Welcome, ladies and gentlemen, to AstraZeneca's Meet the Management event, ADA 2026. Before I hand over to AstraZeneca, I'd like to read the safe harbor statement. The company intends to utilize the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements with respect to the operations and financial performance of AstraZeneca. Although we believe our expectations are based on reasonable assumptions, by their very nature, forward-looking statements involve risks and uncertainties and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these forward-looking statements. Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements. Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation and webinar. There will be an opportunity to ask questions after today's presentations. Please use the raise a hand feature to indicate you wish to ask a question and remember to unmute your line when invited to speak. With that, I'll now hand you over to the company. Thank you so much, operator. Good evening, everyone. My name is Ruud Dobber. I'm the Executive Vice President of the BioPharmaceuticals business at AstraZeneca. I would like to welcome you and thank you for joining us today to hear about the phase IIb data for our oral GLP-1 receptor agonist, elecoglipron, following the presentation here at the ADA, and how this promising molecule fits into our broader CVRM strategy. As always, the materials presented today will be published on AstraZeneca's website in the investor relations section following the presentation. Next slide, please. Here are our usual forward-looking statements, which I encourage you to read. Next slide, please. This is the agenda for today's call. We are delighted to be joined by Dr. Vanita Aroda, the Director of Diabetes Clinical Research of the Brigham and Women's Hospital and Associate Professor at Harvard Medical School, who will walk us through the two phase IIb trials for elecoglipron just presented here at the ADA in New Orleans. Next slide, please. Many of you will recall that our Investor Day in May 2024, we set out our $80 billion risk-adjusted total revenue ambition for 2030. Since then, we have delivered substantial pipeline progress, underpinned by an exceptional run of positive phase III readouts over the past 18 months, which further strengthens our confidence in the growth trajectory through 2030 and beyond. CVRM will be a major driver of that growth. Just weeks ago, the FDA approved baxdrostat, now launched in the U.S. as BAXFENDY for patients with uncontrolled hypertension, a medicine which carries peak sales potential above $5 billion. In the second half of this year, we expect phase III data for WAINUA in ATTR-CM, another asset with peak sales potential above $5 billion. Momentum continues in 2027 when we anticipate the first phase III readouts for our multi-mechanism dapagliflozin combinations, zibotentan, zibodapa, and Belsudepa, each having between $3 billion and $5 billion peak year sales potential. Also our oral PCSK9 inhibitor, laroprovstat, in 2027, which has peak sales potential above $5 billion. This is only within CVRM. We have also multiple upcoming readouts across the rest of Biopharma, as well as in oncology and rare disease, reinforcing the breadth and durability of our long-term growth outlook. Next slide, please. Obesity and overweight are major drivers of cardiovascular, renal, and metabolic complications such as insulin resistance, hypertension, dyslipidemia, and inflammation, all of which can lead to downstream organ damage and diseases, including type 2 diabetes, CKD, and heart failure. To put the health impact into perspective, obesity and overweight increase the risk of type 2 diabetes sixfold, chronic kidney disease threefold, and heart failure twofold. Nearly nine out of 10 individuals living with obesity or overweight have at least one CVRM comorbidity, and many have more than one, highlighting the significant unmet patient need that exists today. Our strategy recognizes that while obesity is a central driver of these interconnected diseases, other elements must be addressed in parallel to improve patient outcomes. We believe we are uniquely positioned to do this by targeting interrelated disease pathways through mechanistic combinations approaches. Next slide, please. Obesity is a true global epidemic. There are expected to be more than 200 million people living with overweight or obesity in the U.S. and more than 3 billion ex-U.S. by 2035. We are confident AstraZeneca can be one of the leading companies in this space, driven not only by our exceptional pipeline, but also by our commercial strength in both specialty and primary care, our global footprint as a top pharma in over 100 countries, our strong consumer expertise, and our experience building new markets and segments. The clear example being FARXIGA, which is the leading SGLT2 inhibitor, with nearly 60 million patients being treated. We have rapidly established significant penetration in heart failure and chronic kidney disease. In addition to this commercial presence, we believe we have the portfolio and assets such as elecoglipron to win in this space. Next slide, please. With that, I will hand over to Dr. Vanita Aroda to share the data from the VISTA and SOLSTICE trials. Thank you kindly. It's such a pleasure to be here. I'll start with VISTA. Elecoglipron was evaluated for treatment of overweight or obesity in the phase IIb VISTA study in adults with BMI of 30 or higher, or 27 or higher with at least one weight-related comorbidity. 