming years. With our easy-to-use solution, which addresses the shortage of skilled labor, as I mentioned earlier, as well as the lack of standardization and automation, plus it has high level of synergy with our existing serum work area, the launch of MassSpec presents a real opportunity for us to expand our existing leadership in the core lab. So on the theme of expanding our leadership, I'd like to talk about our COBOT 6800 and 8800 version 2. Now, I'd highlight that the CE launch of our version 2 update of our high-throughput PCR systems The Covax 60 and 8800 will further extend our competitive lead in the molecular lab and is field upgradable to our installed base of thousands of 6800s and 8800s around the world. These were the workhorse systems where we responded to the COVID-19 pandemic, and they're going to be an engine for our growth into the future. This update is fully compatible with our new TAGS multiplex assay. such as our respiratory syndromic panel flex test, which we launched last year, which tests for 15 different viruses from a single well sample, and will strengthen our position in the mid- to high-throughput segment of the molecular diagnostics market. We will have the only high-throughput platform capable of syndromic panel testing. With this update, we introduced increased testing flexibility, such as the addition of a stat lane for urgent samples, greater automation of molecular workflows, flows through being able to batch up to six assays in a single run. And we will offer customizable quality controls that will enable improved run costs. So in addition to those upgrades, we also improve the throughput. The Covax 6800 will increase from 384 to 576 tasks per eight hour shifts. This further solidifies and provides an opportunity to expand our leading position in molecular diagnostics. So not only are we leading on the platform side, I'd like to talk about some of the innovation that we're introducing as well in terms of the next generation of diagnostic assays. I specifically present the recent clinical study results for a Lexus amyloid plasma panel, which consists of two blood-based biomarkers, PTAL-181 and apolipoprotein E. Alzheimer's disease continues to be a global burden, affecting more than 50 million individuals annually, and is projected to reach over 80 million people by 2030. However, two-thirds of people experiencing cognitive symptoms remain undiagnosed, and diagnosis usually takes more than a year and up to two years, requiring subjective cognitive tests as well as imaging analysis. In this study, we enrolled 492 patients with suspected cognitive impairment across 30 different study sites. Our results demonstrated excellent clinical performance and a negative predictive value of over 90% independent of comorbidities and demographics, for both the EAPP panel as well as PTAL 181 as an individual biomarker. Pending regulatory clearance, we hope this test will provide a minimally invasive blood-based test to rule out Alzheimer's disease and decrease the time to definitive diagnosis. This will have a significant impact on patients, their families, and healthcare systems around the world. So we talked about favorite slides, I guess, and I'd like to say this is certainly my favorite slide. You know, last year we said 2024 was going to be the biggest year for diagnostic launches, and what I'm proud to say is that we achieved all of those. We received all 12 key launches shown here, including our first CGM, the AccuCheck Smart Guide, our serology blood screening solution for the United States. We're already taking significant market share and winning business. The first clinical mass spec solution, as I mentioned earlier, as well as our next generation clinical chemistry and ISE solutions. Now, in 2025, we have additional important launches. I like to call it a few by customer area. The first is what we just spoke about, our Alexis P-Tau 181, which, as I mentioned before, could provide a convenient test to roll out Alzheimer's disease. Furthermore, we'll expand our mass spec menu with more than 40 assays in the first wave. For the molecular lab, we will launch CoBOS BVCV. It's a molecular test to aid in the diagnosis of bacterial vaginosis. and Candida vanginitis, which will help complete our menu in the rapidly growing STI market segment. Now, we're also approaching this from the point of care side. For near patient care, I'd like to call out our Covost-Liet CTNG, which is our first green tick of the year, a rapid multiplexing test that can detect and differentiate chlamydia and gonorrhea at the point of care in a CLIA wave setting, which we just received FDA approval. In pathology, we will have a major update to the Roche Digital Pathology platform, with enhanced image management, a fully redesigned user experience, and enhanced interoperability with third-party scanners. Combined with the primary diagnosis claims for our DP200 and DP600 scanners last year, this positions us well for the rapidly growing digital pathology market segment. And last, but certainly not least, I'm pleased to invite you to our upcoming diagnostics IR events. We at AGBT will be unveiling our core sequencing technology, and I'd like to invite you to an IR event taking place virtually on February 20th. During this event, we will provide an update on our sequencing technology as well as hold a Q&A session. And second is our annual Diagnostics Investor Day on May 27th. This is going to be a hybrid event held in London and online. We have an exciting agenda covering all of our customer areas where we will further discuss our forthcoming Roche sequencing solution as well as our entire pipeline across all customer areas. So I look forward to seeing you there. And with that, I will hand it over to Bruno.

