Roche Holding AG (ROG) Earnings Call Transcript

Kindly note that the webinar is being recorded. [Operator Instructions] 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/investors to download the presentation. At this time, it's my pleasure to introduce you to Thomas Schinecker, CEO Roche Group. Mr. Schinecker, the stage is yours.

Thank you very much, and hello, everyone. Good morning, good afternoon, good evening. I'm very much looking forward to sharing our Q3 2023 results with you today. Now for the first 9 months of 2023, we continued to see strong growth for both divisions, resulting in 1% at constant exchange rates for the group. If we exclude COVID, we're growing at 9%. Combining COVID and the effect from AHR, we are compensating CHF 4 billion, and we're growing. So you see this is a very strong performance by the organization. Year-to-date, Pharma grew 9% at constant exchange rates with the newer medicines really as the key growth drivers. And Teresa will talk about that a bit more. And let me especially call out two medicines. One is VABYSMO, where we now expect annual sales to be above CHF 2 billion. Also, I would like to call out POLIVY in first-line diffuse large B-cell lymphoma, where we see a rapid uptake in the U.S. after the FDA approval, but not only there but also in other countries. The Diagnostics base business is also doing extremely well, now growing at 7% year-to-date in constant exchange rate, much faster than the market. Again, you see the strong portfolio that we have in Diagnostics. We expect COVID-19 sales now to decline with roughly CHF 4.5 billion and the AHR biosimilar erosion to be roughly CHF 1.1 billion. Now given our good base business growth and the headwinds of now about CHF 5.6 billion, we'll end up at the upper end of our guidance. In Q3, we've also achieved a number of very important milestones. TECENTRIQ for the subcutaneous formulation received its first approval in Great Britain. And with that, we have the first PD-1/PD-L1 that is available in subcutaneous formats. We received the EU approval for Evrysdi for babies under 2 months old. And this is now available for babies from birth onwards. For ELEVIDYS for the first gene therapy in Duchenne muscular dystrophy, we received two approvals outside the U.S. And we expect the pivotal Phase III EMBARK results for ELEVIDYS shortly. We also had a number of very important readouts. One is the pivotal Phase III ALINA results for ALECENSA in adjuvant ALK-positive non-small cell lung cancer. These results will be presented at the Presidential session at ESMO on October 21. These are really unprecedented results if you look at the hazard ratio and in terms of improvement above the standard of care. Let me also highlight the positive Phase II KARDIA-1 results for zilebesiran in hypertension. Now only 2 months after we signed the agreement with Alnylam, we already had a positive Phase II result, so very happy how this is progressing. We also had two important launches in the Diagnostics division, the CCM Vertical, which is an automation that Matt will talk about that will enable more automation through different floors and in less space of laboratories. We are the first to market with an IL-6 immunoassay that detects early onset of sepsis in newborns, again filling our medical value pipeline on the Diagnostics side. Finally, we have a number of important newsflows coming up in Q4. Now let's take a closer look at the sales. So year-to-date, group sales are at CHF 44.1 billion. You see we're growing at 1% in constant exchange rate. Excluding COVID-19, that's a very strong 9%. And you see both Pharma doing well with 9% and Diagnostics doing well with 7%. You also see the currency headwinds that we had. Especially also, the headwinds got stronger in the third quarter. Now let's look at the quarterly results over the past quarters and especially Q3 2023, where we're growing at 7%, which again very strong results. If you exclude COVID, we're growing 10%. And also, the AHR biosimilar erosion is slowing down. The negative impact of COVID-19 will now last only another 2 quarters. And I actually have one slide on that, so you exactly see how the COVID business will continue to develop. On this slide, it's easy to then also see the base business, the underlying business, and how this has been performing. And it's performing extremely well in both divisions. On the Pharma side, you can see that the two lines are basically identical. So we had no COVID effect so far this year on the Pharma side. On the Diagnostics side, we had significant effects. But the base business is doing very well as you can see on this slide. Now going to the COVID effects. Let me highlight that Roche had played a very important role during the pandemic. And you can see that with 3 million patients treated, more than 2 billion COVID-19 tests sold and more than CHF 18 billion in sales generated, and that at a very ethical pricing. If you look at the development of the sales over the last quarters, you can see that we're now at a very low level of COVID-19 sales. And we believe this is the level that approximately we will continue over the next quarters. And you can see that in Q4 2022, we still had CHF 1.7 billion of COVID sales. A large part of that, in fact, about CHF 1.1 billion, was one Ronapreve order in Japan, so on the Pharma side. And then you see another effect of about CHF 0.9 billion that we have in Q1 2023. Again, we had a Ronapreve order in Japan of approximately CHF 600 million. But this will wash out completely. And the underlying very strong performance of the organization will shine through as soon as we have those 2 quarters behind us. Now let me highlight the performance across the different parts of the group. Here, you can see a strong base business growth of Diagnostics, the 7%, contributing almost CHF 700 million. I mean, not many companies in diagnostics actually have that size. So you can see we're adding a company almost every year in our Diagnostics business. On the Pharma side, the newer products are performing fantastically well. We're almost adding CHF 4 billion here. You see the reduction in COVID sales, Ronapreve only, almost no effect so far. But what becomes very apparent is the foreign exchange effect of about CHF 3.4 billion. On the right-hand side, you can see the portfolio diversification. AHR is now a much smaller slice of our sales. So we've really been growing through the erosion of biosimilars and actually also through the situation that we've had with COVID-19, really being able to replace those sales as you can see in the first quarters. We have launched 20 new medicines since end of 2015. And with that, those medicines are really driving the growth. And on the right-hand side, you see that we now have about 50% of our sales that are coming from these medicines, and this year will go up also in the coming months. Now let's move to the newsflow. As mentioned before, in Q3, we had positive readouts for ALECENSA in adjuvant ALK-positive non-small cell lung cancer. We had a positive readout for PHESGO, the on-body injector in HER2-positive breast cancer. We unfortunately had one negative readout for VENCLEXTA. And we expect additional readouts towards the end of the year for TECENTRIQ in adjuvant head and neck cancer; for VENCLEXTA in MDS; and very importantly, ELEVIDYS in Duchenne muscular dystrophy. In Diagnostics, we had two launches that are on this list. But Matt will talk about a number of additional launches. And the other three will come before year-end. So overall, we've updated our guidance on the Diagnostics side in terms of good base business growth. We've updated our guidance in terms of COVID-19 sales with roughly now minus CHF 4.5 billion, the AHR sales of roughly minus CHF 1.1 billion. Now given our good base business growth and the headwinds of now, in total for the year, CHF 5.6 billion, we will end up at the upper end of the guidance. So overall, the sales guidance remains unchanged. And the same goes for our core EPS guidance, broadly in line with sales decline. And also, we will further increase dividends in Swiss francs. With that, I hand over to Teresa.

