Good morning and good afternoon, and welcome to the Novartis Renal Portfolio Conference Call and live webcast. Please note that during the presentation, all participants will be in listen-only mode and the conference is being recorded. After the presentation, there will be an opportunity to ask questions by pressing star one and one at any time during the conference. Please limit yourself to one question and return to the queue for any follow-ups. A recording of the conference call, including the Q&A session, will be available on our website shortly after the call ends. With that, I would like to hand over to Ms. Sloan Simpson, Head of Investor Relations. Please go ahead, madam. Thank you, Melanie, and welcome everybody to our renal portfolio call. First, 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. And with that, I'd like to hand over to Shreeram to start the presentation. Thank you, Sloan. Good morning. Good afternoon, everyone, and welcome to our investor call focused on our renal portfolio. With me are Victor Bulto, our President for the US Business, and Dave Soergel, who heads up development for the cardiorenal and metabolic portfolio. Next slide. Our agenda today will cover our aspirations for a portfolio in renal diseases. We'll discuss our launch capabilities that we're building and then give you an insight into our advancing renal pipeline, and then have time for a Q&A. We expect to speak for about between 35 to 40 minutes, and we'll leave enough time for adequate questions. Next slide. As you know, as we transform Novartis into a pure-play medicines company, the core principle behind it has been that focus allows us to build compounding competencies across all parts of our organization, from research, development through commercial. And we believe that these competencies then allow us to exercise better judgment, make good decisions, and have a competitive advantage in being able to advance our portfolio in the disease areas of choice. Our focus today is on renal disease. On this slide, you see our long journey and legacy in the field of transplantation. I should say that this slide actually looks like my own life cycle at Novartis. As a transplant nephrologist myself, I came to Novartis, because of its commitment to transplantation. We made transplantation possible with the introduction of Sandimmune cyclosporine in the 1980s, added Simulect as an induction agent, introduced Myfortic, a formulation of mycophenolic acid, and then brought Certican and everolimus to patients with renal transplantation. And while the focus there was the ability to ensure that transplants avoided acute and chronic rejection, our focus now shifts to how we might work on preventing the need for transplantation by targeting glomerular diseases, which carry significant risk of progression to end-stage renal disease. And to that end, we are deploying iptacopan, our internal complement factor inhibitor, as internal innovation, and I have acquired external opportunities through the recent acquisition of Chinook, giving us atrasentan and zigakibart. Next slide. Bringing all of our competencies, we are now focused on building a comprehensive renal pipeline, as you see on slide six, with multiple products, being in the pipeline, Fabhalta on the inside and atrasentan and iptacopan and zigakibart from Chinook. And then on the right side there, a large number of programs at an earlier stage that you'll hear about from Dave during his presentation as well. Next slide. The primary reason to focus on glomerular diseases is that we are able to build our long understanding of immune-mediated injury to the kidneys and then evaluate how we might reduce the risk of progression to kidney failure. The multiple glomerular diseases that you see listed here account for over two million patients worldwide, and our focus is now on making sure that we can introduce both targeted and foundational interventions to delay the progression of loss of renal function in these patients and reduce the need for renal replacement therapies like dialysis and transplantation. Let's start now on the next slide with IgA nephropathy. IgA nephropathy is the most common glomerulonephritis. The prevalence is as shown to you there. It's a disease that has varying manifestations. Kidney biopsy is the gold standard for diagnosis, and nearly 50% of patients with this disease and persistent proteinuria progress to end-stage renal disease over 10 to 20 years. I have to say that we are at a very exciting time in the care of this heterogeneous and variable disease, where for the longest time when treatment was simply supportive care, we're now at a phase in clinical practice where multiple agents are becoming available. And if you look at the next slide, this is now reflected in the fact that treatment guidelines are evolving with the guidance to ensure that patients are given both drugs that are able to control the source of injury, which is the immunoinflammation that results in the primary loss of nephrons. And then on the right side, interventions that ensure that the remnant nephrons and the proteinuria that comes from the glomerular injury and the associated inflammation is controlled with blood pressure control, reducing glomerular hyperfiltration and proteinuria, as well as managing other risks. On the next slide, we are very proud of the fact that given these emerging guidelines, we have a broad portfolio that allows