Good afternoon, good evening, everybody, probably good morning or lunchtime for people joining us online. Thank you very much for gathering here together at the Meet the AstraZeneca Management at ASCO 2026. It's been an exciting couple of days, and I'm sure we can continue the excitement in our session this afternoon. Before we start. Thank you. Oh, that's one too much. I would like to draw your attention to the safe harbour statement. Thank you. Which you are all familiar with, but please have a look at it. It's available here and online. We have a very exciting agenda this afternoon. We'll start with an introduction by our CEO, Pascal, and then we have the pleasure and honor to welcome Dr. Abou- Alfa, who is the principal investigator for EMERALD-3. It's going to be a very exciting session. Dr. Abou-Alfa is also professor of medicine at Memorial Sloan Kettering. After that, we'll go deeper into our ambition in oncology, and we'll also have a deep dive in the pipeline with Dave and Susan. There is two opportunities for questions, one right after the presentation of Dr. Abou-Alfa and right at the end. Here in the room, it's very easy. You just need to raise your hand, and please use the button. Online is the same functionality, the raise your hand button online to ask any questions. With that, I have the honor to ask Pascal to come to the stage and kick us off. Thank you. Thanks, Joris. Good evening, everybody. Really a pleasure to have all of you here tonight. It doesn't work. Thank you very much. Another ASCO, another exciting few days. Lots of great data, and two plenary sessions that this year were not ours, but certainly were very exciting and showing that this industry continues to shape the future of cancer care. It's really exciting to see the progress that we are all making, addressing unmet needs. On our side, as a company, we've made really great progress. You know this graph. We actually showed it to you the first time back in May 2024, if you remember. We always refer back to it because that is really our roadmap. This is what we work on constantly to try to prepare for today, for tomorrow, and the day after. If you look at our existing portfolio, it's doing quite well, as you know. We are making really good progress with our new molecular entities. We got approval for Baxfendy recently. That really is looking good. Camizestrant, we just received CHMP positive recommendation in Europe. We are in discussion with FDA, I'm sure you'll have questions for it tonight. Certainly, we're making progress. We interestingly got approval in UAE and Saudi for both cami and Baxfendy, first in the world. It shows you the world is changing, right? I mean, those countries, a few years ago, they were like four years, five years after everybody. Now they are leading the pack. We're making very good progress with a number of the other products on this list. AZD0120, really, we have very exciting data. Now, laroprovstat, our PCSK9 oral is now in full phase III. Tozorakimab, we announced, as you know, positive results for a drug that will have or has efficacy in COPD across all EOS levels. We believe that is going to be really a very important product for the treatment of COPD. We will actually next weekend at the ADA present our phase II data for elecoglipron, our oral GLP-1, and we will also introduce to you the outline of our phase III plan. We're making good progress with the Alexion portfolio, efzimfotase and eneboparatide, gefurulimab. Those products are really becoming reality. When we presented this, they were obviously hopes and dreams, but now they're becoming reality. We are also making very good progress with what we call the day after tomorrow, beyond 2030, because our goal is really to be a growth company until 2030 with our ambition to reach $80 billion, but also importantly past 2030. I know that within two or three years, all of you will be asking us how do we replace products we love like Tagrisso, Imfinzi, and they will be on your horizon. We're working very hard to bring these technologies forward to continue to grow. We have very strong pipeline momentum. Actually, these readouts are what we've experienced this year in the first half, as you can see here. The newest one is VOLGA. Actually, over the last three years, a little bit more than three years, we've had one positive phase III readout every month. One every month. This year, since the beginning of the year, we've had several approvals across the pipeline. Of course, as you know, the second half will be a very rich half. Everybody's waiting for AVANZAR and also SERENA-4, but there's more to those two. In 2027, we will continue with a very rich series of readouts. Actually, in 2027, we have more important readouts than we have in 2026. In terms of these technologies that I was referring to, we're making good progress with our weight management portfolio. I just talked about the GLP-1 and PCSK9. PCSK9 is very exciting. I must say the elecoglipron GLP-1 also looks very good, and we're moving those at speed into phase III. We're also building the long-term weight management portfolio with a number of new mechanisms and new agents. ADC and Radioconjugates, we're also making very good progress there with AZD2225, our radioligand, and we have now eight already honed ADCs in the clinic with three in the phase III, as you can see here. Puja is probably in the room today. She's working hard on new targets and new payloads and new technologies. We're progressing our IO bispecifics. We are making really nice progress and exciting new data are produced with our cell therapy, the lead product being AZD0120, but also our TCE, surovatamig, is really looking very exciting. Early days, of course, we have to remain cautious and humble, but very exciting product, I must say. More to come. Finally, we now have our first gene therapy for rare disease in the clinic. This is the ASCO this year. We had 80 abstracts. The world has changed in the last few years, and companies spread their abstracts and their presentations across the ASCO and the ESMO. ASCO remains very important, you tend to have also a lot of presentations at the ESMO, so the number of abstracts at ASCO is less than could have been in the past. A large number of very important presentations this year and very large number of poster as well, and I'm sure we'll be talking about many of the data that are listed here and were presented over the weekend. Of course, tomorrow morning, I'd like to attract your attention to the SERENA-6 new analysis that we will talk about tonight a little bit. The data will be presented tomorrow morning. Please stay tuned and look at this because it's a very interesting analysis that we believe will reinforce the value of the SERENA-6 algorithm. With this, let me hand over to Dr. Abou-Alfa, who is going to take you through the EMERALD-3 study. Thank you. Good evening, everybody. It's a great delight to be here. It was an exciting day, and really, it's a great honor to present again one more time today the EMERALD-3 trial. Very important for us to realize that chemoembolization, which in other words, inserting that thread through the artery to feed small beads into the liver, is a key element of treatment for liver cancer, which has been there with us for almost 25 years+. However, we realize that by itself only limit progression-free survival to about 8 to 10 months. As such, the understanding of probably an enhancement of the release of certain antigen of cancer and also enhancement of the immune checkpoints will be an opportunity to induce and control the disease by adding on checkpoint inhibitors. For that concept, we brought in the anti PD-L1 being durvalumab, and of course, this is to be kind of managed by a more immune cycle, the anti-angiogenic like lenvatinib. Of course, on the top of the chain of command is the CTLA4 represented by tremelimumab in the lymph node itself. That triplet led to the study, which looked into, number one, the triplet combination of the STRIDE regimen, which is the durvalumab plus the tremelimumab plus the lenvatinib add to the chemoembolization. Arm B is the tremelimumab plus durvalumab, which is called the STRIDE regimen plus chemoembolization. Of course, the reference point is the control arm is the chemoembolization itself. The study was available for all patients. This is very important that we give credit for all the co-authors and the collaborators of the study that we really looked at the study that it is more realistic. It really looked at real-world eligibility for the patients. These are patients who are really not eligible for any resection or curative intent, but they have disease which locally advanced in the liver only, and as such, applying the immunotherapy plus the chemoembolization will be an appropriate regimen. The study was stratified based on the regions in regard to