Thanks, Matt. And I will just quickly use the opportunity to have here a final slide to sum up on the upcoming IR events. A couple of them we touched upon already. The next one is to come already next week, Friday, February 7th. This will be immunology. The data, the in lupus nephritis, which are presented at the World Congress of Neurology, which we will have some time to discuss. Then the update of MGS mentioned by Matt. And then on April the 4th, we'll have a neurology update. Here we have a couple of topics to cover. First of all, it's the LVDSM mark two-year data in DMD, where we just had the top-line release, which we expect to be presented at MDA. And then two additional data sets from ADPD, trasinesomab, the Padova data from end of last year, and then the latest data cut for the brain shuttle. You see then, as mentioned already by Matt again, that Diagnostics Day is scheduled for May 27th as a live event again in London, with the NGS solution being the highlight this time. And then we already set also a date for Pharma Day in the second half, which is now scheduled for September 22nd, so that you can put it in your calendars. Just looking at the, you know, intense new flow ahead of us in 25, I think there will be many more IR calls, especially in the second half. I can imagine we will have something on hematology mid-year, but then also I would say EASD, CTET, just to call out a view of the upcoming medical conferences in the second half where we are likely to have additional calls. And with that, I think we can open the Q&A session. The first question would go to Richard Foster from JP Morgan. Richard, please.

Thanks very much, Bruno. Two questions from me, please. Firstly, one on the Vibismo. I think we understand the temporary weakness in the quarter, but I wanted to ask about the launch of a pre-filled syringe for high-dose ilea and how you would see that affecting Vibismo. Obviously, very key, and you're doing really well with yours. But in Europe, they have a pre-filled syringe for high-dose ileus, so thinking about how that might affect you in 25. And then second question, just on giridestrin, maybe a little bit of a push-out on the Persevera data into Q4 and October on clinical trials. Just what do you see as the implications for that on your thoughts around the expectations for the results of the trial? Thanks very much.

We'll start with the last one. So I don't think that has really any implications on the results. Just sometimes these things take a little bit longer. And that's what we saw with Geradustrin. The pre-filled syringe. So I would just like to say right now, we're really not seeing any impact in any part of the world from high dose ILEA. And the pre-filled syringe that we have in the market is materially different than the pre-filled syringe that ILEA has. It has one-hand administration, which when you think about it, if you're doing 1,000 shots or 100 shots a day, having that really ease of administration is super important. So I would say we definitely have device preference going on our side. And quite frankly, I think just what is inside the syringe matters a lot. And the Vizmo is clearly continuing to distinguish itself from an efficacy and safety standpoint with the added convenience of the pre-filled syringe. I would just continue to see it growing and continue to establish itself.

Maybe, Richard, let me quickly add to your first question on duradestrin. I think there was no real change in the underlying timelines. That's more, you know, an issue with when certain things get updated at clinicaltrials.gov. For the both studies, IVIRA and PASIVIRA, we expect the data to come in somewhere around, you know, mid-year, second half. We cannot be more specific. As you know, these studies are event-driven, but nothing really fundamental that changed here. Any additional questions from your side?

No, Bruno and Theresa, thank you very much. That's great. Thanks a lot.

Thanks, Richard. Thanks. Then the next question will go to Emily Fields from Barclays. Emily, please.

Thanks for taking my question. Just on that last point, I think Theresa said during the prepared remarks that Persevera would come in Q4. So I just wanted to clarify that and make sure that's correct. Yeah, so then my last two questions. Firstly, the high-dose Ocrevus. So you've helpfully quantified the incremental revenue opportunity that you see from subcutaneous Ocrevus. But I was just wondering if you could help us frame how to think about the commercial potential for high-dose Ocrevus. Obviously, this trial is versus the standard dose. So do you see this as additive to the franchise or just transferring patients over? And does high-dose provide any opportunity to extend IP? And then secondly, you know, I know that you were expecting first pivotal readouts from Orfaglipron later this year, and you'll be getting, if successful, a royalty from that. But I wanted to ask more just on, you know, whether you see the success or failure of that compound as having a read across to CT9 and 6. And if you could just remind us on how the two molecules are differentiated. Thank you.