us to intervene for patients with IgA nephropathy at different parts on the pathogenesis of their disease, as you will hear about from Dave further. On the right, of course, we have now introduced Fabhalta, which targets complement inhibition and reduces inflammation. We brought atrasentan, which reduces glomerular hyperfiltration and can be a part of foundational therapy, and zigakibart, which is the anti-APRIL antibody that has the opportunity to potentially reduce the very source of the pathogenic abnormal IgA production, which is at the basis, which serves as the primary driver of the disease. On the next slide, super proud, all of us just came back from the American Society of Nephrology. Fabhalta is now approved as the first-in-class oral Factor B inhibitor for the treatment of IgA nephropathy on the basis of an accelerated approval and proteinuria reduction. We presented some great additional data at ASN and a New England Journal publication. I'm personally very proud of the fact that there are very few teams that actually have two New England Journal papers and an editorial at the same time as an American Society of Nephrology meeting, and we just came back from there, and with all the excitement that I heard, this Fabhalta launch in IgA nephropathy is going to serve, as you'll hear from Victor, as a blueprint for all of our future renal launches. Dave and I are, of course, super excited about the fact that this gives us the opportunity for gathering insights that fully inform all the plans that we are making in this disease area. With that, Victor, let me hand it over to you. Excellent. Well, thank you very much, Shreeram, and good morning, good afternoon, everyone. Highlighting what Shreeram mentioned at the beginning, you know, we designed our current strategy also commercially to focus on four key therapeutic areas, and we wanted to build both depth and breadth in these areas where we believed we could establish a leading position, and the renal space is certainly one of them. This allows us to create synergies, both on the cost side, but also on the top line, and also compound commercial capabilities. And in renal, we're building this breadth and depth with a multi-product and multi-indication approach. And today I wanted to walk you all through our thinking from a commercial standpoint. So if we move to the next slide, you will see that as the most common glomerular disease, actually, IgA nephropathy is the ideal entry point for our renal portfolio. With an incidence in the U.S. of between seven to twenty-one per million, it mostly affects younger adults, which means that, they'll be mostly covered through the commercial coverage, and up to 50% of these patients with persistent proteinuria do progress to kidney failure within 10 to 20 years of diagnosis, which highlights, on the one hand, the urgency to treat these patients, the unmet need, and the fact that the options that were available up until recently were really not addressing all the drivers of IgA nephropathy and, you know, are prime for the entrance of new compounds. Now, when we look at the 2024 draft KDIGO clinical practice guidelines for the management of IgA nephropathy, they've actually have added a new preferred threshold for proteinuria of 0.3 grams per day, while maintaining the recommended threshold of 0.5 grams per day. Again, reinforcing the importance of aggressively managing this disease. Moving to the next slide, I wanted to quantify the opportunity specifically for the U.S., where we see that we have approximately 185,000 prevalent IgA nephropathy patients, 80,000 of them, biopsy confirmed, for diagnosis. And when we account for severity of disease progression and eGFR values, we end up with a population of about 45,000, that will be potentially eligible patients to be treated with our medicines. When we look at how these patients are currently treated, we will see that 80% of these patients are actually treated with supportive care already, which is typically a mix of RAS inhibition and potentially SGLT2 as well. It is already a combination market with more than 60% of the patients treated with more than one therapy, typically starting with that foundational therapy and adding from there, and we do expect combination therapy to grow on the one hand, as these new therapies are approved, but also going back to the draft KDIGO guidelines, they do support the use of multiple mechanisms, including combination therapy. It's also important to know that about 40% of these patients use steroids on an annual basis. In our conversations with both patients and HCPs, that's certainly something that we would like to spare these patients from. And it's also a marker, a direct marker of the underlying inflammation that these patients have. Also important to note that, you know, newer IgA nephropathies, recently approved, account today for less than 15% of these therapies, highlighting, again, the potential that we have with our Novartis medicines to support these patients. And, as I'll describe on the next page, we do see atrasentan ideally suited for 100% of these eligible patients as a foundational ERA therapy, and Fabhalta more specifically for patients with both persistent proteinuria and also glomerular inflammation. Now, moving to the next slide. Nephrologists, as we speak with them, want multiple treatment options for their patients, and we will see that atrasentan, as a baseline therapy, you