Roche Holding AG

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In addition to that, you may also raise your virtual hand to address your questions verbally. For participants joining via phone, to raise your hand, use star nine on your phone's dial pad. When you then get selected to ask your questions, please follow the instructions from the phone and dial star nine and then star six to unmute yourself. One last remark, if you would like to follow the presented slides on your end as well, please feel free to go to roche.com slash investors to download the presentation. At this time, it's my pleasure to introduce you to Thomas Schieneker, CEO Roche Group. Mr. Schieneker, the stage is yours.

Good morning and good afternoon, everyone. Together with my team, I'm looking forward to presenting the Q1 2023 results. So let's get right into it. Group sales declined by 3% and this was driven by the expected decline in COVID-19 testing. The underlying base business in both divisions reported strong growth results, which meant for the group plus 8% for the base business. Pharma had a very strong performance in Q1 with plus 9%, and this was driven by the ongoing portfolio rejuvenation. We had also a good diagnostics base business growth of plus 4%. The COVID-19 sales decline is in line with our full year 2023 expectations and our full year guidance of roughly minus 5 billion Swiss francs. The growth in pharma was strongly supported by the key products and new medicines, Vabaismo, Ocrevus, Hemlibra, Evristi, Ticentric, Progetta, Fesco and Polyvi. And we've had a number of key approvals already in the first quarter. Let me highlight PolyV in first-line diffuse large B-cell lymphoma in the US, Hemlibra in moderate haemophilia A in the EU, and Columv or glufitinib in third-line DLBCL in Canada. And we are now rolling it out also into other countries. In diagnostics, we launched several new oncology tests and navigated digital solutions. Let me also give you an update on the pipeline in the first quarter. We had a positive phase three study, IAMBRAVE050, of Dicentric and Avastin in adjuvant hepatocellular carcinoma, where we hit on the RFS primary endpoints. and overall survival is still immature. We've had also a positive phase three study in Krovalumab with Krovalumab in PNH. For the remainder of the year, we expect at least another 14 late stage readouts. And among those are a number of line extensions and pivotal readouts for another two NMEs. and we also have a strong pipeline of upcoming launches in diagnostics. On this slide, you see the Q1 sales development for the group and for the divisions. Group sales reached 15.3 billion Swiss francs, down 3% in constant exchange rates, and excluding the impact of COVID-19 sales, you see we grew by 8%, which is a fantastic growth. COVID-19 sales erosion in Q1 was only in the diagnostics division, which you can clearly see on this slide. Diagnostics declined by 28%, and excluding COVID testing sales, diagnostics grew by plus 4%, and Matt will give you more details here. Pharma grew strongly with 9%, driven by ongoing portfolio rejuvenation. And you see that COVID-19 didn't have any material impact on the sales growth rates. This slide summarizes the key and most important movements in Q1. The diagnostics-based business grew with 146 million. And here you also see a strong decline in diagnostics COVID-19 sales by minus 1.6 billion. So we had roughly 300 million testing sales in Q1. The pharma underlying business continues to do extremely well based on the new medicines. growing by 1.3 billion. And I would say the buy small really stood out again with sales of 432 million. So really being now the biggest growth driver in our portfolio. AHNR is completely in line with our expectations. And on the right hand side, you see how our portfolio diversification is ongoing. In the light orange, you can see AHNR back in 2018 made about 40% of our total sales and oncology was about 50% of our total sales. Now, moving forward in 2023, while growing, you see that AHNR is now a significantly smaller part of our business, and also we have diversified into other disease areas, such as neuroscience, playing a much bigger part, Haemophilia A, but also ophthalmology, where you see that Vabaismo is taking a bigger share of the cake, and this will continue to go into this direction. This slide shows the underlying performance by quarter. Pharma growing 9% and having no impact from Ronaprev. Diagnostics-based business growing with 4%. Again, Matt will take you through those numbers in more detail. Since 2015, we've launched 19 new medicines, and these new medicines are expected to deliver growth in the next years. We've had the latest launch of Columv or Clovitamab, a bispecific CD20, CD3 antibody. The first launch was in Canada, but we are in the process of rolling this out throughout the world. The Biduva date is set for July 1st. We have the possibility for two further NMEs this year, Crovalimab in PNH, where we already had a positive phase III readout, and SRP9001, which is a gene therapy for Duchenne muscular dystrophy. Now, there is the expectation that the Phase III will read out at the end of the year, but depending on an FDA approval, we have the opportunity to launch in a number of countries ahead of this Phase III readout. On the right-hand side, you can see that the new launches now account for more than 50% of the pharma sales, which is eight percentage points more than in Q1 2022. And you can also see the increasing contribution from Vabaisement, which has achieved blockbuster status after only four quarters and is one of the best launches in the history of Roche. And it is already approaching annualized sales of about two billion, if you extrapolate the March sales numbers. Now, let me provide you with a quick update on our pipeline, and I'm sure Theresa will take you through those in more detail. I've already mentioned the positive phase 3 T-centric and Avastin study in adjuvant HTC. The data was presented at AACR. We've had a negative trial outcome for T-centric and chemo in adjuvant triple negative breast cancer. I've already mentioned the positive phase three data for Crovalimab in PNH, and we have already shared the positive news on SOSFIMO in DME and DR in the full year 2022 presentation. Now, let me also share quickly an update to my team. Since April, we now have the team complete, and I'm very proud of this team because I believe we have a very strong team that will take this organisation forward. We have two new CEOs for both divisions. Theresa Graham as the Pharma CEO, Matt South as the Diagnostic CEO. In addition, we have two new people with two roles that were not present on the CEC in the past, now part of the CEC. First, Levi Gerway, our Head of Pharma Development and our Chief Medical Officer. who is now part of the Corporate Executive Committee. Now, with this move, the entire pharma research and development now have a seat at the Corporate Executive Committee, including people like Hans Klevers and Avriv Rejev, who are leading the early research and development organizations and who were already part of the CEC in the past. Together with James Sabri, our head of partnering, they will work closely together to make sure that we have a clear focus on our pipeline going forward silke hernstein has also joined the corporate executive committee it's again a new role as head of strategy and sustainability and she will help lead our future esg activities and also our strategic initiatives This slide should be very familiar to you as we presented it at the full year 2022 presentation. Let me reiterate, the guidance remains unchanged and we see that the sales drivers continue to perform as we had expected in the beginning of the year. In pharma, we have our key products, new medicines, new launches with strong growth and momentum. as you've already seen in Q1. In diagnostics, we expect good base business growth. We do also expect a significant decline in COVID-19 sales of roughly 5 billion Swiss francs across the two divisions, with a decline of 1.6 billion already in the first quarter. And this is in line with our expectations. H&R sales are expected to erode by roughly 1.6 billion. In the first quarter, we had an erosion of 330 million. This is also in line with our expectations. We confirm the full year 2023 guidance. Group sales to decline in the low single digit range. Core EPS is broadly in line with the sales decline and dividend to further increase in Swiss francs. And with that, I hand over to our new CEO for Pharma, Theresa Graham.