Emily, maybe just to quickly add, I think I said on the timelines of your restaurant, mid year to second half, it's of course, you know, we cannot be more specific right now as that event driven, we will get the information as soon as we have it. And then the other question.

Yeah, so as far as high dose goes, I don't think we've actually shared what our commercial expectations are for high dose. Once we get the data, we will be able to share some additional information with you, assuming that that data are positive. From an IP perspective, I think, you know, should high dose be positive and we begin to look at putting it into devices, I think there is definitely some opportunity for expanded IP, and we'll be able to comment more on that once we get the results.

Should I take the left?

Oh, yeah.

Yeah, so on that one, I would say the difference clearly is that CT996 is actually a small molecule. So from a production standpoint, it has advantages versus a peptide. So it's very different in terms of the two molecules. Regarding royalty income, that would not be obviously this year. But in case it's positive, then in future years, there would be additional royalty income.

Emily, did we answer your questions, or do you have a follow-on question?

Yes. That was great. Thank you.

Okay. Then we move on. Next one in the row is Sachin Jain from Bank of America.

Hi there. Thanks for my questions. Two, please. Theresa, just on the two surgeries, why don't you just give a bit of big picture on Avera, Persevera, how you think about the probabilities of those two studies differing. And perhaps you could just touch on the commercial opportunities of both. I think Avera is generally perceived as quite small. If that's incorrect, if you could just clarify. And then, Thomas, just a big picture question. Your second favourite slide after cash, I think, was the group sales slide, showing sequential growth at 9, 9.11 in the last few quarters. So I just wanted to touch on what you think the 25 headwinds are that slow this to mid-single digit for this year, other than that Temera, which I think is less than 1%. Is there anything we're missing there? Thank you.

Do you want to start with that?

Sure, I can go first. I think one of the headwinds was mentioned by Matt. So the volume-based procurement that's happening in China. And other than that, I would say, look, we're at the beginning of the year. We have almost one month behind us. And let's see how the year goes.

And in terms of geradustrin, I think, you know, we do believe that this has the opportunity to be a multi-billion dollar franchise when you look at all of the different indications. And I think Persevera has that patient population is first-line endocrine sensitive. That's 60% of first-line patients. The Pioneera patient population is the first-line endocrine resistant. That's another 40% of patients. So, you know, between the two of them, we really get the full first line covered. And, you know, Evira, again, gives us another set of that patient population that we would need to cover the entire spectrum of endocrine sensitive patients. So I think we believe that we actually have the trials that would allow us to cover every single patient population and ultimately get to that multi-billion dollar opportunity.

just anything on the relative probabilities of the two studies defend you're willing to comment yeah i think the i think when you know such what we have been communicating is of course the success likelihood for the later lines is a bit lower than for example the edge of the setting next year This is just, you know, logical if you look at it. You have the treatment on top of other treatments and you have a more diverse patient population which has some level of resistance which was building up over time. It's not only ESM1 mutants, it's also other resistant mechanisms which come to play. And I think this just leads to an overall lower success likelihood. Next year, then, 26, I think this is the big one, the study to watch out. And I think this is also the, you know, the most opportunity, which will allow us, if successful, then really to reshape the landscape and the treatment paradigm.

Thank you.

Any other, Sachin, any other questions or from your side?

I know, that's perfect. Thank you.

Yeah, okay. Then we move on. Next questions would go to Matthew Weston from UBS. Matthew.

Thanks, Bruno. Good afternoon, everybody. Two for me, please. The first on Akrivas Zenovo. It's clearly launching well. One thing Thomas called out in terms of the sustainability of growth at Roche was the limited biosimilar exposure. Obviously, one of those in the future will be normal dose Akrivas. Can you help us understand of any additional IP that Zenovo brings? What should we be thinking of in terms of the long-term potential there? And then secondly, sorry to stick on patent expires, but one of the statements that captured a lot of attention at the Pharma Day was that you had high confidence that we would not see US Zola by a similar entry in 2025. Can you now give us any understanding of how far you think that protection will go and especially given you called out investing in Zola as one of the reasons for investing in significant SG&A in Alan's comments.

