Thank you very much, and welcome everybody, and good morning and good afternoon as well. Thank you so much for taking the time to participate in this iptacopan update. People are a little surprised as to why we're doing an update on a single molecule. As you'll see, and you probably know from having read some of the slides, it's because we've got a number of indications for iptacopan, and we thought it was a good time up around this stage to actually go through in a little more detail, the various indications and the way we're trying to develop iptacopan in the two therapeutic areas of nephrology and hematology. It's my great pleasure today to have two speakers on the line who you'll probably be very familiar with if you listened to our call on CRM just about a month ago. We've got David Soergel, who's our Global Head of Cardiovascular, Renal and Metabolism Development, and we also have Rod Wooten, who's our Global Head of Marketing at Novartis Pharmaceuticals. I'm Samir Shah from Investor Relations. Before we start, I just wanted to go through 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 actual 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 that, I'd like to hand across to David. Great. Thanks a lot, Samir. It's great to be here, and especially to be here to talk about iptacopan because we think that this is a medicine that could fundamentally change the way that complement-driven diseases are managed and improve the lives of many patients who today have no good alternatives. Iptacopan, as Samir mentioned, is indeed a pipeline in a pill. It has potential in a wide variety of diseases because it inhibits a foundational aspect of the immune system, the complement system, but it does so in a very targeted way, as we'll get into today in some detail. Health authorities worldwide have recognized the potential of iptacopan with key regulatory designations in several indications as listed on this slide. Today, we will talk about the very compelling Phase II data and our future plans in several indications, and then we'll briefly outline the rationale to expand into a growing list of additional indications. We can go to the next slide five. What distinguishes iptacopan is that it's an oral, first-in-class, highly potent, small molecule, specifically targeting Factor B of the complement system. Unlike some other complement-directed agents, iptacopan specifically targets one branch of the complement system, the alternative pathway. Normally, the alternative pathway is responsible for surveillance for foreign matter like microbes, and the way it works is by operating at a low level until it encounters a signal and then it snaps into action, amplifying the response to clear material from the body. There are intrinsic inhibitory mechanisms that hold this amplification system in check unless it's needed. Things can go wrong with this elegant system that then lead to unnecessary activation of the alternative pathway with damaging consequences. For example, the inhibitory mechanisms might not function properly, or the amplification system itself can be ramped up inappropriately. By inhibiting factor B, Iptacopan inhibits the amplification process, thereby dampening an inappropriate activation response. Importantly, though, Iptacopan does not fully inhibit the classical or lectin pathways, so important parts of the system remain intact to fight off infections. Next slide, please. There are several molecules either on the market or in development that target the complement system. Iptacopan is differentiated from these other approaches by its oral delivery, its specificity for the alternative pathway, and the breadth of its development program, as we're going to get into today. We believe that these features will lead to the greatest impact to improve patients' outcomes. Next slide. Okay. With that background, let's talk about how iptacopan is progressing in development. As you can see, there is a lot going on. Next slide, please. Yeah, thank you. 2021, we're initiating four phase III programs in IgA nephropathy, C3 glomerulopathy, and paroxysmal nocturnal hemoglobinuria. We'll give you a detailed update on these three exciting programs. We're also initiating a phase III program in atypical hemolytic uremic syndrome later this year based on the importance of the alternative pathway in the disease pathophysiology and the phase II data that we've generated in other indications. Four additional indications are either entering or are in phase II development. idiopathic membranous nephropathy, lupus nephritis, idiopathic thrombocytopenic purpura, and cold agglutinin disease. The scientific rationale and summary plans are included in the deck for your reference. As you can see from the graphic on this slide, we expect the earliest filing to be in PNH in early 2023, with indication expansions into C3G and IgAN later that year. Next slide, please. First, let's talk about IgAN. IgAN is the most common cause of primary glomerulonephritis, affecting approximately 1.3 million people in major markets. I want to talk a bit about a patient that we had a chance to meet with recently because her story really crystallizes many of the characteristics of IgAN and its impact on patients' lives. This woman was diagnosed with IgAN when she was a teenager, and her presenting symptoms were quite subtle, like fatigue, flu-like symptoms, and malaise. At her doctor's office, she was found to have protein excretion in the urine, which in IgAN reflects ongoing kidney damage. It took about six months to finally make the diagnosis. In her case, the proteinuria was difficult to control, therefore the kidney was experiencing ongoing damage, even with recurring rounds of steroids, which made her feel absolutely horrible. Like 30% of IgAN patients with persistent proteinuria, she progressed to end-stage kidney disease within a few years, required dialysis, and needed a kidney transplant. Just consider that this person at her young age, consider the toll that this took on her life. Because of stories like these, health authorities see the need for treatment options for patients with IgAN. They recognize the strong relationship between proteinuria and disease progression, as we show you on the figure of this slide. Therefore, they consider accelerated approval of new treatments that demonstrate proteinuria reduction in well-controlled trials. Next slide, please. Our phase II IgAN trial was designed to be data-rich and to accelerate development employing adaptive dose ranging of twice-daily iptacopan to evaluate its effect on urinary protein excretion. In the first part of the trial, patients with biopsy-confirmed IgAN were randomized to one of three active doses or placebo and treated for three months. After part 1 of the trial, the interim data were evaluated for an efficacy signal, and the sample size and dose levels could be adjusted then in part 2. In the second part of the trial, patients were randomized to one of four active doses or placebo, again for three months. After patients in part 2 reached the 90-day time point, the data from both parts of the trial were pooled by dose level. Importantly, operationally, our phase III program was triggered by the interim analysis that we performed after part 1 of the trial, where we saw a reassuring trend of an improvement in urinary protein excretion. This allowed us to move seamlessly into phase III without a delay once the 90-day data were available from the full study, and we could select the final dose for phase III. Next slide, please. Here are the data from the phase II study. At the day 90 interim analysis, iptacopan resulted in a robust reduction of proteinuria and a compelling dose response. There was a 23% reduction in urinary protein excretion compared to placebo at the 200-milligram dose at day 90. It's important if you're looking across studies with other molecules, that the day 90 time point is a bit earlier than one typically looks at efficacy within phase III studies. As I mentioned earlier, proteinuria reduction can be the basis of an accelerated approval, but not surprisingly, there also has to be a signal supporting stabilization of renal function to go along with it. This is indeed what we saw in this phase II trial, a trend of stabilization of glomerular filtration rate, which is the measure of kidney function. Next slide, please. There were additional important data coming from this phase II study. Here, you see the effect of iptacopan on activation of the alternative pathway. The wide range of doses that we explored in this phase II study gave