Good morning and good afternoon. Welcome to the Novartis Cardiovascular Update. With that, I would like to hand over to Mr. Samir Shah, Head of Investor Relations. Please go ahead, sir. Thank you very much. Good morning and good afternoon to everybody. A big thank you for joining us this afternoon, the European time, for the Novartis Cardiovascular Update. With us today, we have quite a lot of speakers, but hopefully, we'll leave enough time after the presentation for the questions and answers. We have David Soergel, who's the Global Head of Cardiovascular, Renal, and Metabolism Development. Rod Wooten, who's the Global Head of Marketing, Novartis Pharmaceuticals. Victor Bultó, who's Head of Novartis Pharmaceuticals, U.S. Our external speaker is Matt Whitty. He's the CEO of the Accelerated Access Collaborative NHS Group, and he'll be talking about the population health program, which we're expecting to start this year. There's myself, Samir Shah, Global Head of Investor Relations. Before we start, I just wanted to read you the safe harbor statement. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties, and other factors. These may cause the results to be materially different from any future results, performance, or achievements expressed or implied by such statements. For a description of some of these factors, please refer to the company's Form 20-F and its most recent quarterly results on Form 6-K that respectively were filed with and furnished to the U.S. Securities and Exchange Commission. With respect to the slide sets, you can follow it on our website. We did post it earlier in the day. I think I'm going to hand across to David Soergel from our development group. David? Great. Thanks a lot, Samir. Really appreciate it, and thank you all for joining. It is great to be here to talk about the cardiovascular renal metabolism portfolio, and especially about the cardiovascular medicines we have in our portfolio. We have the ambition to reach hundreds of millions of people with these innovative therapies and therefore improve cardiovascular health. Rod and I are going to start today with Entresto. If we flip to slide six. As you all know, Entresto has been improving and extending the lives of heart failure patients since 2015, and recently, earlier this year, we expanded Entresto's indication to include patients with heart failure with preserved ejection fraction with below normal ejection fraction. This then covers about five out of every six heart failure patients in the U.S. are now covered by Entresto's label. If you look at this timeline, about 18,000 patients have been enrolled in randomized controlled clinical trials with Entresto across the spectrum of heart failure in rigorously designed active controlled studies versus the standard of care. This really, I think, underpins our ambition to transform the care of heart failure. Slide seven. We're going to talk about PARADISE-MI now, which was a landmark study in post-acute myocardial infarction patients and talk to you a little bit about how PARADISE-MI fits within the clinical trial evidence basis in heart failure. PARADISE-MI, the aim of this trial was to show whether or not Entresto could prevent the onset of heart failure in high-risk patients after they have had a heart attack. As many of you are probably aware, in the post-myocardial infarction setting, RAAS inhibition, renin-angiotensin system inhibition with ACE inhibitors like ramipril or with angiotensin receptor blockers are the standard of care. We set a very high bar, again, with the ambition to transform the care of these patients to show that Entresto was superior to this standard of care approach. About 5,600 patients were enrolled in this trial. Let me reinforce, these are patients who are within a few days of having a heart attack. These are patients who are fragile, who are sick and have had a life-changing event. We have therefore had an opportunity to evaluate Entresto's efficacy as well as tolerability in these fragile patients. The primary composite in PARADISE-MI was cardiovascular death, heart failure hospitalization, or patient heart failure visit, the first occurrence of any of one of those three events. Slide eight shows you that the results of the primary endpoint from PARADISE-MI, again, cardiovascular death, heart failure hospitalization, or outpatient visit for heart failure. As you can see, despite a trend favoring Entresto in this trial, unfortunately, we did not hit statistical significance for superiority versus ramipril in this study. Slide nine shows you a bit of context for why the PARADISE-MI trial was setting a high bar for Entresto to transform care. This shows you a historical view of the care of post-MI patients over the last 30 years. What you can see if your eyes go to the top of the graphic on the left-hand part of the slide, you see the 1990s, a year after having a heart attack, about 20% of patients would be expected to die. As you can see, over the last 30 years, care of these patients has improved substantially, so that now that one-year mortality rate is more in the 5% range. This has happened for a variety of reasons. Renin-angiotensin system blockade is part of it. Early percutaneous coronary intervention is another part of it. High-intensity statin use post-MI is another. Just quality metrics with respect to how these patients are cared for, I think, have really changed the outcomes in a positive way for these patients after a heart attack. These numerical trends we see in PARADISE-MI are on the basis of already substantial improvements over the last 30 years. Slide 10 shows you other endpoints from PARADISE- MI, again, consistent with the primary endpoint, where we saw the trend towards an improvement in cardiovascular death, heart failure hospitalization, and outpatient heart failure visits. We see the secondary endpoint similarly show a trend towards a benefit for Entresto in a variety of measures. Next slide. On slide 11, we're calling out two additional pre-specified analyses that I think provide additional color on the importance of PARADISE- MI in the context of the treatment of heart failure patients. If you look at the left-hand graphic first, this shows you the total first and recurrent adjudicated primary events in the trial. What this shows you is that the relative risk reduction of 0.79 is better than what we saw on the primary endpoint, which was 0.90. What this probably reflects is that patients who have a first event of heart failure are starting to perhaps receive some benefit from receiving Entresto as they continue on in the trial. What you see is future hospitalizations after that first hospitalization are then prevented compared to the ramipril group, I'm sorry. The next graphic on the right-hand part of the slide shows you that when you look at investigator-reported events, when instead of looking at the CEC adjudicated events where stringent documentation is required to document a heart failure hospitalization or outpatient visit, and instead you rely on the wisdom of the investigator, who in most cases is a cardiologist, you see that there are more events and therefore a nominally statistically significant result with hazard ratio of 0.85. This gives you confidence that trend that we see in the primary analysis may actually be a true incremental effect of Entresto in this population. Slide 12 shows you the adverse event profile. Again, in this very fragile population of individuals who had just had a heart attack, we see that Entresto was well-tolerated. This actually was also despite the fact that there was no run-in in this trial. Patients were just started on therapy once they were randomized in the trial. As you can see, there were no new safety findings in this study. As we expect, we see more hypotension events in the Entresto group and more cough in the ACE inhibitor group. Importantly, if you go to slide 13, you see that actually fewer patients discontinued due to adverse events in the Entresto arm. Again, this gives you confidence that Entresto can be used in these fragile patients and used safely. Slide 14 shows you just that there's a substantial amount of evidence now underpinning the utility of Entresto in the treatment of heart failure. Over 50,000 patients have been enrolled in clinical trials, and over 320,000 patients' experiences in real-world evidence trials have been tracked now. This really gives us, I think, a strong basis of support for continued use of Entresto in heart failure. In addition, probably also reflects the fact that guidelines now support Entresto as standard of care in heart failure with reduced ejection fraction. Slide 15. What's next? Well, Entresto also could meet a major unmet medical need in Asia in the treatment of hypertension. Very early on in its development path, Entresto was considered for development in hypertension. What we saw was in Asia, where there's an especially high proportion of individuals who are elderly and have a higher sodium intake, they might be particularly amenable to Entresto's mechanism. Indeed, in clinical trials, we showed that Entresto was superior to the then commonly used olmesartan angiotensin receptor blocker in Asian studies. Currently, the hypertension indication is undergoing regulatory review in China and Japan. Now I'm going to pass it to Rod to give an update on the commercial side. Thanks, David. Let me just take a moment and give you some additional context on the PARADISE-MI study to market performance and treatment guidelines as we move forward. On slide 16, if we look at the size of the opportunity that still exists in the significant unmet need that exists in congestive heart failure, we have 