310 participants were randomized to elecoglipron at 5 or 15 mg without titration, or to 50 mg in 4-week titration steps, 75 mg with weekly titration steps, or to 75 mg with biweekly titration steps. Co-primary outcomes included% change in body weight from baseline at week 26 and achievement of at least 5% weight loss. With secondary endpoints including a longer view at 36 weeks and% achieving 5% or greater, 10% or greater, and 15% or greater weight loss, with exploratory endpoints of cardiometabolic parameters and traditional safety and tolerability assessments. Next slide. Here's the baseline characteristics. Average age was 48 with a higher predominance of females at 73%, consistent with some weight management studies, and a fairly even split across the BMI above 30 categories. Baseline BMI was 38, consistent with Class 2 obesity, with a fair representation of obesity-related comorbidities such as hypertension, dyslipidemia, obstructive sleep apnea, and pre-diabetes. Next slide. The primary outcome is shown here at week 26, which demonstrated patterns consistent with GLP-1 receptor agonist efficacy, namely a higher weight loss at higher doses without plateau yet, even going out to 36 weeks. The range of placebo-corrected weight loss at 36 weeks was 2.4%-11.5%. Here we see that a significant proportion of patients achieved weight loss of at least 5% at weeks 26 and 36. Looking at at least 5%, it ranges from 40%-89% at week 26. Looking at 5% or greater at week 36, it's at 41%-85% at the different ranges. For 10% or greater at week 36, we have 35%-63%, and for 15% or greater weight loss at week 36, we have up to 40%. Exploratory endpoints included effects on cardiometabolic risk factors. Here we see reductions in systolic blood pressure, diastolic blood pressure, and improvements in hs-CRP, indicating improvements in cardiovascular inflammation. There were modest increases in heart rate seen consistent with what we know about GLP-1 receptor agonist effects. Next slide. The safety profile of elecoglipron was also consistent with what we know about the GLP-1 receptor agonist class. That's shown here. Consistent with the class, we see that at higher doses, we have generally higher adverse events compared to placebo, with higher SAEs in the 75 mg group. Consistent with the GLP-1 receptor agonist class, the gastrointestinal events were the most common adverse events, with mostly reported of mild to moderate in nature and generally present at higher doses. I personally tend to zone in on vomiting as an objective measure of gastrointestinal events. Here again, you can see a pattern consistent with the GLP-1 receptor agonist class, with higher prevalence at higher doses. Liver safety was also a focused area of interest. As shown here, there were no liver safety signals detected, with the few abnormalities that were noted continuing on target dose. Next slide. We also know that obesity, overweight, and type 2 diabetes as well is associated with hepatic steatosis. Of note, we saw improvements in ALT with greater reductions present at higher doses. To summarize VISTA, the Phase IIb VISTA program demonstrated elecoglipron's potential to treat obesity and its related complications. To summarize the points, daily oral elecoglipron demonstrated clinically meaningful weight reductions in adults living with overweight or obesity without type 2 diabetes. At this point, without indication of plateau at 36 weeks, the safety and tolerability profile was consistent with the GLP-1 receptor agonist class without any unexpected safety signals. In terms of a unique feature of elecoglipron, it did not have any food or fluid dosing restrictions, potentially offering a convenient, effective, and safe oral therapy for people living with obesity or overweight. These findings directly inform the advancement of elecoglipron into the Phase III EMBOLD program. Next slide. Moving on to SOLSTICE, which is the Phase IIb program in type 2 diabetes. Next slide. SOLSTICE evaluated elecoglipron for the treatment of type 2 diabetes. As a Phase IIb study, it tested multiple doses. I'll talk you through it step by step. Here we see that 406 participants with type 2 diabetes with an A1C range of 7% to 10.5% managed with diet and exercise alone or stable metformin or SGLT2 inhibitor with a BMI of 23 or higher were randomized to one of eight arms. The first three arms at the top are the fixed flat doses of 5 mg, 15 mg, and 25 mg. The next three arms are looking at higher achieved doses of 50 mg, 75 mg, and 75 mg with the two different 75 mg arms reflecting different starting doses and titration increments or titration escalation schedules. There's matched placebo and as an exploratory benchmark, oral semaglutide arm open label with the currently approved 14 mg dose for treatment of type 2 diabetes. The primary outcome or endpoint was change in A1C from baseline to week 26, with secondary outcomes of achievement of glycemic targets, change in body weight, and achievement of weight targets, as well as a detailed evaluation of safety and tolerability. Here are the baseline characteristics for the SOLSTICE population. Mean age was 58, with 58% male, 42% female, 65% with an A1C of less than or equal to 8%, and all of this reflects an early treatment population with diabetes with a duration of around five years, an A1C at baseline of 7.9%, and a baseline BMI of around 34. Next slide. Here's the primary endpoint. I'll take it through again step by step. Here you see with placebo at 26 weeks, you have a 0.2% reduction in A1C. Even at the lowest