know, will be mostly positioned for patients with proteinuria, despite RAS inhibition and, potentially SGLT2s. We do see it as a foundational ERA therapy added to that supportive care with a seamless addition to supportive care that does not require discontinuation or adjustment of the background therapy. On the other hand, the orally administered Fabhalta is going to be best used initially in patients with persistent proteinuria and glomerular inflammation. Dave will go through it in more detail, but these are patients that have persistent proteinuria... persistent hematuria, eGFR decline, and where a different approach to managing patients with addressing the complement activation is creating a lot of excitement in the space, and where Fabhalta is the first and only treatment to target this alternative complement pathway in IgA nephropathy. Now, going to the commercialization strategy, we see in the next slide that having a renal portfolio is absolutely critical in rare or ultra-rare disease because it makes each future launch more effective and efficient. I think it's important to note that two-thirds of nephrologists manage less than three IgA nephropathy patients and about one C3G patient, and that there's about 10,000 nephrologists in the U.S., which makes, of course, reach challenging if we're only launching one indication. Now, you will see on the right-hand side that about two-thirds of the nephrologists treating C3G do overlap with IgA nephropathy-treating HCPs, which allows for substantial synergies as we go to market. Now, also, important to note that, of course, there's 100% overlap between the HCPs that would potentially use atrasentan, iptacopan, and zigakibart in the future for the treatment of IgA nephropathy, creating those portfolio synergies. Now, in order to optimally address this market, we have deployed a robust renal footprint early. So we deployed our medical field teams about two years prior to launch, our commercial teams about nine months prior to launch, and we have an integrated customer-facing team of more than 100 FTEs that have been working on this launch and now executing on it. That, of course, will be also launching the future potential indications and assets. If we move to the next slide, this robust footprint now allows us to cover more than 70% of all IgA nephropathy HCPs, with an initial focus of about 800 early adopters and 14 key accounts. That's important because of the long tail of prescribers that I described. If we think about the early adopters, for example, these 800 HCPs, they currently treat about 25% of the IgA nephropathy patients, and they have been selected both based on the number of patients they treat, but also based on their attitude towards ETA antagonism and complement inhibition for the treatment of these patients. I have to say that so far, the launch is progressing well since the approval in August. We have strong engagement with 100% of the top accounts. We have already reached 70% of these HCPs, these priority HCPs, and we see more than 90% of the top accounts with at least one REMS-certified HCP. So we have about 1,000 HCPs already REMS-certified, which is a proxy for interest in using the therapy. So very pleased so far with how the launch is going. Now, if we move to the next slide, I also want to highlight one of the key challenges in rare and ultra-rare launches, that is understanding where patients are. It's important to note that for these diseases, typically, ICD-10 codes are not as useful to identify where the patients are. Particularly, the IgA nephropathy codes were only available up until only October 2023 onwards. We had to leverage our machine learning models that we have developed in the past for PNH, SMA, CML, and others. We're combining our capabilities to work in renal diseases and other therapeutic areas, to really predict where the IgA nephropathy cases are, link them to specific nephrologists and accounts, and then we've been validating this with our field teams, and we have about an 84% accuracy in predicting those. Now, that's important, as you will see on the right-hand side, because it gives us a very granular understanding of where geographically all these patients are, allows us to deploy our HCP resources in the right place, but also, as you will see in the next slide, implement very targeted DTC capabilities to more effectively reach the right IgA nephropathy patient at the right moment through the right channel, right? By really reaching relevant audiences that we define by aggregating different data sets and engaging in the high relevancy moments where they're ready to absorb the information and, and use it, and connecting through multiple channels, we're able to, for example, reduce the audience size by 88%, which means our resources are way more efficient, but also effectively bring the right information to patients so that they can be empowered to discuss with their HCPs what options might be best for them. Moving to the next slide, I wanted to highlight our market access strategy. Now, of course, as you know, payers have been increasingly suppressing coverage to new specialty drugs in the U.S., and the mitigation requires a scale and also a flexible distribution model. In this case, the scale is achieved by having a multi-indication product. We started with the launch of Fabhalta and PNH last year, and I'm very pleased to say that we very rapidly established leading