Great. Thank you, Thomas. So, as Thomas mentioned, Pharma had a very strong start to the year. We have sales of 11.7 billion in Swiss francs at constant exchange rates with a growth of 9%, approximately about 977 million in additional sales. All regions delivered strong growth and new products more than offset the generic erosion. Sales in Japan grew by a healthy 18%. That was due to about 600 million in Ron-approved sales, which represents the final tranche of a prior government contract. If you exclude those sales, Japan still grew by quite a healthy 10%. Overall, farmer volumes were up by 13%, prices were down by approximately 14%, and we faced increase in currency headwinds of about 4%. So where is that growth coming from? As Thomas mentioned, we are very pleased that we have one of the youngest portfolios in the industry, and our sales are largely driven by products that will continue to be able to provide value for us well into the decade or throughout the decade. especially Vibismo, Okravis, Hemlibra, Evrizdi, Tecentric, Perjeta, Fezgo, and Polivi. Vibismo is clearly leading the growth, our strongest growth contributor, after only five quarters, already annualizing out at about $2 billion, as Thomas mentioned, one of the strongest launches that we've had at Roche. We're going to go into all of these in more detail in later slides, so I will just take a moment to talk about a couple of things that we actually won't discuss in other parts of the presentation. Tamiflu and Zofluza both experience growth largely due to a strong flu season, particularly in And then we're also seeing the Avastin, Herceptin, and Mabthera decline of hitting about 3.5 billion, which is very much in line with the approximately 1.6 billion decline that we expect for the full year. I also did want to touch quickly on Ronaprive. We mentioned that there was a remaining or residual purchase that went to Japan, the residual part of a Japanese contract that was fulfilled primarily last year in Q4 for approximately 1.2 billion. That added a very incremental amount of Ron Apprieve sales to Q1. So I think it was less than 50 million. So really had no effect on our overall Q1 sales, but this really is the last, these are the last sales of Ron Apprieve that we expect to see. So now let's move on to looking at the portfolio in more depth. So we'll start with oncology. Oncology sales grew at approximately 4% year to date at constant exchange rates. That's almost an additional 4.9 billion compared to fiscal year 22. In particular, we see the HER2 franchise growing strongly. Kedsyla had 5% growth, primarily driven XUS and adjuvant breast. This compensates for some of the competitive decline that we're seeing in the metastatic setting. We also saw the Chinese NRDL listing granted for Kedsyla. Progetta continues to grow strongly, 11% in Q1, driven by US and international sales, and is expected to grow going forward. We are also seeing strong conversion to Fezgo in most countries around the world, particularly in our launch countries, but we'll talk about that momentarily. We will also spend considerably more time on Ticentric, but we are seeing strong, solid growth in Ticentric of 15%, again, driven primarily by our first-mover markets in adjuvant non-small-cell lung cancer and first-line HCC. And then the hematology franchise continues to expand. Strong sales for Venclexta with expanding patient share in first-line AML and first-line CLL, we see two additional pivotal trials reading out for van clexta this year, which we've actually been long awaiting, the multiple myeloma study as well as the MDS study. Strong growth in gaziva, driven primarily by first-line follicular and first-line CLL, in many cases in combination with van clexta. We'll talk about Polivi in more detail, but clearly strong growth owing to the first-line DLBCL uptake. And as Thomas mentioned, Lunsumio received its first global approval in Canada, and third-line follicular, that launch is, I'm sorry, Lunsumio has received its global third-line plus follicular lymphoma approval in many parts of the world. That launch is ongoing, and we are part of the NCCN guidelines, Glowfit, or Columbia just received its first approval. Allicenza continues to show remarkable growth. This is just a wonderful product. First line, ALK positive non-small cell leadership continues in our major markets, and we are anxiously awaiting the ALENA data and adjuvant ALK positive non-small lung cancer, which we expect in 2023, and we anticipate will drive significant new growth for Allicenza. So Polivi approval was granted just last week, which is extremely exciting. I think everyone knows that for patients with first-line DLBL-CL, about 40% of them do not receive, are not cured by RCHOP. So the approval of Polivi in this setting is really important for patients. The approval follows an 11 to two ODAC that voted in favor of the approval of Polivi given the clinical benefit that we saw in first line DLBCL. That US label does include patients with IPI scores of two to 5%. This is a high degree of overlap with the clinical trial population for Polivi and represents about 50% of the first line DLBCL market, which is a very significant portion. It has been included in the NCCN guidelines as category one since January, which is fantastic. And we are beginning to see reimbursement around the world for Polivi. We have a very strong NHL development program that is currently progressing. We've talked quite a bit about the SUNMO and STARGLOW programs in second-line DLBCL for Lunsumio and Columbia, respectively. We will see the results of that data here very shortly. in second half of 2023 and in first half of 2024 respectively. And we're also pleased to announce that the enrollment will begin for our first line DLBCL study with Columbia plus Polivi plus Archip. So lots more coming in NHL and this is just a really important space to watch as we begin to really see Polivi bring benefit to patients around the world. Fezgo continues to drive a high conversion rate. Our conversion rate in our early launch countries has reached 35%. If you look ex-US, that rate rises to, I believe it's 43 or 46%, which is incredibly impressive. Fezgo reduces administration and time and cost to the healthcare system dramatically. We go from anywhere between two and a half to seven and a half hours, depending for administration with the IV formulation to just 20 to 30, minutes for the sub-q so this is really just a huge benefit to patients and a huge benefit to systems 85 percent of patients prefer fezgo and subcutaneous administration over intravenous formulations unsurprisingly again we're seeing strong conversion rates in our early launch countries including strong uptake in some markets where we might not traditionally think that we would see conversion to a subcut formulation. In particular, the US and Germany have conversion rates that are approaching 20%, which is impressive, and we would expect to continue to see those grow. We also have a pivotal phase one result expected And second half of this year for Fezgo OB, this is an on-body injector, actually quite a cool device, which is expected to enable patient self-administration. So certainly we have not seen the full story yet written on Fezgo and would expect to see considerable growth in this. Very excitingly, we now see Devarisip in CRC, our positive early combination data presented at AACR just last week. This is our KRAS G12C molecule. You've heard us talk quite a bit about this in the past. We believe that this molecule is more potent and selective in vitro than its competitors. It has been granted FDA breakthrough designation for second line non-small cell lung cancer and as we all know KRAS is the most frequently mucated oncogene and is present in many cancers. This initial phase one B result in metastatic colorectal cancer was extremely well received, very promising results with an unconfirmed confirmed ORR of 66% and 62%. with a very manageable safety profile. This supplements the strong responses and several other indications that we've seen, including second-line plus non-small cell. And so we are very pleased with the results that we're seeing with the KRAS, and we expect to be able to bring you some additional data on this drug going forward. Ticentric, as I mentioned, has solid growth across all regions. Very excitingly, we are the first PD-L1 with pivotal sub-Q results, which have been filed, and the PDUFA, as Thomas mentioned earlier, is set for September 15th. Again, this represents a significant advance for patients and healthcare systems, and for payers as well, particularly where resources are constrained. When we think about Ticentric overall, in addition to the strong growth that we saw in Q1, we did also release our Embrave 050 results in adjuvant HCC. This is Ticentric plus Avastin in adjuvant HCC. This is the first trial to demonstrate RFS benefit in this patient population. The OS was extremely immature at this first read, only about 7%, but I think that, again, the results were extremely well received And we're very eager to see this trial mature over time and really see the benefit that we can provide to patients. As Thomas mentioned, the IMPASSION-030 phase three trial on adjuvant TNBC has been discontinued at interim analysis due to futility. It's important to note that this does not impact any other adjuvant TNBC trial that is currently ongoing, nor does it impact any of our other adjuvant trials in Ticentric. And we saw nothing in this trial that leads us to have any questions about the efficacy or safety of Dicentric in any additional indication. We continue to see strong adjuvant growth in our EU launches. And again, the US continues to grow in its early lead indications. The HCC franchise is continuing to grow as we continue to penetrate in newer launch markets and also in our core markets of the EU, US, and Japan. And then finally, the phase three invoke O and O studies in adjuvant head and neck are expected in H2. This is a very significant patient population and a place where we have the opportunity to have a first mover advantage. And then as you all know, the phase three skyscraper, one data to centric in combination with tiragolumab and first line non-small cell has passed its interim, it's continuing to final analysis. And we are expecting that trial to read out in Q3, but again, it is event driven. Switching now into benign heme, Hemlibra remains the global standard of care. We've reached 37% of patient share in our largest markets. We now have 20,000 patients treated globally, and we continue to penetrate across all approved patient segments. The EU recently approved a label expansion to moderate patients, which is fantastic for those patients to have another option. We expect further patient share gains in the non-inhibitor population, and we also have the SPARC gene therapy pivotal phase three to be initiated this year. Moving on crevalumab so Thomas had mentioned this as well, we have now seen three positive phase three trial results and P and H and will be expanding into additional diseases, the Commodore one two studies and both. Switch patients and naive patients will be presented at EHA here shortly. That will be accompanied by a virtual IR event. We also see the phase three China Commodore 3 studies, which we had already reported, showed a positive result. That has been filed in China with breakthrough designation and priority review. We expect that to be Roche's first China-first approval, and that is expected later this year and global filing plans Global flying is planned for half one of this year. As you can see, we have quite an extensive development program for Krivalumab and a number of complement-mediated diseases, including AHUS, sickle cell, and lupus nephritis, which will be initiated shortly. For immunology, we saw about a 15% decline in quarter one. This is largely driven by COVID-19 sales and the loss of Esprit exclusivity. Excitingly here, we see the auto-injectal approval and a phase three food allergy readout expected in 2003. This is a wonderful continuation of the Zoller story. Zoller is a little bit the energizer bunny in some ways. It's a molecule that just keeps going on. We do actually now believe that we will not see biosimilar competition for Xolair until 2025, and it continues to be a market leader in asthma and show very strong growth in CSU. In other news in immunology, we have the phase three Regency-Gaziva trial in lupus nephritis fully recruited with a readout expected next year. Many of you will know that I'm actually personally very excited about the lupus nephritis trials based on the strength of the nobility trial, the phase two that read out some years ago. This is an area of extremely high unmet need where there's a strong scientific rationale for B-cell therapy and could represent a very significant market opportunity for gaziva. And also for gaziva, we have initiated a phase three in pediatric nephrotic syndrome. Switching over to multiple sclerosis, Ocrevus remains the standard of care reaching 22% market share. We have reached a milestone over 300,000 patients treated globally. We have the number one treatment in both total share and brand share in both the US and the EU5. We have a much higher retention rate we're seeing with other medicines. We will see the phase three results for this every six month at home subcutaneous Ocrevus device expected this year. and we are also getting very close to completing enrollment for the high-dose study for Ocrevus. We continue to expect further market share gains and additional growth with Ocrevus. That sub-Q data will allow us to tap into an entirely new part of the market for multiple sclerosis and could drive considerable growth for Ocrevus going forward. We also have the first phase two data for Phenobrutinib reading out in RMS. This is the Phentopia biomarker data actually that will be coming out this year. This is the first data set for Phenobrutinib in MS. But it is sort of important to note that I think this is actually a molecule that we haven't necessarily talked a lot about, but that is actually pretty exciting. This is a highly selective non-covalent BTK molecule. We have two phase three trials or three phase three trials ongoing in MS. We would expect the PPMS trial to read out this year. And we are very much looking forward to seeing the results here. This is a drug that has been studied in a number of different indications. We have safety data in 2,000 patients across multiple indications. 1,000 of those patients are NMS, and we have not seen any cases of confirmed Hyde's Law in fenbrutinib to date. So still much more to see here, and this is gonna be one to watch. Moving on to spinal muscular atrophy, another pillar of our industry-leading neuroscience set of products. Evrizdi is the market leader today in the US and Japan. We are increasingly penetrating in the treatment naive patient segment. We have reached 8,500 patients treated worldwide with a retention rate of about 90% of patients globally in the first 12 months of treatment, which is very significant. In the U.S., we see that growth driven by both switch and naive patient starts, including patients under two months of age. And in the ex-U.S., we're seeing continued strong growth in share gains in all major markets. I think the other thing that's actually interesting to note here is that, you know, we've talked previously about the need to penetrate in the adult segment for Evrizdi, and we are now seeing significant penetration happening in the adults segment, which is globally, which is actually a really great advance for these patients. We'll talk a little bit more about the sunfish data on the next slide, but those data were recently presented at MDA. In the outlook for 2023, we continue to see continued growth in market share gains for SMA. And in the EU, we are awaiting label expansion from the rainbow fish data for the under two-month-old babies. The Evrizdi four-year data, again, these were presented at MDA 2023. These are very solid data. And you can see here that the increase in motor function scores achieved in that first year are sustained after four years compared to natural history, where you would normally expect to see a decline in motor function for these patients. I think what's particularly impressive about the Sunfish data is that this was a very diverse study population. These patients were between two and 25 years old. They had considerably more advanced disease. The fact that more than 65% of them had scoliosis I think gives you a sense of the severity of the patients enrolled in this trial and frankly just reflects a much more real world population. than we typically see in clinical trials. So this is a great indication of what your average treater is going to see in their own patient population. You can see very good functional score maintenance, but also very encouragingly, our AE rates decreased over this 48 month period with both AEs and SAEs reflective of the underlying disease. Treatment adherence was at 99% and there was no AE that led to withdrawal or discontinuation during this trial. So again, I think another data set that really just continues to underscore that Evrizdy will continue to have very important leadership place in SMA for many years to come. And finally, ophthalmology. So this very strong Vibismo launch continues. We have hit double digit market share in AMD and mid single digit in DME. So based on our February claims data, we see 12% market share for AMD and 5% in DME, and we see corresponding decreases in the competitive set. We have strong uptake with switches primarily coming from ILEA with use in naive patients further accelerating. We have over 860,000 vials shipped globally in the first 24 months of launch. This is up from I think 430, but just three months ago. So you can really see the acceleration in adoption happening here. This is all demand driven. And so I think you can really see the dual action, the drying and the durability story is really resonating with patients and physicians. And we're just seeing incredibly positive uptake and feedback from the entire community around Vibismo. We're gonna talk in a minute about the positive phase three results for Vibismo and RVO, which we'll see at Angiogenesis 2023. And then we have the phase three post hoc analysis in both AMD and DME, which indicates greater retinal drying for Bovismo versus ILEA, which was presented at ARVO. So again, I think just really underscoring this idea of drying in that dual action is really important and a very key thing that retinal specialists look for when they treat their patients. For Bovismo, we would expect to see continued growth in market share gains in both AMD and DME while we pursue filing in RVO. And I think we have every reason to believe that Vibismo will become a standard of care for patients who require IVT therapy. It's also worth noting that we have seen positive phase three data result, we have seen positive phase three results for SysVimo in both DME and diabetic retinopathy. Both of those data sets were presented and we continue to work very diligently to make the improvements which will allow us to bring SysVimo back to patients in the US and restart our clinical trials and resume our filing activities. In Vibismo, we have positive results in RVO. And I think in particular, the improvement in macular leakage compared to ILEA is impressive. Vibismo achieved robust BCVA gains and reduction in CST across both studies. At week 24, you can see that more patients achieve that absence of macular leakage, which is a very important clinical data point for treating physicians. and these results are to be filed globally with regulatory authorities. But I think the body of evidence around Vibismo just continues to grow, it continues to improve, and it's worth noting that the RVO patient population represents about 15% of the $15 billion retinal market, so not an insignificantly sized opportunity that we will be pursuing. And finally, the 2023 key late-stage news flow. So Thomas covered much of this, and we talked about many of these things throughout the course of my presentation, so I won't duplicate. Just a couple things to maybe call out that we haven't spoken to precisely. Thomas mentioned the DMD. the phase three Embark study. This is the Serapta 9001 trial in combination or in partnership with Serapta. We believe this to be approximately a $2 billion market and has the potential, I think, to be one of the most successful gene therapy launch, XUS. These boys really have no other option. The data so far has been very compelling and I think we're very much looking forward to being able to launch this drug. And then also the TNK's timeless study we'll read out later this year. And this allows us to actually potentially expand the window for stroke patients up to 24 hours, which again, just dramatically increases the number of patients that you might be able to successfully treat for stroke and would potentially mean that there's a lot less disability for these patients over time um so many more uh line extensions to read out some exciting new enemies to read out um and overall another another very busy year for roche and pharma and so with that matt i will pass it over to you to for an overview of the diagnostics division thanks very much theresa so good morning good afternoon everyone it's my pleasure to present the q1 2023