Asia, excluding Japan, understandably, because of the different etiology, and of course, the rest of the world as well. Also, we looked into how many prior embolization, if there was a local therapy being less than six or none to six. The primary endpoint was progression-free survival, and this is very important to stress it out. As you know, the mindset for oncologists, and I'm one of them, is to look into OS, OS. Here we're looking at a different category of patients altogether because number one, the survival is longer relatively speaking, and this is what we are anticipating. Number two is really we are keen on seeing what is the local effect of the intervention that we did. For that reason, we chose the progression-free survival as a primary endpoint for Arm A, which is the STRIDE plus lenvatinib plus the chemoembolization compared to the chemoembolization in Arm C. Also we looked in regard to the evaluation of the overall survival for Arm A. Of course, we look also for comparative Arm B, which is a STRIDE plus chemoembolization versus chemoembolization for progression-free survival and overall survival. The study accrual was about 760 patients. They were in initial phase, a certain number of patients to be accrued on. Then a certain extension up to 218 patients was available for Arm A and C to further enhance the power for the survival and the progression-free survival. This is the statistical consideration for the study, and it was designed in a hierarchical method that will permit us to, number one, analyze all of those at the same time. However, the affirmative confirmation of the statistical analyses will all depend on what happened to the step beforehand, i.e. A rm A versus C, which as you see in the first box, if it was really met, then we go to the formal analysis of Arm A versus C in regard to survival, then we go on to B versus C, progression-free survival, and ultimately to B versus C overall survival. It was very important for my colleagues who are listening in to us this morning to express that this does not mean that we did not but provide data for all those four analyses. However, the affirmative and confirmatory analysis is to be followed for those that did not meet the statistical significance. This really first, the primary endpoint, which is the progression-free survival for Arm A. I remind you it is the TACE, durvalumab, tremelimumab plus lenvatinib plus chemoembolization versus chemoembolization A rm C. As you can see over here, the median progression-free survival was about 13 months compared to 9.8 months for the chemoembolization, which is exactly where we expect it to be for the standard arm or the control arm. The hazard ratio was 0.7, and the P value was 0.0007. This did permit us to carry on to the OS. Before I go on, I'm going to show you the PFS, as we said, because we did them all anyway. I'm going to show you the PFS for the STRIDE + TACE, which is Arm B versus, of course, TACE. As you can see over here, despite this is really not a formal analysis yet, it's relatively mature. As you can see here, 75.1% maturity, we can see 12.9 months for the median progression-free survival versus 8.1 months for the TACE itself, with a hazard ratio of 0.71 and the P value of 0.0062. This gives us an opportunity to start analyzing a little bit of subgroup analysis. As you can see over here, we kind of looked into Arm versus A versus C, which is to the extreme left. You can see that truly, all the subgroups independent did show a certain benefit or further benefit for the STRIDE lenvatinib plus the TACE. On the other hand, to the extreme right, you can see now we're looking at Arm B versus C, and one more time, we can see that there was also benefit for all the subgroup analysis for the TACE plus the STRIDE. I'm sure it caught your attention in regard to that standout for the patients from Japan, where it's favoring more the STRIDE plus lenvatinib plus TACE. If anything, there was a little bit of a understanding that maybe the better tolerance for the lenvatinib because of the experience in Japan add to one more thing, which is the non-viral nature of the disease that really is controlled mostly in Japan could have contributed to that. I would caution, though, that the Japanese cohort was very small. It's about 7.5% of the study, and this has to be put within that context. We took the plan, we took the opportunity to further analyze the components of what really is more of a pre-planned analysis of Arm A versus B. You'll be surprised how many people ask me about Arm A versus B, what's going on there. We went ahead and we showed it at the presentation, and as you can see, truly, there was no difference at all. If anything, it may really, in other words, conclude to you, did it really matter to add the lenvatinib? Probably not. Maybe with the exception of that Japan thing, which as we said, is a minor component, but as you can see, everybody did benefit from A or B independent. As such, of course, less toxicity, and we know lenvatinib sadly is a drug which is very efficacious, but sadly it carry on lot of toxicity. This will save a lot of that toxicity for the patient and make the benefit from the STRIDE regimen specific. Now that we look at the subgroup analysis, we can carry on to discuss the overall survival. As you can see here, the trend is positive for all that I'm going to show you. Number one, we're going to look into the Arm A, STRIDE lenvatinib plus TACE. As you can see here, it is showing that trend positively, 39.5-month median survival for the STRIDE lenvatinib or Arm A versus 34.7 for Arm C with a hazard ratio of 0.84 and the P of 0.18. This, however, will caution this only at 40.3%, 40% maturity, and of course, we'll await for more results as well. The nice surprise is what we saw with the Arm B versus C. As you can see here one more time, the median survival for the Arm B was not reached yet. It was non-calculable. At the same time, it was 32.9 months for the TACE, hazard ratio 0.7 with a P value of 0.02. Again, maturity is at 45%. In regard to the adverse events, truly, the three ARMs, independent what therapy we're giving, being the TACE itself or the STRIDE regimen or the lenvatinib, did not show anything that we don't know. All of those are adverse events that we are commonly learned or know about and we are commonly used to know and manage as well. I probably will pinpoint here that the drop-off in regard to the Arm A and B was similar. Of course, there was a standout in regard to more drop-off in the Arm A because of the lenvatinib toxicity, which I think was close to about 80% or 78%. If anything, we can conclude that the STRIDE plus lenvatinib plus the TACE definitely significantly improved the PFS versus TACE alone with hazard 0.7, P value 0.0007. This is a primary point of the study. Number two, the STRIDE lenvatinib TACE showed a favorable overall survival trend, favoring the STRIDE lenvatinib TACE compared to TACE with hazard ratio 0.84 and the overall survival maturity, as we said, about 40%. Lastly, the STRIDE plus TACE showed clinically meaningful improvement in regard to PFS and OS. At the same time, as we mentioned, maturity for the OS is about 45%. I can add on here that A versus B did not show any difference, the STRIDE as such provide efficacy in EMERALD-3 and the acceptable safety profile consistent with what we know about those three regimen being the TACE, STRIDE or lenvatinib. I think we'll stop here, always I will say big thanks for all the collaborators and of course big thanks for the sponsor of the study. AstraZeneca did a great job helping us with achieving those results today. Thank you very much. Thank you. Do you want to take a seat? Thank you very much. Thank you, Dr. Abou-Alfa. We will have ten minutes or so for Q&A specific to this study, and we can start here in the room, I think. Are you going to go around as well with the microphone or yours? Perfect. Yes, please. Hi. Thanks. Richard Vosser from JP Morgan. Maybe on EMERALD-3, how are you seeing the potential of EMERALD-3, given you've now seen all the data and we've seen it as well? There was some discussion today on the overall survival, and the need there to see more data from the discussant. How important is that in unlocking the potential and how should we think about the ramp? Yeah. Maybe Dr. Abou-Alfa, I would like to start first with how you think that for yourself you'll incorporate this into your clinical practice decision-making, and what do you think the decision-making will be with colleagues of yours? Then I can answer specifically a view from there. Yeah. Thanks so much. You're absolutely right. There was some kind of question about the maturity of the overall survival. I would say that as of tomorrow morning, our standard at Memorial Sloan Kettering is actually STRIDE plus TACE. The drugs are available, it's approved, at the same