Thank you, Thomas. So as Thomas mentioned, it was another strong quarter for Pharma. Year-to-date, we had sales of CHF 33.6 billion at a constant exchange rate growth of 9%. That was 11% alone just in Q3. All regions have delivered strong growth. And new products more than offset biosimilar and generic erosion. As you heard from Thomas, accelerating currency changes in Q3 are likely the cause of some of the smaller sort of misses that we saw in consensus as the fundamentals of our core products remain strong. And let's talk a little bit in that -- about that in more detail. So as you know, we have one of the youngest portfolios in the industry, comprised of best-in-disease products: VABYSMO, OCREVUS, HEMLIBRA, POLIVY, Evrysdi, PHESGO, TECENTRIQ. These continue to drive significant growth. And combined, these added CHF 3.9 billion of new sales at constant exchange rates. VABYSMO continues to be our #1 growth driver and is well on track to achieve CHF 2 billion in sales in Swiss francs for the fiscal year. OCREVUS continues to deliver double-digit growth. And we are excited by the recent subcu positive data that was released and the opportunity that, that twice-a-year subcut will provide to us an opening of new markets for OCREVUS. POLIVY is the next drug that I'd like to highlight as it consistently beats consensus expectations. This strong growth performance of 126% at constant exchange rates really underscores the strength of the first-line DLBCL launches that are happening around the world. And we'll talk about that in more detail in the coming slides. On the negative side, I'd also like to mention the total AHR erosion. Thomas highlighted this as well. We're at about CHF 850 million, which is less than we had anticipated at the beginning of the year. We suspect we'll end at about CHF 1.1 billion in erosion, which is a little better than we had anticipated as we began to see a leveling off in some regions. So now let's start to take a closer look at our overall performance. And as always, we'll start with oncology. Oncology sales are up by 5% at constant exchange rates to CHF 14.5 billion. That's up 1 percentage from half year. In honor of Breast Cancer Awareness Month, we're going to start with a deep dive on the HER2 franchise. As we have previously guided, KADCYLA has modest growth, which is driven by international in early breast cancer compensating the decline that we see in the U.S. and the EU in the metastatic setting. KADCYLA sales are expected to remain stable going forward. PERJETA remains driven by international with conversion to PHESGO ongoing. PHESGO continues to impress, 66% growth with a 37% conversion rate in our 44 early launch countries. We are seeing strong conversion in even some of our most difficult markets like the U.S., where you wouldn't necessarily expect strong conversion. We're 20% now in the U.S. We expect PHESGO to achieve blockbuster status by the end of the year. And our ambition is to reach a 50% conversion rate for PHESGO in the coming years. While it is noteworthy that we have -- what's also noteworthy, I think, is that as PHESGO has continued to gain momentum in certain markets, we actually see an overall increase in our HER2-positive breast cancer franchise there as more patients actually get more access to PHESGO. So I think there were some questions about the performance of PERJETA in Q3. So maybe I just want to pause here and try and address some of them. So first of all, I think when you look at that sort of dip in PERJETA in Q3, that's actually not uncommon for Q3. We seem to have some phasing effect that happens with PERJETA in Q3. Last year, I believe we were down 3.3% in Q3 year-over-year. But I think largely what you're seeing is that the success of the PHESGO conversion. I mean, I think Spain is actually a really great example here. Spain launched in May of this year and already by September had a 21% conversion. So what I think you're seeing is some of that PERJETA business moving more quickly into PHESGO than maybe was anticipated. Overall, the HER2 portfolio has a strong and consistent growth of 14.4%. And so I think there's really nothing different underlying the fundamentals here. I'm going to skip TECENTRIQ in hematology as we'll talk about them in more detail in the coming slide and head straight to ALECENSA, which continues to perform strongly with 9% growth in constant exchange rates in our core indication of first-line ALK-positive metastatic non-small cell lung cancer with a whopping 70% share in her major markets. I think we were very excited to share with all of you the ALINA data, which is our positive Phase III adjuvant data in ALK-positive non-small cell lung cancer, which you all got a little bit of a sneak preview on, on Tuesday. So fortunately, that means we can share a little bit more detail with you now. The results that we saw in ALECENSA in the ALINA trial were unprecedented. We saw a staggering 76% reduction in the risk of disease recurrence or death, which -- with a hazard ratio of 0.24, which is really just amazing. Additionally, we saw a clinically meaningful improvement in CNS-DFS as well with a hazard ratio of 0.22. So these are really just breathtaking results. The full results were selected to be presented in the Presidential session at ESMO this Saturday, so see you there. And we have a first-in-class global filing, which is currently ongoing. We would expect U.S. and EU launches to commence in 2024. And we would expect to add about 50 -- I'm sorry, $500 million in sales with this indication. I think it is really noteworthy to just kind of pause and reflect on the fact that this is one of the patient populations that actually is more likely to get tested early on. About 45% of patients that we believe will be eligible for this drug will actually get tested early enough to take advantage of treatment in the adjuvant setting, which is a really great signal that many patients will be able to benefit from ALECENSA and actually have a better outcome with their cancer. But this is not the end for development with ALECENSA. We have additional growth possible through our ongoing Phase III in unresectable non-small cell lung cancer. That's the HORIZON trial as well as another ongoing Phase III TAPISTRY in the tumor-agnostic setting. So ALECENSA is just a really tremendous molecule and something to definitely keep your eyes on. Moving on to hematology. I think we've said for some time that malignant hematology is a place to watch. And I think we now see a rejuvenation of this portfolio as new medicines begin to come into the market. I'm going to start here in the obvious place, which is POLIVY. The strong performance of the first-line DLBCL launch continues. And we now have over 10,000 commercial patients on the POLARIX regimen. We see strong first-line shares in the IPI 0 through 5 achieved. The U.S. is at 14%, Germany is at 29%, the U.K. is at 23%, Japan is at 32%. So you really see adoption beginning to take hold and accelerate in these key markets. In addition, we have 4 to 5 years before we would expect any additional competition in the first-line DLBCL space, which not only means that we can entrench POLIVY as the standard of care, it also gives us our own opportunities to further improve that standard of care by developing new in-house combinations such as SKYGLO, which is the COLUMVI plus POLIVY plus R-CHP trial, which was initiated in Q3 and has already had its first patient in. Similarly impressive is the growth that we're seeing with GAZYVA. This is driven primarily by GAZYVA in combination with VENCLEXTA and ibrutinib in first-line CLL. And then again, we have our two bispecific launches that are currently ongoing. LUNSUMIO, which is having just a really great launch in third-line follicular lymphoma, we are already seeing double-digit market shares in key early launch countries, including the U.S., Germany and Switzerland. And COLUMVI, just recently approved in the U.S. and the EU in Q2 in third line plus DLBCL, and that launch is ongoing and again going fairly well. We do have additional opportunities for much more significant growth with both LUNSUMIO and COLUMVI as we look into the additional trials, which will be launched in earlier-line settings. But again, I think these bispecifics are unique. They have great competitive differentiation. And it will be very exciting to actually see them get their new data in and begin to be able to help patients in earlier lines of therapy. In terms of key data, we have two key datasets that have been submitted to ASH: the Phase Ib LUNSUMIO and COLUMVI combos in DLBCL; and then we will also see some DLBCL subtype data for POLARIX. So look forward to that. Moving on to TECENTRIQ. I'm going to spotlight actually two new areas that have had the most activity during Q3, subcu and HCC. And to be fair, I should also mention that October is Liver Cancer Awareness Month, just so that everybody is treated equally. For TECENTRIQ subcut, we have achieved our first approval. We were the first subcu PD-1/PD-L1 to be launched with approval in Great Britain. We dosed our first commercial patient several weeks ago. As a reminder, PHESGO in the U.K. is at 92% conversion rate, which shows high demand for something like this