Diagnostics Division sales results. So with sales of 3.6 billion Swiss francs, the Diagnostics Division declined by 28% compared to Q1 2022. And this decline is entirely driven by the expected decrease of COVID-19 testing sales by minus 1.6 billion Swiss francs. When excluding COVID-19 testing sales, our base business growth is plus four percentage points. So if you look at the sales, both of our COVID-19 business, as well as our base business, from Q1 of 2021 through Q1 of 2023, what you see is in Q1 of 2023, COVID-19 testing sales were at 300 million. Now this is down 85% versus Q1 of 2022 when COVID-19 test sales and COVID-19 related business peaked as a result of the Omicron wave. As I said, in Q1, base business growth was plus 4%, excluded COVID-19 testing sales. Now, when taking into consideration all sales impacted by COVID-19 testing, which we call COVID-19 related business, the growth in Q1 2023 would have been actually three percentage points higher. For our upcoming quarters in 2023, we are expecting a mid to high single-digit growth of our base business, while our COVID-19 testing sales will continue to decline significantly along with the incidence of COVID-19. So if we take a step back and look at this by product category, sales in our core lab business increased by 7%. The base business, excluding custom biotech, which is related to COVID, grew at plus 10% with very strong momentum driven by our immunodiagnostics and clinical chemistry. Our molecular lab had a decline of 48%, and this is due to lower COVID-19 PCR-based testing sales. However, excluding the COVID-19 related business, molecular lab is growing at plus 7%, and this is due to strong growth in virology-based business at plus 12%, our blood screening franchise at plus 15%, and our cervical cancer testing business at plus 22%. Now, looking at point of care, you see a decline of 72%, and this is driven entirely by lower COVID-19 rapid antigen and COVID-19 molecular point of care testing sales. The base business grew at plus 13%, and this is due to a high incidence of seasonal respiratory virus testing driving LIAT sales, particularly in the US. Our diabetes care business had a 5% decline, and this is driven really by the continuous market shift from traditional blood glucose monitoring to continuous blood glucose monitoring, or CGM. Sales in our pathology lab grew strongly at plus 7%, and this is mainly driven by advanced staining immunohistochemistry reagent growth and companion diagnostics. So if we look across our different geographic regions, what you see is the impact of lower COVID-19 testing sales across all of our regions. However, excluding the COVID-19 related business, we see strong base business growth across all of our regions. In North America, the divisional base business excluding COVID-19 related business grew at plus 6%, and this is driven by all of our customer areas. In EMEA, the base business excluding COVID-19 related business grew at plus 3%, and this is really driven very much by our core lab business. In Asia Pacific, sales grew at 11% when excluded the COVID-19 related business, again, due to strong growth in the core lab. And in Latin America, sales grew by plus 21%, again, excluding all COVID-related business, and again, driven by the core lab business. So when you really take a step back and look at what's driving the growth of the diagnostics business, a big part of it is the expansion of our installed base. And so what you see here is the growth of some of our different product lines in 2022. And I'll take you through a few high systems, the Cobos Pro, which is higher volume. And we launched this in 2018, December, 2018. And the CoBOS Pure, which is mid to low volume, which we launched in April of 2021, these are growing at 122%. You see this heavily reflected in the growth of our core lab business. In the molecular lab, our CoBOS 5800, 6800 and 8800, which are fully automated systems for low to high throughput testing in molecular diagnostics, grew by 33% in 2022. And this will be an engine for future growth and menu expansion. I call out that this was 30% growth in the third year of the pandemic, which shows really resilient demand for these products. I would also like to point out the great growth of Cobas Liat. This is our molecular point of care system, which grew at 24% in 2022. So moving to the pathology lab, you see our digital pathology systems, the DP200 and DP600 slide scanners grew at 29%. And our workhorse instruments, the HE600 for primary staining, as well as our benchmark Ultra and Ultra Plus for immunohistochemistry analysis grew at a healthy plus 12% and plus 10% respectively. So this expansion in our installed base is really gonna ensure future growth for reagents in the years to come. So, While it's important to grow your installed base, it's also important that you continue to have a healthy and innovative reagent portfolio. And so I'm gonna focus here a little bit on our core lab menu. And with over 240 assays, we have the broadest clinical chemistry, immunoassay menu, what we call serum work area in the industry. And every year we are launching additional indications and tests for our already industry leading menu in core lab. For example, as an average over the last three years, we achieved on average six FDA approvals and 11 CE marks per year. And you saw it in the slide from Thomas, and you also see it here across the three different years that we call out, a growth in our hepatitis portfolio. And having a full comprehensive hepatitis portfolio is really critical because customers in the infectious disease segment of immunoassay really wanna see that full menu, and that makes us even more competitive in this growing market segment. But we're also investing in line extensions for some of our existing products, such as NT ProBNP, where we recently added a claim extension for heart failure based on our StrongHF trial. And you also can see in the left side middle column at the bottom are Alzheimer's cerebral spinal fluid biomarker, which received FDA approval last year in 2022. This biomarker had actually previously received FDA breakthrough designation. And in the coming years, we're gonna continue to grow the neuroscience portfolio because we see this as an important area to innovate for patients, but also an important market section going forward. So now I'd like to turn to our digital solutions. And we're really committed to building digital solutions for our laboratory customers that enable more efficient laboratory management, but also clinical decision support for physicians. If you look on the far left, you see an example of a laboratory. All of our laboratory customers are potential customers for our digital solutions. And this is where we can add additional value to customers and also deepen our relationships. In addition to revenue that these digital solutions will deliver, they will also make us stickier, and have higher customer retention in the labs and hospitals that adopt our solutions. Like I said, every one of our customers is a potential customer for our digital solutions, and they can access our digital applications for improved laboratory efficiency as well as clinical insights through our Navify portal, if they're an existing customer, or if they're not an existing customer, through our Navify marketplace. And you can see on the far right, some of those solutions that will add additional operational efficiency, such as Navify Inventory or Navify Analytics. This helps our customers run their lab in a more efficient manner to achieve better economies of scale, better control of their inventory. But I'd also like to call out the launch of our new Navify Algorithm Suite. This will help physicians by delivering clinical decision support. We will continue to populate this with clinically validated algorithms to aid and improve clinical decision making in the future. And so, You know, we really talked a little bit about some of the high medical value, like, for example, with Alzheimer's. And I want to call out that it's important to have, yes, the broadest menu in the industry, but it's really important that we deliver innovative medical testing solutions that change the standard of care. And so here I'd like to focus a little bit on our Ventana Full R1 RxDx assay, which is the first FDA approved companion diagnostic test for ovarian cancer. Ovarian cancer is a terrible disease affecting about 322,000 women each year. And I'm sure most of us all know someone who has been diagnosed with ovarian cancer. It's got a high disease burden and the severity really drives the need for new therapeutic options. Our fall R1 immunohistochemistry test has been co-developed with a new drug for second line treatment in ovarian cancer. It recently received FDA approval as the first companion diagnostic test, enabling pathologists to identify patients who may be eligible for the new therapy. And this really highlights Roche's commitment to have the broadest menu, but again, importantly, high medical value tests that deliver critical answers for patients. So you'll see here the list of launches that we have in 2023 across instruments and automation, new tests, as well as new digital solutions. We're off to a good start and I look forward to updating you on our progress in future calls. And so with that, I'll hand it over to Alan.