time, we are seeing positive results over here, so there's no concern at all in regard to really move forward with this. As far as the overall survival, exactly as you mentioned, we oncologists are kind of like mindset in regard to OS, but I really try to make the argument for the PFS, at the same time as we see the OS, even though it doesn't have the maturity, the suppression already there. I think it's just a matter of time that hopefully we'll see this improvement. Specifically on the potential, I have said in the past, and I believe that EMERALD-3 with approval is a blockbuster opportunity globally, and I continue to believe that. I think that we will have different conversations with health authorities. Dr. Abou-Alfa quite rightly points out in Japan we might have a different set of discussions than we might have in some other jurisdictions. I also think that this should be practice informing in the United States for many in the community straight away, and we have an opportunity for the overall survival data to mature into 2027, and I think that's going to be important for another part of the community. Thanks. Thank you. It is Michael from Jefferies. Just to follow up on that, Dave, is your comment an expansion of TACE applicability within the patient population, or is your blockbuster potential comment restrained by what the TACE eligibility is today? Great. Can I also though start with Dr. Abou-Alfa? Can you give your view on TACE and TARE and globally the evolution of that? By all means, Michael, you're absolutely right. Actually, the question was brought in right from the start because there's, to be fair, in certain early regions the applicability of TARE. We made it very clear that the TACE is the most common used therapy for HCC worldwide. At the same time, the data is definitely for TACE. It's not for TARE yet. However, as you heard, there are some other studies that are evolving to really answer the TARE question. To give you an argument why this is important, as you know, at Memorial Sloan Kettering, at some point we did this study comparing TACE to bland embolization with TAE. In other words, one without chemo. There was no difference at all. Interestingly, as much as we are really bought into this, and we do give bland embolization, when it came to adding on the checkpoint inhibitors, we actually switched to doing TACE. Why is that? All what I mentioned in regard to that induction of the immune checkpoints, if you don't have the chemoembolization, it's not going to happen. What will happen with TARE, we don't know yet, but we have to wait and see until this happen. At the moment, this applicable for TACE. Michael, from my standpoint, we would expect with these data that we would see that TACE would be something that would be seen as the right combination, from EMERALD-3. At the same time, to Dr. Abou-Alfa's point, obviously we're doing evidence generation work to answer the unanswered question about what about with TARE, which we would expect to be practice informing and potentially guideline informing depending upon how those data net themselves out. Okay. Why don't we go to one in the room and then I can come to the one that's online to Sam here. Thank you. Sam Fazeli from Bloomberg Intelligence. Dave, your strategy for registration, are you going to go alone for STRIDE plus TACE or would it be both Arms? How are you thinking about that? Do you want to comment on registration? Yeah. Happy to, and thanks for the question. Obviously we've met the primary endpoint for the primary comparison of Arms A plus C. I think what we will do is go and have discussions with the regulatory authorities. Obviously, the contribution of components is likely to be a question with the different regulatory authorities, but it's a primary endpoint, so we'll submit the whole study, and we'll have a discussion. There are some regions, as we've discussed, particularly when you've got this non-viral etiology, which is actually now nearly the majority of patients in Japan, interestingly, since hepatitis C is now a curable disease, and hepatitis B has decreased because of vaccination. The predominant form is the non-viral etiology. What we've seen in Japan as well is the Japanese investigators are very good at managing the lenvatinib toxicity with rapid dose decreases. That may help to explain, as Dr. Abou-Alfa explained, why we're seeing a difference there. I think it's important that physicians around the world get to have a choice about the regimen that they have. We will present the whole study. Thank you, Susan. I will go online to Colin White from UBS, who has a question. Colin, please go ahead. Hi, it's Colin White from UBS here. Thanks for taking my question. I wanted to ask about the other regimen that was presented during the same session, the camrelizumab plus rivoceranib. Just to try and understand if STRIDE plus TACE and this regimen, once they're both available, I was wondering if you could help us understand how they might both be used in practice, and which would be preferred. Just another quick question was what proportion of patients in this setting wouldn't be eligible to receive the STRIDE plus TACE regimen? Thank you, Colin. Again, I think maybe Dr. Abou-Alfa, I'd be interested in your perspective on if both of those were available. I think that what's important to note is that the PD-1/VEGF is in a Chinese-only population, so I think that if it was available is a question that has a big hypothetical to it, but perhaps you could answer your perspective on that. No, by all means. We know very well about the CARES regimen, which is the camrelizumab plus rivoceranib. I think I point exactly as Dave said, is a rather robust anti-angiogenic. As we know from the first study that they did, we have a little bit of concern about the toxicity. That's really mainly with regard to the anti-angiogenic. Add to this, as we know in the Western Hemisphere, these are not approved yet. I would say that the data was trending, but definitely appeared for the investigators and we're, of course, talking among ourselves, not really at the same kind of robustness that we have seen with EMERALD-3. By all means, we'll wait to see how this will translate, but I think with the HIMALAYA study, which was at the core of the current EMERALD-3, I think we're definitely leaps ahead in regard to that regimen. Thank you, Dr. Abou-Alfa. You can go online. Hi there. Chris Uhde from SEB. Thanks for taking my question. I guess the question I have is sort of the big picture from this. It seems, at least to me, that this speaks to the power of CTLA-4 in early settings or early-ish settings in cancer in general. What can you say about how you expect that role of CTLA-4 to evolve long term and perhaps any role for AstraZeneca in that? Yeah. Perfect. Osama, and I think it'd be great if you could offer your perspective, and maybe Dr. Abou-Alfa before Osama - Yeah - goes, you can offer your view on CTLA-4. Osama, you can comment on how AstraZeneca's pursuing. Wholeheartedly, we're very connected to CTLA-4 at Memorial. As you know, it was defined by our previous CEO. Jim Allison's work and anti-CTLA-4 came afterwards, then we carried on with the HIMALAYA. What's important and fascinating about the specific CTLA-4 being the tremelimumab is not necessarily with every anti-CTLA-4. It's really a very robust anti-CTLA-4 that actually is even more potent than the CD28 that we have in our own body. Really it stands out as being one drug only. Can you believe it? Like, a patient getting one drug only in their lifetime. Especially that we saw in the HIMALAYA study, we reported the six-year survival and just still standing, and always we tell that this is based on a therapy that patients were given six years beforehand. I would say that you're right, and I like the way you pinned it down. It's definitely the story is about CTLA-4, and that's why I smiled what you're saying it, so it's good. Just for those who may not know, Dr. Osama Rahma leads our GI work within AstraZeneca. Please, Osama. Thank you so much. Thank you, Dave. I would add to Dr. Abou-Alfa comment about the power of CTLA4, especially in this disease, which is very pronounced in HIMALAYA when you look at the six-year OS that we have released. This is the only IO in this disease actually that has a long OS data. How do we apply this to the EMERALD-3 and what we've seen with the overall survival? The OS data that Dr. Abou-Alfa showed is 40% mature. If you really apply what we've seen with HIMALAYA, the longer you wait, the longer for usually the OS benefit to become more pronounced. I would really encourage you obviously to wait for the final analysis for EMERALD-3. Great. Thanks, Osama, very much. If we continue on then, and thank you again, Dr. Abou-Alfa for the comments on that, and continuing with some of the work here. EMERALD-3, we've spoken