8 million patients alone in the U.S. and the EU5 that could benefit from Entresto today and achieve and get the standard of care. If we put the context of the population that David described, we've got 1.5 million myocardial infarctions annually. Knowing that approximately a third of those patients are likely to develop congestive heart failure, we see that there's a significant opportunity that those patients will eventually develop heart failure, and they will be among the labeled population for Entresto, an opportunity to upgrade into the standard of care. If you flip to slide 17, as you see on the left-hand side from the weekly NBRx data, the market performance is incredibly strong. The trajectory that you see from January post is really driven by three main factors. One is the COVID recovery. We're seeing more access to customers again, and actually patient office visits are exceeding pre-COVID levels. The second major factor is the ACC expert consensus guidelines, which I'll talk a little bit more about in a minute. It's had a powerful impact on increasing Entresto first-line use ahead of ACEIs and ARBs. The third major factor is the momentum that we're seeing from the launch of the expanded label and the early positive indicators that we've seen from customers and new prescriptions. Looking ahead at future growth opportunities, we're confident that Entresto can continue to maintain this strong growth trajectory globally. On the next slide, we've mentioned a number of times the importance of these ACC expert consensus guidelines, and they're incredibly clear in terms of focusing on and recommending ARNi as the preferred first-line use ahead of ACE and ARBs, and considering the other mechanisms as add-on therapies to ARNi therapy or Entresto in this case. This really puts Entresto in the pole position for 70% of the HFrEF patients who are still on previous standard of care and not yet receiving Entresto as their foundational treatment. We know very well from experience in cardiovascular with cardiologists that guidelines drive prescription behavior, and we're certainly seeing that with the change in clinical practice, particularly from the release of these guidelines in January of 2021. If we turn to 19 and just summarize where we're at with Entresto overall, it is clearly our anchor brand in the cardiovascular space. It's backed by a very comprehensive evidence package establishing a leadership position in chronic heart failure. As David said, while PARADISE-MI didn't meet the primary endpoint, the results did show incremental benefit versus a ACE inhibitor or ARB and confirmed a very important safety profile in the most fragile of patients. We expect Entresto's momentum to continue very strong throughout the globe as we continue to reinforce and educate on those treatment guidelines, educate our customers on the new expanded label and the opportunity for patients to receive Entresto, the first approved therapy for this patient population, and maintain our strong market access. With the potential indication in Asia in hypertension, we could see some acceleration of momentum in the case of positive approval and broad reimbursement. The outlook for Entresto continues to be very strong. David, I'm going to hand it back to you to discuss one of our other major assets for the franchise, LEQVIO. Great. Thanks a lot, Rod. I appreciate it. I'm back again to talk about LEQVIO along with Victor Bultó, head of Novartis Pharmaceuticals, and Matt Whitty, CEO of Accelerated Access Collaborative for the NHS. Let's turn to slide 21, and there have been variations of this slide shown many times, and it doesn't change. Despite the advances over the last several decades in cardiovascular care, there is still a huge burden posed by cardiovascular disease, both in terms of morbidity and mortality and in terms of cost for health systems. If you look on the left-hand part of the slide, we see that about a third of all deaths now are attributable to cardiovascular disease, more than any other disease and more than all cancers combined. This poses a huge cost challenge for health systems, expected to exceed $1 trillion per annum by 2025. Of course, the number of lives lost is huge and staggering. 18 million lives lost globally to cardiovascular disease last year, and about 60 million patients are at risk of having cardiovascular morbidity and mortality due to ASCVD in the U.S. and the EU5. Slide 22. For the last 50 years, we've shown that as a medical, academic, and scientific community, there's a strong link between LDL cholesterol and cardiovascular outcomes, and that lowering LDL-C can improve cardiovascular outcomes in actually a rather reliable way. As you see in the graphic here, about a 40 milligrams per deciliter reduction in your LDL cholesterol reduces your relative risk of having a heart attack or dying of cardiovascular disease by about 20%. This has been confirmed over many years with many agents in a variety of settings, over 500,000 patient lives in this particular analysis. The other important thing to derive from this particular graphic is the importance of adherence and persistence of therapy on outcomes. What the colored lines represent here is a situation where you have a therapeutic that achieves 100% adherence and full reduction of LDL cholesterol by 40 milligrams per deciliter, and the fact that that can improve cardiovascular outcomes, as you see on the Y-axis, better than other agents that perhaps have more administration or patient burden in terms of taking them. For example, monoclonals or statins. This is an analysis that was published by Kausik Ray and his colleagues in Circ recently. This relationship is critical. Slide 23 shows you that guidelines have, of course, adopted this recognition and have become more and more specific and more aggressive about lowering LDL as an important way to reduce cardiovascular risk. As you can see in the left-hand part of the slide, the AHA and ACC have, for individuals at very high cardiovascular risk, recommend an LDL-C reduction to less than 70 milligrams per deciliter, and in Europe, those same patients, less than 55 milligrams per deciliter. Remarkably, despite what we believe are effective therapies and effective ways of being able to reduce LDL cholesterol, about 80% of patients are not able to achieve these targets. If we look at slide 24, this is where we believe LEQVIO fits in. Based on its phase III profile, we see that LEQVIO provides sustained and powerful efficacy on LDL lowering with two administrations per year. As you can see in the graphic, in three phase III trials, ORION 9, 10, and 11, we see up to a 52.3% reduction in LDL cholesterol in patients with ASCVD on top of statin. Next slide 25. While we saw this powerful sustained LDL lowering efficacy, LEQVIO was also very well tolerated, which is an important factor when you're thinking about a chronically administered medication to sick patients. As you can see from the adverse event table, LEQVIO was very well tolerated, and really the one finding we had was self-resolving injection site reactions that really posed no burden. This is a game-changing profile that we believe will really be able to improve cardiovascular health. Now I'd like to pass it over to Victor to talk about our plans in the U.S. Well, thank you very much, David. If we move to slide number 26, I wanted to focus here on the particulars of the U.S. unmet need. You can see here that we have around 20 million patients treated with statins today, ASCVD patients, and that the vast majority of them are not at goal as of today. Also notable that we see a small penetration of the non-statin therapies as well. We have identified three main factors that drive this unmet need. The first one being adherence to therapy, the second one being access to these therapies, and the third one being patient affordability. We believe that LEQVIO has the potential to uniquely address them. Now as we move to slide 27, we focus on the first one of these factors being adherence. On the left side, you can see how adherence remains a challenge both for statins and PCSK9s. On the right side, you can see how different adherence levels may influence the cumulative incidence of events. If we move to slide 28, here we focus on the potential that LEQVIO has to address adherence challenges based on three factors. The first one David just shared with us is the clinical profile and the effective and sustained LDL-C reduction that we see in the clinical trials. The second one is the twice-yearly dosing in the maintenance phase. Thirdly, the HCP administration. As we move to slide 29, the HCP administration has also implications for access. LEQVIO was studied as an HCP-administered drug, and as such, we expect that the majority of LEQVIO patients will be covered by the medical benefit, which we believe will have the potential to reduce access hurdles. On the table below, we have summarized the main differences between the pharmacy and the medical benefit reimbursement. Here you can see that LEQVIO will have the potential to be acquired via buy and bill, and that for certain populations, like the Part B fee-for-service population that represents around 40% of the ASCVD population, LEQVIO will be covered to label, which means no step edits, no prior authorizations, and therefore much less hassle for HCPs and their offices. Moreover, for buy-and-bill, practices will be reimbursed for their administrative efforts, which is not the case for the drugs covered under the pharmacy benefit. One question that we get quite often is the impact of the availability of CVD outcomes evidence as a driver for access decisions at launch. Here