dose of 5 mg elecoglipron, we see a 0.9% reduction in A1C. Then stepping up from there, higher reductions as we get to higher doses of elecoglipron with the highest dose achieving a mean reduction of 1.9% from a baseline A1C of 7.9% at week 26. Inclusion of the oral semaglutide arm was also an interesting benchmark, and here we see with oral semaglutide a mean A1C reduction of 1.3%. A large majority of participants receiving the 75 mg elecoglipron achieved guideline-recommended glycemic targets with up to 90% achieving an A1C of less than 7% and 85% achieving an A1C of less than or equal to 6.5%, which we consider a more stringent and aspirational glycemic target. Next slide. Here are the secondary outcomes for weight in the SOLSTICE study. Elecoglipron at doses of 25 mg or higher achieved significantly greater weight reductions compared with placebo. As we can see at week 26, we have mean weight reductions of up to 7.7%. Another important picture for type 2 diabetes is cardiometabolic risk, here we see improvements in cardiometabolic risk factors, specifically in triglycerides, where we see reductions of up to 36 mg per deciliter compared to baseline. We see a modest effect on LDL and a significant and clinically meaningful effect on hs-CRP of up to 57% reduction. Next slide. Here's the safety profile of the elecoglipron class. The details are very consistent with what we've seen with other developmental programs with the GLP-1 space. I'll highlight what I think were the personally most interesting. One is if you look at the people who start on the fixed dose and stayed on the fixed dose throughout, we see a higher occurrence of adverse events leading to dose discontinuation when we start off at the higher dose of 25 mg. Participants tell us the same, where we've learned to start low, go slow in some instances. We also see a relatively higher adverse event leading to discontinuation at the 75 mg dose group that starts at 10 mg. Next slide. In terms of other safety, gastrointestinal effects were the most common adverse events and were of mild to moderate severity. Breaking it up again within the flat dose arms of 5, 15, and 25, you see the highest occurrence at 25 mg and modest occurrence at the lower doses. Looking at the higher target doses achieved of 50 and 75 mg, you see a higher dose of gastrointestinal events at the highest dose of 75 mg and at the higher starting dose of 10 mg. Now moving on to liver signals. There were no liver safety signals observed in SOLSTICE. Next slide. Concomitantly, we were keen on looking at ALT in terms of, again, the comorbid condition of steatosis in persons with type 2 diabetes. Here you see that there are dose-dependent reductions in ALT observed at all doses, and the yellow or gold bar represents the oral semaglutide benchmark. In summary, what we see is that in the SOLSTICE phase II program, we saw potential for elecoglipron to become an important treatment in the toolbox for patients with type 2 diabetes. To summarize the key findings, daily oral elecoglipron achieved clinically meaningful and statistically significant A1c and fasting glucose reductions across all doses from five mg to 75 mg. Up to 90% of participants receiving elecoglipron achieved diabetes treatment targets of an A1c of less than 7% and an A1c of less than or equal to 6.5%. At doses of 25 mg or higher, elecoglipron achieved significantly greater reductions in weight compared with placebo, and the safety and tolerability profile of elecoglipron was consistent with the GLP-1 receptor agonist class. All in all, it's been exciting to be part of these programs and to see that SOLSTICE will support advancement of elecoglipron into the phase III ELUMINATE programs. It's my pleasure to hand it over to you, sitting to my left, Dr. Mikhail Kosiborod. Thank you very much, Dr. Aroda, for sharing the details of our phase IIb programs. Next slide, please. As you just heard, the phase IIb VISTA and SOLSTICE trials demonstrated the potential of elecoglipron, our small molecule GLP-1 receptor agonist, as a multi-blockbuster asset for AstraZeneca. We observed clinically meaningful and statistically significant weight loss and improvements in glycemic control. As you just heard, in the VISTA trial, we saw up to 10.5% body weight loss at week 26, and importantly, continuing weight loss of up to 11.8% at week 36, without evidence of a plateau. We also observed up to 1.9% reduction in hemoglobin A1c at week 26 in the SOLSTICE trial, which randomized people living with type 2 diabetes, with the vast majority of those patients reaching their glycemic goals. We saw a favorable safety profile with no unexpected safety signals, low discontinuation rates, and tolerability that is consistent with the GLP-1 receptor agonist class. The phase II tolerability data have informed the dose escalation schedule in the phase III program to further enhance the tolerability profile. Finally, it's worth emphasizing that elecoglipron is a small molecule GLP-1 receptor agonist. Accordingly, this once-daily treatment promises to be simple and easy to administer without fasting restrictions. It can also be combined with other small molecules to target multiple disease drivers, thereby addressing not one, but multiple chronic conditions at the same time. The efficacy and tolerability findings of elecoglipron are competitive with phase II findings from other oral GLP-1 receptor agonists, providing further rationale for advancement to phase III. Next slide, please. We have previously disclosed that our