access with 73% of the patients covered to label six months post-launch, and a path to coverage for about 90% of the patients. So that's going really smoothly. And now we can leverage that coverage to establish coverage in IgA nephropathy as well. I'm pleased as well to say that since launch, we have established coverage to label in about a third of the patients. We expect to, in the coming months, achieve another third and very strong access pathways for the rest of the population, given that this is a rare disease.... So this is another capability that we will be leveraging as well for the future indications with the ability to establish fast coverage once they are approved. Now, finally, I also wanted to go in the next slide to our patient support offerings as well. As part of our commercial model in at Novartis in the U.S., we have established a function, patient support, that focuses 100% on patient support programs. We have heavily invested in it for the past years to do this fully in-house, building our own data and technology stack, when most of our competitors rely on third-party vendors. This patient support program, you know, has been built based on the expertise that we have in all the other rare diseases that we operate in. It was refined for Fabhalta and PNH, so it's well tested now and will be, of course, deployed for the subsequent indications and assets in the renal space. It offers patient enrollment, REMS validation, vaccine support where needed, access and affordability support, therapy initiation, and ongoing support as well. And today, you know, with Fabhalta, we are offering a $0 commercial copay, which is relevant because the vast majority of these patients are commercial. A twelve-month reach program to make sure that any patient can start right away their therapy if needed, while we establish full coverage. And on average, it's taking us about 15 days to dispense the patients, creating very strong satisfaction among both HCPs and patients. So in conclusion, and as I hand it over to, Dave, I just wanted to highlight on the next slide, that we're working to compound capabilities and experiences on the commercial front as well, to support all future renal launches. And Fabhalta, in IgA nephropathy, of course, offers an ideal entry point for our future renal portfolio. We are leveraging portfolio synergies, co-positioning multiple MOAs to address what is known to be a highly heterogeneous disease. We're also creating go-to-market synergies across a broad renal portfolio, making launches more effective and efficient, and of course, leveraging a long company legacy in rare, ultra-rare spaces. And we are adding that to capabilities that apply across the patient journey and that we are developing for the entire portfolio, like effective DTC, very effective payer strategies, and of course, robust patient support programs. So with that, let me hand it over to Dave. Dave, over to you. Thanks a lot, Victor. Really appreciate it. So we'll spend the next few minutes first talking about how we've built depth in IgA nephropathy by adding zigakibart and atrasentan to our portfolio through the Chinook acquisition. And then second, talk about how we're building breadth in our portfolio by expanding iptacopan into other glomerular diseases and approaching new research targets. Go to the next slide, please. So Shreeram showed you this schematic earlier. This is. It's a relatively simple schematic showing the progression of IgA nephropathy from the initial insult to mucosal associated lymphoid tissue, to the production of galactose-deficient IgA, production of immune complexes, and the deposition of those immune complexes in the glomerulus, with subsequent inflammation and kidney damage. What, what this simple schematic does not show you, though, is the complexity that underlies this disease process. Specifically, each part, each stage in this in this pathophysiology has its own variability and its own heterogeneity. And this is why the KDIGO guidelines have recognized that multiple therapeutic options need to be available for patients. And as Shreeram mentioned, that one needs to take care of two processes in parallel, the production of abnormal IgA, and secondarily, the protection of renal function and the remaining nephrons in the kidney. So this provides you a rationale also for the for why we have multiple assets in development for IgA neph IgA nephropathy, with diverse mechanisms of action and different points of intervention. Next slide, please. So we'll talk first about atrasentan. So let's talk about endothelin as a target first in IgA nephropathy. Endothelin is an excellent target for IgAN because the endothelin receptors are typically elevated in IgAN patients and are located at various points in the glomerulus. By preventing binding of endothelin, what we know is that you can reduce mesangial cell activation, kidney fibrosis, and inflammation, and then also reduce glomerular pressure and proteinuria, and thereby protect the kidney. What we also know is that atrasentan is an excellent molecule to target the endothelin receptor. It's highly potent and highly selective. It has a very well-characterized safety profile with over five thousand patients exposed to this medicine during development. And it can be seamlessly added to the current standard of care and be a foundational therapy to prevent future nephron loss. Next slide, please. In phase 3, we've