you can see that for the Part B fee-for-service population, again, around 40% of the population, we expect access to mirror the FDA label. For the rest of the populations, our experience with payers in the U.S. is that the focus is mostly on efficacy, safety, and cost. Moving on to slide 30. If we move to patient affordability, as you can see on the left side, the out-of-pocket cost for patients has a substantial impact on the abandonment rates in this market, highlighting the importance of patient affordability. As you can see on the right side, the medical benefit coverage for LEQVIO creates the opportunity for a $0 copay for up to two-thirds of patients at launch, and we believe this will be a strong driver. Now as we have just seen, inclisiran's clinical profile and the possibility of the medical benefit reimbursement have the potential to address the three key unmet needs in the market, being adherence, access, and affordability. Now, for this to happen, cardiologists will have to grow increasingly comfortable with the buy-and-bill process, which is a new process for them and which will take time and effort to establish. Now, if we move to slide 31. In order to support this process and to comprehensively manage these non-clinical barriers, our U.S. launch focuses on partnering with healthcare systems. As you can see in the graph in the center, the majority of U.S. cardiologists today are employed by healthcare systems. Importantly, these systems have already buy-and-bill infrastructures implemented for other specialties, which should help with the process of establishing buy-and-bill in cardiology. Some of these healthcare systems also have centralized prescribing influence and centralized EHR systems that enable granular patient identification. Importantly as well, when we talk about the top 200 healthcare systems in the U.S. who take care of two-thirds of the ASCVD patients in the U.S., 45% of these systems already have ASCVD as a key strategic priority, which makes them strong partners for this launch. Moving on to slide number 32. We've here shown the example of one of those systems of care, these large systems of care that we're going to prioritize for the launch. There's two things that are interesting to note here. One is the size of these systems of care. I mean, this one in particular has 23 hospitals, one dedicated lipid center, seven advanced cardiac hospitals. They own 40 cardiology groups, and they already have 10 outpatient infusion centers that do buy and bill for other therapeutic areas. The other interesting thing is understanding the granular data available to identify the ASCVD population who is not at goal today, and the fact that many of these systems already have population health experts working within the system trying to address these challenges. Finally, moving to slide 33. I wanted to quickly recap this section saying that we believe that LEQVIO has the potential to become the leading choice for ASCVD patients. On the one hand, by providing effective and sustained LDL-C reduction, on the other hand, we believe that LEQVIO is uniquely positioned to address the three key unmet needs in ASCVD, which are adherence, access, and affordability. In order to prepare for the launch in the U.S., we are focused on approximately 200 prioritized healthcare systems, and we're deploying a highly experienced reimbursement team to help systems and HCPs navigate the early reimbursement complexity with buy-and-bill. With that, I would like to hand it over to Matt Whitty. Many thanks. Yeah, really grateful for the opportunity to talk through this really exciting partnership work that we at NHS England have been working with Novartis on for the last year or two. I'll start, if I may, just by briefly introducing the work of the Accelerated Access Collaborative. This is a convening board that brings together industry, government, regulators, patient groups, and the NHS. The aim is to remove barriers to access to accelerate the adoption of the most important medicines, diagnostics, devices, and digital products. You can see on the slide the range of partners that we bring together, but it's probably just worth highlighting that there isn't really anything else like this in the U.K. where you get the Chief Exec of NHS England meeting with the Chief Exec of the Medicines and Healthcare products Regulatory Agency, with the Chief Executive of NICE, with representation from trade bodies and also other parts of government and research and the research infrastructure as well. It's a really unique group, with a really senior buy-in and expertise to help us solve these bigger challenges. It's hosted by NHS England, as I mentioned as well. That's just a bit of background to what the Accelerated Access Collaborative is. It's a really important group for driving this work through and other work with regards to the adoption of innovative technologies. Moving on to talk about the population health approach, and I think I won't go through all the detail on these slides. I'll just talk to the highlights in the interest of time. I think the important things to note on this are that there's a really strong alignment with this work with the aims and the specific commitments in the NHS Long Term Plan around reducing the impact of cardiovascular disease. I think when we look at why we at NHS England wanted to undertake this partnership, it was really because there was a strong clinical case for the improved reduction in LDL cholesterol lowering that really aligned with the Long Term Plan commitments. We have strong support from the national clinical directors. We have the key opinion leaders at NHS England who are supportive of the approach. We also recognize that other therapies in this area, specifically the PCSK9 inhibitors, had lower levels of uptake than we would have liked, even though they had approval from NICE and the regulatory and the NICE HTA body. I think the opportunity to work in an area that was strategically important, had the clinical buy-in and the timing of the work enabled us to actually start planning to overcome some of these obstacles to adoption in a timely manner so that we weren't in a position with NICE approving something and then the uptake being slower than we would have liked. There were three key areas really that we focused on here. One is really positioning this treatment as a primary care intervention. Typically, a lot of the uptake for new medicines would be focused in secondary care. Secondly, was efficient patient identification, so working with NHS Digital and GP system suppliers to make it easier to identify the patients most at risk. Thirdly, working with stakeholders and making sure that the consultation and the training program is in place. The education for clinicians is being developed as well, and we're working really closely with delivery partners called Academic Health Science Network. This is a network of 15 organizations that have got really good local relationships with NHS organizations, but at a national level of coordination that we work with on a range of our implementation programs. I should say as well, all of this is contingent on or linked into the deal that was agreed with NHS England, which is contingent on the NICE approval as well. Yeah, really strong alignment and timing-wise makes perfect sense. Moving on to the impact. We already know, and I've mentioned the NHS Long Term Plan, that heart and circulatory disease causes a quarter of all deaths in the U.K. and is the largest cause of premature mortality in deprived areas. It's already been recognized as the single biggest area where the NHS can save lives over the next 10 years. In terms of the level of importance of addressing outcomes in this area, it doesn't really get more important than this. You can see on the slide here, we've got a program of work where we're looking at what the impact this could have on cardiovascular disease deaths and health inequalities across the U.K. Then moving on to the implementation planning. We've been working really closely between ourselves and Novartis and the Academic Health Science Networks to agree the objectives, to agree the implementation plan, looking at the trajectories and the key performance indicators that we're putting into the agreements with the Academic Health Science Networks. We're taking a local focus to looking at what the implementation looks like in the different geographical regions and also looking at targeted roll out in areas where we think this is where we're going to have a biggest impact. I briefly mentioned patient identification already, and the collaboration with NHS Digital has been key to being able to effectively identify these patients in primary care, and it's something that we haven't done before for outside of COVID. It's a really good test case for how we can do this. I mentioned education, so it's critical that we're educating the clinicians who are going to be the prescribers for these, both in terms of what the intervention does, but also in terms of the model for how this can work. Recognizing that this is slightly different to how the NHS would typically adopt a new medicine, which might be a little bit more cautious in keeping things within a secondary care setting. We really see this as a primary care intervention. We've got a range of engagement program that is kicking off next week. Finally, we've got adherence support as well, linking in with the NHS Digital collaboration. We've got various system prompts that we built into the system as well, including recall for patients that have been initiated on treatment. I think that was everything that I wanted to cover. Hopefully, that's