strong data put us in a great position to initiate an ambitious phase III program that will start in the second half of 2026. It will have three key components. The first is our obesity program, EMBOLD, which is studying elecoglipron monotherapy with a primary endpoint of body weight loss in patients living with obesity or overweight, both with or without type 2 diabetes. Second is our type 2 diabetes program, ELUMINATE, which will evaluate elecoglipron both as monotherapy and in combination with dapagliflozin in patients living with type 2 diabetes. We plan to launch five global trials designed to investigate the effects of elecoglipron across a diverse population of patients with type 2 diabetes, from treatment naive to those with advanced disease, and with use of different comparators. Third, very importantly, we plan to initiate an ambitious indication-seeking outcome program that is designed to demonstrate the value of elecoglipron in patients with heart failure and chronic kidney disease. ELEVATE-HFpEF will evaluate elecoglipron versus placebo on top of the background of dapagliflozin and other standard of care therapies in patients with heart failure and mildly reduced to preserved ejection fraction, with the primary endpoint being a composite of cardiovascular death and heart failure events. ELEVATE-CKD is an outcome trial which will evaluate a broad population of patients with chronic kidney disease, both with and without type 2 diabetes at baseline. Patients will be randomized to elecoglipron or placebo on the background of dapagliflozin and other standard of care therapies with a primary endpoint of kidney events. This ambitious program has the potential to demonstrate the value of elecoglipron for obesity and type 2 diabetes and highlight its potential differentiation in terms of organ protection and outcome benefits in patients with heart failure and CKD, and for both elecoglipron monotherapy and in combination with dapagliflozin. Beyond this phase III program, we continue to explore additional potential opportunities for elecoglipron, both alone and in combinations. Next slide, please. One of our key objectives at AstraZeneca is to build a leading portfolio in weight management. A tiny fraction of eligible patients living with obesity, less than 5%, are being treated today all over the world. It will take multiple innovations and all of us as a community to adequately address these unmet patient needs. Elecoglipron is the backbone of our oral weight management portfolio. We believe that GLP-1 receptor agonists will continue to be foundational for patients living with this disease, and we plan to introduce this treatment not only as once-daily convenient monotherapy, but also in combination with other foundational mechanisms such as SGLT2 inhibition. Recognizing that the science in this area is moving rapidly, we also know that the market will segment further based on individual needs. Our emerging portfolio is designed to be tailored to those needs. Amylin receptor agonists can improve GI tolerability and offer real alternatives for patients who lack treatment options in clinic today. Accordingly, we are developing a once-weekly highly selective amylin, AZD6234, which is currently in phase II trials. There are also growing numbers of patients living with severe obesity and multi-organ complications who will require maximum efficacy in terms of weight loss. This is why we are developing AZD9550, part of our triple combination of a dual GLP-1/glucagon receptor agonist that is being combined with a once-weekly amylin, AZD6234, and that is also now in phase II trials. In addition, we have a number of early assets in development. You've heard about our acquisition last year of an activin monoclonal antibody, AZD1043, which we are studying as potential treatment for lean body mass-sparing weight loss that may offer a treatment option for patients at risk for sarcopenia and frailty. Improved adherence and convenience are also important for a large segment of patients. Several months ago, we announced a collaboration with CSPC to develop less frequently administered injectables. You can see how the portfolio we're building is purposefully designed to address unmet needs and deliver a tailored approach to treatments that can unlock broader benefits for those living with obesity, type 2 diabetes, and other comorbidities, has significant market potential. With that, please advance to the next slide. I will pass it on to Sharon Barr to tell you about our overall CVRM R&D strategy at AstraZeneca. Thank you, Mikhail. We have just shared strong Elecoglipron data and a clear strategy for our weight management portfolio. Our broad clinical development program is designed to demonstrate a differentiated approach, evaluating Elecoglipron as a monotherapy as well as in mechanistic combinations designed to address excess weight, obesity, type 2 diabetes, and the associated comorbidities to deliver improved health outcomes. AstraZeneca is uniquely positioned to win in this space with our CVRM expertise and our broad portfolio. We continue to explore additional opportunities to maximize the potential of Elecoglipron. We have an extensive portfolio that is designed to deliver organ protection across CVRM, including numerous high-value phase III programs, which will begin to read out in the second half of 2026 and 2027. Within dyslipidemia, our oral PCSK9 laroprovstat has both monotherapy and combination approaches, with the first phase III readouts expected in 2027. In hypertension, we