us a strong understanding of the pharmacodynamics and the potentially effective dose range of iptacopan in IgAN, which could also be used to model the expected effective doses in other indications. The 200-milligram dose of iptacopan, as you can see on this graph, resulted in a rapid, robust, and sustained suppression of the alternative pathway, which is especially important when we talk about diseases like PNH, where persistent complement suppression is critical to prevent hemolysis. Remember this figure when we get to the PNH section. Next slide, please. As I mentioned, we already initiated the phase III APPLAUSE-IgAN study, which is essentially a larger version of the phase II trial that we've already conducted, and focuses on the 200-milligram iptacopan dose. As agreed with health authorities, we'll do an interim analysis when about 250 patients reach the nine-month time point and evaluate the effects of iptacopan on protein excretion. This, as I mentioned, could be the basis of an accelerated approval. The study will continue in order to confirm the benefit of iptacopan on preservation of renal function by looking at the eGFR slope over the 2-year timeframe. In all, 450 patients will be enrolled and randomized 1-to-1 to placebo or iptacopan, both arms including usual care with maximally tolerated ACE or ARBs. Importantly, the trial was designed to deliver positive data on both UPCR reduction at nine months and on eGFR stabilization at 2 years. We expect the 9-month UPCR data to be available in 2023 and the final results from APPLAUSE-IgAN to be available in 2025. Next slide, please. For this, in summary on IgAN, a lot to look forward to here. Our strong phase II data give us a lot of confidence that the phase III program will deliver a medicine for patients with this difficult-to-treat disease, where better options are really needed to help patients ward off the specter of dialysis. Next slide, please. Shifting gears a bit, we're going to talk about a different kidney disease, C3 glomerulopathy or C3G, which is another devastating, but thankfully rarer kidney disorder that often affects adolescents and young adults, and also leads to dialysis in many affected people. As you can see on the figure on this slide, about 50% of patients develop renal failure within 10 years of diagnosis. Think about the fact that this disease affects adolescents. You're talking about teenagers or people in their early 20s who, after 10 years, have developed renal failure, have to undergo dialysis in preparation for renal transplant. As the name implies, the pathophysiology of C3G is directly related to overactivation of the complement system, resulting in consumption of C3 and deposition of these C3 fragments in the glomeruli. This results in progressive kidney damage and to end-stage kidney disease in many patients. Because it's a systemic disease, the real tragedy, the additional tragedy, is that C3G will often recur in transplanted kidneys. Iptacopan directly intervenes at a key point of the disease pathophysiology in C3G. It's expected that Factor B inhibition will quell the abnormal consumption of C3, and for that reason, iptacopan has the potential to be disease modifying and prevent the need for dialysis or transplant for these patients. Next slide, please. The phase II trial in C3G was an open-label study to evaluate the efficacy of iptacopan in patients with native kidneys or transplanted kidneys. In patients with native kidneys, the key measure was change from baseline and urinary protein excretion at week 12. In patients with transplanted kidneys, C3 deposition by histology will be assessed at week 12. We also evaluated other effects, including biomarkers and GFR. Next slide, please. We're on slide 16. As you can see from these data, the phase II trial demonstrated a profound reduction in urinary protein excretion in patients with native kidneys. This result might not surprise you because, as I just told you, iptacopan targets the disease process at its root. As we all know, pathophysiology is often complex. A 49% reduction in urinary protein excretion after 12 weeks is truly a remarkable result. Next slide, please. Slide 17. Importantly, even in this modest-sized phase II trial, we were able to gain confidence on the impact of iptacopan on kidney function. While the understanding of C3G has advanced rapidly, the relationship between urinary protein excretion reduction and GFR maintenance is less well-validated in C3G than it is in IgAN. The fact that eGFR appears to stabilize in patients after 12 weeks of iptacopan treatment is incredibly promising for these patients. We show you on this graph is that the patients in the phase II trial with C3G have a progressive decline in their renal function over a 2-year timeframe prior to receiving iptacopan. After 12 weeks of iptacopan treatment, these patients appear to experience a stabilization of their renal function. Slide 18, please. Building on this phase II experience and these very promising data, in the phase III C3G study, we'll enroll patients with native kidneys and persistent proteinuria of greater than or equal to 1 gram per day. The primary endpoint will be reduction in urinary protein excretion comparing iptacopan to placebo on top of usual care. This primary endpoint will be supported by secondary measures like preservation of GFR and pharmacodynamic markers. After the primary analysis at six months, patients will receive open-label treatment for an additional six months and then may enroll into a longer-term extension trial. If positive, these data will support global registration in C3G. Slide 19, please. In summary, iptacopan promises to be the first oral therapy targeting the primary disease pathophysiology in C3G. The phase II data show profound reductions in UPCR and signs of stabilization of renal function, and these give us confidence that this promise will be delivered for patients in need of better options. Next slide, please. Shifting gears a bit now to hematology. In paroxysmal nocturnal hemoglobinuria or PNH, iptacopan again has the potential to transform the treatment paradigm by being the first oral monotherapy to treat this life-threatening disease. Anti-C5 agents are the current standard of care for patients with PNH and were an important advance in the care of these patients. Unfortunately, about 40% of PNH patients have residual anemia because blocking the terminal complement cascade still allows red blood cells to be coated by C3 fragments, which leads to their destruction by macrophages, primarily in the spleen and liver. This is what's referred to as extravascular hemolysis. By inhibiting Factor B, iptacopan will inhibit C3 fragment generation and reduce both intravascular hemolysis and extravascular hemolysis. Ultimately, this is expected to reduce the need for blood transfusions in patients who have persistent anemia on a C5 inhibitor or in those individuals who've never received a C5 inhibitor. We've already presented the phase II data showing that iptacopan can improve hematologic outcomes in patients receiving anti-C5 therapy with residual hemolysis. Today, we'll share data from patients naive to anti-C5 therapy. These data show iptacopan's promising effect as a monotherapy. Next slide, please. The phase II design is summarized here. The phase II study was an open-label trial enrolling patients naive to anti-C5 therapy. Patients were randomized to one of two dosing groups, as shown in this slide, either escalating from 25 milligrams to 100 milligrams or from 50 milligrams to 200 milligrams. Lactate dehydrogenase or LDH levels were compared to baseline after 12 weeks of treatment. LDH is a marker of red cell destruction. Other measures such as hemoglobin concentration and the need for transfusion were also captured to better understand the clinical profile and the phase III trial design. Slide 22, please. These data were recently presented at the EHA meeting. Two graphs represent the two dosing cohorts. On the top, the 25 mg BID-100 mg BID cohort, and on the bottom, the 50 mg BID-200 mg BID cohort. As you can see, iptacopan treatment resulted in a profound, rapid, and sustained reduction in LDH, indicating that iptacopan effectively reduced hemolysis in these patients. The efficacy was most promising at the 200 mg dose level as you can see on the lower graph. Slide 23, please. In addition, patients also experienced a clinically meaningful increase in hemoglobin concentration, almost all patients remained transfusion-free. Even from a small open-label trial, we see that iptacopan could be an important