given a good flavor of why we were, from an NHS perspective, interested in this collaboration, how we've gone about it from an implementation planning perspective and how this is different from how things have been implemented in the NHS previously. I think that's all I wanted to cover, really. Thanks very much, Matthew. Appreciate it. If we flip to slide 38, the current submissions in the U.S. and globally are supported by the trials that have been completed already, ORION-9, ORION-10, and ORION-11. As you all know, we expect our cardiovascular outcome study, ORION-4, to yield data in 2026. We have a robust evidence generation plan behind those studies as well with the aims of really better understanding how best LEQVIO can be used, in which patients and in which settings. As you can see, we're in the process of planning several trials to support this evidence generation. We'll be providing more information and more detail in good time as we get more details on the program. In summary, slide 39. The burden of cardiovascular disease is indeed rising despite effective therapies. We know that LDL cholesterol is one of the most modifiable risk factors to improve cardiovascular outcomes, yet patients are not optimally managed mainly due to adherence, access, and affordability challenges, as Victor talked about. The U.S. launch is focusing on partnering with health systems to manage non-clinical barriers, and in the U.K., as you just heard, the NHS and Novartis are partnering on a population health approach to impact cardiovascular disease at scale. We'll now turn to pelacarsen, and Rod and I will walk you through this exciting program as well. Slide 41 introduces you to lipoprotein(a). Lipoprotein(a), if you haven't heard about it before, is an LDL-like particle but is highly atherogenic, pro-inflammatory, and thrombogenic. It is an independent cardiovascular risk factor that's genetically determined. Currently, there are no known therapies that reduce lipoprotein(a). In fact, diet and exercise don't improve your lipoprotein(a), statins, et cetera. None of those therapeutic alternatives will improve your lipoprotein(a) or reduce your risk. We have an opportunity to develop a new therapy for patients with cardiovascular risk that's currently not managed. Slide 42 shows you the evidence that links elevated lipoprotein(a) to cardiovascular risk. You see there are a variety of sources of data. On the left-hand part of the slide, we show you epidemiologic data showing you on the x-axis as your lipoprotein(a) blood concentration goes up, your risk ratio for non-fatal MI and coronary death increases. On the right-hand panel, you see a Mendelian randomization study showing you similar data, whereas you have elevated as your Lp increases on the y-axis, your hazard ratio also goes up. There are several lines of evidence that link lipoprotein(a) to increasing cardiovascular risk, and indeed, guidelines are increasingly recognizing Lp(a) as an important risk factor to assess in patients with ASCVD. Slide 43 shows you an important piece of information, which is, I said at the beginning that Lp(a) looks a lot like LDL cholesterol, but interestingly, they're not very highly correlated. The reason why this is important is because if you have a patient with moderately elevated or normal LDL cholesterol, you still should measure an Lp(a) if they've had a heart attack or if they have ASCVD, right? To appropriately assess their risk. What this tells you is because these two risk factors are independent, LDL and Lp(a) are independent, you need to measure both of these risk factors in order to really judge a patient's risk for cardiovascular morbidity and mortality. Slide 44 shows you a potential approach for the treatment of elevated Lp(a) and the reduction of cardiovascular risk. That's pelacarsen. Pelacarsen is an antisense oligonucleotide which specifically reduces Lp(a). As you see from these phase IIb data, doses of 20 milligrams a week or 80 milligrams a month reduce Lp(a) substantially, getting about 90% of patients below the higher risk threshold of 50 milligrams per deciliter. This is exciting data that shows us that we can specifically target lipoprotein(a) in the blood and reduce it in patients. The question then is how this influences patients' cardiovascular risk. As we also saw in this phase IIb study, pelacarsen was very well tolerated, again, important when you're talking about treating patients chronically with a medication. On slide 45, we have two studies running right now. On the left-hand panel, we have Lp Heritage, which is a prevalent study which seeks to evaluate Lp levels in patients with established cardiovascular disease. It's a very large trial where we evaluate prevalence. We initiated this trial in April of 2019 and expect results later this year. The phase III outcomes trial is called HORIZON, which is summarized on the right-hand part of the slide. This is a cardiovascular outcome study looking at major adverse cardiovascular events in patients with Lp greater than 70 milligrams per deciliter. This study was initiated in 2019, and we expect the primary outcome in 2024. Next slide, I'll pass to Rod. Thanks, David. We flip to slide 46, and we look ahead to the commercial opportunity that exists for pelacarsen, we'll really build on our strength in cardiovascular and leadership position that we've had in heart failure with Entresto, and we've just shared with you our plans with LEQVIO so that we can address another very large, significant addressable population and have the potential to impact cardiovascular disease at scale. We see already that one in five people worldwide have elevated Lp(a). That's 1.4 billion people that have one of the strongest genetic cardiovascular disease risk factors. While that prevalence can vary globally, in the U.S. and Europe alone, over 200 million people have elevated Lp(a). The real problem if you flip to slide 47 is the lack of awareness. Since there are currently no treatment options to modify Lp(a) levels, awareness overall is very low, particularly among general practitioners. What we see from our data, if you look at the middle table, you see that the risk is similar, as David shared, to that of elevated LDL-C, but the physicians rank its importance much lower, and many of them misperceive that it could be treated with current cholesterol-lowering therapies, which just isn't the case. When you combine that low awareness and knowledge, it also translates, as you see on the far right, to incredibly low testing rates. That's the real challenge and the opportunity, because even amongst diagnosed ASCVD patients, the rate is significantly below 1%. That will really be the focus of our efforts is truly around education to raise awareness and level of testing, leveraging the HERITAGE study that David just talked about earlier. On slide 48, one of the things that we have in our favor, and we'll continue to work towards stronger education, is the guidelines are very clear and they're progressive on this particular topic. In the U.S., the recommendation is to test patients with a history of ASCVD for Lp(a), and in Europe, it's recommended to test everyone once in a lifetime. As we prepare for launch and why it's so important that we do this early and educate through medical education and other efforts is really about raising awareness of Lp(a) and the need to test, and that will be our primary focus. The other thing we'll leverage on slide 49 is clearly there are synergies that we'll leverage in the marketplace, but the one as the head of the commercial organization that I just referenced, for me, it's all about education. It's about education to the key prescribers, the healthcare systems and systems of care that Victor Bultó alluded to earlier in the U.S. and that Matt Whitty acknowledged in the U.K., and the importance of working with medical and professional societies and patient advocacy groups. As David Soergel alluded to earlier, again, it's so critical that we educate and focus our efforts on making sure that this deadly cardiovascular risk factor is more acknowledged and testing rates dramatically increase, which is why we're focused over the next four years in doing that. LEQVIO will continue to be our cornerstone in ASCVD management, but pelacarsen has the potential to promote CV health on a completely another level. If we go to the last slide, just to summarize the opportunity and the focus we have for pelacarsen going forward. Lp is a significant independent and genetic risk factor for ASCVD, and with no current treatment option available, we still need to drive access to Lp testing and a significant increase so that the patient's other cardiovascular risk factors can be optimally managed. While the awareness of Lp is very low right now and the rate of testing is low, we know that guidelines are very strong and clear in the importance of testing for patients, which will drive our education efforts and ultimately lead us up to the potential launch where we know pelacarsen significantly reduces and modifies Lp in cardiovascular disease patients. With our strong capabilities that we've built in cardiovascular disease with Entresto and heart failure, the footprint that we have with LEQVIO around the globe, we anticipate a significant opportunity for pelacarsen and a leadership in ASCVD long into the future. Now let me hand it back over to Samir for the Q&A. Thank you very much, team, and perhaps we can go to the question and answer session. If the operator could start taking the questions, please. Thank you. We'll now begin the question and answer session. As a reminder to ask a question, you will need to press star and one