that could actually not only provide more convenience to patients but also help increase -- freeing up resources in health care systems. Subcut reduces admin time to 7 minutes from a 30- to 60-minute infusion. And so we would really expect again for those health care systems, where they have constraints, that we would see similar adoption to what we have seen with PHESGO. We expect to see -- receive EU CHMP opinion in Q4 for TECENTRIQ subcut and U.S. approval in 2024. Taking the next step in HCC, our Phase III TECENTRIQ plus tiragolumab plus Avastin trial in Phase I -- I'm sorry, in first-line HCC was also initiated in Q1. And that follows the positive Phase I/II MORPHEUS data that was presented earlier in the year. For our in-line indications, sales growth is largely being driven by HCC in some EU markets in the ongoing adjuvant non-small cell launches ex U.S. as well as just sort of general global expansion. Through the end of the year, we've mentioned that we are expecting the first approvals for CHMP with TECENTRIQ subcu but then also the data from the adjuvant head and neck trial, which is coming in Q4. This is a very large potential indication in an area of very high unmet need. And then obviously, the SKYSCRAPER-01 results with TECENTRIQ plus tiragolumab in first-line non-small cell lung cancer with those final OS results expected in Q1 of next year. And just as a reminder, that is an event-driven trial. So moving on to hemophilia. In Q3, HEMLIBRA continued its trajectory of extremely strong growth, adding 17% in constant exchange rates. And we would expect this growth to continue. HEMLIBRA is unquestionably the global standard of care in hemophilia A with more than 22,000 patients treated globally and U.S. and EU patient share increasing to 40%. And that's a single percentage point gain in just 1 quarter. Growth is expected to continue globally with patient shares in France and the U.K. already exceeding 60% and continuing to climb. And why is it that we have such confidence in HEMLIBRA continuing to be able to entrench itself? It has just a fantastic profile. The key differentiators of HEMLIBRA remain extremely strong, which just does make it the treatment of choice for prophylaxis in heme A. More than 60% of patients are already on every other week or every month dosing with 0 risk of developing inhibitors over time. We have a wealth of long-term safety and efficacy data, which shows superior benefit versus the factor VIIIs and an improvement in joint health. We are currently approved in over 100 countries for non-inhibitor, we're reimbursed in 60, so again even more geographies could potentially seek to benefit. And so again, as we look forward into the rest of 2023, we would expect further patient share gains in that non-inhibitor population as well as expanding share in key accounts with additional growth potential. But I think when we ask around HEMLIBRA, the #1 question on everybody's mind is actually what's going on from a competitive standpoint. So not unexpectedly, we're seeing very little, no impact from the first generation of gene therapies, which have been approved. I think not unsurprisingly, we're not really seeing the pickup of those therapies at this time. And then with the approval of ALTUVIIIO, again very much as we had expected, we're primarily seeing share being taken from other factor VIIIs. And we're -- in the very handful of instances where we hear about these HEMLIBRA "switches," this is largely people who remain on HEMLIBRA, but just switched their factor VIII. And again, we're talking about a very small number of patients even in that bucket. So again, we feel very confident about the growth trajectory and the potential growth rates for HEMLIBRA going forward just based on a very differentiated profile. Moving on to immunology. We see overall sales in immunology were stable in Q3 despite the loss of Esbriet sales to generic competition. XOLAIR sales increased by 3%, driven primarily by the growth in CSU. Earlier this month, the FDA approved the XOLAIR auto-injector, which provides patients with new options for dosing convenience, very important in this very competitive field. You can see that ACTEMRA delivered a very solid performance in its chronic indications, driven by the U.S. and EU. It is worth noting that there's no remaining COVID sales for ACTEMRA at this point. So this -- its performance is really driven by its core indications. This is a little bit higher performance than we might necessarily have expected for ACTEMRA. And that's probably due to some turbulence in the year-over-year sales as COVID has sort of washed out. But we really are seeing a good and positive growth in our core indications here. Through the end of the year, we look forward to updated Phase II data for ASO Factor B in IgA nephropathy, which will be shared at the ASN Kidney Week at the beginning of November. And then we are still awaiting the XOLAIR OUtMATCH study results in food allergy. Switching over to neuroscience. It has been quite a busy quarter for OCREVUS. OCREVUS remains the leader in MS market share in both the U.S. and in the EU. It is now at 24% global share and growing, which is supported by a much higher retention rate than we see with other MS medicines. We've seen strong year-over-year growth of 12% at constant exchange rates. And we do expect this momentum to continue for 2023 and beyond. Last week at ECTRIMS, we presented multiple new datasets for OCREVUS and fenebrutinib. I will talk about those in a moment. But before I move on, I would be remiss if I didn't highlight the fact that we have a neuroscience update call happening on October 30. That will discuss not only in more detail the trials that I'm about to cover at a very high level but will also cover our R&D activities in other areas like Alzheimer's and SMA, including the data that will be presented at CTAD for trontinemab. So now on to the data. So OCREVUS subcu. In July, we announced the positive top line results for OCREVUS subcut. And last week at ECTRIMS, we provided the detailed results. The study met all of its primary and secondary endpoints and demonstrated that OCREVUS subcut twice a year is non-inferior to OCREVUS IV and RMS and PPMS. This can be seen in the B-cell depletion graph on the left as well as the MRI data on the reduction of brain lesion, shown in the table on the right. Combining the safety and efficacy of OCREVUS IV with the added convenience of a subcut has the potential to expand overall anti-CD20 usage and really drive OCREVUS class share. As you know, I really think of the IV and the subcut markets very different markets. And this gives us the opportunity to reach a base of patients that we just simply haven't been able to reach with the IV formulation. This is going to be particularly meaningful in treatment settings that have limited infusion capacity or when health care systems have more limited resources. The initial launch, which is expected in 2024, will be with a syringe pump. And it will be able to be administered at home by a health care professional or in an office or in a pharmacy. In addition, we are currently evaluating self-administration options via an on-body injector, a patch pump. And we expect this option to be available in the mid-term. More details on this program will be provided at a later point in time and a little bit closer to launch. But the OCREVUS subcut is a very significant potential, a new opportunity for OCREVUS. And we're excited to be able to bring that to patients next year. Moving on to our 10-year results and the real-world family planning data for OCREVUS. It's almost hard to underscore how important these data are when you really think about what is the most meaningful to patient populations. The 10-year follow-up data for RMS and PPMS adds to the impressive body of evidence that we already have for OCREVUS in safety and efficacy. Over 80% of RMS patients were free from disability progression and 92% were able to walk unaided. For PPMS, we observed that more than 1/3 of patients were progression-free after 10 years. And what is important to MS patients? It's important that, that progression is delayed. It is important that they can continue to work, that they can continue to be active with their friends and their family. These are typically very young and active people who are stricken with MS. So these data are again, frankly, just stunning and put a lot of confidence into the need to treat early with OCREVUS. Similarly, using real-world data, we performed the very first analysis of the effects of anti-CD20 MS treatment on family planning, again highly relevant for MS patients, who on average are 29 years old when they're diagnosed. This is the time of life when they're just starting to begin their family planning. These data showed minimal MS disease activity was observed in patients from preconception to pregnancy and in the first trimester postpartum and that OCREVUS did not increase the risk of adverse pregnancy or infant outcomes. As you might imagine, we have been sharing these data quite extensively with physicians around the world. And one physician shared back with us that OCREVUS is the best treatment option for patients considering family planning. And I