already have the first U.S. approval of BAXFENDY. We have multiple combination studies with DAPA already in progress. In heart failure and amyloidosis, in addition to the upcoming CARDIO-TTRansform results, we have also now initiated a phase II trial combining eplontersen with our TTR depleter, cliramitug. In 2027, we will have phase III data for the valsartan plus DAPA combination in patients with heart failure and renal impairment. Moving to kidney disease, we expect the results from ZENITH, the phase III trial of zibotentan plus DAPA in patients with CKD and high proteinuria in 2027. Our combinations address multiple comorbidities across the CVRM spectrum. Elecoglipron, similar to DAPA, is designed to be a backbone therapy of our CVRM portfolio. We have a very broad and deep CVRM portfolio. I am excited about the catalyst-rich period ahead. Next slide, please. As Ruud highlighted in his introduction, we have delivered strong pipeline momentum since announcing our $80 billion 2030 ambition at Investor Day in May of 2024. CVRM is positioned to be one of the primary contributors to that growth through 2030 and beyond. By the end of the decade, we expect to have five CVRM franchises with multiple launches, each with peak sales potential exceeding $5 billion. This reflects both the breadth of our portfolio and the substantial value creation opportunity ahead. Next slide. Before we go to our Q&A, our CEO, Pascal Soriot, will provide some concluding remarks. Thank you, Sharon. Thank you, everybody, for this great presentation. Let me just try to bring some context to what you have heard before in the last few minutes, but was not mentioned. I think it's important to remind ourselves there are more than 2.5 billion people in the world that are either overweight or obese, 2.5 billion. We focus a lot on the U.S., and it's an important country, but the great majority of people live outside Europe and the U.S., as we all know. 2.5, 60%-70% of these people suffer from at least one comorbidity, the most frequent being hypertension, but diabetes is also a complication, kidney disease, dyslipidemia. That's 1.5 billion-1.7 billion people who are either overweight or obese. In fact, two-third are overweight, one-third obese. Out of this 2.5, 1.5 billion-1.7 billion have a comorbidity. That is an important point because it gives you a sense of the size of the unmet need. That really brings the conclusion that you need more products. You need several products to address this unmet need. Physicians, patients need more choice. That's really an important part, an important background. The second comment I will make is, from what you've heard, we have a competitive profile with elecoglipron. Very nice profile from an efficacy and tolerability viewpoint. The tolerability we will further improve in phase III, so an optimized duration and escalation regimen that you've heard a little bit about. That's a very good starting point. We have a competitive profile. How will we make a difference? First of all, you've heard Mikhail tell you about the broad, ambitious phase III programs that we have in weight management, type 2 diabetes, and renal outcomes. It doesn't stop there. We will also continue exploring additional indications, there are many indications that can benefit from a weight loss agent. Many of those indications actually fit in these areas where we have presence. Of course, in cardiovascular metabolism, but also in respiratory disease and beyond. We actually will build a very ambitious phase III program. That's the first thing we will do to build on what we have. The second thing we will do is we will work on fixed-dose combinations. As I said a minute ago, many of these people who are overweight suffer from one or several comorbidities. Many of these people are receiving multiple medications. Developing fixed-dose combinations suddenly will improve compliance, and I also think if we actually can price this FDC appropriately, it will also help access, because we can price those product at affordable level, not only for American patients, but also for everybody around the world, where price, of course, becomes a very substantial issue in many countries. We have combination with DAPA, and we have combinations with some of our other products in the cardiovascular pipeline. That's the second thing. The third is we actually will do what our mission is. Our mission is to bring medicines to as many people as possible around the world. As a reminder, we are the largest pharma company in the emerging markets. We are number one in China, and of course, we are also strong in the U.S., in Europe. We're number one in Japan. Our intent is to leverage our geographical footprint, leverage our expertise in primary care, importantly, leverage our connections and our presence with cardiologists, nephrologists, endocrinologists, diabetologists, beyond primary care physicians. We are present in all those specialties through the various products we have. You can imagine that we have the ability to really build on this product and commercialize it strongly. Of course, in the U.S., we will use consumer strategies like our competition does. I think where we can really differentiate ourselves is outside the U.S. through our commercial expertise. Those are the three things we want to build on and differentiate. Just as a last quick comment is, as a proof point, FARXIGA today, 20%-25% of our sales before we lost patent protection, of course, 20%-25% of our sales were in the U.S. The great majority was