seen excellent UPCR reduction, as we saw in phase 2, with atrasentan. In ALIGN, we saw a statistically significant and clinically meaningful reduction in UPCR of 36% at week 36 at an interim analysis. Importantly, when you look at all of the subgroups in ALIGN, we saw benefits across all subgroups of baseline demographics or disease characteristics. In addition, in an exploratory SGLT2 inhibitor-treated subgroup, we saw consistency of the result with a proteinuria reduction of 37%. This has resulted in a New England Journal of Medicine publication as well during the same week as the APPLAUSE data. And the ALIGN study is the basis of our submission to the FDA, which occurred in the first half of this year. So go to the next slide, please. Zigakibart, we'll move to zigakibart now, which is our anti-APRIL targeting molecule in phase 3. So APRIL is a cytokine that promotes B-cell survival and class switching, and produces that results in the production of abnormal galactose-deficient IgA. These abnormal galactose-deficient IgA molecules then stimulate immune reaction to them, which results in the production of immune complexes, which deposit in the kidney and then attract complement and produce inflammation and fibrosis. What we know is that blocking APRIL decreases the production of this abnormal IgA and prevents the formation of these pathogenic immune complexes. We've seen... Next slide, please. In phase 2, that when you treat with zigakibart, you can see a profound reduction in UPCR of up to 54%, and stabilization of eGFR. We have data now that we showed at ASN, up to a year and a half of exposure to zigakibart. This just shows that these effects are sustained over a year-and-a-half timeframe, and the drug continues to be well tolerated, without adverse events leading to study drug discontinuation, or deaths in the trial. So next slide. So, on the basis of these very strong phase 2 data, we started the phase 3 BEYOND trial, which is enrolling patients with biopsy-confirmed IgA nephropathy, with proteinuria greater than one gram per day, and on stable optimized RAS inhibitors with SGLT2 inhibitors or ERAs and MRAs allowed in the trial. Two hundred and seventy-two patients will be randomized, and we expect a UPCR interim analysis in 2026, with the study continuing to confirm the effect on eGFR out to two years. Next slide, please. So now we'll touch on the expansion to other renal indications, and first, we'll talk about iptacopan and C3 glomerulopathy, and then, lupus nephritis and how we're building a portfolio there, and then, future research efforts. Go to the next slide, please. So we'll start with C3G. C3G is an ultra-rare, severe form of primary glomerulonephritis that's often diagnosed in adolescents and young adults. It affects about ten thousand individuals in the US, and it typically manifests with a variety of symptoms that are typical of kidney disease, like fatigue, edema, hypertension, proteinuria, hematuria, and reduced GFR. The diagnosis requires a kidney biopsy and immunofluorescence microscopy, and importantly, there are no approved treatments targeting the disease pathogenesis, which we'll touch on in a second. About 50% of patients who are diagnosed develop kidney failure, requiring dialysis or transplant within 10 years of diagnosis. So if you look on the right part of this slide, it describes the disease pathophysiology. C3G is a disease of the alternative complement pathway. It's characterized by abnormal production of proinflammatory C3 fragments that deposit in the kidney and cause inflammation and fibrosis, resulting in proteinuria and progressive kidney damage. And so the really exciting thing about iptacopan in this disease, if we go to the next slide, is that it's a targeted therapy that specifically inhibits the Factor B of the alternative pathway. As you can see on this slide, in phase 3, iptacopan reduced your UPCR and stabilized GFR at six months. We showed those data at ERA several months ago. Now at the ASN, we've shown the 12-month data in showing the crossover of patients who had been on placebo, if you look on the left-hand part of this slide, to iptacopan, confirming that the effect, this effect on UPCR in those individuals exposed to iptacopan for six months. In addition, we show persistence and stabilization of effect on proteinuria through 12 months on UPCR, and then on the right-hand side, on GFR as well. An important feature of the APPEAR-C3G study was we collected historical GFR data from patients who were randomized into APPEAR. And so what you see on the right-hand slide is the historical slope on the left-hand aspect of the graph pre-iptacopan treatment. And you see a decline in GFR of 7.6 cc per kilo per year, which, if you think about it, after 10 years, would be about 70 cc per minute decline in GFR, which would lead most patients to require dialysis after about 10 years. And so what you see, very importantly, is this sort of progressive and relentless decline in GFR when patients are treated with iptacopan is abrogated, and you see a stabilization of GFR that lasts up to a year. So this is an incredibly exciting result that suggests that iptacopan may be an effective agent for these individuals who really have no targeted therapies now. If you go to the next slide, importantly, when you look at even the highest-risk patient population, individuals who have nephrotic range proteinuria of greater than three grams per