think these data really go a long way to giving young people who want to delay progression, who want to start families, all the reasons in the world to say that OCREVUS is the right therapy for them. And last but not least, before we leave MS, let me talk a little bit about fenebrutinib. As a reminder, fenebrutinib is a potent, highly selective and the only non-covalent, reversible BTKi in Phase III for MS. It has the potential to be a best-in-class BTK. And this is underlined by the positive Phase II FENopta results in RMS, which met all the primary and secondary endpoints. We had previously presented this data based on MRI results for brain lesion reduction. And they show how fenebrutinib patients are four times more likely to have no new T1 or T2 lesions at key time points versus placebo. And the efficacy that we observed in this trial is consistent with other high-efficacy, disease-modifying therapies in MS. At ECTRIMS, we added to this with the CSF data on brain penetration, sort of a holy grail in MS treatment. And the graph in the middle demonstrates that fenebrutinib was able to efficiently penetrate the blood-brain barrier. And this is where we do believe we will be able to deliver potentially differentiated efficacy outcomes. The updated FENopta data was very well received. And it has actually been selected as a clinical highlight by ECTRIMS 2023. No new safety data was identified in the study and across all -- nor has any new signal been identified across any of our ongoing clinical trials. We have no confirmed cases of HISLA across any of our trials. And we currently have a large safety database with more than 2,500 people dosed across multiple indications. Our Phase III studies in RMS and PPMS are ongoing and do include a head-to-head in OCREVUS and PPMS. This is the only trial that is actually directly comparing with the current standard of care, which is OCREVUS. And those trials are expected to read out around 2025. So again, another important new molecule to watch. And before we leave neuroscience, we will touch quickly on Evrysdi. Evrysdi is on track to become the #1 SMA therapy globally in the coming quarters. We are now at more than 11,000 patients treated globally. As a reminder, we were just 7,000 patients at the end of last year, so a really great ramp rate. Evrysdi is well-tolerated with the retention rate in the first 12 months of more than 90% globally. And we have already reached market leadership in the U.S. with 25% share. In Japan, we are at a whopping 58% share for Evrysdi. U.S. growth is driven both by switching and naive patients with increased penetration in that treatment-naive patient setting. And again, as you've heard me say repeatedly, it's really important to penetrate that naive setting. Those are mostly adult patients. Those are patients that have not really ever treated their SMA. It is the largest group of patients that are out there. And we continue to see good inroads into actually helping those patients actually begin to treat their disease. We have positive -- the positive Phase II RAINBOWFISH results, which confirm that strong efficacy and safety in patients that are less than 2 months old. Those results were presented at WMS this year. And we achieved that EU label expansion just back in August. So what are we expecting throughout Q3 -- I'm sorry, throughout the rest of 2023? We would just continue -- we would expect to see continued growth in market share gains, again driven by both switch and naive patients. It's again hard to underscore what a transformational drug SMA really -- or Evrysdi is for SMA patients. And it's definitely another one to keep your eyes on. So no pun intended, something else to keep your eyes on, ophthalmology. And of course, VABYSMO with strong growth, we've already hit blockbuster status year-to-date on sales. We are well on our way to more than $2 billion in sales for the full 2023. That growth is driven by the unique clinical profile of VABYSMO. So those 3Ds, the dual pathway, the drying, the durability, we're just coming off of EURETINA. And I think we heard in the hallways that the clinical experience that you see from physicians treating patients matches the real-world data experience that we see in things like TRUCKEE, which match our clinical trial experience. So again, we are -- continue to be really confident in VABYSMO as a potential new standard of care. U.S. market shares in AMD and DME have further expanded to 19% and 12%, respectively, based on August claims data. That's up from 15% and 9% back in May. In the U.S., use in treatment-naive patients has accelerated. It now accounts for 37% of all new treatment starts. In the ex U.S., that is actually 40% of our patients are now naive. And that's up from the teens in the U.S. back in Q1. Outside of U.S., launches are also exhibiting very strong uptake. Many of our early launch countries have already achieved double-digit market share just after a few quarters of launch, including Japan, Germany, U.K., Switzerland, Australia. And impressively, the U.K. and Switzerland have reached more than 20% market share in just 1 year after launch. In the second half, the global rollout will continue with several key EU markets getting reimbursement. By the end of 2023, we expect to have reimbursement in all of the EU5, which will drive further growth. And looking forward, the U.S./EU filing for the potential third indication of VABYSMO has been completed and an FDA decision for RVO is anticipated by the end of this year. Before we leave ophthalmology, I think it's also good to mention where we stand with our latest developments for SUSVIMO. SUSVIMO, as a reminder, is that device that is implanted in the eye. The root cause for a voluntary recall last year has been identified and a technical solution is now in place. SUSVIMO trial should restart by the end of the year. We anticipate a U.S. commercial relaunch in 2024. In ex U.S., we would expect to be able to bring SUSVIMO to patients in 2025 and beyond. And then last but not least, I wanted to highlight our partnership with Alnylam with zilebesiran, a potential best-in-class treatment for hypertension. Compared to existing hypertension treatments, zilebesiran represents a novel drug modality, which also has a slightly different and potentially improved MoA. It has already achieved positive Phase I results. Thomas mentioned earlier that in September, we saw the Phase II KARDIA-1 study of monotherapy zilebesiran, met its primary and key secondary endpoints. And those results will be presented at AHA in November. Zilebesiran has the potential of improved adherence and compliance to treat with a possible biannual subcutaneous dosing regimen, which when you think about the 1.2 billion people in the world, 80% of whom can't control their hypertension, and we know that leads towards cardiovascular outcomes, the potential addition of zilebesiran twice a year could really be incredibly meaningful for those patients. Working closely with Alnylam, we continue to assess the potential expansions of zilebesiran, exploring other cardiovascular diseases, including things like heart failure or other potential opportunities to maximize this therapy's potential. The clinical development program, as you know, is ongoing. KARDIA-1 has read out positively. KARDIA-2 data, which is an addition, an add-on to 1's standard of care data will come in the beginning of next year. KARDIA-3, which is a third Phase II trial, which is an add-on to 2's standards of care, that will initiate in 2024. And Alnylam has recently announced that we plan a cardiovascular outcomes trial with patients who have uncontrolled hypertension, at high risk for CV -- negative CV outcome. These will have a MACE-type endpoint. And that trial design will be based on the KARDIA-3 readout. So more to come here. And finally, before I hand it over to Matt, I want to take a quick look at the changes in our key newsflow side since half year. So from a regulatory perspective, we mentioned the RVO filing is complete for the EU for VABYSMO. And the PDUFA is set for the end of the year with the FDA. For our Phase III readouts, we talked about the positive readout with ALINA. Thomas mentioned the positive PHESGO on-body injector, pivotal Phase I readout a little bit earlier. Those data are going to be shared at the beginning of next year. And then we did hear from AbbVie a couple of weeks ago that the CANOVA trial in a relatively small subset of patients with multiple myeloma did not meet its primary endpoint. We have the zilebesiran Phase I KARDIA-1 data that also released positive results. And that was in addition to the initial newsflow slide. And then through the end of the year, I think Thomas mentioned all of these head and neck, VENCLEXTA -- for TECENTRIQ, VENCLEXTA in MDS, ELEVIDYS in DMD, long awaited. And then of course, we had one trial actually pulled forward into Q4 2023. And this is our PI3 kinase in combination with palbo and fulvestrant, the INAVO120 data, which is expected in Q4 of this year and could potentially be the first positive readout for our PI3 kinase, inavolisib, which is also in a broader development program. So sorry, Matt, I went a little bit over. But with that, I will hand it over to you.