Great, two good questions. So when you look at the Okravis franchise between Zenovo, between other device formulations that we might be looking at high dose, I think you can assume that we are considering ways to extend the patent life of Okravis. So I can't say more now, but I think you should take comfort in the fact that we're looking at this quite actively. In terms of patent expiry for Xolair, we can confirm that there will not be biosimilar entry in 2025.

And maybe to add here, Matthew, on the IP situation for Ocrevus, I think, you know, in case Ocrevus hydros would work out, I think this would have given additional patterns. If a combination of Ocrevus hydros and subcutaneous would then be another development opportunity, would come with a newly developed injector, for example, would give another layers of IP. So I think there are several layers which should help us to prolong the franchise.

Bruno, if I'm allowed... Apologies to others. If I can just ask one additional follow-up, because you raised high-dose Akrivas. Emily asked about it as well. It's obviously one of the next readouts for Roche. You've got two arms. The people who are, I guess let's call it overweight, and I understand why you hope it will work there. In the normal weight cohort, what evidence gave you confidence that more Akrivas might give you more efficacy? Because I recall in the past Roche always being very... strident about the fact that Acrevis gave full CD20 inhibition in the setting. So what can more bring?

Yes, I think as we designed the high dose studies, we looked very carefully at the phase two studies where we actually saw the increased efficacy when you reached higher saturation points. So I think that certainly would make sense in overweight patients. But I think our assumption is that that might actually also extend into normal weight patients. And that's just based on the data that we've seen to date.

Thank you.

Thanks, Peter. It was a retrospective analysis, which we did, Matthew, I think, and we have looked into all, you know, confounding factors and imbalances in the different subsets, but it's not that we believe that the effect we have seen would be primarily driven by weight.

Exactly. And, you know, again, in those exploratory analyses post the phase three, what we did see was just slowing of disease progression with higher exposure to oprahis. So, hence the inside your study.

Thank you all.

Okay. Then next questions would go to Simon Baker from Redburn. Simon.

Thank you, Bruno, and thank you everyone else. Good afternoon. Two questions, if I may, please. Firstly, one for Alan. I know you don't guide on cost lines, but I just wonder if descriptively, if there's some indication of the movement we should expect in the various cost lines to get to the implied margin expansion within the 25 guidance. And then secondly, on the anti-TL1A, the move into MASH, it's obviously a very interesting and potentially very large category. I think you're the first person or first company to move into the clinic in that indication. I just wonder if you could give us some color on the basis for moving into MASH with the TL1A. Thanks so much.

Do you want to take the costs question?

Okay. Yeah, I think first of all, I have to say, Simon, guidance is the guidance. I think for 2025, that's what we orient ourselves on. Everything in between certainly needs flexibility and will allow us to have. I think we have said that we want to be, how Shay said, flattish about R&D. I think that's pretty clear. That's why I can mention it. I can also mention And other operating income, we expect a little bit less gains from product disposals. I think that's another one. I would argue all the other lines, we will apply the best cost discipline, which makes sense to do that. But overall, the guidance is the guide.

And I think, as we mentioned, TLNA is a very clinically validated target in immune disease, but it also has an antifibrotic component. And so I think as we were considering where were there opportunities to expand, looking at diseases that have fibrotic pathogenesis, it just made sense to kind of look at something like MASH with TLA.

Thanks so much. I am struggling here. I have a technical issue. I cannot open my screen window right now. It's hidden somehow, so I don't know what to do. I think we probably have to stop the call for some technical reasons.

I basically cannot help this anymore.

Bruno, it's asked me to unmute. Should I ask a question? Yes, please. Hi everyone, it's James Creavy here from Goldman Sachs. So two questions please. So first one on the margins. So Alan, you had some nice increase in the margin across both divisions this year. Given this increase and with the move over time away from specialty farmer areas that have been higher margin, maybe to some more primary care areas, how does it impact your ambition to defend the margins? You're keeping R&D flat, as you just mentioned, in 25, but how should we think about the margin levers over the medium term? And secondly, on PRAZE, as you mentioned, we're going to see some next steps this year, but what are the potential options here, given the data you've seen so far? what is the probability that you could potentially move straight to registration, or would you need to run a, is it more likely that you need to run a phase three, and then again, how long could that last? Thank you.