gram, on the left-hand part of this slide, where you see a tremendous decline in GFR over time of twelve cc's per minute per meter squared in the pre-iptacopan period. Again, you see stabilization of GFR when iptacopan is started in these individuals. So this is an incredibly compelling result, I think, that shows that iptacopan can be an effective agent, even in the severest, most severely affected patients. Next slide, please. Now we'll move to lupus nephritis briefly. Lupus nephritis is the most severe organ manifestation of systemic lupus erythematosus. It affects about 110,000 individuals in the US, and its clinical manifestations are variable as the manifestations of SLE are also variable. But are typically sort of characterized by progressing nephrotic syndrome, nephritic symptoms like hematuria, proteinuria, and abnormal kidney functions, and typically is confirmed by kidney biopsy. The current management is limited to corticosteroids, which are really the foundation of care, and broad-spectrum immunosuppressants. About 10% to 20% of individuals develop kidney failure and require dialysis or transplant within 10 years of diagnosis. If you look on the right-hand part of this slide, the disease is really characterized by abnormal B-cell function, production of autoantibodies, with again, deposition into the glomerulus, resulting in inflammation, fibrosis, proteinuria, and declining renal function. If you go to the next slide. We have a diversity of approaches in lupus nephritis that leverages all of our capabilities as a company. So iptacopan, ianalumab, and YTB are all different targeted agents that may be effective in lupus nephritis. They're all different modalities, small molecule, monoclonal antibody, or cell therapy, and the administration varies as well from oral, subcutaneous, intravenous infusion. So there, this, this I think, this diversity of approach offers an opportunity to approach this very heterogeneous and diverse disease with such severe consequences for patients. So we really look forward to seeing the results from these studies and hopefully delivering a new therapy to patients to improve their outcomes. Next slide. Lastly, I'll touch on some of our early research efforts. As was announced recently, we worked together with investors and former Chinook associates to create a renal-focused and RNA-focused biotech company. The opportunity here is really to leverage our increased understanding of renal disease pathophysiology, and using a novel approach to try to target therapies to molecules that haven't been approachable with other interventions previously. We have an option. As part of this deal, we have an option to acquire two future development-ready compounds on agreed terms, and so we really look forward to seeing Borealis succeed and participating in their success as well. Next slide. So I think what you've heard is that we have compounding competencies across research, development, and commercialization, where we've continued to build depth in IgA nephropathy, and then from that, that depth in IgAN, are expanding our presence in other glomerular diseases and other kidney diseases. And with this approach, we expect to bring treatment options to patients and their physicians that protect renal function and prevent the need for dialysis or transplant in the future. Thank you very much. And I think we'll go to Q&A. I expect sure. Thank you. As a reminder, to ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Please limit yourself to one question and return to the queue for any follow-ups. Please stand by while we compile the Q&A queue. Our first question comes from the line of Peter Welford from Jefferies. Please go ahead, your line is open. Hi, thanks for taking my questions. I've got two. Firstly, if we can ask on the C3G data that you've got with iptacopan. Curious, we see other data for drugs in the complement pathway, and curious how you would compare, particularly focusing on what a lot of clinicians seem to comment on, which is the proportion of patients that manage to achieve at least a 50% reduction in proteinuria, where I believe the proportion with iptacopan was relatively modest. So I guess how, you know, how important is that as an endpoint, and how do you sort of position this in the complement landscape? And then just a similar one, if you don't mind, but for zigakibart, which is just the... There's this antibody, I believe, that's just recently read out similar data, similar mechanism. Sorry, that's a few years ahead. I wonder if you could sort of contrast how you would compare yours, your approach to theirs, and perhaps both in terms of the patients that you're targeting and beyond, and the mechanism or compare if there are differences. Thank you. Dave? Yeah, great. Thanks, Peter. So for the C3G question, I think it's really difficult to compare across trials. And I think, even if you look at the baseline characteristics, you know, comparing VALIANT to APPEAR, it's very difficult to make a direct comparison. In addition, proteinuria, you know, itself and its response is highly variable within this disease. So I showed you a very simple schematic of how the alternative pathway is, you know, the stimulus for this disease, and it is. But how patients manifest in their progression of disease can be highly heterogeneous. And so when you get into these small sample trials, you know, in ultra-orphan diseases, it's very difficult to