on your telephone and wait for your name to be announced. To withdraw your question, please press the pound key. Your first question comes from the line of Laura Sutcliffe at UBS. Please ask your question. Your line is now open. Hello. Thank you. I've got two questions on TQJ230, please. Firstly, for the HORIZON trial and the 80 mg dose, are you expecting the same sort of efficacy that you've got for the 20 mg once weekly just with pure discontinuations, or is that not the right way to think about it? Secondly, if you just think about what the Outcomes are for these trials is sort of getting below a threshold, as you've named here on your graph, the most important thing, or is it more about an absolute reduction in Lp(a) for these patients? I think there's some literature that suggests that the latter is important when it comes to changing risk profile. Thanks. Thank you very much, Laura. Perhaps I can ask David to address both the questions. The first one with respect to the dosing and the second one with respect to absolute threshold or not, please. Yeah, great. Thanks for the question. If I understood your first question, you are asking if 20 milligrams per week is equivalent to 80 milligrams per month. The answer is yes. We saw in the phase IIb study that it was actually a very nicely designed trial looking at different doses and intervals, which gave us very strong ability to be able to predict what is going to happen with the 80-milligram dose. Your second question is a great one. Being first in class is a great opportunity, but it comes with some scientific questions that we have to answer. I think that your question is exactly along those lines. The good news is that pelacarsen's incredibly effective on both angles, both in terms of percent change and in terms of absolute reduction. When you see, for example, an Lp(a) of 100, we expect to get that patient down below 30 with pelacarsen. This it's a very strongly effective agent, and so we think no matter how you look at it, whether it's a threshold or a% decline, that we'll be able to achieve that. Okay. Thank you, David. Thank you, Laura. Operator, next question, please. Thank you. Your next question comes from the line of Keyur Parekh at Goldman Sachs. Please ask your question. Your line is now open. question comes from the line of Keyur Parekh at Goldman Sachs. Please ask your question. Your line is now open. question comes from the line of Keyur Parekh at Goldman Sachs. Please ask your question. Your line is now open. Thank you, thank you Team Novartis for hosting this deep dive. I really appreciate it. Two separate questions, please. First one on LEQVIO. Am I right in interpreting the tone of the launch as being different to your previous tone about being cautious and a slow launch? A lot of commentary today seemed to be very bullish about near-term estimates. Perhaps you might want to address that in the context of 2025 consensus of $1.5 billion or kind of The Medicines Company's target of $1.7 billion-$1.8 billion when you acquired them. I guess simplistically, are you guys more excited about it than The Medicines Company was, do you think consensus is getting it wrong? Any color there would be helpful. Secondly, as we look at the outcome study for Lp(a), can you help us think about the potential for interim analysis and when potentially that might happen? Thank you. Great. Thank you very much, Keyur. If I could put the first question to Rod and the second question will then go to David. Thank you. Yeah. Thank you for the question. I think if we think about the LEQVIO launch and particularly what you saw today from Victor and how we've established it, we know it will take time to establish the infrastructure for buy and bill and how we're working with healthcare systems. We know that will take a few years in order to be able to develop those relationships and the comfort in working within the flow of their systems to identify the patients and treat them. That will be a main driver in some of the early launch. We've also acknowledged the fact that as we look at ex-U.S. market, it will take outcomes data before we get to the build. I think the most important position for us is to establish those foundational partnerships that we would have with healthcare systems in the U.S. and major healthcare systems like Matt Whitty talked to in the U.K. to ultimately maximize the asset in the long term. That's how we're continuing to think about it, is tackling ASCVD in a new way, addressing the non-clinical barriers with these partnerships, access, affordability, as well as adherence, and continue to be optimistic in the long term. Rod, I think the question was also how optimistic are you or how comfortable are you with the consensus in 2025? I think we continue to be confident in the consensus that we have and the expectations that we have of the outlook for 2025. Thank you, Samir. Great. Thank you. Coming back to David for the second question on potential interim analysis. Yeah. I love the question because I'm going to assume it's because of the person's confidence in the trial. As in most cardiovascular outcome studies, there is indeed an interim analysis built in. This is an event-driven trial, and the interim analysis is dependent on a certain number of events accruing, so I can't say exactly when that's going to happen yet. The bar is high for an early stopping for a cardiovascular outcome study, especially for a first-in-class therapy, where you really want to accumulate long-term efficacy and safety data in the population. Our expectation is that it'll run to the end of the trial, but there is an IA built in. Cool. Thank you, Keyur, and thank you, David and Rod. Operator, next question, please. Thank you. Your next question comes from the line of Emmanuel Papadakis at Deutsche Bank. Please ask your question. Your line is now open. comes from the line of Emmanuel Papadakis at Deutsche Bank. Please ask your question. Your line is now open. comes from the line of Emmanuel Papadakis at Deutsche Bank. Please ask your question. Your line is now open. Thank you for taking the question. A couple if I may. Just a bit nearer term, let me go to the refile you've reiterated Q2, Q3. It does, however, seem as an FDA inspection is likely to be warranted, whether you file on third party and/or your internal tech transfer third facilities. The FDA does have quite a backlog. Could you just talk to your degree of confidence around timing of approval in the first half of next year and how that regulatory process is proceeding? Second question on the. Thank you, very helpful on the NHS collaboration. To my knowledge, you haven't actually given us any commercial details in terms of the terms around arrangement. Is there anything you can say to pricing or value associated with that contract? Indeed, by extrapolation, is there anything you can say in terms of pricing benchmarks we should think relevant to the U.S. market and PCSK9 antibodies, for example, are relevant factor to consider? Thank you. Okay. Thanks, Emmanuel. On the first question with respect to the timing of, A, the refiling and, B, when we're likely to get FDA to review things, that could be for David. The second question with respect to NHS and how to help Emmanuel model from a pricing et cetera, and benchmarks that I'll give to Rod. The first question, please, on timing for refiling. David? Yeah, got it. Thanks, Samir. Yeah, thanks for the question. Yeah, we remain confident in the refile Q2, Q3 as we've said. It's up to the FDA, as to whether or not to conduct an inspection. What we can say is that typically these reviews take six months, and that our expectation is to make the refile as we said. Thanks. Rod? Yeah, thanks for the question, Emmanuel. With our agreements with the NHS at this point, what I can say is we signed memorandums of understanding. The contract we expect to be signed in July, prior to our launch in Q3, it's still subject to NICE outcome. I can't share any details in terms of the benchmark or pricing at this time until we've established that contract and the NICE outcome, which is why at this point with Matthew and his colleagues, we're focusing on once those are established, how do we start to identify those patients, work in their primary care networks, and make sure that we're giving the prescribers the confidence and the education they need with patients, more details to come later following the NICE outcome. Great. Thank you. Thank you, Emmanuel, for the questions. Next question, please, operator. Thank you. The next question comes from the line of Andrew Baum, Citi. Please ask your question. Your line is now open. Mr. is now open. Mr. Baum, please ask a question. Yeah, sorry about that. A couple of questions to John and to Victor. In relation to the PARADISE-MI dataset. With PARADISE-MI, it was clear that the FDA was keen for you to file despite the 0.06 p-value for the primary endpoint. In relation to the PARADISE-MI dataset, how much push is there compared to pull in relation to the dynamic between Novartis and the FDA, given the interactions you've had to date? Second, I'm sure that you've done a very comprehensive cardiology survey in terms of the desire to use inclisiran in the absence of outcome data. Perhaps you could share with us the differences in the U.S. in particular, how much reluctance is there and how much do you believe you can overcome once you're out in the market, given it's going to be a while before the outcome data comes through. Many thanks. Thank you very much, Andrew. On the first one about PARADISE-MI and push versus pull from the FDA. David, would you like to take that one, please? Sure, Samir. Thanks for