I can take the first question. As I stated before, the goal is to at least keep the margins as percent of sales stable. That means, of course, in absolute terms, we'll continue to increase the margins. And I always say at least ambition, it can always be higher than that. But the point is to at least keep it stable. And as you can see, for 2025, we actually intend to expand our margins. So we'll give you more updates then as we get to the 26, about 26 and so on. But the long term, that would be my clear guidance.

And as far as PRASI goes, so the open label extension study is continuing, and we will evaluate that data over time, talk with regulatory authorities, and see if the signal that we saw in the first part of the trial sort of continues to reveal itself. A decision on what we will actually do with that trial I think will come after we see more information. It would be highly unlikely that we would move straight to registration. This remains, I think, as we've always said, a very high-risk, high-reward program.

Henrik, maybe you can please take over the moderation and just ask the next one in the row to open the line and ask them to ask the questions.

Sure. So next one in line is Richard Park. So Richard, I open now your line.

Hi. Thank you very much for taking my question. First one, I'd just like to push you a little bit more on giridestrin because generally investors are quite skeptical about the classes potential outside of the ESR1 mutant population. So can you just help us understand what gives you optimism in the Persevera study around broader potential outside ESR1 mutant patients? And can you confirm that the Evvera study is powered to show a benefit in that population, therefore obviously would be lower risk? And then secondly, on TL1A, obviously with another competitor showing proof of concept data, the potential of that class has become a lot more visible to investors. And speaking to KOLs, it sounds like development of a biomarker is an important aspect to driving uptake of the class, which seems to position you quite positively given your experience in inflammatory bowel disease and with biomarker development. So can you talk about where you're differentiated in development of a biomarker and how yours differs to other companies? Thank you. Yeah.

So let's start with PLNAs. So, I mean, I think that we haven't said much about the biomarker other than it's there and we will consider it through the development program. I think we are very excited about this molecule and this pathway. And to your point, Our prior experience in IBD and our experience with biomarker development, our experience in many different therapeutic areas and diseases where TLNA could potentially be relevant, makes us very excited about the full opportunity of this molecule over time. As you know, we're in a head-to-head race with Merck. We've got another molecule that's sort of further behind. But I think all of the data that we continue to see across the different molecules are out there, reinforces that this is a valid pathway, that these molecules have benefit. And I think we're, yeah, we're really eager to actually see what it can do in patients. So definitely more to come on TL1A. To answer your last question first, so Evera is powered for both IPT and ISR1 mutants. So we are confident that we have powered the trial appropriately. Just to remind everyone why I think we are so, why we were so excited about deiodesterone when the program kicked off. I mean, it is the highest preclinical potency of any oral SIRD that's out there. It seems to be combinable with all CDKs and it's well tolerated at all doses, which I think, again, it makes it quite different. It has true endocrine backbone potential, which is very different than what we've seen with some of the with some of the other drugs that are out there. Gyrgestrin has shown robust data in early trials and in metastatic settings and as a monotherapy and in combination. So I think the trials that we have out there right now, they start to answer some questions. The big kahuna is kind of coming in 2026, but I think this is a molecule which we've seen evidence of efficacy. And so now we just need the trials to read out.

Thank you. Can I just ask one follow-up? Can you just confirm that with your L1A, you do have a biomarker integrated into the phase three trials that are underway and planned?

Yes.

Thank you. Great. So Richard, I hope that answered all your questions. In that case, the next person in line would be Rajesh Kumar. So I'll give you now the possibility to ask a question.

Hi there. Thank you very much for taking my question. On the GIM assets, can you talk through what your ambitions are in combination with obesity development, please? That would be very helpful. And then swiftly revisiting Toronto New Map, can you give some color on the timelines of you know, when are we going to hear from you again and what should we be looking out for when you update us on your go and no-go decision?

Yep, great. So as I mentioned, GIM329 is active in a number of places. So we've got the combination trial with Evrizzi as well as the monotherapy trial in FSHD. But we are also looking at it in combination with our obesity assets. We have some preliminary data in-house. We have made the decision to move forward into combination trials. And it's still very early days, but I think we can easily say that this is definitely something that we'll be taking forward. So more to come, probably not too much more I can say right now. With regards to Tronte, we'll share additional data cuts of the ongoing dose finding study at ADPD. and half one, and it's CTAD and half two. We're currently awaiting the completion of the part two expansion cohorts to inform the final dose. Once we have the final dose, we'll be able to move into phase three. I think you heard at Pharma Day last year, and I reiterated at J.P. Morgan at the beginning of the month, that trontinumab is one of the fast track assets that we've been really focused on through R&D Excellence. And so we've been working very closely to actually do as much of the front loading for that phase three trial as we can so that once we get the final dose, we'll be able to move very, very rapidly into phase three. So expect to hear more from us on that this year.