option for patients who currently are treated with parenteral therapies that leave some of the disease smoldering. Slide 24, please. With these results in hand, we've initiated an open-label phase III study enrolling PNH patients with residual anemia despite being on stable dose of anti-C5 therapy. Patients will be randomized to continue anti-C5 treatment or to switch to iptacopan after a short interval of overlap. Those endpoints are the proportion of patients with greater than equal 2 gram per deciliter increase in their hemoglobin without a need for a red cell transfusion, and second, the proportion of patients achieving a hemoglobin concentration of greater than or equal to 12 grams per deciliter without the need of a transfusion. These endpoints will be analyzed to demonstrate superiority of iptacopan compared to an anti-C5. Based on the phase II data at 12 weeks in both C5-experienced and C5-naive patients, we're confident that this trial will show that iptacopan could become an effective oral monotherapy for PNH. Slide 25, please. In summary, in PNH, as in IgAN and C3G, iptacopan's unique oral targeted profile makes it a potential game changer in the treatment of this rare hemolytic disorder with significant remaining unmet patient need. I'll refer now on the next slide to a variety of additional indications. We've just summarized the expanding list of opportunities here that we're pursuing with iptacopan, the ever-growing list that the team continues to evaluate where we could deliver a real important new medicine for patients. In each of these cases, there are data suggesting that the alternative pathway plays an important role in the disease pathophysiology and therefore that Factor B inhibition may have beneficial effects. As we move phase III rapidly forward in IgAN, C3G, PNH, and aHUS, we're building a pipeline out of this groundbreaking medicine. Now I'll move to slide 31. I'm going to hand off to Rod, to describe our preparations to deliver this transformative treatment to patients who really need it. Thanks, Dave. As we look at slide 31, Dave already highlighted the parallel development that we have with an industry-leading eight programs. What I want to highlight in particular on the left-hand side of slide 31 is the fact that while these rare or ultra-rare diseases may be smaller in nature individually, collectively in the U.S. alone, they add up to more than 400,000 patients. The unmet need is significant, and the total population and potential for iptacopan is substantial, and that's why we see it as a global multi-blockbuster potential, if approved. If you turn on to slide 32, I just want to take a moment to highlight some of the work that we're doing and the effort we're putting towards our pre-launch, three years prior to launch. What we've learned from our experience in launching medicines. In particular, I want to highlight three things that are critical success factors as we launch into these specialty areas. The first is clearly to establish for nephrologists or hematologists easy access of prescribing early in the treatment process iptacopan. The second key factor will be to make and ensure that the onboarding process for patients is as easy and seamless as possible. The third, of course, is to ensure that the healthcare system, that we're delivering value. For that, they expect a robust clinical and real-world evidence package that iptacopan can deliver the outcomes in their patients in the real world. We've engaged with payers very early in this process to ensure that they see the value of an early initiation of iptacopan in patients, so that they can maximize what the benefit, delay that progression of very costly and significant quality of life burden on patients by initiating iptacopan early in the disease course, and the value that can add to the patients and to their system. We've also, of course, been working with the scientific community, whether that's our established footprint in hematology or building up our scientific presence in nephrology, it's clear that these two specialty groups are eager for innovative medicines that are truly disease-modifying and can change the course and the nature of these rare and ultra-rare diseases that have a significant impact on patients' lives. If you turn onto slide 33. Building on the success factors from how we're preparing for launch, iptacopan clearly has the potential to address significant unmet needs in both hematologic and renal disorders. Based on the disease-modifying potential, we believe that iptacopan has the potential to extend dialysis-free life in these renal disorders that David Soergel described, as well as become the potential standard of care for PNH in a single pill. Also having a very safe and tolerable profile based on its targeted mechanism of action relative to the other therapies in these treatment areas. Which may be particularly welcome for the younger patients like David Soergel talked about, that are looking to get back control of their lives and know that their disease is under control. Our last slide on slide 34, I just want to bring it all to a close and summarize that iptacopan is a pipeline in a pill and addresses a number of very rare or ultra-rare and severe conditions for patients that collectively add up to a very large number in the U.S. alone, let alone globally. The data so far that we're seeing, we're incredibly impressed and pleased with what we've seen in the four phase II studies that have read out and an industry-leading eight indications that we'll pursue in parallel that are either in phase II or phase III. We expect the first filings in 2023, and we're investing early in the launch because based on the significant unmet need, the compelling science that we've already shared and we continue to expect to see in the phase III programs, we see multibillion-dollar potential for this molecule, and ultimately a significant impact on the lives of patients living with renal and hematologic disorders. Samir, with that, I want to hand it back over to you. Thank you very much, Rod. Operator, we're ready for questions, and I think we've got quite a number of questions already lined up. If we could begin with the first question, please, operator. Thank you. The first question comes from the line of Laura Sutcliffe from UBS. Please ask your question. Your line is now open. Hello. Thank you. First question is on the APPLAUSE-IgAN trial, please. Do you need to demonstrate superiority on the eGFR endpoints or further down the line in order to convert to a full approval, or would non-inferiority do for that later endpoint? Then just a couple on the new indications that you're adding. Could you maybe speak to the level of unmet need that you think there is in ITP, perhaps the merits of Factor B inhibition versus BTK, SYK, and so forth? Then, finally, what do you think the appropriate comparator or comparators for your lupus nephritis trial? Thanks. Okay, great. I think all the questions will be for Dave. The first question was, do we need to demonstrate superiority in renal function as measured by eGFR for full approval? The second question relates to the unmet need in ITP, and the third one is the comparator for lupus nephritis. Dave? Yeah. Great. Thanks a lot. Great questions. Thanks, Laura. With respect to APPLAUSE-IgAN, let's start there. I mean, we've got wide-ranging questions here, so we'll start with IgAN. Your question was whether we have to show superiority on eGFR slope at the end of the 2-year period. I think the first thing to recognize is that proteinuria reduction is very strongly linked to preservation of renal function in IgAN. That's why the FDA and other health authorities recognize proteinuria reduction as a potential early approval time point. Indeed, you also want to be able to show that you're improving renal outcomes for these patients and you're maintaining renal function. The key comparator, though, is placebo, and what you're looking at is an improvement in the decline in eGFR slope, right? Normally, patients who have persistent proteinuria their renal function will decline over a particular time frame with a particular rate. What you want to show in your phase III trial at that two-year time point is that you're able to preserve renal function while also improving proteinuria. As I mentioned during the presentation, we've made statistical assumptions around the historical decline in renal function, given persistent proteinuria in IgAN, and based on our effect size that we've seen in the phase II study, we fully expect to be able to show that