to this and I think addressed this. Clearly, a large patient population in terms of embolization-eligible HCC patients across the globe. We've got an opportunity with final analysis of OS in 2027 to certainly be able to use that data as we go forward into our discussions. In the meantime, we do see this as absolutely having impact on practice in certain parts of the globe. What you can also see is that we've got a maturing pipeline of innovative regimens across a range of GI cancers, right? You're very well familiar with the work that we're doing in biliary tract cancer. This builds on what we're doing within HCC and then a growing presence within the gastric cancer space. Why is all this relevant? This is really relevant because right now with Imfinzi, we're continuing to expand with multiple indications that are not only producing positive phase III results, but are resulting in approvals. I think that you've seen that that is driving pretty impressive growth for this brand. Right now, Imfinzi's the fastest-growing PD-L1 within the class, and that's coming off of a strong foundation that we've established with the six studies that you see in the bottom left. We're really with the move into early cancers, and whether that's early non-small cell or small cell or the work that we're doing in gastric together with bladder, GI, et cetera, you can really see that that's making a big move. We've got the recent approval within the U.S. for POTOMAC. We also then look out further. Pascal highlighted a number of readouts that are coming, whether that's with AVANZAR, a series of studies that we've got in combination with Dato and breast cancer, additional work that's happening within PACIFIC. There are a number of opportunities for us to continue to have a series of strong growth catalysts on IMFINZI. The other area that I think has been really exciting for us to be able to share data on is that we had data at this year's ASCO in all three major subtypes of breast cancer. Obviously, we're familiar with the SERENA-6 study and the importance of the additional PFS2, as well as ctDNA clearance data, which is going to be presented tomorrow. You certainly saw from the abstract that the PFS2 data is supporting the durability of benefit beyond PFS1. You'll have to have an opportunity to learn more about the ctDNA clearance tomorrow, and the data that's in there. We think that it's supportive of a biologic hypothesis around SERENA-6. TROPION-Breast02 and DESTINY-Breast09, we continue to bring our antibody-drug conjugates further and further into a leadership position. We're really excited about the approval again in the U.S. with TROPION-Breast02. We have an opportunity to see really that the key secondary efficacy outcomes are supporting this regimen as standard of care in this area, very high unmet need of triple-negative breast cancer. We've got teams that are hitting the ground running, working to drive adoption here within this setting. I think that it's really done a lot to de-risk much of what is in the data consensus sales at this particular point, which we think is important as we look towards the second half of the year and some key lung readouts. On DESTINY-Breast09, importantly, we see really some data that I think what's key about this is about the sustained durability of benefit resulting in long-term outcomes on DESTINY-Breast09. Why is that important? We know that there were questions that came out of DESTINY-Breast09 around whether or not we should be tinkering with the duration of therapy above and beyond how the trial was designed. While that remains an unanswered question for some, I think that what you see from the data that we're sharing here at this year is that it reinforces that the design is the way that it should be followed if we want to get the outcomes that are within it. Those are really important studies. When you take a look at the commercial opportunity that just this slide represents, just even on the right-hand side with TROPION-Breast02, DESTINY-Breast09, these are major growth drivers that we have within our portfolio. With that, I'd like to turn it over to Susan, who's going to take us through other elements of the pipeline for tomorrow. Thank you, Dave. It's great to be back at another ASCO. Thanks to you all for coming and your interest. I just want to talk a little bit about some of the progress of the assets from the early program, as Dave has said. Puxi-sam, as we call it, is our leading homegrown antibody-drug conjugate targeting B7-H4. We had a presentation in the gyne session. What you can see here is the waterfall plot from patients who were treated with puxi-sam at the 2.4 mg per kg dose level in second-line plus B7-H4+ advanced endometrial cancer. I think a couple of things that are important to note about this. B7-H4 is the most prevalent target that is seen in endometrial cancer and goes across histologies. You can see the histology color-coded at the bottom of this. We saw a 47% response rate with a good median progression-free survival of 7.2 months, and even better in patients that have had prior IO. These data have underpinned the U.S. FDA's designation of breakthrough therapy designation, which we received earlier this month. We are the leading ADC targeting B7-H4 in endometrial cancer. We've started a phase III trial in the second-line plus setting based on these data, and we're planning additional studies beyond this. I think that's a great start. One question then is, given the prevalence of ADCs that are coming through in the gynecological space, how are we positioning this versus the other options? The second of our antibody drug conjugates that are homegrown is torvu-sam. Torvu-sam targets the folate receptor alpha, which is already a strongly validated target in ovarian cancer. A couple of things to note on the target. Some ADC targets that also have prognostic implication are really important because if you're also removing the signaling from that target, I think that can help. For example, high folate receptor alpha is known to be a negative prognostic factor in ovarian, and that increases with the increase in the receptor expression. If you just look at the number of molecules per cell, folate receptor alpha has about tenfold the number of molecules per cell in a B7-H4 in ovarian cancer, and a higher overall prevalence. Depending on the cut point, if you use a sort of one plus cut point or 25% of the tumor cells expressing at that level, it's 72% versus 49%, just illustratively for folate receptor alpha versus B7-H4. In fact, the vast majority of ovarian cancers express some level of folate receptor alpha. It's over 90%. We are looking at the activity of torvu-sam in those lower expressing as well as in the higher expressing patients. What we've seen with tovosutumab is a 54% response rate across dose levels in heavily pretreated patients, and that was published at the ESMO meeting last year. We are broadening the torvu-sam phase III program based on the strong data that we have seen here. We have a second line plus platinum-resistant and refractory monotherapy study, the TREVI-OC-01, which will have data beyond 2027, but two additional phase III trials initiating later this year. Again, we've got other combinations that we're excited about with torvu-sam, and we're also looking at this in other folate receptor alpha expressing tumors beyond ovarian cancer. We think we've got a best-in-class profile here with a really good and validated linker payload. Moving on to the Claudin18.2 ADC. This was one that we licensed from KeyMed and that has been ongoing in now the CLARITY-Gastric01 phase III program in the second line setting. We published at ASCO. Kohei Shitara presented the data from the CLARITY-PanTumor01 phase II study with sone-ve in the second line plus patient population of gastric cancer. Actually, 60% of these patients had third-line disease. We saw a 28% response rate in this disease with median progression-free survival of 4.2 months and a significant number of patients with really prolonged stabilization of disease, which is a feature that we see with this drug, not just as monotherapy, but also as we're looking at combinations in earlier line settings, not just in gastric cancer, but also in other tumors that express Claudin18.2, such as pancreatic. We also now started a first-line study. I would just remind you, when you look at the combination of the ADCs with IO and you see them in the first line settings, the data that we've seen, for example, in bladder cancer with an MMA payload like this has looked really interesting. We are very excited about the CLARITY-Gastric02 data set, which will also have data greater than 2027. I think with this program, this is the leading Claudin18.2 ADC. I think it is going to be a really exciting time for both gastric and pancreatic cancer to create regimens and combinations that really can change the outcome for this disease. Moving on now to our IO bispecific portfolio. We had a number of different presentations here. Again, I will draw your attention to the GEMINI-Hepatobiliary data on the left-hand side, phase II. This is looking at rilvegostomig in combination with chemotherapy in patients with advanced biliary tract cancer. Again, here, one of the things you see, which we're seeing across multiple phase II data sets now is prolonged stabilization of the responses that we see. 16.9 months median overall survival from that prolongation of disease. This is a durability, is a key feature that we're seeing with rilva. It builds on the ARTEMIDE follow-up that we showed at the ESMO meeting last year in lung cancer. Again, the other aspect of rilvegostomig is it's really a safe asset including in combination. We've seen this in the DESTINY-Gastric03, phase I-B/II study here. Very favorable profile looking at the rilvegostomig plus ENHERTU plus chemotherapy ENHERTU + in advanced gastroesophageal junction cancers. On the right-hand side, you've got data from rilvegostomig in the eVOLVE-02 phase II study in patients with head and neck cancer. Again, highly durable responses. 