Thanks very much, Teresa. So good morning, good afternoon, everyone. It's my pleasure to present the third quarter 2023 Diagnostics division sales results. So with sales of CHF 10.4 billion, the Diagnostics division declined by 18% or minus CHF 2.5 billion at constant exchange rate compared to the first 9 months of 2022. And this decline is entirely driven by the decrease of COVID-19 testing sales by minus CHF 3.2 billion at constant exchange rate and is offset by strong base business growth of plus 7%. So on this slide, you see the performance of the Diagnostics business over the last 7 quarters. And I'd like to start by focusing on the orange line. This represents our base business performance. In Q3 of 2023, our base business continued to grow at plus 7% with strong sales momentum across all regions and across all product categories. Now I'd like to turn your attention to the total Diagnostics division sales, which includes COVID-19. The impact of COVID-19 is less in the third quarter with total sales in Q3 2023 declining by 5%. This trend confirms what you heard from Thomas that the COVID-19 business is washing out of our overall Diagnostic sales. For the remainder of 2023, we're expecting mid- to high single-digit growth of our base business while overall COVID-19 sales will continue to decrease. Now let's go through this by the product categories. So first, sales in Core Lab increased by 9% with very strong momentum driven by immunodiagnostics and our clinical chemistry business. Base sales, excluding COVID-19, increased by plus 12%. Our Molecular Lab, our PCR business, had a decline of minus 35%. And this is due to lower COVID-19 PCR lab-based testing sales. However, excluding the COVID-19-related business, our Molecular Lab is growing by plus 7%. And this is due to strong growth in cervical cancer testing, blood screening and our virology-based business. Pathology Lab, which is really focused on helping people in diagnosing cancer, had strong growth at plus 15%. This is mainly driven by advanced staining, immunohistochemistry reagent growth and our companion diagnostics. Our Diabetes Care business had a decline of minus 6%. Now this sales decline is driven by the shift from traditional blood glucose monitoring to continuous glucose monitoring. Finally, in our Point of Care business, we had a decline of minus 70% and again driven entirely by COVID-19 rapid antigen and molecular point-of-care sales. The base business grew by plus 5%. And this was due to a strong respiratory season in the Northern Hemisphere in Q1 and good Q3 performance. So let's look at this across the different geographies. Overall, when you're excluding COVID-19, we saw strong base business growth across all of our regions. So starting in North America, the base business growth, excluding COVID-19, grew at plus 6%; in EMEA, excluding COVID-19, plus 5%; in APAC, excluding COVID, plus 11%; and in Latin America, excluding COVID-19, an astounding plus 21%. So really, all of the regions have seen a strong growth of their base business and good competitive market share capture and overall performance. So now I'd like to talk a little bit more about some of the innovation that you heard a bit about from Thomas in his opening, specifically some of our innovative products for the clinical laboratory. So now maybe talk a little bit about the cobas connection module, CCM Vertical. Post COVID-19, many laboratories are dealing with challenges related to availability of skilled workers and high pressure for cost savings. Creating efficiency in the laboratory and workflow automation is a critical success factor for our business in the central lab, winning more customers, consolidating and growing market share. The CCM Vertical provides automation for our Core and Molecular Lab product lines and can process up to 2,500 samples per hour. Now this is an extension of our existing cobas connection module sample conveyor system. But with the newly developed elevator and overhead modules, now this enables vertical sample transportation in the lab and also between floors and between different rooms. This high-throughput solution enables a reduction of laboratory errors due to manual transportation as well as space optimization in the laboratory and allows us to compete in tenders where funds for building works, et cetera, aren't available. It makes us competitive anywhere automation is a requirement. So continuing on that theme of innovating on the automation side, I'd like to talk about the launch -- the upcoming launch, pardon me, of our c 703 and cobas ISE neo analytical units. Now we unveiled these units in May 2023 at EuroMedLab for the first time. These new additions to the Serum Work Area family provide the highest throughput and automation in the industry for ISE and clinical chemistry, again creating further differentiation for our core automation laboratory portfolio. The smart hardware design reduces maintenance to once per month and features simplified serviceability with 56% less calibration events than our current analyzers. This allows laboratories to address labor shortages, increase efficiency and improve output. The new systems will launch in the second quarter of 2024. So all that automation makes us very competitive in terms of delivering the best analytical solutions for our customers. And what's also important is that we continue to innovate in menu and give more medical content that enables us to deliver answers to patients. Our Serum Work Area consists of over 240 assays, which makes it the broadest core laboratory clinical chemistry/immunoassay menu in the industry. Every year, we are expanding our already industry-leading menu with new launches and indications. Over the last 3 years, we've achieved 16 regulatory approvals per year on average. This is a mix of CE Mark and FDA. And I'd like to call out the additions to the menu in hepatitis, which increases our competitiveness in the always-growing infectious disease market, and also some of our recent high medical value launches, such as GAAD, a new multivariate index assay for the prediction of liver cancer caused by hepatitis C infection, and the NT-proBNP claim extension in heart failure, where our STRONG-HF heart failure protocol was recently added to the European Society for Cardiology guidelines. Additionally, I want to point out our latest FDA approval of the cerebrospinal fluid Alzheimer's biomarker test for total tau protein. We plan to continue to expand our menu for Alzheimer's and neurological disease as a driver for our future growth in Diagnostics. So this broad menu with differentiated high medical value, combined with our best-in-class automation, will continue to differentiate us in the largest diagnostic segment in the market. Again, following on what you heard from Thomas, I'd like to speak a little bit about some of our high medical value solutions, specifically sepsis. So in the third quarter, we obtained the IL-6 CE claim extension for neonatal sepsis in countries that accept the CE Mark. Each year, there are 3 million cases of sepsis in newborns, causing 400,000 to 700,000 neonatal deaths. This makes it one of the leading causes of mortality among neonates. Sepsis progresses rapidly with mortality rates increasing 8% per hour that treatment is delayed. The current standard of care is blood culture, which has a long turnaround time, approximately 48 hours, and requires 1 mL of blood, which is difficult to obtain from newborns, especially newborns with low birth rate -- low birth weight, excuse me. The Elecsys IL-6 demonstrates excellent performance for the detection of neonatal sepsis. And our test is capable of providing results in just 18 minutes. Roche is the first company to offer IL-6 on an automated platform with a dedicated claim for a neonatal sepsis diagnosis. So similar to Teresa, I'll take you through our Diagnostics key launches in 2023. What we're really proud of is that of the launches you see here, we've achieved 9 of those in 2023 already. And the rest are all on track for delivery by the end of the year. So with that, thank you very much. And I'll pass it to Alan.