preservation of renal function at that two-year time point. Second question. Yeah, ITP. Yeah. We didn't talk a lot, obviously, about the scientific rationale for the various indications that we're approaching. Let me give you a bit of a framework for how we're looking at iptacopan and its expanding list of indications. There are certain indications where the alternative pathway is clearly a bad actor in the disease, and I think C3G is a great example of that. We know that the alternative complement pathway plays a major role with respect to amplification of the consumption of C3. There's a very strong scientific rationale for alternative complement pathway, disease pathophysiology, and therefore iptacopan. In other disease areas, the complement system plays a role in the disease process. The relative contribution of the alternative pathway versus the classical pathway, for example, there might be some shared responsibility. This is why we're conducting a phase II trial, to be able to evaluate the effect size and the efficacy of iptacopan in a smaller study before we move into phase III. Whereas in a disease like IgAN, again, where the pathophysiology is directly linked toward damaging of endothelial cells from accumulation of C3 on the endothelium, we can go right into a phase III program. I think the answer is that about a third to a half of patients with ITP, there's evidence that complement plays an important role. The extent to which the alternative pathway is important, that will be borne out by our phase II trial. Your last question was LN, right? How we see iptacopan in lupus nephritis. Again, coming back to that framework that I just talked about, clearly complement plays an important role in the ongoing kidney damage and inflammation in lupus nephritis. The question is, how much of a contributor it is. The way we think about iptacopan in lupus nephritis is as a way of being able to quell those inflammatory mediators that trigger recurrent worsening of renal function in patients with LN. Maybe the way to think about it is as more of an induction therapy, trying to avoid the use of steroids and then, having patients be on a different maintenance therapy, for example. Again, this is why we're conducting a phase II study to really see what the efficacy of iptacopan is in this patient population, and then to best position it in phase III for success. David, I think the question from Laura was, what sort of comparator would you be thinking of for the lupus nephritis indication? Yeah. It's a good question, and we're in the process of designing that phase II program now. The comparator right now would be steroids or the typical induction therapies that one uses in patients with a lupus nephritis flare. What we'll try to do is show that we can avoid the use of steroids in these patients or minimize the use of steroids in these patients, by offering a different way of controlling the inflammatory process in the kidney. Great. Thank you. Operator, next question, please. Thank you. Our next question comes from the line of Matthew Weston from Credit Suisse. Please ask your question. Your line is now open. Thank you very much. Two questions, please. The first is a very fundamental one just about the pathway and why do you think Novartis is the only company pursuing factor B? On slide 6, you very clearly set out the competitive environment, and it's just very notable that many other companies went after factor B. I'm just curious if there's something around the biology, that meant that factor B was seen as more challenging or why it appealed to you. A second question, I guess, at the other end of the spectrum around pricing. I realize it's very early for a drug that's only going to read out fileable data in 2023. You've set out the idea of a pipeline in a pill, and you've given us an extremely broad range of target indications with very different price points in the market, from ultra-rare to more mainstream. I'd just be very interested, given you've already set out your commercial strategy as starting, how you see that you're going to try and position it in that very broad setup, because it has a huge implication for the peak sales potential. Thank you. Thank you very much, Matthew. The first question of Factor B versus Factor D and the rationale for iptacopan in the many indications is for you, Dave, and the second question clearly for Rod. The first one, Dave? Clearly for Rod. Yeah. It's a great question, and to be honest with you, I can't answer the question with respect to other pharma companies and why they're not pursuing this great target. That's up for them to decide, I suppose. As Samir just alluded to, there are a couple of programs targeting Factor D, which is a regulatory component of Factor B. They work very much in tandem. I think, with respect to iptacopan, what we see is a highly potent orally bioavailable compound that our chemists at NIBR were able to come up with. I think we should just take credit for that. There's also, if I remember correctly, an antisense oligo that's targeting Factor B. So it's not like there haven't been attempts at this target in the past. There have been. My understanding, a very rudimentary understanding of the chemistry and discovery process, for a factor for this compound is that it's a challenging target to drug. In this case, we happen to have a great molecule, so we're looking forward to progressing it. Great. Thank you. Rod? Thank you for the question, and you're right. Obviously, it's too early to talk about pricing, and we haven't seen the phase III data yet from the programs. Maybe I share just the way that we're thinking about it and the degree of confidence that we have in blockbuster potential and potentially multibillion-dollar blockbuster potential, depending on the outcome of the programs and getting approved and all. I see, we've got that breadth of indications overall that we've got to consider, and we've considered all levels of sequencing in that indication. I think rest assured, it'll be value-based pricing, across the breadth, recognizing that we've got both rare and ultra-rare diseases. We've looked at every scenario, but ultimately it's going to have to wait until we see the final readout of phase III programs and the progression of the other phase II programs. Thank you, Rod. Next question, please. Thank you. The next question comes from the line of Graham Parry from Bank of America. Please ask your question. Great. Thanks for taking my question. Firstly, on IgAN and the phase II data, just could you talk to the clinical relevance of a 23% reduction in proteinuria and how comfortable you'd feel with getting approval on the back of something similar being replicated in phase III? The reason for the question is, if you look at steroid treatment, I think you see closer to 50% reductions in proteinuria, but possibly after longer periods of time. There's a couple of more recent studies in STOP-IgAN in the TESTING trial, showed that that proteinuria benefit then wasn't associated with renal outcomes. Also in terms of positioning in the marketplace, how are you thinking about this? Is it a post-steroid therapy or is it just post-RAS cascade inhibitor therapy? The last question, how do you compare this to other products in development in IgAN? There's a phase III targeted steroid, for example, that is also looking for approval and data in the same sort of timeframe that you are. Great. Thank you very much, Graham. If I can just boil those out. The first question, which Graham asked, all three, I suppose they're going to be for Dave again, was on IgAN, and I think he's questioning the 23% at three months versus what appears to be higher with other therapies, albeit with a longer duration of time. The second one was respect to positioning versus the RAS cascade before or after or together with. The third one was compared, again, for the IgAN, versus other therapies which are being developed. In a way, I think what Graham's after is clinically, why are we so excited for IgAN, Dave? Right. Why are we so excited about IgAN? It's a really good question, Graham, and I'm glad you asked it. As I said during the presentation, it's really important to compare apples to apples when you're looking at IgA nephropathy trials. The way that these trials are conducted, in order to make a comparison across them, you have to make sure that background therapy, first of all, is maximized. Right? This is a really important aspect where in some studies, maybe RAS blockade was not optimized in advance, and that makes it very difficult to compare