60% of the patients that responded in this study still ongoing well beyond a year, if you look at the poster. This has informed the ongoing phase III study, the eVOLVE Head and Neck Trial. Finally, I draw your attention to an oral presentation we had from one of our hematology assets, AZD3470. This is a leading epigenetic targeted asset. It targets the MTAP selective. It's a PRMT5 inhibitor, but it's designed to be selective to improve the overall profile. What we've discovered with this is that actually if you look in Hodgkin's disease, the Reed-Sternberg cells have epigenetic silencing and are MTAP depleted in over 80% of cases. What this means is it's particularly sensitive to PRMT5 inhibition. What we've seen at the higher end of the dose escalation at the 450 and the 600 mg QD is we're starting to see not just partial responses, but complete responses, and actually 44% complete response rate at the top dose. This is higher than any single agent response rate that's been seen in this disease, and these patients were heavily pretreated. There's one patient that's had 11 prior lines of treatment. To see a complete response with an oral well-tolerated medicine was remarkable. I think this has potential to be a first-in-class oral PRMT5 inhibitor in this disease, but also has opportunity beyond hematologic malignancies in solid tumors, including, of course, in pancreatic cancer, in combination potentially with our pan-KRAS inhibitor. Now, I'm pleased and proud to present on behalf of Gianluca Pirozzi, who's leading our Rare Disease Development program, the data from the CARES study showing the benefit of anselamimab in kappa isotype light chain amyloidosis. Just as a reminder, amyloid fibrils, both kappa and lambda, are deposited in tissues in this disease that cause organ dysfunction and damage. The current standard treatments are targeting the actual underlying plasma cell disorder to decrease the production of these misfolded proteins, but they don't actually clear the misfolded proteins from the organs and the deposits. Anselamimab is an anti-fibril antibody, which actually clears the pathogenic fibrils. We had two phase III CARES study in patients with severe light chain amyloidosis. Just to be clear, the primary endpoint was not met, but what we've presented here is data in the kappa subtype. In that subtype, we saw highly meaningful 62% reduction in all-cause mortality and a 71% reduction in cardiovascular hospitalization. It was well-tolerated in this disease, and therefore represents, from this subgroup, a new potential treatment option in this difficult-to-treat disease. I think just to summarize the overall presence that we have in AstraZeneca for our oncology portfolio, there's really been significant progress against the five trends that I talked about at the investor event in May 2024. First of all, you can see not just from our own portfolio, but across the industry progress in the ability of novel antibody drug conjugates to potentially replace backbone chemotherapy in different settings. You're also seeing the advent of Radioconjugates, and we're pleased to see the progress that we've had with our own leading Radioconjugate, the PSMA, with the actinium payload in prostate cancer going into phase III, the VECTRA-01 study. We also have the second trend that you're going to see segmentation of the IO space, and I think we've seen some more data as well in this regard. The expansion of the IO sensitive space with the introduction of the novel technologies of cell therapy and T-cell engager, and then the importance of bringing different mechanisms together into combinations and moving those into the earlier setting where the potential for improving long-term outcome is greatest. With that, we'll stop now and we'll have the opportunity for Q&A. I think Dave's going to moderate the Q&A. Thank you. Thank you, Susan. All right. We've got an opportunity for a Q&A. We'll come into the room. James, why don't we start with you? Thanks very much. Is this turned on? It is now. Great. Thanks very much. James from Barclays. I saw the comment on replacing the backbone of chemo. On that then, for Datroway AVANZAR, the latest confidence in AVANZAR's success and also the competitive bar posed by sac-TMT. We saw the data this weekend, and the efficacy looked quite good, but then can we read that data? Does this say that TROP2 ADCs are good, so it validates it, or is it a competitor to worry about? Anything else that reinforces or otherwise around the TROP2 biomarker. Have you analyzed anything else that gives you more confidence there? Okay. Susan, you want to take that? Yeah, sure. Okay. I'll take that question. Thank you. Again, I think over the last year, you've seen a number of key points that I think help support that the TROP2 ADCs are going to be active in a number of different diseases. Obviously, in breast cancer last year at the ESMO, we saw the TROPION-Breast02, and I think what that gave us the opportunity to see in a setting where there was also a competitor TROP2 ADC is that we've got a best-in-class profile. That's built based on the design of the ADC. It's got a stable linker payload. You see that reflected in the longer half-life and lower bone marrow toxicity, which is one of the reasons why we can combine it in the case of AVANZAR with platinum, which we think will help deepen the response. The reason why that might be important, if you look at, for example, when we looked in HER2 in the DESTINY-Breast11 setting, the monotherapy arm for ENHERTU was good, but actually what we needed is to have displacement of some part of that combination chemotherapy regimen. That's the approach that we've taken with the Avanza study. I think to answer your question about the sac-TMT data, I think what it does do is show that there's potential for TROP2 ADCs in this setting to have an important added benefit. Of course, there's questions about the relative hazard ratio when you've got a control arm that doesn't represent the current standard of care in the West. Nonetheless, I think it does represent a further data point that helps improve confidence. I think we're really well-positioned with AVANZAR. We're going across different PD-L1 levels across our program in the first line with the AVANZAR TROPION-Lung07 in the PD-L1 less than 50% and TROPION-Lung08 in the greater than 50%. We've got the combination with platinum and as a doublet. We've got the biomarker. I do think we've got multiple data sets with the biomarker that can help further build on the intent to treat opportunity. Overall, I feel really confident we can be the first TROP2 ADC in combination with IO in first-line non-small cell lung cancer and have a differentiated profile and a really strong data set overall. Thank you. Thanks, Susan. I think we've also, James, come a long way from questioning whether TROP2 ADCs have a role in lung cancer to asking how do we optimize delivery of the TROP2 ADCs in lung cancer. I think that's an excellent evolution over 12 months in my view. Yes, please. Thank you. Hi, Mike Nedelcovych from TD Cowen. I have three questions, if you'll let me. My first is on actually camizestrant, your oral SERD. Tomorrow we're going to get phase III data from Roche's persevERA trial. I'm curious if there is a PFS hazard ratio that you would view as encouraging vis-a-vis SERENA-4's upcoming readout or one that might be discouraging. My second question is on your radioligand therapy portfolio. Forgive me, I believe this is the first time you've announced that your PSMA radioligand therapy with an actinium-225 label is headed to phase III. If I'm wrong about that, please disabuse me