Thank you. Do you have any follow-up questions? No, thank you. All right. Thank you so much. And the next one in line will be then Justin Smith on Bernstein.

We can't hear you.

Can you hear me? Yes. Yeah, thanks to you for me, Justin Smith Bernstein. Number one, just on 007, and sorry if I missed this, but it seems as though since the CMD it's been moved up to a non-risk-adjusted peak sales target, over 3 billion Swissies, just wanted some color on that. And then just one on astragolamab, might be a little bit too early to ask, but one of your competitors sort of suggested that severe COPD, there's more sufferers, but efficacy of the biologics is probably likely to be lower than in severe asthma, so just wondered if you had any thoughts on that. Many thanks.

Yeah, so I'll answer the ASTI question first. I mean, that's why you run the clinical trial, right? So we'll see. We think there's a good scientific rationale for why this could work in COPD. We're covering a very broad patient population, an area of very high unmet need. So yeah, we'll know this year if it works. So stay tuned on that. But again, to your point, it's a little bit early to speculate. In terms of Nex007, if this molecule lives up to what we believe it can do, it will for sure become a new standard of care in hemophilia and therefore easily a multibillion-dollar indication. But, you know, the data that we've seen so far is exciting. It's early days. More to come.

Thank you.

Okay, I'm back. So finally, I made it. Had to restart my computer. I think we have one final analyst in the row. I think it's Ben Jackson from Jefferies. Ben, please.

I think you may be on mute. We can't hear you.

Ben, can you hear us?

Yes, we hear you. Thank you. Sorry about that. So just two quick ones from me, if okay. The first would be if you're able to provide any colour about the shifting back of vermiculobar in DMA into 26. Is there any particular reasons behind that and perhaps is there any competitive thoughts behind that decision? And then second, just to finish off, any additional changes in thinking about BD, especially with areas of interest following the Posido acquisition? Does that perhaps associate the need for adding more oncology to the pipeline? or is that all still within scope? Thank you.

Yeah, let me just answer the second question first, and then I can hand over to you. I mean, you've seen the five therapeutic areas that we are really focusing on, cardiovascular metabolism, oncology, neurology, those three contributing about 50% of global disease burden. Immunology really plays across many disease areas. And then we have, of course, a very strong franchise in ophthalmology. So you can imagine that these are the areas that we are looking into in terms of further strengthening our pipeline. Now, as we've done over the last couple of years, we always look very much at the science. You know, how much data is available that gives us the confidence, like we've had the data available for CL1A. Um, and, and then we also look at the financial terms and we try to just think about whether or not it makes sense. I think we've been very diligent on that. And I think we've made a number of very interesting, um, uh, acquisitions. Now, let me just highlight on, on Poseida because we already had the partnership with Poseida in oncology. Um, and, uh, we actually saw some of the data in the lupus nephritis, and there were some publications on that. And so in order to go and move into autoimmune disease, where we see that there is a big role for Cortis in the future, we also said we'll go into this acquisition. So deals like that, I think, are really in a sweet spot. And you can see that we will continue to be very disciplined and we'll continue to make sure that the deals fit into our strategic agenda.

And in terms of Mickey Bart, we expect to have data in-house. later this year, and we'll then obviously be making decisions about how we move that program forward. I think it's worth noting that we have several different opportunities to advance IL-6 in ophthalmology, including bispecifics and trispecifics. So the Mickey Bart is certainly only one molecule in a whole collection of molecules that could potentially bring IL-6 promise into ophthalmology.

Ben, did we answer all your questions? Okay. If there are any additional questions, If there are no additional questions, then I would hand back to Thomas for a final remark. Thomas, please.

Yeah, thank you very much, Bruno. And thanks to everyone for your great questions. I believe we managed to deliver great results in 2024. And I hope it shows that we do what we say and we also deliver. You can count on that. And we have a great momentum as we go into this year. And we also have a rich pipeline news coming this year. And as mentioned, we're very focused, we're very disciplined so that we continue to deliver for our investors. Thank you very much.