compare across. What we've seen with iptacopan, I think is incredibly compelling, is that we've seen a clinically meaningful and statistically significant reduction in UPCR. We've achieved the objective, right? Which is stabilization of GFR, right? With an orally delivered, easy to administer agent. So I think, you know, we're very excited about iptacopan and C3G, and look forward to its regulatory approval. With respect to... Do you wanna add anything, Victor, to that? No, the only thing I would add, and I think we've gone through the presentation, is that we also see the importance of having a presence, establishing access, and having synergies from a commercial standpoint that will help us, you know, launch these subsequent assets. In an environment, as you mentioned, where the heterogeneity of the disease, you know, and the sparsity of these patients, right? Requires, you know, much of a broader footprint. And we're very confident about our ability to, you know, once and if approved, bring this medicine to market. Particularly as well, noting the difference in route of administration, right? In our discussions with both patients and physicians, the fact that iptacopan is an orally delivered drug, particularly for these patients that will be on these treatments chronically, is extremely important as well. I think, Peter, your second question was on zigakibart. I mean, you know, we're in the midst of running the phase III trial. You know, I think the anti-APRIL mechanism is a particularly compelling mechanism for this disease, for the reasons that I just talked about. It, you know, directly targets the production of this abnormal galactose-deficient IgA, and has the opportunity, I think, to, you know, stanch the production of these immune complexes that cause renal damage. We'll see what the data show. I mean, I think that's the important thing. We're very confident, based on the phase II experience, with zigakibart from Chinook, that this will be an important medicine for patients with IgA as well. I think, and Peter, the only thing I'd add is that like Victor said about iptacopan, that even though we may be a little bit behind, the reality is that having access to a portfolio and having built all the capabilities, the opportunity to then bring to bear a drug like zigakibart, as the therapeutic landscape evolves on people trying to understand in which setting should the drug be used, the ability to then introduce it and get it to patients is significantly enabled by the broad portfolio and our presence in the field and our relationships in the community, as well as payers. So, thanks for your questions, Peter. Operator, the next question? Thank you. One moment, please. Our next question comes from the line of Richard Vosser from JP Morgan. Please go ahead, your line is open. Hi, thanks for taking my question. It's just a question on the commercial uptake of Fabhalta in PNH and thinking about the bridge support. So just, you know, if you could give us an update on that launch, what proportion of patients are now commercial pay, how the bridge program is going, and how you expect that proportion on the bridge program to change over time, over the next six to nine months? But just an update on the launch would be great. Thanks. Great. Well, thank you very much, Richard, for your question. I mean, we will go into more details tomorrow in the part of the earnings call, but what I can tell you is that the launch is progressing very well. As you saw on the market access slide, we very rapidly established access with about 70% of patients covered to level, which is actually translating into paid fills already. Of course, we have patients going through the bridge, but we're already seeing a good proportion of patients going straight to paid fills. We're very pleased with the high percentage of physicians already REMS certified, so again, a good proxy to interest. We have established leading market share already in the market, you know, eight months we've been on the market. And we're getting mostly switchers, just for your information, right? So these patients were treated with another therapy, and they're switching now to iptacopan for two main reasons. One is optimal hemoglobin control, right? We're seeing patients that are, you know, coming with all ranges of hemoglobin. We see good control, extremely high satisfaction from patients and HCPs. But we're also seeing patients switching that had hemoglobin levels of 10, that are compelled by the idea of an oral treatment in the space for the first time. We're also very pleased with both compliance and persistency that we're seeing on these patients, right? That's actually tracking ahead of our expectations. In summary, all in all, a very good platform. It's working very well, and it's a great, you know, as I mentioned, platform for the launch of Fabhalta in IgA nephropathy, even though in another therapeutic area, there's a lot of common elements that are enabling and allowing an acceleration of Fabhalta launch as well. ... Thanks very much. Next question, operator. Thank you. Thanks, operator. Please stand by. Our next question comes from the line of Simon Baker from Redburn Atlantic. Please go ahead. Your line is open. Thank you for taking my question. It's on C3G, but from a slightly different angle. Given that there are two genes that are implicated in C3G, and given Novartis' expertise in gene therapy, I was just wondering