outside the U.S. We built FARXIGA into an $8 billion product, which could have continued to grow, by the way, but an $8 billion product with only 60 million people receiving it. 60 million is a lot, of course. We manufacture 10 billion tablets, which shows you we also have the manufacturing capacity, and we're building more. With 60 million people treated, we achieved $8 billion revenue. You can imagine that we can certainly do very well with an oral GLP-1. We have a competitive product, we have an ambitious plan, and we believe we can do well. With this, I'll hand over to Sharon, who will manage the Q&A. Okay, here we go. The first question is for Richard Vosser at JPMorgan. Richard? Hi, thanks. Two questions, if I can. First question is just about drug-drug interactions. We saw orforglipron data and put up on the screen that there are restrictions around simvastatin use, CYP3A inhibitors, inducers. Just thinking about any restrictions outside of food and water that elecoglipron might have. Then the second question is just on your heart failure study, ELEVATE HF. Obviously, GLP-1s work very nicely there, as do SGLT2s. I just don't know why you don't go for the triple or the Holy Trinity, if you like, in terms of adding your balcinrenone or baxdrostat in there and getting the CV risk down further. Just thoughts on that. Thanks very much. All right. Both of those questions sound like they are perfect for Mikhail Kosiborod. Thanks very much for the question. On question one, which is a DDI profile, as always, in our clinical development programs, we do all the work that is necessary to characterize the profile of the molecule, including the DDI profile. That work is currently ongoing. I will say that statins were allowed on a phase II program, but the full profile is still being characterized. On your second question, which is a question very near and dear to my heart. You guys may not know this, but I actually led the semaglutide heart failure program and very much care for the field of heart failure with mildly reduced or preserved ejection fraction, which in many cases is a overweight and obesity-related disease. Because we believe that this is largely driven by cardiometabolic risk, we believe that the combination of a GLP-1 receptor agonist and an SGLT2 inhibitor is potentially ideal combination for that patient population. Of course, the way we designed the ELEVATE-HFpEF trial is specifically to understand the value that GLP-1 receptor agonist brings on top of SGLT2 inhibitor. If all goes well and if the trial is positive, we expect to have indications for both elecoglipron and FDC with dapagliflozin in that disease space. You ask about other molecules like baxdrostat or balcinrenone, and of course, as you well know, the balcinrenone-dapagliflozin combination is already being studied in a BALANCED-HF phase III program, which is currently ongoing. When all is said and done, I think heart failure with preserved ejection fraction, just like HFrEF, will have multiple pillars. We believe that GLP-1 and SGLT2 combination does have a potential to be foundational in that disease. The next question is from Seamus Fernandez at Guggenheim. Go ahead, Seamus. Thanks so much for the question. Just a couple of quick ones. First, can you just help us understand, I know there were no obvious bilirubin elevations or LFT elevations that were cited in either program. I guess in the publication, there was some evidence of bilirubin elevation that appears to be related to the inhibition of one of the enzymes. Can you just help us understand that and if that was a factor that was corrected for or there were any modifications necessary relative to the measurement of bilirubin? I only just wanted to ask that because it was interesting to see that in the other paper. I know that the other orforglipron scaffold assets do appear, I think it's mentioned that they inhibit the same enzyme. It seems like this might be a grouping effect with that scaffold, but just wanted to understand that better. The second question for you, Pascal. Historically, AstraZeneca has really come with a highly differentiated asset when they are second or third to market, or with a highly differentiated clinical program. It seems like the differentiation here is your ability to combine assets, your unique oral PCSK9, other assets along those lines. Do you see an opportunity to differentiate, either with an oral GLP-1, plus another incretin mechanism, from your perspective in the oral space, or is it really with these combinations that you're most focused? All right. Let's tackle the questions in those orders. Seamus, let me start by saying it's important to know that in our phase II-B trials, we saw no safety red flags that gave us any hesitation about launching ourselves into an expansive phase III set of studies. We really got the data that we needed to give us the confidence to make those phase III investments, specifically about bilirubin. Mikhail, if you would like to give some more color to that question. Yes, absolutely. Thanks, Sharon. I think the bottom line here, what we're seeing with bilirubin, I think it's illustrative to look at the two cases that Vanita showed you in the safety table, where there were bilirubin elevations, three times or more normal. There were two of those cases in VISTA. One of those patients, by the way, had Gilbert syndrome history, which, of course, you know people with Gilberts have asymptomatic, clinically irrelevant bilirubin elevations already. Both of these patients were