the question, Andrew. The data from PARADISE-MI are still relatively fresh. We're still doing analyses. The first presentation was just at ACC this past weekend, as you know. We continue to do analyses, and we will update you on any future discussions with FDA as warranted. At this point, we do plan to share the ACC presentation with FDA, and we will see their feedback. Great. Then with the second question, I think we'll split it into two parts. First, I'll go to Victor. The importance of outcome data for the U.S. and perhaps Rod could then subsequently take outcomes data for Europe. The importance for uptake, Victor, of outcomes data. Thank you very much, Andrew, for the question. We don't believe this will be a challenge at launch, having discussed and surveyed cardiologists. On the one hand, there is a strong body of evidence linking LDL-C and outcomes. When talking to cardiologists, the linkage between LDL-C and outcomes is really clear. On the other hand, inclisiran works within a pathway of LDL-C lowering that has already been shown to improve outcomes. On the access front, because we will be routed to the medical benefit mostly, for 40% of that population, the coverage is to label, and therefore we don't expect an impact on the CV outcomes evidence. For Medicare Advantage and commercial populations, the focus is mostly on efficacy, safety, and cost. Thank you, Victor. Rod, importance of outcomes in Europe, please. Yeah, thanks, Andrew. I think we can acknowledge that the importance of outcomes and for reimbursements and broader access overall, outcomes are important. That's to a limited population of patients with very high CV risk. While the feedback has been physicians are impressed with the immediate drop that they see in LDL-C that they've spoke to and the sustained efficacy that they see. Our strategy, including Europe, is for LEQVIO to benefit a much broader number of patients and overcome those non-clinical barriers. While we will pursue the outcome study and know those markets look at it as an important piece, we are actively exploring commercial partnerships, like we talked about today with Matthew in a number of countries around the world, and making sure that LDL-C and targeting a larger population that ultimately could be benefit is a cornerstone of our cardiovascular disease health promotion strategy. The first of which obviously will be the U.K. when we would expect that launch in Q3. Thank you, Rod. Operator, we are ready for the next question, please. Thank you. Your next question comes from the line of Graham Parry at Bank of America. Please ask your question. Your line is now open. you. Your next question comes from the line of Graham Parry at Bank of America. Please ask your question. Your line is now open. you. Your next question comes from the line of Graham Parry at Bank of America. Please ask your question. Your line is now open. you. Your next question comes from the line of Graham Parry at Bank of America. Please ask your question. Your line is now open. Great. Thanks for taking my question. Just going back to Entresto. Just to be clear, what's the base case for Novartis or the range of possibilities you see on PARADISE-MI label inclusion? Do you see there's a possibility you could get label inclusion of the data or possibly even an indication? Do you just see this as a sort of not negative, positive trend, so that helps the overall perception of Entresto and its safety, particularly in fragile patients. Secondly, a question for Matthew Whitty. There are obviously approved and reimbursed antibody-based PCSK9 inhibitors available in the market already. Why wasn't a collaboration like this possible with one of those products and their manufacturers? Was this just proactivity from Novartis that led to the current collaboration, or is it just the less frequent dosing? Could you just help us understand the reason why this product could be treated differently? Then lastly, on pelacarsen, you flagged Lp(a) as being a causal risk factor for MI, stroke, and PAD. Can you just remind us how causality is being established given today I think we're just looking at observational epidemiological data. So what are the risks that modulating levels doesn't have the impact on outcomes as we've seen with some other CV biomarkers, and you just said a bit of this being a coincident finding. Thank you. Thank you very much, Graham. Perhaps I can start with the first question from Matthew. I think the key point from Graham was why are you working now with inclisiran with Novartis, whereas you didn't work with, oh, not you, the NHS didn't come up with population health for PCSK9. Matthew. Thanks very much, and it's a great question. I think there's a couple of things to note, really. Firstly, as part of the Voluntary Scheme, so the pricing scheme that was put in place, there was an agreed element of that for NHS England to produce something called the Commercial Medicines Framework that was published in January, but we actually started using it about a year or so ago. Timing-wise, it fitted really well with sort of a newer and more innovative approach to commercial models that NHS England was looking for. That was a big part of why we were able to use that greater commercial innovative, more innovative commercial approaches for this drug which wasn't in place at the time for the PCSK9 inhibitors. Also, I think there was a sort of proactive approach as well in that the other companies when they approached us went down a different route for looking at how they would use their commercial freedoms in a more traditional approach, if you like. It was sort of a partly timing in terms of the new flexibilities afforded to us under the Commercial Medicines Framework and partly Novartis having a more innovative approach to pricing than the competitors. Thank you, Matthew. Graham, I think the other two questions are for you. The first one relates to the range of possibilities which you could get vis-a-vis the label. I think Graham was also trying to work out what you think is most likely. Be careful with that one. The second part of the question, apart from the interest of a potential label, is with respect to pelacarsen. You said, yeah, a number of potential markers which suggest increased disease activity. How confident are you that reducing Lp will be established as a therapeutic agent? Okay, great. Yeah, I got it. I guess first, Graham, on Entresto and PARADISE-MI, clearly we saw numerical trends favoring Entresto on the primary endpoint, but we didn't reach the pre-specified superiority statistical threshold. We did not succeed in the trial. The P-value, as you saw on the slide, was 0.17. I think we have to acknowledge that. There are clearly supportive analyses through the secondary endpoint hierarchy that support the numerical trend. At the end of the day, the trial was neutral. I think what we see from this study is that patients post-MI have much better care than they did 30 years ago. Entresto may have an incremental benefit on top of that, but this trial did not prove that finding. What we did see is that in these patients who, again, are very sick patients a few days after having a heart attack, Entresto was well-tolerated. The data from PARADISE-MI in terms of safety and tolerability complement trials like PIONEER-HF and TRANSITION in heart failure patients who've been hospitalized to give practitioners confidence that this drug can be used in fragile patients. Turning to TQJ230 and pelacarsen. You raised a great point. Again, coming back to a comment I made earlier, is when you're first in class, you weigh the scientific evidence supporting your target and the likelihood of success. Why do we believe in this case that we have a greater likelihood of success than previous efforts? Well, first of all, it's the weight of the evidence. I showed you two lines of evidence, epidemiologic data, Mendelian randomization data. There's also data from statin trials and meta-analysis from statin trials. All showing us that elevated Lp(a) confers higher cardiovascular risk. The question is, if you reduce that pharmacologically with pelacarsen, the scientific question is, and medical question is, when you reduce Lp(a) pharmacologically, do you achieve an outcomes benefit? What we see from pelacarsen is that the degree in Lp(a) lowering and some of the other salutary effects that they saw on other lipids in phase IIb gives us more confidence that we're going to have a beneficial effect in this population. At the end of the day, that's why we run the trial. Okay. Great. Thank you, David. Thank you, Graham. Sorry. Operator, we're ready for the next question, please. Thank you. The next question comes from the line of Jo Walton at Credit Suisse. Please ask your question. Your line is now open. question comes from the line of Jo Walton at Credit Suisse. Please ask your question. Your line is now open. question comes from the line of Jo Walton at Credit Suisse. Please ask your question. Your line is now open. Thank you. I've got three questions, please. Firstly, on Entresto. We know that patients with heart failure tend to be old. They tend to be on lots of medicines. They are rattling around. Entresto is one of the branded products, which is more expensive for them. Do you have any real-world adherence data showing what proportion of patients are still taking the drug one year on? Given that, particularly in the U.S., they are still having to pay a reasonable amount of co-pay. Secondly, on inclisiran, I wonder, just so as I understand this, do you not have a deductible with your medical benefit? You talk about patients being able to get this drug essentially free from the point