of that notion, what are the data that support that advancement? Maybe you could tell us about the cadence of readouts from here. Lastly, on your PRMT5 inhibitor, your comments, Susan, were very encouraging. I'm curious where that fits into your long-term revenue ambitions? All right. In terms of cami and persevERA scenarios, maybe Susan, I can ask you to take that. If you want to make any comments on the radioligands, you can. I also think it'd be an opportunity for Ravi Madan - Well, Ravi. Yeah - to comment on that. It's a good chance, Ravi, where are you? Oh, there you are. We can do that in front. Then on PRMT5, we can come back to you on that. Fine. If, Anas, you want to add anything as well, we can do that. On the persevERA data, again, I think it's obviously going to be important to have a look not just at the hazard ratio but also the shape of the curves. The key questions are going to be, with the design of the trial, how successful were they in actually recruiting an endocrine-sensitive population and what's the read across? I would remind you, of course, that SERENA-4 is a larger trial than persevERA, so it's powered. I think if you look at the median improvement, that's also another factor together with the actual hazard ratio for PFS that will be important in that context. Those are the factors that we'll obviously be looking at. We look forward to seeing the results of the SERENA-4 data. The other thing we'll be looking at, of course, is the safety profile. Okay. Great. Thank you. Ravi, just to introduce you, Ravi Madan has been with us for weeks now, joining us in leading our prostate development work. Ravi, please, on the radioligands, the PSMA, and the confidence in the phase III. Yes. Thanks. The data supporting the phase III will be presented at a meeting later this year, but the VECTRA-01 study did launch, and we had our first patient on the study a few weeks ago. It is in the post-chemotherapy setting after docetaxel in prostate cancer. In general, we think that alpha will be superior to beta therapeutically, and we think that there's a real opportunity here also to move it up earlier, and we'll have other phase IIIs looking at that as well. Yeah. I think it's an exciting time in prostate cancer at AstraZeneca, and I'm very happy to be here. Thank you, Ravi. I think being able to attract people like Dr. Madan here is also testimony to the portfolio that we have. Susan, do you want to speak about the PRMT5? Yeah. I'll start. I can make a comment afterwards too. I'll start, and then perhaps Anas Younes, who's an expert in Hodgkin's disease, can add some commentary. The PRMT5 inhibitors, we're in the sort of second generation now that have this MTAP-selective design that improves the tolerability profile, therefore, you can actually get the hit and the target that you need. I think that's one thing that has been seen that needs to be improved. Actually, the prevalence of MTAP deletion is actually not uncommon. It's 10%-15% of all cancers, as I said, in this particular disease of Hodgkin's, it's 80% of the tumors have this epigenetic loss of And so you see the loss of the protein in their cancers. That's one of the reasons why I think it may be particularly sensitive. What we've seen, though, is it extremely well-tolerated. I think that it means it's easy to combine potentially with other assets. Within the context of pancreatic cancer, with RAS-targeted agents becoming a backbone element, that ability to combine is going to be an important component. I think it has potential not just in pancreatic cancer, but lung cancers and other settings in solid tumors beyond hematology. Anas, do you want to talk about the hematology opportunity? Yeah. Sure. As you know, Hodgkin lymphoma, it's a highly curable disease. When patients relapse from the two classes of drugs that are approved, the brentuximab and the PD-1, there's really nothing there. What you've seen in the data here, almost all patients was exposed to these two agents, and then they have no other options, and still had about 60-plus overall response rate, 40-plus CR rate, which is really unprecedented. That's why we're excited about it. There's another opportunity within the heme malignancies. 15%, 20% of large cell lymphoma have the MTAP deletion, 40%-60% of primary CNS lymphoma have MTAP deletions, and many others. There's more indications beyond Hodgkin lymphoma. Yeah. Thank you. All right. Back to Oh, Chris. Yep. Chris Uhde, SEB. Thanks again for the questions. Sticking with the PRMT5, obviously some baggage historically with the class. Would you please talk a little bit about the 3470 mechanism, and how it's differentiated versus those, well, or any other PRMT5s? Susan, you mentioned the pan-KRAS combo, could you talk about the mechanistic rationale then f or that, is it just orthogonality or is there something specific about PRMT5 and a TKI specifically? A second question on the competitive outlook for multispecific IO. We saw CStone with a tri-specific going for monovalent binding of CTLA-4. What are your thoughts on how that profile that they've started to show compares to what you're doing with volrustomig and rilvegostomig? Thank you. Okay. As I alluded to, the first generation of PRMT5 inhibitors weren't truly MTAP selective, you're inhibiting this in the wild type as well as in the MTAP-deficient tumor types. It wasn't possible to get to a dose level where you were really hitting the target hard because you got generalized, often GI side effects that were associated with that. I think it's just fundamentally a better molecular design to have that MTAP selectivity built in. Right. Sorry, I can't hear you. MTAP was involved in the second generation? Yes, it was. Again, within the second generation, there were going to be differences in terms of the overall profile. What we're seeing with our profile is really excellent tolerability relative to the rest of the class, and good MTAP selectivity. I think the data from a particularly sensitive disease like Hodgkin's is helping us emphasize the importance of getting up to the higher dose levels. You see that there's a dose response in terms of the activity going from partial responses to complete responses, and then a 44% at the top dose. I think that's helping us make sure that we understand what level of target inhibition you need to really drive efficacy. To your question about the combinations, there's about 25% of pancreatic cancers that have the MTAP deletion, so it would require selection for that. The preclinical data on combinations with RAS inhibition look good, but I'm not sure that I would argue that it's greater than additivity, in terms of the two different mechanisms. What you tend to see with PRMT5 inhibitors is prolonged stabilization of disease, and a lower response rate. What you're clearly seeing with the RAS inhibitors that are potent is something in the range of the 30%-35% response rate, at least in the second-line setting, may increase in the first one. Thanks, Susan. Let's go to a question online, Graham Parry, Citibank or Citi. Graham? Hi. Thanks for taking the question. Firstly, on the sac-TMT data that came out, obviously you saw some strong hazard ratios there, but against a relatively weak control. In the PD-L1 high patient population, KEYTRUDA is standard of care, and there is a very good hazard ratio there. Just your thoughts on the bar in that setting, and do you think we could actually see a market that gets fragmented across the different ADCs? Second, we've had some physician feedback that sees the linker technology there as better than your linker technology, so any comments on that would be quite useful. Again, the KOL feedback seems to suggest that for AVANZAR, the bar is an overall survival hazard ratio of 0.75 or better, across both AVANZAR and TROPION-Lung07. Just your thoughts on confidence in getting there and whether we think we, at first readout, would have mature enough overall survival data. Secondly, on persevERA, you talked about the things you're looking for out of the giredestrant data. Can you clarify, if we look at the recruitment criteria in the trials across persevERA and SERENA-4, they look very similar. Did you actively recruit more patients who were naive to endocrine therapy? Could there be a higher percentage of those patients in SERENA-4 than we see in persevERA when we see the data tomorrow? Thank you. Great. Okay, thanks, Graham. I think, Susan, on this within sac-TMT, there's a question on could we see segmentation with ADCs based on what we saw on the PD-L1 highs? There's a question on any differentiation around linker technology and the importance of OS. I think while you said that was one, that's three. I think that those were those. Good. I think there was continuing on persevERA and the scenarios. Okay. All right. Puja Sapra is in the audience who leads our Biologics