Thanks a lot, Matt. Quite a pleasure. Hello to everybody. I hope you're all safe and healthy. Happy to lead you through a couple of additional information about the sales. And certainly, the exchange rates -- I think let me remind, well, all of us that we are going through a period of fast-changing exchange rates. And I think really there is diligence needed that we draw the right conclusions here. Good. So let's go into it. I think really when you look where we have landed, I think I'm very pleased with the performance of the company, really outstanding. I will make a comment here. I would like to thank the employees as well because all of them have made great contributions that we have done well for patients. As I said, I think the group sales have increased by plus 1% in constant rates, strong base business growth, which we cannot emphasize enough, and we will do it again and again, which is certainly overcompensating for the COVID-19 sales decline and certainly as well the impact of biosimilars for AHR. When you look at volume, which I think is quite helpful to have that information addition, I think in Pharma, we achieved a strong volume growth of 14%. In dia, certainly, volumes declined by minus 18%, whereby the group volume has increased by 5%. Good. I think really, as said, since half year 2023, the strengthening of the Swiss franc against other currencies has progressed and even accelerated. I will share the additional information. And I understand it offers us a little bit of a challenge to do the right modeling with these fast-changing currency rates. Therefore, I think really reporting in constant rates is certainly a helpful tool here. Let me go to the guidance very quickly, and I'll come back to that. As you've heard, I think really guidance remains as it is. We have provided some additional information about our expectation for the COVID-19 sales loss for 2023. We think it's roughly minus CHF 4.5 billion now. I think originally, we have given information of roughly minus CHF 5 billion. And when it comes to AHR and the biosimilar impact, we think now it's going to be more minus -- at roughly minus CHF 1.1 billion for the year instead of the originally said CHF 1.6 billion. So as Thomas said, I can emphasize, well, our expectation is that we definitely end up full year 2023 on the upper end of the guidance. And let me emphasize as well here that we have a connection between sales development and core EPS development. So very clearly, I think these things, if you like, move into the same direction. So let me now go through the regional sales development. As outlined, I think if you exclude the COVID sales, I think we have grown with 9% in constant rates. I think last time we had such a dynamic, and I really had to look it up, that was in 2019, so really quite a while ago. It's a fantastic dynamic that we are showing here for the underlying business. So let me go through the regional topics here. Pharma had a strong growth. And Teresa has elaborated about it. Pharma growth was 9%, so in constant rates, CHF 2.9 billion. And all regions, as you can see, contributed quite nicely to this. I think at the forefront is the U.S. with the plus 8%, in constant rates, CHF 1.4 billion. Region international, as you can see in the middle, has also shown a strong sales performance with an increase of 12%, equaling CHF 800 million and then followed by Europe with 7% or CHF 400 million and then Chugai with plus 10% and CHF 300 million. So really, I think, hitting on all cylinders here. And then the Diagnostics division, and Matt has explained it, on one hand, certainly we had the sales loss due to COVID. But that was really mitigated quite significantly by the base business, which has grown 7%, so roughly CHF 700 million. So really, overall, there is a currency impact for me, more a reporting topic. I'll come to that later on when I go to the results. Because you see really in all major markets where we all have major value chains and major spend, we're doing pretty well and generating good cash. So let's go to the currency rates right away. And what you see here on the left-hand side is the growth in constant rates of plus 1%. And then you see on the right-hand side, the growth in Swiss francs of minus 6.3%, which leaves us with a difference of minus 7.3 percentage points and the already mentioned CHF 3.4 billion currency impact. You see where it was driven by and which currencies. I think dominant is the U.S. dollar. We've even seen an acceleration over the recent quarters. And you see here, down by minus 2.4 percentage points, which equals CHF 1.1 billion. So that's the major piece here. And then we have APAC. And here, certainly, it's the renminbi with a minus 1.6 percentage points, so roughly CHF 500 million. And then last but not least, the Japanese yen with minus 1 percentage point, equaling roughly CHF 500 million. The euro contributed another CHF 230 million or minus 0.5 percentage points. So I think very clearly, the Swiss franc had strengthened basically against every other currency. I think now we come to the expected currency impacts for 2023. And let me start really with the left-hand side. And you know these tables. And I think the -- how should I say it, it's pretty obvious that for both tables on the left-hand side, you see that the 2023 average currency rate is below 2022. Okay, that in itself is not surprising. And what you see on the right-hand side then is that when you bring all of that together, you see really the minus 7 percentage points for year-to-date September 2023. And then there is our projection. And the projection is assuming that the currency rates at September 30, so end of September, remain stable until year-end of 2023, which now we don't have a lot of time left in 2023, is rather tangible. And you see really what that means. I think you see really on sales, the minus 7 percentage points, so that remains stable, on core operating profit, a minus 10 percentage points and the core EPS, a minus 12 percentage points. Is that a completely new phenomenon for Roche? I also looked up that a little bit when looking backwards. I think we had such a spread between sales and core operating -- or respectively, core EPS already in 2009, in 2011, in 2015. So this is nothing really new. What I want to say is this is absolutely manageable. And let me give a little bit of background here why at least I feel like perhaps not so much of a big deal here. Certainly, I think, on one hand, with the weak U.S. dollar, will the U.S. dollar stay as weak as it is, we can debate here. But we have seen a strengthening in these periods since 2011 or 2009 quite significantly. But what is, for me, much more important is that we have a very, very good natural hedge in our company. That means when you look at the minus 7 percentage points, a major driver here is the U.S. dollar. When you look at the core operating profit, so the currency impact is even more pronounced. What does that tell us? Well, it tells us that the profit portion of the U.S. dollar is even larger in the core operating profit than it is in the sales. And I think, honestly, then you look really at the U.S. dollar itself, while we have the major part of our financial debt, USD 18.7 billion, that means the major part of the interest that we're paying, we pay in U.S. dollar. We have a lot of our R&D spend, the largest portion of our R&D spend, in the U.S. dollar. We have high operational costs in the U.S. dollar. On top of that, basically every M&A transaction, every licensing transaction that we're doing, we pay in U.S. dollar. What I want to say is I think the natural hedge that we're having is pretty clear. I think that also applies to China, if you like. That applies to Japan with Chugai. That applies to Europe. So I would argue, I'm not too concerned about the currency impact here. And therefore, I think it's really good to follow the constant exchange rate concept. Good. With that, I think you see the outlook is confirmed. Once again, I think what we've adjusted, as you know, the AHR biosimilar impact now projected to be at roughly CHF 1.1 billion. The COVID loss impact are now projected at roughly minus CHF 4.5 billion. And the last point I'm having is to do a little bit of promotion for upcoming IR events. Teresa had already mentioned the neuroscience update on October 30, which will be certainly exciting with the ECTRIMS data and CTAD data. And this, on the subcutaneous version of OCREVUS, will be fun to look a little bit deeper into it, some data on fenebrutinib, which is good. The brainshuttle will be a topic here. I'm personally looking forward to the Digitalization Day on November 29, where we certainly will talk about artificial intelligence and machine learning. And we'll also show a couple of use cases, where we think we will make a difference. That is a pretty tangible event, where we really show quite some use cases. The ASH update is to follow, will be a virtual event, but here about LUNSUMIO and COLUMVI, I think, quite interesting. And then we have the Diagnostics Day in May of next year at the 22nd, where we will have definitely deep dives in the new technologies with mass spectrometry, CGM, but also other things here that might be on the plate here. And I'm sure that will be a very, very exciting event. And with that, I think we're looking forward to your questions. Thanks.