across trials. It's always difficult to compare across trials, of course. Second important thing, as Samir just alluded to, is that we're looking at a 3-month effect in this phase II trial. A 23% reduction in urinary protein excretion in a well-designed phase II study is a very strong result at that early time point. If you look back at the natural history papers in IgAN, this 23% reduction would correspond to about a 35% reduction in renal outcomes. It's a substantial effect. Now, of course, that 23% that we saw in our phase II study is a point estimate, and there's the possibility that the effect is larger or could be smaller, depending on the actual effect over time. I think that's an important thing, and obviously, that's why we run the phase III trial. The 9-month time point is recognized as the registration for accelerated approval by health authorities because of this strong relationship between proteinuria reduction and renal outcomes. As I've said, we've discussed the design of our trial of APPLAUSE-IgAN with health authorities and have their buy-in to how we're conducting the trial and the effect size that we're powered to. That gives us a lot of confidence moving into this phase III study and really deliver an important therapy to patients. I think your second question had to do with RAS blockade, Samir. Am I right? Yeah. Positioning vis-à-vis RAS blockade before, after. Whatever. Yeah. Yeah, steroids as well. Yeah. Well, first of all, RAS blockade is the standard of care, right? All patients should be on maximally tolerated renin-angiotensin system blockade. There's plenty of evidence indicating that that's important to reduce proteinuria and improve renal outcomes in patients. That's our expectation and how we've designed our phase III study. With respect to steroids, the whole idea, as I shared in my vignette during the presentation, patients hate steroids. They really are not very well-tolerated. Honestly, avoiding steroid use is a very important clinical goal for a lot of these patients. Our expectation is that if we're better able to control the disease with iptacopan, patients won't need to go on steroids and have to endure all of the challenges that come along with steroid therapy. That's the second point. The third point? Compared with other phase III targeted therapies, do you want to comment on what others are developing in IgAN? Yeah. I think there's a broad-based approach. You can think about them with respect to hemodynamic approaches, drugs that work like renin-angiotensin system inhibitors like ACEis or ARBs, but maybe provide some additional improvement in proteinuria. Anti-inflammatory types of approaches like iptacopan or more broad-based steroid use. Again, our expectation based on iptacopan's efficacy and tolerability profile is that it's going to be a great option for patients who have persistent proteinuria despite being on good hemodynamic therapy like a RAS inhibitor. Great. Thank you. Operator, if you could have the next question, please. Thank you. The next question comes from the line of Emmanuel Papadakis from Deutsche Bank. Please ask your question. Your line is now open. Oh, thanks for taking the question. Maybe kick off with just the relative positioning versus the C3 efforts. We've seen them now through in PNH for the relatively broad label and deep juice, fairly + 90 data. It sounds like the differentiation you're expecting really is more on the formulation rather than the clinical side of things, but please correct me if that's wrong. Just follow-up with just off IgAN. It sounds like you're saying we shouldn't cross-read too much from that failed immunosuppressive approach because it was to do with the design of study and background therapies. Do I understand that correctly? Then just final question on safety profile for the 200 mg. If this is going to be a longer-term chronic therapy. Seen some safety disclosures, it seems relatively clean so far, but is there anything you're watching out for, particularly in the pivotal studies that we should be thinking about as potential points to watch? Thank you. Thank you very much, Emmanuel. Sorry, David, you're on the hook again. There's three questions. The first one was differentiation in the PNH indication, noting the results from the C3. Is it just because of the formulation being oral? I'm sure you can answer that one. The second one was on IgAN. Any read-through from the failed immunosuppressive study, and the third one was how confident are you with respect to the safety and tolerability of the 200 milligram dose long-term? Great questions, Emmanuel. Thanks. PNH, if you think about PNH generally and how one could approach it from a complement system standpoint, as I mentioned, the C5 inhibitors target a relatively distal part of the complement pathway, and they leave a substantial part of the complement pathway sort of still smoldering, right, as I said during the presentation. This is what leads to extravascular hemolysis and where an alternative complement pathway inhibitor could show a benefit. The C3-targeted therapy also can reduce that C3 consumption and extravascular hemolysis, which is what they showed. The problem is that the further you get down towards the distal part of the pathway and the membrane attack complex generation process, the more you open yourself up to other effects, potential effects, for example, encapsulated organism infections and so forth. With iptacopan, what we believe is that we can actually address, well, what we've shown is that we can address this extravascular hemolysis component while leaving the other parts of the complement cascade open, which the C3-targeted therapy wouldn't do. This would confer a theoretical safety advantage in that patients would still be able to fight off encapsulated organisms more effectively. That's the first important thing. I think from a pharmacodynamic standpoint, and there's an important differentiator beyond the formulation, but I also do think the formulation is a very important differentiator as well. The C3-targeted therapy, if I understand correctly, is a twice-weekly subcutaneous administration of about 1 gram per day, and that comes along with other side effects. We believe that iptacopan's safety and tolerability profile, as we've seen it to date, in admittedly relatively small studies, is very compelling when you compare it to what's been seen with that agent. I guess then drafting directly to the question around safety and tolerability, I made the comment with respect to the specificity of targeting and the potential safety advantage around encapsulated organisms. We are still in phase II development, and we're expanding our patient numbers substantially. Our expectation is based on what we've seen so far, that this will be a well-tolerated medicine. We, of course, have to run the trials. Okay. Next question please, operator. Thank you. The next question comes from the line of Sarita Kapila from Morgan Stanley. Please ask your question. Your line is now open. Hello, Sarita from Morgan Stanley. Thanks for taking my question. I have two, please. The first is on the potential label. Some of your competitors come with a black box warning for meningococcal infection. Is this something you think you can differentiate on, given the potential lower infection risk seen through targeting the alternative complement pathway? The second is there any rationale to developing iptacopan in neurology indication? Could you branch out into myasthenia gravis or NMO, for example? Thank you. Great. Thank you very much, Sarita, and both questions, again, for Dave. One is possibility of avoiding a black box on things like meningococcal infection, and the second one is additional indications even beyond the eight which you've listed, particularly in the neuroscience area with NMO and myasthenia gravis. Yep. Yeah. Good question. The first one, it's too early to tell. We don't know ultimately what the label's going to look like until we have those discussions with the agency. As I said, there is a theoretical advantage from a mechanistic standpoint around preservation of the classical pathway and lectin pathway and targeting only the alternative pathway. What it takes to demonstrate that and avoid the class black box label, I think, will be a matter of discussion with health authorities. Your second question around neurology indications, we have eight indications now, and I think there are more that we're continuing to evaluate. What I tried to do is give you a bit of a framework of how we think about additional indications from a