asymptomatic. Both of these patients continued on treatment. There were no concomitant ALT abnormalities in either of those patients. Overall, when we look at these cases of bilirubin elevations, it clearly appears to be a lab abnormality, which is asymptomatic and not clinically relevant. You saw a discussion in a paper where we refer to OATP1B1 and UGT1 transporter inhibition, and that's exactly the patterns that you would expect with that. It's not clinically relevant and does not represent a liver safety issue from our standpoint. I'm going to hand it over to Pascal to address the next question. It's a good question, Seamus. Fundamentally, we have a profile that is similar to the existing oral GLP-1s, but we can differentiate through our phase III program. We've showed you some of what we're planning to do, but we haven't showed you everything we are planning to do. We will actually look at differentiate through smart studies that will help give us a potential advantage. Then, as I said, we have the combinations, but also we have our strengths outside the United States, where clearly we can actually make the difference because of our commercial muscle. I'd just like to remind you of eight, 10 years ago, when we took FARXIGA, we went through a pretty difficult time. We didn't have it from the very first day of launch. It was really quite difficult, and we found our way to build it into an $8 billion product. I have no doubt that in a market that is even bigger than the SGLT2 market, we can actually do very well. There is really an unmet need. These products are going to be or can be a revolution for many, many patients around the world and a revolution for medicine if we can actually price them at the right level, make it accessible, then come up with some differentiation on the clinical front. Okay. Next question, James Gordon, Barclays. Hello, James Gordon at Barclays. Hopefully, you can hear me okay, and thank you for taking the questions. My quick questions are about what's next beyond your lead program, which really looks exciting, what's going to lead? The presenter today suggested that elecoglipron was effectively at efficacy about the same as Vanquo, but not better. Are you working on any orals that will do more than just target GLP-1, as Lilly have already done this? When could those enter the clinic? The second question, less frequent injections were mentioned, and that was the other theme of the conference with the Mounjaro data. Pfizer are already starting a phase III. When you're talking about monthly, are you looking at doing just GLP-1, or would that be a combination approach that's something that builds upon that? James, I'm so sorry, your connection is very muffled. Do you think you could give us those questions one more time? I don't know. Can you hear me any better now? Much. Yes. Thank you. Right. Apologies for that. Sorry, just the airport. There was two questions. It was about what you're going to do next to be leading. The first question was, elecoglipron looks a bit like a catch-up with Vanquo. The presenter said that the efficacy was about in line, rather better. Are you going to do any orals that do more than just target GLP-1, as Lilly are already there? When could those enter the clinic? From the oral, what's next? Are there combo targets? The other one mentioned was injectables that are less frequent. It sounds like you're going to do a monthly, but when could that enter the clinic? Are you just going to do a GLP-1 that Pfizer's already having in Phase III, or will you do some other sort of combination of molecules that could be monthly? Okay. Thank you for the question. Understood that clearly the second time. Thank you. Thanks so much. At this meeting, ADA, we shared data that clearly demonstrate that we have a strong contender with elecoglipron as the backbone oral therapy for our CVRM portfolio. We also have demonstrated, I think, that we have the potential to be able to combine this with other small molecules that are already in our portfolio, which is a clear point of differentiation for AstraZeneca. There is no other company that is in a position to create these mechanistic combinations that really allow us to address the complex comorbidities that wrap around excess weight, obesity, and type 2 diabetes. Mikhail, would you like to add more color to that? Yeah. Look, our strategy is very clear when it comes to FDCs. We believe the field is transitioning and will continue to be transitioning from kind of an old paradigm, which is FDCs of convenience, to the new paradigm, which will be the FDCs that transform care. In order to do that, you need to combine complementary mechanism and disease drivers. Not just things that happen to live together, but things that really enhance the efficacy or potential tolerability and safety, or both, for the patient. That's when you can actually deliver real value to patients and clinicians, by giving somebody an easy once-daily pill that could potentially address not one, but multiple chronic conditions at the same time. That's really at the core of our strategy in CVRM. We already mentioned, of course, a GLP-1 SGLT2 inhibitor combination, but we are working on others as well. I'll follow up with your second question, which was, what else is in our weight management portfolio, broadly? As Mikhail clearly outlined, coming next, we are currently pursuing in phase II AZD6234. That's our selective amylin receptor agonist. AZD9550, that's our GLP-1 glucagon dual agonist. We're pursuing those as monotherapies