Oh, thanks, Matt. Yeah, I think Theresa, Thomas and Matt explained the sales development already, so I don't want to be redundant either. Let's jump really directly to slide 45, because I want to certainly talk about the currency impacts as a sales call. So what you see on slide 45 is, on one hand, the sales development over the region on the pharma side. And I think pharma really developed very, very well, as explained. And then you see the decline in the diet division. I think Matt pointed out, I think underlying, the business has grown 4%, perhaps even a little bit more if you look at the COVID-related sales. So really underlying, really great momentum, which leads us to the minus 3% sales decline for group in constant rates. If you then move over on the right hand side to the Swiss franc, then you see really a minus seven percent. So evidently we lose an additional minus four percentage points due to currency impacts. And I would like to explain now these minus four percentage points on slide 46. So one more. And what you see here is really basically every currency has weakened against the Swiss franc in that period. And you see, really, on one hand, the Euro weakened. You see, really, APAC here, the renminbi, plays a major role. And then I think you see the Japanese yen, which has also contributed to the development quite significantly. So now the question is a little bit, okay, what's going to happen further? And you know these tables, so let me start on the left-hand side. And there you see these dark blue bars, and they once again highlight what has happened with the US dollar and the Euro against the Swiss franc in the first quarter. And what you see is, as mentioned, I think really roughly a minus 4% triggered by the euro. You see a pretty stable situation, Swiss franc, US dollar. And then I think when you move over to the right-hand side, you see our projection for half year and for full year. And you know how that projection is done. It's basically assuming that all currency rates at the end of March 2023 remain stable until the end of the year, which is a pretty unlikely scenario, but I think directionally, perhaps at least a certain level of orientation. And you see for Javier, what we expect if we do this and if you model it like I explained, you see sales a minus five percentage points, the cooperating profit a minus five percentage points and on core EPS a minus six percentage points. When you then go for the full year projection, which is very hypothetical admittedly, but nevertheless, And you see really in sales a minus four percentage points, incorporating profit a minus four percentage points and in core EPS a minus five percentage points. Good. With that, I think, as Thomas said, we confirm the guidance for the full year 2023. And that certainly includes the roughly five billion loss in COVID sales. And it also includes the roughly 1.6 billion loss in AHNR due to biosimilar competition. In addition today, I would like to promote an event from Investor Relations about ESG and this time we will dig deeper into environmental sustainability. Certainly the major lever for Roche when it comes to sustainability is access to medicines and to tests. Nevertheless, I think certainly we take care of the environment as well and we would like to demonstrate to you what we do in these areas, because we have quite something to provide. Good. With that, I think we're all happy to receive your questions. Thanks.