scientific standpoint, and the relative evidence that the alternative pathway is a fundamental part of the disease process versus the classical pathway, for example. Beyond neurology, we look at a whole wide variety of potential indications and make that assessment. Then, we'll propose additional indications as we move forward. I guess, to answer your question directly, in principle, there's no reason why one could not approach those diseases with this molecule. Thank you very much, Soergel and Sarita Kapila. Operator, next question, please. Thank you. The next question comes from the line of Kerry Holford from Berenberg. Thank you very much. Just a couple left from me, please. Just on the formulation, just curious to see whether you are working on a once-a-day formulation rather than the current twice-a-day that you're moving forward with, and that's an element of convenience you could offer in future. Secondly, I believe you were targeting the start of the phase III by the middle of the year, and it seems that has slipped slightly into the second half. Any specific reasons for that delay? Thank you very much. Kerry, on your second question, which indication were you referring to, please? I missed it. Sure. aHUS, AUD. Okay. Perhaps with the second question first for Dave, and the first question on the value of once a day versus twice a day, I'll give back to Rod. The second question first for Dave on aHUS, just from a timing perspective. I think the timing of the start of the phase III study has undergone some evolution as we've come out of COVID and had further refinements of the study protocol and approach through health authority interactions. That's the shift. As we've been talking about, this is a relatively early-stage program, and we're going directly into phase III, without a phase II study. Just a little bit of shift, I think, in planning. With respect to once a day, I can talk from a technical standpoint first. From a once-a-day standpoint, there isn't any reason why one could not formulate iptacopan into a once a day, and then the question would be, is it clinically important then to do that? I think, most importantly, in general, twice-a-day oral therapy compared to subcutaneous or intravenous injection, which is what most of the other approaches are, I think is attractive to start with. Great. Do you have anything to add on that, Rod? Twice a day oral versus once a day oral? No, David Soergel really nailed it. In our engagements with the nephrologist community, the advancement and convenience of an oral therapy relative to the injectables is a significant one, obviously. The package that David Soergel's already alluded to, when you have an oral therapy that's not effective and safe and tolerable, the twice a day versus once a day isn't really a material differentiation in this case, given the advancement they're already seeing. Great. Thank you. Thank you, Kerry, as well. Next question, please, operator. Thank you. The next question comes from the line of Simon Baker from Redburn. Please ask your question. Your line is now open. Thanks for taking my questions. Two, just going back to Matthew's earlier question. Firstly, given the range of age of onset between and within these various indications, could you give us an idea of the payer mix in the U.S. across this totality of diseases that you're pursuing? On the Factor B versus D, I wonder if you could remind us why you terminated your own Factor D program. Final question, do you have any data at this stage to show whether the efficacy is consistent irrespective of Factor B mutation? Thanks so much. Okay, great. If I just go through the questions, there's two for David Soergel and one for Rod Wooten. Rod Wooten, I'll come back to you later with the payer mix, but the first two questions for David Soergel. Is there some relationship between efficacy and Factor B mutation? The second question from Simon Baker was, "Why did we terminate our own Factor D?" David Soergel first. Maybe I'll answer the second question first, with respect to the Factor D compound. I think that compound, if I remember correctly, that was quite early. I think LNP023, which became iptacopan, its development and discovery process accelerated and overtook that program. It became a question of what would the differentiation be between the two targets and, the fact of the matter is that Factor B inhibition is going to give you the alternative complement pathway inhibition that you're looking for in most of these diseases. Factor D inhibition wouldn't really add that much to it. I think that's the answer. It's sort of a partial answer to that question. I'm not aware of any data we have on Factor B mutations and iptacopan efficacy, so I can't answer that question. I'm sorry. Okay. Thanks, Dave. Rod, on the potential payer mix, knowing the different ages of the patients in the U.S. Yeah, Graham, there's differences, of course, among the eight programs. Broadly speaking, you're correct that because this affects a younger population, it skews much more to the commercial side of the payer mix, which obviously also has implications on our strategy. As I said earlier in our launch preparation, a key element of the onboarding and ease of physician prescribing, but it will be largely a commercial population. Thank you. Thanks. Operator, we're ready for the next question, please. Thank you. The next question comes from the line of Richard Vosser from JP Morgan. Please ask your question. Your line is now open. Hi, thanks for taking my question. Couple of questions, please. Firstly, just back to the safety profile, there was a little bit of a headache signal or an increase in headache and one discontinuation. How are you looking to mitigate this in phase III? Maybe what could be behind this safety signal? Second question, just on the APPOINT-PNH PNH study, in the naive patients, notice it's a single arm trial. I realize you're going head-to-head in refractory patients, but why not go head-to-head as competitors are versus Soliris in naive patients? Maybe just one final question, just thinking about the level of reduction of protein in a year in IgA that is acceptable for regulators, is that similar to the level that you've seen in phase II, 23%, or do you need sort of more than that? Thanks very much. Thank you very much, Richard. I think, three sets of questions. They're all for Dave, I'm afraid. The first one is perhaps to go over again this link between the level of proteinuria reduction at three months, longer time period, et cetera, and is 23% sufficient or not? The second question was, competitors are doing head-to-head versus PNH in naive patients, whereas we're doing it in refractory patients. Perhaps just comment on that. His first question was, I think Richard characterized it as a signal, but it was one case of headache. Perhaps you can talk a little bit more about it as to what the potential cause might be and mitigating strategies, et cetera, Dave. Mm-hmm. Yep. Great. Thanks. Thanks, Richard, for the questions. I'll go in the order that you presented them, and talk first about the case of headache, and how we think about the tolerability profile in general in these indications. The first thing I'd say is that we're still in phase II and continuing to gather data on the tolerability of the compound. In general, this drug has been very well tolerated. We did have the case that you're talking about, and we'll continue, of course, to evaluate the tolerability profile as we move forward. There's no mechanistic rationale for why this would have happened, why an individual would have had a headache in a study. As you're aware, headaches are relatively common in clinical trials. We'll have to see how that pans out over time. Your second question had to do with the open label study in naive patients versus a head-to-head versus Soliris. The fact of the matter is that the pathophysiology of PNH is fairly well understood, and the role of the complement system is also well understood. Data, as we've already shown in phase II in naive patients, and head-to-head data in refractory patients on C5s is a compelling data set. I mean, it shows you that iptacopan can be effective at reducing hemolysis and potentially improving anemia in patients who have PNH, whether they've been on a C5 or whether they've never been on a C5 inhibitor. The need for a head-to-head trial versus Soliris in the naive population and in the refractory population, I think one could argue that you have the data you need from either the one or the other. That's how we've approached it. I think