Thanks a lot, Alan. And with that, we will open the Q&A session. The first questions actually come from Mark Purcell from Morgan Stanley.

I have three. Firstly, on POLIVY, clearly a very strong uptake you're seeing, not just in the U.S. but ex U.S. in particular. I think you've historically targeted a 50% share of the first-line setting. Can you provide an update on that, given that the launch appears to be above your expectations? Secondly, more strategically, following the acquisition of the Alnylam sRNA in hypertension, your ambition to go into other cardiovascular disorders, including heart failure, could you sort of maybe talk a little bit more about how you're thinking about heart disease more broadly? Is it inflammation? You've got a heritage with IL-6. Do you see IL-6 and targeting inflammation more broadly as an exciting opportunity across heart failure, kidney disease and chiming in with the Alnylam collaboration? And then the last one is on tiragolumab. Following the inadvertent disclosure of the data, has there been any uptake -- has there been any impact such as post-progression switching of patients, anything with respect to regulators in terms of [ this is called ] penalties? So just trying to understand if anything has changed as we wait for what is anticipated to be a 20% overall survival benefit in Q1 next year.

Thank you very much for the question. I will take the more strategic question. You were talking about the deal we made with Alnylam for zilebesiran. So every year, we look at hundreds of companies. And we do the same this year. And we continuously evaluate early-stage opportunities and also late-stage opportunities to see which molecules would make sense. Where is the scientific rationale? How does the financials look like? And with that, we're looking for really transformative medicines, first-in-class medicines, potentially best-in-disease medicines. And based on that, we make the decisions. And we felt that with this deal, we have a potentially transformative medicine that could be applicable to a large proportion of the world because hypertension is one of the biggest disease burdens in the world. And so we are open to looking at those opportunities. You were mentioning other things. If there is really a transformational medicine, then we're open to do it. We will not do something that wouldn't go into that category.