Thanks, Alan. And with that, we will open here the Q&A session. We have 10 people in the row and 40 minutes left. So I would recommend that each analyst sticks with two questions. And I would also recommend that we try to get the answers within four minutes then done. The first two questions would come from Matthew Weston from Credit Suisse. Matthew, please.

Thank you very much. Hopefully you can hear me. Two questions, please. The first one, a simple one. Obviously, the ramp up of the BISMO has been a very positive surprise to many. Was it a positive surprise to you? Can you make enough? Is there a risk that supply shortages become a challenge later in the year? And then Thomas, a much bigger strategic question for you in your role as a CEO. You flagged the changes to the exec. You also, as Roche, spend a great deal on internal R&D. You've basically added more cheerleaders for innovation to your management committee. How can you be sure that you're getting value for money for that R&D? Do you think M&A has a more significant role at Roche in the coming years? And if so, what therapeutic areas are interesting? I'm going to take the quick one.

No, we do not expect any problems with supply.

Lots of time for the long one.

Yeah, exactly. So let me start with M&A. We are always open to M&A and we always check all the opportunities that are on the market. Now, they have to make sense from a scientific perspective. They have to make sense from a financial perspective. And so we have to have the discipline to make sure that we only buy things that make sense. And with that, I don't think our strategy towards M&A has fundamentally changed. As in the past, we are always looking at all of the opportunities. Now, the early stage opportunities, there may be more opportunities now simply because of the funding issues in the biotech sector. I think in the late stage opportunities, There are not that many and it's much more competitive. So I would say we don't see the same kind of dynamic as we see in the early stage phases. Now, regarding R&D. And I showed it in one of the slides. If you look at end of 2015 or even 2016, until now, we've launched 19 new medicines. And these medicines will carry us for the next few years. It's clear that as an innovative company, you have to keep innovating. And we did have with Levi Garraway, already a head of pharma development and chief medical officer. The only difference now is that they all sit on a corporate executive committee. And I think it's actually a strength because we have three very good leaders, very strong scientific leaders. medical minds that can also challenge each other and make sure that we make sure that as an organization we continue to stay at the forefront of innovation and that's also my goal that we look into our pipeline we look at all the opportunities we have and to make sure that we accelerate our pipeline what we have internally and and that's what we're going to focus on

Thanks, Thomas. The next two questions would come from Lisa Hector from Bloomberg. Lisa, please.

Thank you, Bruno. I have a question, a sort of more general question on the subcutaneous formulations, maybe with a few questions within, but I'm trying to just understand the IP around those. So maybe if we take the legacy subcutaneous offerings that you have, I know that there's some potential for IP to end soon. So how do you expect potential biosimilar competition on those? How do you think subcutaneous formulations will be treated under IRA? And specifically on to centric, what kind of opportunity do you see for the subcutaneous? And then if I'm able to have another one, just maybe a quick comment on the COPD trial, because you have the phase three that started, just anything on profile and how you have learned from competitor studies in the past. Thank you.

So let's start with the potential for sub-Q with Ticentric. So we actually think that the sub-Q for Ticentric has the opportunity to be quite protective for Ticentric, right? It will be the first PD-L1 that has a sub-Q formulation, I think, in those places where Ticentric is currently being used. It's a great convenience for patients that will allow it will allow providers and healthcare systems to actually treat more patients than they have been able to. So I think the potential, while somewhat, what's the word I'm looking for, protective, may also have the opportunity to help us grow slightly with Ticentric. in terms of the ip implications of our subq formulations i think that that isn't something that we would typically comment on publicly other than to say that we will always continue to look for ways to protect the ip of our pro of our programs and it is it is possible that the subq formulations may help extend that ip when it comes to biosimilar competition with some of the more um i would say innovative uh With some of the more innovative devices that we are looking at, I think it clearly would provide some protection against biosimilar competition. I think that's particularly evident in things like Progetta or with, excuse me, Fezgo, where we think Fezgo and the strong conversion that we're seeing to Fezgo will actually help mitigate some of the biosimilar impact for Progetta. In terms of IRA, I think there's a lot that we still don't yet know about how the IRA will be implemented, and so it's probably too soon to really comment on that. In terms of the astagolamab profile in COPD, so I think everybody knows that this is an anti-SD2 ligand for IL-33. This is increased in COPD. Unlike our other IL-33 competitors in COPD, we actually work against the receptor. And so there's a possibility that we would actually have a different mechanistic advantage. Again, that will just have to play out in the trials. We do have a phase three that has been started. I think that the big differentiation piece for us with Astegolamab is really that our trial, we believe, has the potential to help patients who are both xenophilic high as well as xenophilic low. The data that we've seen read out so far has really only been in those ESO high patient populations, but the ESO low patients actually represent the vast majority of COPD patients. with about 80% of COPD patients being ESO low. Our trial also looks at smokers and as well, current smokers, as well as former smokers, which again is a little bit of a subtlety of the patient population that we're looking at in these trials. And it's probably worth saying that the move to the phase three is for astagolamab and COPD, these are gated trials, so they will be gated on an analysis to make sure that we're seeing the benefit that we wanna see before we proceed.

Very good. So I think we are still on time. So next one in the row is Sachin Jain from Bank of America. Sachin, please.

Sachin, please. Hi there. Can you hear me now? Yes. Thanks. A couple of questions. So firstly on Tidget, I wonder what visibility you have on the second interim And does that give you or retain your confidence in the final OS or should we be more muted in our expectations here? Just note some discussion seems to be on further phase three starts for the molecule. So just wondering what's giving you confidence there. Is it the interim? Is it Sky 08 or something else? And then second, just broad question for you, Thomas. You know, you've done a lot of roadshows in your transition period and there's a lot of investor debate. On mid term growth outlook so wonder if you can give us any color your seat now that you've I guess been through business planning process on sustainability. Of the underlying mid send signal digit growth you're seeing this year through the 27 and thoughts post given the young portfolio you reference just sort of interested in how you're seeing growth outlook versus what consensus currently models thanks.