it's also important to recognize that the metrics that we look at, the endpoints that we look at in PNH, and actually in many of the indications we've talked about today, are objective measures, right? They're lab tests that don't rely on investigator interpretation or extensive data analysis. You can see a patient's hemoglobin go up through serial lab tests. Likewise, you can see proteinuria reduce in patients in a relatively straightforward manner. The objective nature of the endpoints, I think, and the totality of the data and the pathophysiology of the disease, I think are the key determinants of the data set that we believe is going to be compelling in PNH. Your next question had to do with the effect size that we've seen in phase II and how that would apply to a phase III registrable endpoint. As I said, we've had discussions with health authorities already on our trial design and our phase II data, obviously. We've designed the study to be registration enabling at that nine-month time point, and then to continue through to the two-year time point on eGFR reduction, as we said earlier. To my way of thinking as a clinician, a 23% reduction in proteinuria, remember at three months, so it's an early time point to be looking compared to that nine-month time point that we'll be looking at in phase III, where you can continue to see efficacy and improvement in patients' proteinuria, by the way. That 23% reduction, if we just recapitulate that at nine months, is a 35% improvement in renal outcomes. It translates to a 35% reduction in renal outcomes. Yes, that's clinically important. What we've discussed with health authorities is our trial design and how we're designing the study and sizing the trial, and they've agreed to our plans moving forward. Fantastic. Thank you, David Soergel. Operator, we're ready for our next question, please. Thank you. The next question comes from the line of Steve Scala from Cowen. Please ask your question. Your line is now open. Well, thank you very much. I have several questions. First, regarding IgAN. Just to be clear, what is the longest duration the patients in the phase II trial have been treated with LNP023? How have their uPCR reductions changed with continued treatment? That's the first question. Second question is, slide 10, footnote two notes that the analysis was adjusted for baseline uPCR and ancestry. What adjustments were made for ancestry? If you hadn't made those adjustments, what would the P value have been? That's the second question. Third question. Back in 2019, I believe the first filing for any indication was to have been in 2022. Now it's 2023. I'm wondering what the push-out was due to. Is that also COVID? Lastly, if you'd like to tell us about IP and the duration, that would be great. Thank you so much. Great. Four questions, Steve, and good morning. Very good that you've woken up early enough to go through the slides, including the footnote, which is fantastic. I'm impressed. I think you need a gold star for that, Steve. Four sets of questions. Regarding the footnote, it was on slide 10, Dave, and related to adjustments made also for ancestry, and would we have got a similar result without that adjustment? That was one of the questions. The second question was a bit more straightforward, I guess, which we could talk about, is pushing out the first registration packages from 2022 to 2023. The third one for Dave is IgAN again. His question was, would the proteinuria suppression have been maintained with longer duration? The question which Steve was asking was, what's the longest follow-up? The last question is for Rod on the IP and exclusivity protection. Perhaps we start with Rod first anyway, and then move back to Dave. Rod, IP protection. Yes, Steve, thanks for the question. The exclusivity planning is through the time period of 2034, but that doesn't include potential for patent term extensions. 2034. Great. Thank you. Dave, I think you might want to start with a footnote. Yeah. Honestly, Steve, I don't know the answer to your question. What we've presented publicly and released is what we've presented during the discussion today, so I can't really comment further beyond what we've already shown. Similarly, we've talked about UPCR reduction at that three months time point, at day 90, in the total phase II trial. Those data were just presented. Most patients in that trial now have their final data, and we expect the final data to actually come out from that trial in the next couple of months. The relative duration of follow-up in the phase II study is going to be more modest compared to that phase III trial, where we're going to be looking at nine months UPCR and 2-year time points with respect to creatinine stabilization. I think that the phase II study is extremely promising because we're not only seeing this robust reduction in UPCR, but we're seeing stabilization of GFR, even in this modest sample size with a relatively short duration of treatment. That gives us a lot of confidence then moving forward into phase III and being able to show the registration endpoints that we've talked about. I think the push-outs from 2022 to 2023, Dave, in terms of the first regulatory submissions. Yeah. I don't recall, actually. If it was PNH moving 2022 to 2023, I can't speculate as to why that shift has happened. What I can say is that, with four Phase III studies starting this year, this team has been working flat out to get this medicine to patients. We've progressed all of these indications, I think, with a great deal of urgency, recognizing the unmet need. Great. Thank you very much, Dave, and thank you, Steve, for your meticulous attention to detail with the pre-reads. Operator, are we ready for the final question, please? Thank you. The next question and final question comes from Peter Welford from Jefferies. Please ask your question. Your line is now open. Hi. Thanks for taking my question. I've got three pretty quick ones left, if you don't mind. Firstly, on aHUS, I wonder if you can comment on the phase III design you mentioned starting in the second half of the year. Will that be also versus anti-C5s, or will it be C5 for fracture patients? How do you think about that? Secondly, on CAD, just curious there, by the time you pursue and finish the phase II, there could well be a drug approved for that. How do you think about that and the pursuit of that disease, what would you be looking for in the phase II to warrant further development? Finally, just in regards to dose, I'm curious whether the 200 milligrams BID dose, is there a potential to consider a higher dose in some indications, or equally lower? Do you think you're maximizing the effect on the alternative pathway at that dose? I guess I'm thinking, coming back to an extent to Matthew's question as well, is there potential for differentiated dosing? It sounds like you're pursuing the similar 200 mg BID in all indications. Thank you. Great. Thank you very much, Peter, for those questions. We may have another question which we'll have to come back to. Just to go through and just to clarify, the last question again was, we seem to be going for 200 mg BID for everything. Is there a potential to do differential dosing and with all the potential consequences of differentiations thereafter, also from a commercial perspective? That's one. I don't know whether Rod wants to take that or Dave wants to take that. The other two questions are for Dave. For aHUS, the question's actually related to what's going to be the choice of our comparator in the phase III program. The second one was with respect to CAD. On the assumption that a product is approved before we start our phase III, how would that influence our phase III design? I don't know. David Soergel, do you want to start with those two questions first? Yeah. Rod can come back with the differential dosing, pricing, whatever else. Yeah. Yeah, absolutely. I'll start with the dosing question a little bit from a scientific standpoint. What I showed you during the presentation was suppression of the alternative pathway by dose. As I said, we've done quite a bit of pharmacodynamic exploration around iptacopan and its ability to suppress the alternative pathway. The question that we had going into the phase II studies was exactly what was asked, can you administer potentially a lower dose in something like IgAN? Whereas something like PNH, where you really need full suppression of the system to prevent hemolysis, would you go with a higher dose? The fact is, as we've shown from the phase II data, the 200 mg dose in all three