Engineering and our Oncology Targeted Delivery group. What she brought to us is real focus on getting the stability of the linkers and looking at that. I've said it once, I'll say it again. I think it's really important that you've got a stable linker, and you can see that in terms of the half-life. It's really important for driving the relative proportion of the drug that's delivered to the tumor from internalization versus exposure to free payload in the peripheral circulation. If you've got an ADC that falls apart in the peripheral circulation within a day or a couple of days, then you've got high exposure just to free payload, which is like a slow-release topoisomerase inhibitor. It's not really driving the mechanism of action for internalization. I think that's one thing that's important. That's important that the thing that we're looking at with the biomarker to enrich for. I think, yes, the data in the PD-L1 high group looks good, but the data across the group is good. It's just harder to judge it in the PD-L1 low because there wasn't the appropriate control arm. I don't think it's necessarily segmenting it by PD-L1 status. I think the segmentation potential may be in the biomarker positive, but actually I think what it does do is increase the probability of success in the ITT as well. It's further enrichment in the biomarker positive. That's why I'm saying I think the design that we've got with AVANZAR enables us to have the best opportunity to have a differentiated asset, particularly when you put it forward with the addition of the TROPION-Lung07 and TROPION-Lung08 data sets as well. I hope that answers your question on sac-TMT. For persevERA, again, I think whenever you're looking at a trial, it's important not to just look at one component. The hazard ratio will be one component, the shape of the curves will be another, including the timing of any separation in the curves. That will help us understand about the proportion of endocrine resistant tumors that are there from the get go. Even when you've got patients that have been enriched for duration of time since adjuvant therapy, for example and de novo, there can be differences in those patient populations, which is what we'll seek to understand when we look at the forest plots, et cetera. I think it's the hazard ratio, it's the shape of the curve, it's the actual distribution of those endocrine sensitive patient populations. We'll be able to look at that and look at what we've actually accrued in SERENA-4 and then make a judgment on that. We're not going to have to wait too long for the results of the SERENA-4 study. We've said it's the second half. It's not far from the second half now. Let's wait and see what the trials run out. The overall profile that we've seen with camizestrant is one that I think is very competitive, and I think there's good things that we're going to learn from these trials that will help us further develop this asset as a backbone endocrine therapy. Super. Thank you, Susan. Let's stay in the room, I think in the back. Yeah, please. Thanks for taking my question. It's Rajan Sharma from Goldman Sachs. Just wanted to get your perspectives on the VEGF bispecific mechanism. It's obviously not something that you have in your portfolio as it stands, but given the mature end data there, is there a point in time when you think that that's something that you do need to have in-house? What do you think about combinations with TROP2 ADCs there? Second question was regulatory related just for anselamimab. Given that you didn't hit in the primary outcome, could you just talk about the regulatory path forward? Is there something that exists there, or is this a new regulatory path that you're going to have to carve? Just on that topic, could you just talk about your latest confidence into approval for SERENA-6 post the adcom? Thank you. All right, maybe Gianluca, why don't we start with you with anselamimab and the regulatory path. After that, I would propose that maybe, Susan, you can talk about VEGF and the mechanism, but then Leora, I think it's a good opportunity to talk about our strategy within lung cancer with rilve and volru on that. Right. We can have the SERENA-6, please. All right, perfect. I'll start with the discussion about regulatory pathways. We've been engaging with regulatory agencies globally about data results. Look, these are the two elements that we are fundamentally using in the discussion with the agency. Very strong data set and high unmet medical need in this patient population. These are the elements that we're using. The strong data set comes from the results you have seen with a 62% reduction in mortality, a 71% reduction in hospitalization, the fact that the subunit was pre-specified, and the fact that we see the effect in each of the two individual studies separately. Although they were combined in the final analysis, each study was done separately with one another. We also see additional evidence of efficacy across the primary and secondary endpoint. You saw the data on all-cause mortality or cardiovascular hospitalization with an improvement in the KCCQ, which is a questionnaire for cardiovascular quality of life, as well as trend of improvement in six-minute walk test. Finally, we saw improvement also in NT-proBNP, which is a marker of cardiac efficiency as well. All of this data has been published on the JCO. Additional data sets we're also using with regulators focus on echocardiographic effect. We're going to disclose this data set soon in the future. We did a number of analyses on echocardiography showing a remodeling of the heart in the kappa subunit, but not in the lambda subunit. Finally, the other very important element is the mechanistic demonstration of treatment effect, which also with data showing the underlying rationale why we see an effect on kappa. There is a logical mechanistic explanation on lambda. Data will also be presented at the AHA conference in just a few weeks. Paired with the very high unmet medical need. Think about in the 3B patient population, 40% of the patient die at six months after initiation of treatment. For those patients, nothing is available as of today. Are patients that already received anti-plasma cell dyscrasia therapy with daratumumab and of course with the CyBorD. In addition to that, just to put in perspective, at the beginning of the study, median survival for this patient population was about six months. Following daratumumab use supporting, sorry, anselamimab use, median survival is at three years. Although there's a number of new therapy, including CAR T and T-cell engagers, they're being developed in this indication, none of them address the actual organ damage. Therefore, that portion of the damage will still stay for any anti-plasma cell dyscrasia therapy. These are the argument that we're using in the agency. The additional data sets is being included in the discussion with the agency as well. Overall, based on the information that I gave you, we are confident there will be the opportunity for us to move this forward globally. Of course, we need to base this on the acceptability and regulatory flexibility, which in an ultra-rare disease should be the case. Thank you, Gianluca, very much. Susan, go, Leora. Leora, do you want to just comment on PD-1 VEGF and if any aspect of our strategy is unchanged at this stage? I think the PD-1 VEGF data is interesting, but also want to highlight that the data that we have with rilvegostomig, which was shared previously, particularly in the PD-L1 high patient population, is similar to what you're seeing with ivonescimab. We have multiple ongoing studies. I know Susan's also mentioned TROPION-Lung08. We have VOLGA, which is looking at rilvegostomig and Dato-DXd compared to pembrolizumab, and we also have a rilvemonoarm there for CoC. We are generating data in lung cancer in several basket studies with rilvegostomig and ramucirumab in our ALTAIR study, as well as rilvegostomig, ramucirumab and Dato-DXd in the LIBRA studies. We also have some ongoing signal-seeking with volrustomig and platinum doublet in one of our other phase II studies. Great, thanks. Just maybe on the last question on the extension to the action date with FDA, certainly the opportunity to continue to have dialogue with FDA, and we look forward to discussing data like we'll present tomorrow. That's better than not having an opportunity to move forward with the conversation. I see that as overall positive. Other questions in the room, please. Thanks. Richard Vosser again. Just a couple of questions. Firstly, just on cami and the safety profile. There's been a bit of discussion post the ODAC on the cardiac safety, particularly in combination with ribo and QTc prolongation. Just your thoughts on the relative safety of cami to other SERDs and how you see that across the trials that you're running. Second