Sure, you take TIGIT first and then I take the growth outlook.

Okay, great. So I think we continue to be really interested in the TIGIT pathway. We continue to think that this has a lot of mechanistic and biologic rationale and could still potentially be something that helps redefine what cancer immunotherapy treatment looks like going forward. So I think in addition to the trials that we're currently running, we do continue to signal-seek in different combinations and in different tumor types. You will likely see us announce additional trials and additional phase three starts, given the evolving data that we're seeing. In terms of SkyOne, we are continuing to final analysis. We expect that final analysis to be in Q3, but it is an event-driven trial. um and there are several other data sets that we'll read out later this year as well so i think you know the story on tiget is far from fully written i think there's a lot we still don't know and we will need to wait for the clinical trial data to read out um but again i don't think that there's anything that we've seen thus far and that would lead us to believe that this doesn't potentially have a meaningful role to play in the treatment of cancer going forward

Yeah, let me answer that question in two parts. First, the next couple of years. And I've mentioned that we have launched 19 new medicines since the end of 2015. And these medicines will carry us for the next couple of years. And most of those medicines, I think there are only two that have patent expiry only at the very end of this decade. At the same time, we know we need to deliver more medicines. So already this year, we're going to most likely launch three new medicines. One with ColoV, so clofidamab, the CD20, CD3 bispecific antibody, then Crovalimab in PNH, which we're taking into also other indications. and then the gene therapy for the chain muscular dystrophy. But beyond that, I think we do have exciting things in the pipeline. If you look at gerodestrin, as we're taking it into the earlier line and looking at that data, we are hopeful that this pathway is relevant in populations that have not been so heavily treated. Tirogolimab. As mentioned by Theresa, everyone's focusing on one trial. We're starting multiple additional trials in phase three. So we have many additional opportunities to go them up. Theresa mentioned gaziva in lupus nephritis. Again, it's a great opportunity. And I could continue. Again, I think one thing that was mentioned was phenobrutinib, PTK inhibitor, which is very differentiated because it doesn't bind covalently and it's very selective and doesn't have the side effects that some of the other pharma companies have been reporting. PD-1, LAC3, Inovalsib, then the KRAS. So I think we have many shots at goal. And at the same time, M&A was mentioned. So we're always open to outside opportunities as well. I mean, that's just part of how we need to do our business. So we know every single medicine that's going to deliver the growth in the second quarter. or let's say in the last couple of years of this decade, but we have many opportunities. And just looking at the track record of Roche, delivering two to three medicines every year, I think you can believe and trust in Roche that we will continue to innovate, to stay in the forefront of innovation. And I can also say it's my biggest focus in this company, and that's where I've spent all my time in the last couple of months. Thank you.

Satya, did we answer all your questions? I think you also had a question on Sky 8. Sky 8, we will provide an update towards the end of the year.

Thank you.

Okay, then we move on. Next one would be Michael Leuchten from UBS. Michael, two questions, please.

Thank you, Bruno. Just one really for Thomas. In your fact-finding in the last few months, just wondering how you... ran the filter over the pipeline? Is it just number of products with a probability assessment? Is it modalities? What's the framework you apply to it? And the reason I'm asking, you have R&D now reporting straight into you, so I'm assuming that this is sort of your initiative on how you would assess the pipeline in that function that is not reporting into you.

Yeah, so I've spent a lot of time in research and development, both in the REDS but also in late stage. Obviously, we have 83 enemies with, I think, 150 different projects. So quantity is not everything. It's also about quality, making sure that we have the right quality of our pipeline. uh pts is obviously something that's important being first first in class best in class also when we bring in opportunities from the outside making sure that those have first-in-class and best-in-class opportunities now when it comes to modalities as a company we've always been open to look into you know other types of you know technologies but also in terms of other disease areas If you look back in the past, we were very oncology heavy. But again, if you look at the pie, you see that we've gone into new areas such as neuroscience, Haemophilia A, ophthalmology, where we were not present in many parts of the world. So, you know, in the past we've said we follow the science, we make sure we have best in class molecules, and that's what we will continue to do. And that's going to be my focus and the focus of the team to constantly up the game when it comes to a pipeline and keep raising the bar. And with that, I think the quality of the pipeline and quantity both make a difference.

Okay. Next question would come from Richard Park Saxon. Richard, please.

Hi, thanks for taking my questions. Firstly, I just wondered if you could just discuss your confidence that the phase one data for Fezgo on body injectors sufficient for approval, looks like that would position you to launch obviously well ahead of expected biosimilars. And it sounds like it could give good protection to the franchise. So could you just discuss your optimism on that and how much of the franchise you think could be protected once biosimilars do become available for Fesco and NeonBody. Then second question was just on backfilling of the late stage pipeline. You've confirmed, I think, three programmes to move to phase three in terms of NMEs, the Factor B, the Haemophilia and the ST2 in COPD. I just wondered if you could talk about what other NMEs you could see move to phase three over the next 12 months or so i got the sense the multiple myeloma by specifics might be ready to accelerate going forward so just wondered if you would be willing to put any kind of numbers around that in terms of enemies moving to phase three thanks

Great. So maybe I'll take the first one and you can take the second one. Okay. So confidence in the phase one being sufficient, I think our intent is to file the trial that we have currently ongoing. That data is expected mid-year. Again, I think it's important to note that that would enable treatment at home. It is a significant advance for patients. So I think we would be excited to bring that to the market. And I do believe it would provide additional franchise protection from biosimilar entry.

Yeah, so from my side, I've mentioned a number of different enemies that we have a lot of hope in. I think pterogolimab, even also beyond the skyscraper one study, but also goceiva in lupus nephritis, in evalsib, PD-1-LAK3, so the bispecific PD-1-LAK3 antibody. So we have a number of new potential medicines where we will continue to start phase three studies to make sure that we have new medicines also coming to the market.

And just think about things that were accelerating quickly out of the reds. I think the ISO factor B in IGA and that was another one that was rapidly accelerated. The IL-6 in UME was another one that was rapidly accelerated. So I think we're always looking for opportunities to bring things forward as quickly as possible.

Thank you. Next questions would come from Richard Fossum. Richard, please.

Thanks, Bruno. Thanks, guys. So first question on to Centric. Could you maybe talk about the competitive environment and how you see that developing, particularly in adjuvant lung cancer and how you see the growth outlook for the product there? And then maybe a similar question on diagnostics. You sort of highlighted the 4% growth, but confidence to get into the mid to high single digits in the second half. Maybe you could talk about what was dragging on the demand in the first quarter or leading to lower growth and maybe talk about what you're seeing in the market, whether you think growth will normalize after this year back to historical levels or you still see a boost on growth there and maybe linked. What sort of benefit from Alzheimer's testing do you think you could have in diagnostics in in 23 and beyond? Thanks.