as well as in a potential combination for a triple active combination. Of course, we announced earlier that we have signed a collaborative agreement with CSPC to be able to create monthly injectable GLP-1 GIP molecules with a liquid gel technology that will allow for extended duration. We are building out this portfolio because we know that, as Dr. Aroda clearly stated, every patient has different needs, and we're creating options that allow us to address those varying patient needs, both their comorbidities, their different phenotypes, their different treatment considerations, and what works best for them in terms of access and availability. Again, elecoglipron remains the backbone oral to our cardiometabolic and kidney and weight management portfolio, but we continue to be building on with a wave of new mechanisms. Thank you. Thanks for bringing up with the acoustics. Thank you. Next question is Benjamin Jackson, Jefferies. Brilliant. Thank you for the question. I guess firstly, can you talk about how you're thinking about titration schedules going into phase III, both in terms of what's important in getting the most out of the asset in the clinical trials, but also what's important clinically to patients in the real world? There was a fair amount of debate at the conference this weekend around that, interesting to hear your thoughts about what's important. Then secondly, is there anything you can add about how you're thinking about weight loss beyond 36 weeks? I think more generally with some small molecules, we've seen that there is some plateauing at that 36-week mark, which many didn't initially expect. Is there any biochemical rationale to why this might not be the case for Eleco? Any thoughts there would be useful. Thank you. All right, Mikhail, why don't we start with you, and then Dr. Aroda, maybe you can comment on your clinical experience. Thanks for the question. First and foremost, I think we heard loud and clear from clinicians in particular in the audience. I'm a former clinician myself, having treated many patients with GLP-1 agonists, that tolerability is very important. We need to have molecules, medicines, that are both effective, provide effective weight loss and organ protection, and also have as optimal of a tolerability as we can achieve with this mechanism. As I previously mentioned, and Pascal reinforced, we are taking learnings from our phase II program to optimize tolerability profile in phase III. What have we learned from prior experience? We learned that starting with a lower, very well-tolerated dose is a good idea. That starting low and go slow is a good idea. Of course, if we implement those learnings, low starting dose and appropriate titration schedule, we can achieve potential better tolerability. Of course, in the phase III trials, that's very important because if patients stay on treatment, the primary endpoint is treatment policy estimate, and of course, that helps you with that as well. That's what I would say, I think from a phase III design standpoint. Vanita, anything you'd like to add in terms of preferences from clinicians in this space? Thank you so much. I have the perspective of being both a clinical trialist on multiple GLP-1 receptor agonist programs over the last 20 years, as well as a clinician in clinic. At the bedside, it really varies depending on the patient. There are some patients who really want the minimal dose possible and wait and see, make sure that it suits them, see what the A1c changes, see what the weight changes, and then have a shared decision process. There are some patients who are ready to go. They want to escalate as efficiently as possible. What I think is needed, and I really appreciate the question, is I think what is needed is an approach of dosing flexibility based on evidence, based on protocols, but allowing some kind of self-empowerment, self-agency that becomes part of the clinical conversation. Of course, maybe just to add even further is, again, in clinic, of course, there is infinite flexibilities that clinicians and patients, at least some patients, may want and need. In a clinical trial setting, of course, it's always a balance between flexibility and the fact that we need to complete these programs within a certain period of time, and patients need a certain duration of exposure. All of that, of course, will be incorporated in how we put our phase III program together. Okay. That brings us to the end of the questions that are in the queue. I'll bring us back to a few key messages as we close our call today. If we zoom out for a minute and think about the problem that we're trying to address as a community, we know that about 3 billion people worldwide are living with obesity or overweight, and that we expect by 2035, that will be over half of the world's population. The really troubling fact here is that nearly 9 in 10 of people living with obesity or overweight have at least one comorbidity. We came to ADA to share the compelling data that we have from two phase IIb studies that demonstrate that we have a strong contender with elecoglipron. We are exploring this both as monotherapy as well as mechanistic combinations that allow us to address the interrelated comorbidities that wrap around type 2 diabetes, obesity, and excess weight, and to continue to explore additional indications beyond. AstraZeneca is uniquely well-positioned to win in this space because of the depth of our CVRM expertise and our portfolio. I'll leave you with those messages, and I thank you for your attention.