question, just a more commercial one. Just thinking about the DESTINY-Breast09 rollout. Dave, you mentioned it, but could you give us how's it going relative to expectations? What are the early signs of uptake relative to what was the previous standard of care? Okay, great. Susan, you want to talk about cami safety, and Sunil, I'll ask you to talk about the DESTINY-Breast09 rollout. Yeah. A couple of things. Actually, the SERENA-6 data really show an excellent safety profile overall for camizestrant. Low discontinuation rate of 1%, very well tolerated and none of the sort of niggly GI side effects that are seen with some of the things. In fact, one of the things we actually saw is that patients feel better on this drug, and this is one of the contributing factors to the delay in the time to deterioration on quality of life, even before you would expect the control arm to have progressed with potential bony metastases. We're also hearing that in the adjuvant studies, and of course, there are large numbers of patients that have been treated in the adjuvant studies. Again, regular safety reviews there that are good. As a reminder, from a cardiac perspective, we don't see a QTc signal with camizestrant. We've done a thorough QTc study. It doesn't show an effect. There is a reduction in the heart rate. Only 7% of patients actually have bradycardia, in fact, as defined on that. That responds to when patients have an exercise demand, the heart rate goes up. Overall, I think the safety profile for camizestrant is excellent. We've got more than 10,000 patients treated on the camizestrant program. I think we're very confident in that profile. Thank you, Susan. Sunil, DB-09? Oh, yes, please. Probably could add that bradycardia has been reported with rilvegostomig. I don't think that there is such a difference here, really. Thanks, Pascal. DESTINY-Breast09 launch? Great. Yeah. No, thank you so much. Maybe two quick points. First of all, we're very pleased with the DESTINY-Breast09 launch. As you know, when DESTINY-Breast03 was approved, there was a subset of patients that could still receive it in the first line. We had already seen uptake in the first line, but we have seen strong utilization since the approval. Dave mentioned that at this ASCO, we presented DESTINY-Breast09 results, updated DESTINY-Breast09 results, specifically looking at the depth of response. As you saw from the pivotal presentation, 15% of patients got complete response, and that was not seen in the CLEOPATRA. In this ASCO, we assured that there was additional 35% who got deep PR greater than 80% reduction. That's pretty remarkable. I think this, along with, of course, the robust PFS of more than 40 months supports, I think what we're seeing, strong signal of early uptake. Thank you, Sunil. I think we can take a couple more questions in the room if we promise to keep the questions to one and our answers to more rapid. We'll do that if you do. Thank you. This is Zach Dunn from Guggenheim on for Seamus Fernandez. I have two questions, but I'll stick to one burning one. What is your take on HARMONi-6? All right. Susan, please. HARMONi-6 is obviously a positive study. That's why it got into the plenary. I think there was a great discussion actually from Julie Brahmer about putting that into context. Obviously, it's encouraging to see the OS hazard ratio. I think there's a couple of questions, though, in terms of what that means for the overall treatment landscape for squamous. First of all, there are exclusion criteria for bleeding risk, and that may represent somewhere around potentially a third of patients. Secondly, I think there's the age effect, and when we look at the global study, it'll be interesting to see whether that's replicated in that study as well in a broader patient population. I think what we've previously known is that both VEGF and PD-1 are clearly active mechanisms in this disease. The question about whether there's a further benefit from it being in a bispecific, that remains a question, but it's clearly an active drug and it's going to be exciting to see the data that come out of the global study, and I think that will help to answer some of these questions. There's also a question about the relevance of it in different histological subtypes and other tumor types. Clearly, there are other tumor types where you'd expect to see benefit from both VEGF and PD-1. Watch this space. Thank you, Susan. Okay. Thank you. James from Barclays again. It was a question about SERDs and adjuvant use. Roche's giredestrant got some slightly cautious comments on Friday at the conference, sort of questioning, should you use a SERD in adjuvant initially, or should you use it after someone's already had a go at using a CDK4/6? I know you've got CAMBRIA-1 and CAMBRIA-2, so you sort of got both, but where do you think it makes more sense to use a SERD? Should you use it up front or to switch? Which are you more excited about? I think there's a couple of points here. What we already know now is that it's possible to improve on the endocrine backbone compared with what's currently available. I think that will be important. What we also know is that CDK4/6 inhibitors can add to a good endocrine backbone in terms of the activity. I think it's really important that you actually get the data so that we have that choice. That's what we'll be able to do with the CAMBRIA-2 study, where we are allowing for the combination with CDK4/6. Again, one question that we had before the SERENA-6 data was out is, in the presence of a CDK4/6, will there be any added benefit of an improvement in the endocrine backbone? I think we've clearly answered that question, actually, with the improvement in PFS there. I think that's an important piece. The second question is, there's a large number of patients who are already on a CDK4/6 inhibitor in the adjuvant setting. It'll be important that they have an opportunity for solidifying the potential for long-term benefit through a continuation on an improved endocrine backbone, and that's what the CAMBRIA-1 switch study is designed to ask and answer. What I think has been seen there is something that improves our confidence in both settings and both studies. If both studies come through, we'll be well-positioned to have the largest segment of patients in the adjuvant setting with an option, and the option and the data to support that option of the added benefit of CDK4/6 or monotherapy switch. Patients want the choice, is what I think. Yeah, I can only reinforce what Susan has said, which is with intention, we've put an investment to answer those questions within the programs. We've got the largest clinical development program within the SERDs with the two studies in the metastatic setting, obviously both within the adjuvant setting. I think very importantly, CAMBRIA-1 gives an opportunity for being as fast as possible into the adjuvant setting in a patient population that we think there's a strong hypothesis that it will work within. You've got a very significant prevalent pool of breast cancer patients who, upon those data being available, could be very good candidates, and we'll see for CAMBRIA-1. We have time for one last question in the room, and it's going to be, okay, here in the back. I think we're going to go with. Thank you. Thank you. Mike Nedelcovych from TD Cowen once more. A quick follow-up on your PD-1, VEGF comments. It sounds like you feel that the jury is still out on whether the bispecific modality specifically is the right way to approach that combination. I'm curious if there are data forthcoming in the future that would convince you one way or the other, and if so, is AstraZeneca still potentially going to pursue that modality or perhaps take other approaches that look more attractive? Well, again, our strategy about segmentation in the IO space remains unchanged. What I would say is, of course, one advantage of having a bispecific is it's easier to combine with the other drugs that are active in that space because you've got one drug rather than a double comparison. Again, I think this space will emerge, but I think there's opportunity for combinations with active drugs in the space. Thanks, Susan. I just want to take an opportunity to thank you all for joining us. Sometimes when we get to this stage, I say it's been an excellent ASCO, and it has been, but it's not over yet. It continues tomorrow. I encourage you to go see the breast cancer session where I think there's going to be some important data that we get an opportunity to present there. We set out at the beginning of this year and articulated that it was a catalyst-rich year. It absolutely has been very much a catalyst-rich year. We have a number of continued opportunities for phase III readouts in the second half. Thank you, as always, for the interest in AstraZeneca. We'll see you at Q2 first half. Thank you.