Starting with Ticentric, I think that the adjuvant lung space is actually really interesting right now. I think what's interesting with being a first mover in the adjuvant lung space, again, we've seen diagnostic testing rates now approaching 90 percent. We see many patients actually being put into the treatment funnel, which is fantastic. This is a place where having first mover advantage, I think, has been really useful and helpful to Centric. We have a very intuitive label based on what our clinical data is. And I think we have some really good installed experience within the adjuvant lung space. What's been an interesting development over the past couple of weeks is sort of the perioperative space. So I think at AACR last week, we had two of the competitor drugs actually shared their data in the perioperative space. And I think what was interesting is that right now with the data cuts that we're seeing, we're actually not really seeing appreciable difference in treatment outcomes for perioperative treatment relative to just treatment in the adjuvant setting. And so what this will actually mean for the treatment of patients is perioperative become a standard of care or not, or does the fact that we have patients we have that first mover advantage in adjuvant lung, I think that actually sets to centric up quite well. Well, our own perioperative study, it was pushed out into 2024. I think the thing that might work in our favor actually, is you may just need to see more time on therapy in order to see the difference between perioperative treatment and adjuvant treatment. And so it might actually help us when we read out our trial, because we'll have patients who will have been on treatment much, much longer. But we do expect Ticentric to grow double digits in 2023, and a good chunk of that growth will be driven by adjuvant lung. It's important to remember that adjuvant lung is just in the process of launching in many parts of the world and gaining reimbursement. So there's still a lot of new patients who could benefit from adjuvant lung. We also have obviously just read out the RAVE 050 data in adjuvant HCC. We have the adjuvant head and neck trial and VOCO 010 coming. So there's a lot of additional adjuvant data coming for ticentric and potentially some very large indications. And again, in at least two where we know we'll have first mover advantage, adjuvant HCC and adjuvant head and neck.

Thanks, Teresa. So good question on on the diagnostics growth. So like I mentioned, we saw plus 4% growth of our base business. And you mentioned a drag. As I mentioned, that is what we call COVID related business. And the example I gave, which I'll just reiterate, is our custom biotech business where we manufacture many of the components for COVID testing for other companies. Now, as that testing goes down, so does that business. And so we estimated in the first quarter that constituted approximately three percentage points of growth. So to answer your question, that's how we see the drag on Q1. We know that COVID testing more or less peaked in the early part of last year, so we expect this to decline over the course of the year. And as far as what we see going forward, I would just reiterate what we've got it for, which is mid to high single digit growth of the diagnostics business. Your second part of your question around Alzheimer's, this is really going to depend on a couple of things, which is some of the adoption of the disease modifying therapies, which you've seen some promising results from a variety of companies and their adoption and reimbursement is really going to lead to some of the increased need for these diagnostics modality. While we're optimistic about the potential for this to change medicine, I don't think we have a specific guidance on it at the moment. Does that answer your question?

I hope so. Then we move on. Next question comes from Tim Anderson from Welfare Research. Tim, please.

Thank you. On Vibismo, you say switches are coming primarily from ILEA, but wouldn't that be fully expected given that that's the product, the dominant market share? Or is there some nuance I'm missing to that comment? And can you say what the market share is in naive patients? And then on TIGIT, if I could just go back to Skyscraper 08, clintrials.gov recently amended to say the primary completion date was more than two months ago. That suggests a milestone has been crossed. You're saying we're going to get data later this year. To me, it raises the possibility that PFS didn't hit and it's still ongoing for OS mirroring what you saw with Sky 01. Is that the right way to look at it?

Yeah, so maybe start with Sky8. I would say that that isn't the assumption that I would draw. And as Bruno stated, the data will be shared later in the year. In terms of the switches from ILEA, clearly ILEA has a dominant market share. And so clearly we would expect from a numbers perspective to just see more patients. coming over from ILEA. But again, I think it speaks very highly for the clinical acceptance of ILEA that we are seeing a move much more into naive market share. And I am actually trying to remember actually what the... what the naive share is. Have we disclosed that yet?

We haven't really disclosed it. I think we've been communicating 70% to 80% are switches from Eylea, depending on the indication, and then 50% to 20% for Lucentis, depending on the indication. So the remainder is basically the naive patients, and they have been keeping increasing over the last three quarters.

Exactly. So I think this is one of those things that we'll continue to see evolve over time. But it is when physicians start seeing the benefit in their switch patients and they start moving in mass to naive patients that we will really start to see the acceleration take off. And I think that's the inflection point that we're quickly getting to.

Yeah, and let me just add one thing on Skyscraper 08. So this is a China-only study comparing to chemotherapy, which now is no longer the standard of care. And so I think it's going to be important to wait for the Skyscraper 07 readout, which is going to compare to immunotherapy.

Thank you. And we go on. The next two questions would go to Marc Purcell from Morgan Stanley.

Yeah, thanks very much, Bruno. I hope you can hear me.

Yes.

Two clarifications, but then just one initial question. On GAV-Cyber, I think you've said this could be bigger in immunology compared to oncology. In oncology at the moment, it's analyzing cells of over 800 million Swiss francs. So I wonder if you could help us understand that ambition and cell potential in lupus based on the Phase IIb data that you described, Teresa. And then two clarifications. On TIGIT, I guess some of the data you've seen that we haven't seen combines TIGIT with chemotherapy, whether that's SkyO6 or SkyO8 in combination with Ticentric, so triple combination, triplet therapy. So is there something mechanistically you can help us understand that chemotherapy actually adds the durability you can achieve with TIGIT in terms of resistance pathways? And then secondly, just going back to Richard Voss's question on on Tocentric in the IO and Tocentric in the adjuvant non-small cell lung cancer setting. Could you help us understand the share that IO drugs have in adjuvant non-small cell lung cancer and specifically what Tocentric's share is of new patient starts in adjuvant non-small cell lung cancer, just so we can understand the dynamics going on there. Thank you.

Great. So gaziva, I think, could be easily a billion dollars plus in immunology if we get lupus nepritis, if we get SLE, if we get pediatric nephrotic syndrome. These are potentially very large indications and ones where today, often they're undertreated because they're just, you know, other than steroids and other things, there's not a significant amount of immunology You know, there's not a significant amount of treatment options available to these patients. So once you actually get something that's available that we know is efficacious and safe and and and available to patients, I think you can oftentimes see these immunological markets actually become bigger than we had originally thought. So I easily think that if this either hits in these indications, these could you know, this could be over a billion dollars just in immunology. um in terms of tidget with the chemo combos triplets does this add to durability no i i don't think that that we believe that it's a durability play i think this is all about trying to get to the right level of efficaciousness um given given the particular treatment setting um and i think that does become important for example you know in in china that that was the treatment setting um ios were not really widely available at that time, so we chose to combine with chemo. And in terms of to centric market shares and adjuvant, I don't believe that we've disclosed those previously.

No. Yeah. Okay, thank you.

Okay, next two questions which come from Emily Field from Barclays.

Hi, thanks for doing my questions. One on hemophilia, you know, your competitor launching the novel long-acting factory product has talked about potentially taking share from Hemlibra and prophylaxis down the road. You know, is that something that you're concerned about as that product is launching? And then has the next generation by specific entered the clinic yet? If so, when could we potentially see some updates there? And then just going back to phenobrutinib, you know, there's been a lot of focus on the toxicity profile of these assets. I think you mentioned phenobrutinib When we could see the PPMS update, I believe that had to have versus late in pivotal trials for the competitors. So just, is it something about your molecule design that's giving you the confidence there or just the number of patients tests that you mentioned? Thank you.

Yeah, great. So for Hemlibra, I don't actually really see the long acting factor being a significant threat to Hemlibra patients that are currently on treatment. We believe that this is primarily gonna impact the factor class, but for patients who are on prophylactic treatment or for whom prophylactic treatment is appropriate and what they desire in their therapy choice, Hem Libra is the standard of care. And so I would be very hard pressed to see patients who are currently well-maintained on Hem Libra actually switching to a long acting factor. The majority of our patients are on at least every other week dosing already. So it's not any more convenient. And again, I just think that the standard that Hem Libra has set for the patients Mary E Gallagher- The annual bleed rate for the convenience for the safety it just hard for me to imagine that people would switch off to go back to factor I just really don't see that happening. Mary E Gallagher- The next generation by specific is currently in phase one that's phase one that's being run by to die and where we're obviously working closely with them on next steps. And then there was one additional question. Oh, fenabrutinib. I think there's a number of things that give us confidence about this molecule. One, I think mechanistically it is different. It is more specific. It is uncovalent, so it has a different binding. And then we also just do have a lot of patient experience across a number of different indications with fenabrutinib. So we obviously are monitoring the, we're monitoring the safety of this program very, very carefully. There's an IDMC that is, is very, very involved in really looking to make sure that we're taking safety extremely seriously in these trials, as we do with all of our trials. But at this juncture, we have over 2,000 patients who have been treated with no cases of confirmed Hyde's Law, and 1,000 of those patients have been in MS. So I think it's just the body of evidence that we have in phenobrutinib, along with the fact that it is just a fundamentally different molecule than our competitors have. Mm-hmm.