Great. And I'll take the other two. So for POLIVY, based on the trajectory that we have and the ambition that we have, it's probably something more like about 65% in first-line DLBCL. So I think we have high hopes based on the pickup that we've seen and where we believe we can go with this molecule. And then with the TIGIT inadvertent disclosure, there has been no impact. We remain completely blinded to the outcome of the study. And we have not had any adverse impacts from that inadvertent disclosure.

Mark, we answered all your questions?

Yes, that's great.

Okay, then let's move on. Next one in the row would be Luisa Hector from Berenberg.

On the -- just some moving parts of sales as we start to look out even into 2024, so we can see there will be significantly less erosion. But I just wanted to check the products to make sure we're modeling correctly. So I have in mind ACTEMRA, LUCENTIS, maybe a bit more Esbriet. And I was just wondering whether any of the subcutaneous patent expiries as something we need to consider around Europe when -- I'm not sure if they kick in next year. And then the offsets, you have all the positive sales. It's even new launches gathering pace. Just to kind of outline the pushes and pulls on sales into next year. And on Diagnostics, I just wondered if you could make some more comments around the mass spec launch plans on track for next year, I believe, just some commentary around what you're offering there and when you might expect to have orders, visibility on orders and to check that there's no cannibalization of your existing portfolio with the mass spec coming online.

Thank you, Luisa. Let me take the first question. I think the COVID sales are pretty easy to model. We've now shown you the Q4 sales we had last year and the Q1 sales this year. And basically, we do expect that after that, pretty much all of the COVID sales will wash out, similar to the levels we've seen in Q2 and Q3 this year. Beyond that, we see AHR erosion slowing down. And beyond LUCENTIS and Esbriet, as you mentioned, the only other medicine where we would expect biosimilar competition is ACTEMRA. And we would expect biosimilar competition in ACTEMRA at the very end of this year and in the U.S. in 2024.

Sure. And I'll take the mass spec question. So again, we're confident about our plan to launch the mass spec instrument in the second half of next year and also very excited about the pipeline. Now the pipeline is going to include things like vitamin D, therapeutic drug monitoring, immunosuppressives and steroid testing. We do not anticipate any cannibalization of our existing business. In fact, given that this will be integrated with our Serum Work Area, this again, similar to what you heard in my presentation, makes us even more competitive in the Core Laboratory that will allow us to also accelerate our share capture more broadly, so very positive on the launch -- for the forthcoming launch.

Forgive me, Matt, I think it will pull through to clinical chemistry and immunochemistry because it will improve our offering overall versus our competition.

Yes. Does that answer your question?

Luisa, did we answer your questions?

Yes.

Okay. Then we will move on in the row. And the next one is from [ Claire Rose ] from Citi.

Yes, it's Andrew Baum here. A couple, please. At the recent Capital Markets Day, you did a lot of self-diagnosis, which was helpful and interesting. But there wasn't so much on the operational details of execution, particularly on narrowing the scope of the pipeline focus as well as addressing the speed and augmenting the pipeline through BD. So the question is when will we start seeing tangible evidence of what I'm sure is the very frenetic activity inside the company? And then the second question is on obesity. So with zilebesiran, you've entered into cardiology, which is a new area certainly for you in the last decade. You have a presence with an anti-myostatin drug. Could this be the basis of a combination therapy with an incretin to accentuate the weight loss? And is this a strategy that you are actively pursuing?

Right. So first, I cannot really go into details in terms of M&A and BD. I hope you understand. So we can announce that when there is a deal to announce. But I wouldn't want to speculate in any direction. Again, we are looking at things all the time. And we'll update you depending on how things play out. Regarding the broader R&D excellence, we are now -- in beginning of September, we informed the organization about all of the findings. And we're now in the rollout in the organization to work on all the different elements where we see areas of improvement. But let me highlight, there are also areas of strength, as we see that in the past, we did launch a number of very interesting assets. Regarding anti-myostatin antibody, yes, it's right now in a study in combination with Evrysdi, strengthening the muscles of people with spinal muscular atrophy. But as you mentioned, the GLP-1s and the GLP-1/GIP incretins have one big problem. And this problem is muscle loss. And so it's an option that we are looking at how this antibody can play a role there in the future.

Okay. Then we move on. And the next one would be Steve Scala from Cowen.

I have two questions on HEMLIBRA and then one on guidance. On HEMLIBRA, why wouldn't the 1/3 of HEMLIBRA patients on QE dosing not be great candidates for ALTUVIIIO. I think the answer is that you think HEMLIBRA is a great drug. But that being the case, then why is Roche developing NXT-007? So that's the first question or maybe two questions. Secondly, on guidance, on Slide 15, the guidance for Diagnostics base business growth is forecast to be good. In the Q2 deck, the guidance was forecast to be solid. I know you will dismiss this as an insignificant change. But the company made the change deliberately to switch these words. And I'm just wondering why, these types of changes typically signal less optimism. So those are the questions.

Great. So I'll go ahead and start with the HEMLIBRA question. So for those folks who are on once-a-week HEMLIBRA, I think we still believe that from those -- for those patients who desire a prophylactic treatment onboard, there's a lot of great reasons, including long-term safety and efficacy data, the 0 chance of developing inhibitors, why someone would remain on HEMLIBRA. I think it's probably also worth calling out that real-world data is beginning to indicate that even the long-acting factors are not always used once per week. So they are often used more frequently than that. And I think we should just remember that the bar for switching a well-controlled patient is extremely high. The patients who are confident in their therapy, who are living the life that they want to live on the therapy that they're on and are having a good experience are very difficult to -- there's really no impetus for them to switch. When it comes to why we're developing 007, we are looking at 007 because we want to think about ways in which we could raise the bar on ourselves. This molecule has a higher binding affinity. It has an improved half-life. It could get to monthly dosing. But ultimately, in clinical trials, it will have to prove that it is better than HEMLIBRA to really have a good shot. Whether that's further reducing bleeding or something around joint health, I mean, I think all of those things are currently under consideration. But 007 is going to have to cross the same bar that everyone else is going to have to cross in order to unseat HEMLIBRA.