instances, including now C3G, appears to be the most effective dose regimen. We did consider that, but the efficacy results, it's a data-driven decision, right. The efficacy results tell us that the dose really needs to be 200 milligrams for all three of those indications. Then, again, likely also aHUS, which is why we'd be going with 200 milligrams in aHUS also. Then to come to your question with respect to the design, we haven't talked a lot about the aHUS design yet because we're still in the process of finalizing it. Once we have the final design and it's all locked down, we'll give you a bit more detail on it at that point. Great. I think, David, you also answered the question on the dosing, which is data trumps everything else, which is great. We then move on. There's actually a couple more questions, as we've still got a little bit of time, we'll go through to the questions again. Operator, next question, please. Thank you. The next question comes from Emmanuel Papadakis from Deutsche Bank. Please ask your question. Your line is now open. Thank you for coming back to me. Just a quick follow-on. I just wanted to come back to the, I may have missed it, but I think it got lost, the question on STOP-IgAN. I'd just love to hear your perspectives on why that immunosuppressive strategy failure does not have implications for the approach you're taking. Since you've come back to me, if I could just squeeze in a follow-on on biomarker diagnosis related stuff, I guess. Are you doing anything on IgAN diagnosis, biomarker-led strategy? I think it's not trivial to diagnose at present, it requires frequently a biopsy. Are you building anything into clinical development program, doing anything on the side in terms of the company diagnostics, et cetera? Thank you. Great. Emmanuel's question was, the one question which we didn't answer was the implication of the immunosuppressant therapy, which was stopped, has that got any cross reads? The second new question is on biomarker, what we may be looking at or not looking at, Dave? Let me get to your Sorry, we missed your question, Emmanuel, on STOP-IgAN. I think the important thing to recognize is with iptacopan, with the phase II results we have with iptacopan now, we already have strong evidence of efficacy. It's also important to recognize that iptacopan is not an immunosuppressant, right? It's a medicine that specifically targets an aspect of the immune system. You're not going to get all the side effects related to immunosuppression. You're not going to get other limitations related to those additional therapies. Based on the tolerability profile that we've seen and the efficacy profile that we've already seen in phase II, we have a lot of confidence moving forward into phase III, and that's what we've tried to convey to you. The answer at the end of the day, of course, is that we have to run the trial. We've designed the study for it to be successful for accelerated approval and to generate the data for the full approval at the end with respect to GFR. Ultimately, we, of course, have to run the trial, and we'll see the results. Your second question is a great question around biomarker-related diagnosis in IgAN. As I shared when we spoke to this patient, one of the things that seemed to be particularly frustrating to her was how long it took for her to get an answer about what was going wrong with her. I think a lot of patients with renal disease are in that bucket, right? They go to their primary care provider, they have elevated protein in their urine, and then they have to get referred to a nephrologist and go through a renal biopsy ultimately in most cases to make a definitive diagnosis. Being able to make the diagnosis without a biopsy would be, I think, a huge advance in the field. With respect to phase III exploratory endpoints and biomarker measurements, of course, we always incorporate those into our trials. As a primary registration pathway, we would not anticipate that that would be our approach. We are always looking for ways to reduce patient burden and to improve their pathway through the disease, through their diagnostic process. Great. Thank you very much, David Soergel. Operator, it is now time for the final question, please. Thank you. Thank you. Thank you. The last question comes from the line of Richard Parkes from Exane BNP. Please ask your question. Your line is now open. Richard, your line is open. Please ask your question. Sorry about that. Thanks very much for squeezing me in. First one's just a clarification on Steve Scala's question around the time course of the proteinuria. I just wanted to clarify, do you have any data over the evolution of that progression, i.e., are you seeing greater reductions over time or is it just the 90-day endpoint that data you have at the moment? Secondly, again, just expanding on the biomarker data. Is there any markers that you can use to select for patients that are more likely to progress to kidney failure, it's obviously a heterogeneous disease, or more likely to benefit from an alternative pathway inhibitor at present? Just a little bit of information there would be helpful. Okay, very good. 1 final 1. One final one on PNH. Obviously, proximal complement inhibition is clearly superior, in terms of EVH and anemia, but I think there's historically been uncertainty over whether proximal inhibition will share the benefits of Soliris on thrombosis, given possible mechanisms independent of hemolysis. I just wondered if you could share your thoughts on that and what longer-term data you're generating, and on outcomes beyond biomarkers and anemia. Thank you. Okay. There were three questions, Richard, but I think one I'll just clarify already, which was do we have data beyond 90 days? We don't. We already got that 90. I think Dave mentioned we got 90-day data very recently, and it's going to be a couple of months or so before we have longer-term data. The other two questions were on PNH and proximal inhibition and its effect vis-à-vis thrombosis. Is there any disadvantage with that? The other question was on can you use biomarker data to predict which patients are more likely to progress or respond to a particular therapy. Those are the two questions for Dave, actually. Yeah. Really good questions. I love talking about advancing the science through biomarker development. I think there's great potential in renal diseases to do this. Indeed, our teams are working through this, trying to find ways in which we can better target our emerging pipeline to patients who are going to derive the most benefit from it. At this point, it's really too early to comment on any biomarker strategies or even more precision medicine strategies than we're already pursuing. The reality in IgAN clearly is that proteinuria has a disease target, and reducing persistent proteinuria appears to be, I mean, is strongly linked to renal outcomes. We already have a precision medicine approach actually in that indication. It doesn't mean that we shouldn't continue to look for ways to identify the patient populations who would benefit most. We continue to do this, but we don't have anything specific to share with you today. With respect to the PNH and thrombosis, it's a really good question. I think if the effect on thrombosis is modulated through the classical pathway, I think you're right that it would be more of a challenge to show that with iptacopan. I don't know that that's the case, though. In fact, I think what we'll need to do is additional work. In our phase III study, we'll see what the clinical profile turns out to be. At this point, what we're seeing are very strong results with respect to improvement in hemolysis and improvements in anemia in our phase II program, and this gives us confidence moving forward. What the ultimate profile will look like will depend on the totality of the data at the completion of the development program. Great. Thank you very much, Dave. Thank you. This brings us to the end of our call. I'd like to say a big thank you to our two speakers, Dave and Rod, and all the teams who've been supporting them over the last few weeks to prepare all the materials. A big thank you. A really big thank you to all of you as listeners. We appreciate you taking the time to listen, to study the slides, and to ask such insightful questions. We hope that this session's been of help to you as you assess the potential of iptacopan. Please do get back to the investor relations team if there's anything which you require further clarity on, which we went through today. Thank you and have a great rest of the day.