And maybe to add one argument on the question whether patients would switch over from Mlibe to L2V, I think there's also, I think, some unknowns still, you know, in terms of the safety and whether such patients then would have a higher risk, for example, for developing a herpes. So I think still some blanks on the data. Okay. Then we go on. Next on the list would be Steve Scala from Cowen. Steve.

Thank you. Can you hear me? Yes. Yeah. So I apologize, but I'm confused on the messaging around Tidget. So on Sky 08, you said that we should not assume PFS was missed. So is there any other alternative than PFS was hit? Is there some other alternative that we should think about? on similarly the teragolamab plus texcentric plus chemo study that completed in March. So what should we think about that? Should we assume PFS hit there as well? And if Roche doesn't wish to answer, I'm just wondering what is the benefit to Roche to not being clear on this point? So that's the first question. Secondly, on texcentric and adjuvant triple negative breast cancer, why does Roche think this failed when Merck was successful? What was different about the study design, the patients enrolled, or some other factor? Thank you.

Yeah. So in terms of the TIGIT question, I think the TIGIT space is intensely competitive. And so I think first and foremost, we have a great excitement around TIGIT. We have a very robust clinical trial program that we're currently running. And we are also aware that it is an extremely competitive space. So I think as we receive data that is meaningful and material, we will share it. when we have the SkyOne result, we will share that and you will be getting the results of the other trials later in the year. In terms of the TNBC adjuvant failure, I think we're currently, you know, that decision to discontinue that trial was recently made and we are actively looking at the results of that trial once it comes in-house and is unblinded to us. to determine why we believe that it may have failed and to see what we can learn from that trial that would help us continue to refine additional programs going forward.

We move on. Next one would be Andrew Baum from Citi. Andrew.

Yeah, thank you. Just following on from the earlier question, and I know Roche historically hasn't done this, but other companies have. Given your greater confidence in the post 26 outlook, would you ever consider giving a point 28 or 29 revenue and earnings number to underpin that confidence to the street? And then second for Thomas, I'm sure part of your under the hood in pharma was you have been interim CEO. has been getting some candid feedback from senior internal employees. We've seen the new leadership structure. Whilst I'll acknowledge the internal discovery across areas outside oncology, as you highlighted, Roche failed to future-proof its HER2 franchise. CLL missed out on BTK. ADCs, despite initial efforts, haven't come through. So could you share anything in terms of learnings different from the new management team that you intend to pursue, narrowing therapeutic areas or whatever? I'd be interested. And then finally, if I could borrow from Michael Luxton in this unused question, I owe Mike and I owe you. Could you just tell me what percentage of target events triggered the Sky One OS interim? That would be helpful. Thank you.

Yeah, good. So let me take the first two questions. As in the past, we've never really guided beyond the current year. What we have already said is that the current portfolio of medicines will continue to carry our growth for the next few years. Beyond that, I don't think we should guide. We have not done that in the past and I don't think we should do that in the future. now uh you said that i looked under the hood and that's that's correct and it's definitely being the interim ceo for a couple of months was definitely helpful and as with any company there are always areas for improvements and you've mentioned areas where we've missed there are other areas where we've been quite successful if you look at the bias more If you look at our CD20, CD3 bispecifics in blood cancers, if you look at M. Libra, Evristi, et cetera. But you're right, there are also areas where we can improve. It's an area and a focus of mine that we continue to prove as an organization. We continue to up our game when it comes to our pipeline, even more in the future, to look at both quality and quantity, to look at speeds in the organization, making sure that we deliver ahead of the competition. And that's something that is definitely ongoing and is not done in one or two months or 40 days being in the role. But it's definitely something where we can always improve. And that's kind of also the mentality I want in the organization, constantly raising the bar. And if you jumped over the bar that you've laid, you need to raise the bar again and again. And I think that's the mentality that I would like to have in the organization.

And to answer the question on the Sky1 target number of events for the IA, no, we don't comment on trial details.

Okay. Then we go on. The next one would be Simon Baker from Redburn.

Thank you, Bruno. Two questions, if I may. Firstly, returning to fenobrutinib. Teresa, you said there were no adjudicated cases of Hies law that you've observed so far. I wonder if you could comment on any observations related to elevated liver enzymes. And then secondly, on DMD gene therapy, could you give us an idea about potential manufacturing capacity for that product? What we've done in the past suggests that the volumes required would be fairly significant. I just wonder, is that $2 billion peak indication dictated by capacity or by opportunity? Thanks so much.

Great. So probably the easiest one to answer for DMD, the gene manufacturing question. So that is being largely handled by Serapta. So it would be inappropriate for me to comment other than to say that in our conversations with them, we have confidence that we will receive the supply that we need in order to launch. In terms of fenabrutinib, we had seen elevated liver enzymes, but those elevations were transient and resolved.

Thank you. And then I think we come to the final questions from Peter Welford.

Hi, thanks very much for fitting me in. Just two questions left. Firstly, just coming back to R&D and the broader question, it seems, perhaps I'm being unfair, but maybe a disproportionate number of assets have originated recently from Chugai, particularly, I think, given their budget, if you like, relative to yours. So I guess there's sort of two parts to this, which is one, do you think this is just phasing, if you like, where the different three of the three organizations within R&D go through ups and downs? Or do you think, are they doing something different? And I guess more importantly, if you looked at what you guys are doing, and equally, could you potentially consider more broadly looking at some of the Chugai assets in the future, given I think you've passed on some opportunities that perhaps were outside your area and now look like it could actually have been pretty meaningful. And then just secondly, on diagnostics, this might be a little bit in the weeds, but just trying to understand the opportunities with multiplexing and what you've done so far with the Genmark acquisition. If you can comment any further on that. We haven't heard a lot about it. Obviously, it happened during COVID. Was that a benefit to you or not? And how are you getting on rolling out that and see that fitting within Molecula?

Yeah, so let me first answer the question on R&D. And you're right, Juga has been very productive in developing new medicines. And I've also spent time at Juga. And I have to say that there are also interesting things in the pipeline that will also help filling more our pipeline as well going forward. Yeah. Then you look at P-RED, you look at G-RED. Just looking at P-RED, you look at the productivity there. Evristi came from P-RED. Babaismo came from P-RED. You know, geradestrin and teragolamab came from gerad. So you see that all of the different early research and development organizations keep delivering across the different parts of our R&D organization. And I think that's actually a strength that we have this diversity of approaches in three different organizations that keep delivering new medicines that can then go from phase two into phase three. And if you look 10 years ago, you probably would have said, well, what's in the pipeline of Zhugei? It comes in waves. And so I'm confident that P-RED, G-RED, and Zhugei will continue to deliver new enemies that will then go into phase three. And with that, we'll have new medicines to launch in the future.

Thanks. And I'll take the second part on Genmark. I think we remain convinced that syndromic panel testing is going to be an important part of diagnostics going forward. And we're happy with the performance of our respiratory panel, our blood culture identification panel, and we're continuing to invest in R&D there and looking at future opportunities for things like a GI panel. But we feel it fits very well with our molecular portfolio. We go from point of care molecular testing, high throughput testing in the lab, and then syndromic panel. I think it gives us a very competitive portfolio. So we're happy with how this is developing so far.

So I think with that, we are at the end of our Q&A session. If there are remaining questions, then please feel free and reach out to the IR team anytime. And then I will hand back to Thomas for a final word.

Yeah, thank you very much, Bruno. And thank you very much to all of you for attending today. I look forward to seeing some of you the next couple of days. And for those others, I'll see you in the next couple of months. So thank you again.