of launch. Wouldn't they have to go through some form of deductible to get that beforehand, before it became free? My third question, I don't know if you can still hear me. We can hear you. We can hear you, Jo. Yeah. Oh, perfect. Good. My third question is on the U.K. side of things. Just so I can understand this, has the system worked so that if a doctor puts the patient on this in the U.K., this is budget neutral for the local trust? Because I'm assuming that this is a little bit more expensive than some of the other treatments that they might choose to use. Is there something built in whereby the doctors get some reimbursement so that there's an actual pull from the economics from the U.K. doctor's practice as well to get involved? Can I understand, just finally, I think you said that the deal was going to be based on how NICE appraised this. The deal will be set irrespective of what happens when you get the final outcome data. It's not a price that will be set and then when we get the outcomes data in, hopefully you find this linear relationship and a fantastic reduction in cholesterol gives a great reduction in cardiovascular death. At that point, does the pricing change, or is the price set now? I'm assuming that Novartis gets the benefit of using this data. Is there any way that this could bring forward the global knowledge about cardiovascular risk? Could U.K. data, real world data, get there faster than the clinical study that you're otherwise doing? Many thanks. Hey, Jo. Thank you very much. I think I've got four questions there. What I'm going to do is, first of all, I'm going to ask Rod to talk about the pricing issue with respect to the U.K. partnership. I'll ask Matthew to specifically talk about the trust versus the doctor practices and how the economics works there. The other two questions which you had, both with respect to Entresto in terms of adherence in the U.S. at one year, as well as the deductible will go to Victor. First question, Rod, simple one. Can you talk anything more about what happens from a pricing perspective post outcomes, pre outcomes? Yeah, Jo. Thanks for the question. As it relates to the U.K., we have Matthew on as well. We throughout this process, whether it was The Medicines Company We're now through Novartis. NICE has been a critical player at the table as we've continued through the process, and we've always acknowledged and expected that the NICE outcomes were still an important part of the evaluation that would occur prior to the final agreements and contract signing. To your specific question, another expectation is then as we would get the availability of the data of the outcomes trial, we would re-look at, and that's been part of the agreement, the pricing and the cost-effectiveness analysis in the populations that we've studied. That is an expectation that we would revisit at the appropriate time. I think the important thing that Matthew acknowledged and what we're excited about is with this program, particularly addressing some of those non-clinical barriers, we'll be able to generate strong evidence, real-world evidence, as we lead up to those outcomes data with our colleagues in the U.K. and NHS England and see the real impact that we're making on the disease as we address both the clinical and non-clinical barriers. It's an exciting opportunity. Thank you, Rod. Matthew, if you could perhaps address the issue of the local trust versus the doctor practice and the economics and how that would work, please. Yeah, thanks. I think one thing to note really is that the typical launch for a new product, as I mentioned earlier, really would be sort of focused around specialists in secondary care initiating and then that practice and prescribing sort of slowly diffusing into primary care. We really saw this as a primary care intervention. A lot of the incentives and the payment flows that we've been looking at are sort of how we can support that money flowing through to primary care. That's in a number of ways. We're looking at whether there's a more efficient way to identify patients, as I mentioned, through the NHS Digital work in primary care. We're looking at the payment flows to GPs. We're looking at exploring whether or not we can actually have a direct payment to prescribers as part of the way that we get the drug out to patients. We're also looking at some other areas, particularly around other incentives for primary care clinicians. We've got something called the Quality and Outcomes Framework. This is whereby a payment mechanism for GPs, where if they hit particular clinical outcomes, they get additional points which add up to additional payments. We're also looking to see whether we can include a cholesterol target within that as well. A range of measures we're looking to get those incentives right. Again, it's primary care focused, not secondary care focused. Great. Thank you. Victor, the first of your questions was related to adherence state in the real world in the U.S. for Entresto, the second question relates to the issues about deductibles for inclisiran, et cetera. Thank you very much for the question. If I start with Entresto, we have worked really hard over the past years to make access to Entresto both affordable and easy for patients and HCPs. That has been one of the key pillars of our growth of what we've seen. As of today, more than half of the Entresto patients pay no more than $10 per month. Most of them have preferred access, 99% in the Part D space and 80% in the commercial patients. This is translating around 70% of the patients remaining on therapy at 12 months. Reinforces our strong position in heart failure to continue to grow, just highlighting, for example, that in the rest population, we just penetrate around 30%. We see tremendous space there to continue to grow with Entresto. On the inclisiran side, in terms of out-of-pocket for patients, it depends on the population. We would have for the Medicare Part D population, which represents 39% of the ASCVD patients, 80% of those patients will pay as little as $0 per month because they have supplemental insurance. For the commercial population, which is around 34%, they would be eligible to pay as little as $0 because of our support. Finally, the Medicare and federal population will pay less than $10. The only population that would be left with a little bit of a higher copay would be the Medicare Advantage population, where it varies depending on the plan and the co-insurance. All in all, two-thirds of the patients at launch would be having a $0 copay, which we believe is a very important factor in the uptake of drugs in this space. Thank you. Operator, next question, please. Thank you. Your next question comes from the line of Kerry Holford at Berenberg. Please ask your question. Your line is now open. Thank you. Can I have three, please? On LEQVIO, the associated costs that you see in the U.S., I'm looking at slide 33, where you mentioned developing test injection center networks. Do you aim to do that within each of your target 200 healthcare systems at launch? Who's funding that? Is that something that you are funding or is it in conjunction with these healthcare systems? From a promotional perspective, once you overlap with Entresto prescribing physician base, have you already recruited additional medical reps in order to launch LEQVIO? Is that required? TQJ, I wonder if it's possible to talk about potentially extending. The dosing frequency even further than once monthly is once every six months dosing. Are you similar to LEQVIO a realistic opportunity? Is there actually any value in a combination with LEQVIO? I think perhaps the answer is no, given that correlation in terms of that. I'll be interested to hear your thoughts on that. Finally, a question from Matthew Whitty. You mentioned how CVD was already a sort of key target area within your team's long-term objectives here, and that LEQVIO proposition was a nice overlay with that. I would be interested to hear whether there were any other chronic diseases that are on your target list, perhaps at ACC, where you might be interested in or indeed actually working on similar partnerships with other drug manufacturers. Thank you. Thank you. If we just take each of those questions in turn, I think you have some operational-related questions with respect to LEQVIO, which I'll hand across to the U.S. I think it was about who actually does the injection, setting up of the clinics, as well as the potential overlap with the Entresto field force. That one be for Victor. With respect to the TQJ230 question, which I know David spends days, nights, weekends thinking about, both with respect to can you go from monthly to six monthly as well as combo. I'll let David answer that. Of course, Matthew with other areas other than LEQVIO for potential population health. Victor first, please. Well, thank you very much, Kerry, for the question. As we've stated, one of the key challenges at launch will be to establish the buy and bill processes within cardiologists' offices, because today it's not a reimbursement pathway they use often. For that, we will be working on the one hand with these systems of care because they already have established processes to buy and bill other products in other therapeutic areas. Our efforts are mostly connecting the dots within those systems so that cardiologists can utilize those efforts. On the other hand, we've mentioned that we're developing an alternative injection center network to provide this acquisition and administration flexibility for those cardiologists who cannot or do not want to establish buy and bill within the center or in their office. Basically, those are independently owned injection center networks. The only thing we're doing is helping connect the dots and helping cardiologists understand that they would be able to send their patients to these systems. Now, in terms of your question on the overlap, there's a very substantial overlap, of course, from a healthcare professional, both on the cardiology front and those primary care physicians that do take care of those patients. Also, around 60% of the key Entresto targets are affiliated with these prioritized healthcare systems for LEQVIO. Answering your question on whether we've recruited more reps, the answer is no. We believe that the current footprint that we have with our Entresto field team will suffice. What we are doing, and we have done already, is hire and develop a strong field reimbursement team that will work with these offices and the healthcare systems, as I said, on the one hand, to connect the dots within the system and to, if needed, establish relationships with third-party injection sites. Thank you. On the TQJ230 question, David, with respect to perhaps more prolonged dosing as well as the possibility of a combination. Thanks for your enthusiasm on that, Samir Shah. Really appreciate it. As of today, we don't see a way to easily increase the durability of TQJ230 and increase its duration of action to match the Q6 month administration of LEQVIO. We'll continue to turn this one around and see if there is a way to make that happen. As of today, we don't have a way of designing a way to achieve that. I was only kidding, David. Anyway. Matthew, the last part of the question was in relation to any other areas where you may think about population health. Yeah, thanks. I'm afraid I can't talk about specific deals that we're either pursuing or considering at the moment. I would say that the NHS Long Term Plan gives a really good indicator about the areas that we're prioritizing. One of those other areas being earlier diagnosis of cancer. We've got a specific target in the Long Term Plan to diagnose more cancers at stage one or stage two. Currently, the NHS is at about 56%-57% of cancers being diagnosed at stage one or stage two. There's a commitment to increase that to 75% of cancers. We published information on a deal that we did with a company called Grail on a new cancer diagnostic. The deal was done back at the end of November 2020. Yeah, so the Long Term Plan, a really good idea about the areas we're interested in and how that's driving particular focus for future deals as well. Great. Thank you, Matthew. As we've only got about five minutes left and there are still three people in the queue for questions, could I just ask that each person limits themselves to one question, please. Operator, the next question please. Thank you. Your next question comes from the line of Florent Cespedes at Société Générale. Please ask your question. Your line is now open. Your next question comes from the line of Florent Cespedes at Société Générale. Please ask your question. Your line is now open. Your next question comes from the line of Florent Cespedes at Société Générale. Please ask your question. Your line is now open. Your next question comes from the line of Florent Cespedes at Société Générale. Please ask your question. Your line is now open. Good afternoon. Thank you for taking my question. I will ask one on pelacarsen. What is the level of efficacy you're targeting with the HORIZON trial on the primary endpoint? What is the level of relative risk reduction in the design of the trial? Is it 20% relative risk reduction or more that you are targeting, please? Thank you. Thank you, Florent. David? Thanks very much for the question. We're actually in the process of preparing the study design paper now, which will give you a lot more information. What we've already talked about is we have two tiers of Lp level that we're evaluating as co-primary endpoints. 70 milligrams per deciliter, which would be the total population, and 90 milligrams per deciliter. We have two ways of being able to achieve success. We haven't publicly stated what level of MACE reduction we're looking at within the population at this point. I think, again, if you look at the evidence that indicates Lp's role in cardiovascular risk and the degree to which pelacarsen reduces Lp, you can infer that there'll be a clinically important benefit at the end of the trial. Thank you very much. Thank you, David. Thank you, Florent. Operator, next question, please. Thank you. The next question comes from the line of Charles Pitman-King at Redburn. Please ask your question. Your line is now open. question comes from the line of Charles Pitman-King at Redburn. Please ask your question. Your line is now open. question comes from the line of Charles Pitman-King at Redburn. Please ask your question. Your line is now open. Thank you very much for taking my question. Just on inclisiran, I was wondering how will the rollout be communicated, and will this be done by the NHS or by Novartis primarily? Just in terms of the pandemic, how has this affected the plan, given that on one hand, cardiovascular disease is a risk factor for severe COVID, and the other has created significant disruption and backlogs within primary care? Thanks. Okay, one question becomes two, I think. In terms of communications, Rod could address that. In terms of impact of pandemic and COVID, perhaps Matthew could talk to that. The first question is for Rod. Thanks for the question. I think that's the important element, and Matthew can speak to it, too. From the beginning of the working relationship and the unique nature of the agreement is our teams are really working very closely together, co-creating what that education plan and implementation will look like within the primary care network. It truly will be a joint effort in how we work together within the NHS system and importantly, identify the right patients, the right education process and the right follow-up so that patients can ultimately get the outcome and benefit. Matthew can speak to it as well, but it's been one unique relationship to tackle this together. Thank you. Matthew? Yeah, agreed. It's been the backbone of the agreement, really, that it's been a sort of collaborative effort and it will continue to do so in terms of the communications. In terms of the second part of the question in terms of COVID, clearly we've seen the patients with comorbidities having worse outcomes from COVID. It's really only heightened the importance of this work. I should also flag that my boss has led the rollout of the vaccine program as well. As part of this work, we also had the minister who is overseeing that to feed into our work program. We can understand some of the lessons which we fed in, and that's around easier identification of patients. It's around primarily the importance of primary care leadership as well. We're feeding in those lessons. Yes, it's impacted it in terms of the ability of GPs to engage early on in the process, I would say. We've also learned the lessons from the vaccine rollout program. We fed those into our work plans, it's only really heightened the importance of us delivering. Great. Thank you, Matthew. Operator, we have time for the last question. Thank you. Your final question comes from the line of Richard Parkes at Exane BNP. Please ask your question. Your line is now open. Hi. Thanks for taking my question. I've got two, but I'll just ask the one. If there's time for the second, then you can squeeze it in. It's just one for Matthew. I just wondered if you could give us a sense of what kind of levels of uptake you're planning for within the 300,000 patient target population. I don't know whether you're making any input into the NICE budget impact assessment, so maybe you could talk about that and what you feel is the biggest barrier to achieving that. Thank you. Matthew Whitty, over to you in terms of the question. Yes. It's probably best to pass to Novartis colleagues, really on specific uptake. Okay. If only so that we've got a shared interest in getting this out to as many patients as possible from both a clinical perspective, but also a commercial perspective. Okay. Rod, do you want to give a final word on that? Yeah, I think the ambition is high from both teams, obviously, to try and identify these patients. We know there will be learnings along the way, and that's why the important aspect of the relationship is really focusing on the non-clinical barriers, the identification of the right patients initiating on therapy and the follow-through and follow-up at the regular appointments. While we're very enthusiastic about the partnership and encouraging how we're approaching it, the uptake we'll have to see as we go. We both created ambitious targets for ourselves through the first three years through the implementation science that we'll also be doing so that we can identify are there are other factors that limit uptake and how would we address those, of course, through the course of the relationship and the agreement. It's really meant to be implement together, learn, and continue to work for new ways that we can make sure we get the right treatment back in the hands of the right patients. Thank you very much. This brings us to a close to our conference call. I'd like to particularly thank all the participants and those who specifically asked those questions. I'd also especially like to thank our external guest, Matthew Whitty, for helping us explain what population health is, and also to our Novartis colleagues, Rod Wooten, David Soergel, and Victor Bultó. Have a great evening or a great lunch, depending on which side of the world you are. Thank you, everybody.