what your thoughts were on gene therapy options for C3G. And broadening out that question, on the basis that there are about eighty renal genetic diseases and given your heritage with Zolgensma, what do you see as the opportunity, and what are you doing in the renal space with respect to gene therapy? Thanks so much. Yeah, thanks, Simon. Dave, great question. So what I would say kind of broadly is, you know, we're very committed to being in the renal disease area, as you saw from this presentation, and we're always looking for internal or external innovation. So, you know, as we've shown with the acquisition of Chinook. So, you know, we're always watching and looking for opportunities to intervene that's gonna make a significant improvement in patients' lives. What I would say about C3G specifically is that iptacopan is a highly potent and effective agent at reducing activity of the alternative complement pathway through oral administration. So it provides, I think, a great option for patients with C3G, once it gets approved. So, you know, we look forward to bringing iptacopan to patients with C3G, as of now. Thanks so much. Thank you. Our next question comes from the line of Graham Parry from Bank of America. Please go ahead. Your line is open. Great. Thanks for your good questions. So just actually on the phase 3 iptacopan data. So the proteinuria reduction was noticeably less in phase 3 than we saw in phase 2. Just if you could sort of talk through any kind of explanation for that that you see. I think it was over 50%, although not placebo-adjusted in the phase 2 study. And then secondly, what reimbursement copay or compliance issues do you think you may run into with an oral therapy in C3 glomerulopathy, and how are you planning on addressing those ahead of launch? Dave, do you wanna go first, then Victor? Yeah, sure. So, thanks for the question, Graham. Going from phase II to phase III, I mean, you know, we expect to see differences going from phase II to phase III, especially in you know, modest-sized trials with highly variable endpoints like UPCR. So the important thing is what we've shown is a clinically meaningful and statistically significant reduction in UPCR in the phase III trial, which, you know, is then buttressed by the fact that we could interrupt that decline in eGFR over time and show stabilization of renal function. So I think, you know, the important outcome is that it looks like, if you know, when if iptacopan is approved for C3G, it'll provide an option for individuals right now who don't have an option. and I'll pass it to Victor to answer the- Thank you, Dave, and thank you, Graham, for the question. The majority of these patients in C3G are quite young and are mostly covered through the commercial benefit. This will enable us to offer our $0 commercial copay. We don't anticipate challenges from an affordability perspective or from an access to the medicine perspective. Of course, we have not established policies, and we will only do that once we get approval for C3G, but we do expect to leverage our presence with Fabhalta on both PNH and IgA nephropathy to establish strong coverage to label. That will result in not only, you know, low copays, but also the ability for physicians to prescribe it, hopefully, right away after launch. Graham, I'm just gonna take you back to the fact that each time we talk about proteinuria, the whole purpose of measuring an effect on proteinuria was to get an indication of what's gonna happen to eGFR. And I think when we were at the ASN yesterday, I think it was quite interesting to see that on the C3G data, people described that essentially horizontal line on how the eGFR has basically stabilized to be horizontal with no further decline compared to historical rates. It sort of felt like the primary purpose of treatment had been accomplished, and I think we see that continuing over time. And to that end, I think the numerical differences in percentage proteinuria reductions as a predictor, we feel are no longer that relevant. Given the fact that, you know, population differences across trials, as Dave pointed out, make it hard to compare specific numbers. We are now focused on that stable eGFR and look forward to turning that into a potential benefit for patients. Thanks. Next question, please, operator. Our next question comes from the line of Emmanuel Papadakis from Deutsche Bank. Please go ahead. Your line is open. Thank you for taking the question. Perhaps a few follow-ups. So C3G, you've mentioned a couple of times differences in baseline characteristics. Is there any particular aspect to those you'd mention? And then it doesn't seem, on the basis of UPCR, any physician would choose iptacopan out of pegcetacopan for those patients. So how many patients do you think would actually prefer an oral versus twice weekly subcutaneous? And then maybe a question on overall guidance. I didn't see any update today. I assume the above $3 billion peak guidance is intact. Could you comment to what extent that was constituted by C3G versus PNH and IgA nephropathy? Thank you. ... Yeah, I can take the commercial questions on both the preference between an oral treatment and a sub-Q treatment and also the guidance. So let me start with the guidance. We have guided for about a $2-3 billion peak across indications worldwide. We haven't provided further guidance on the split of the different indications. And in terms of the C3G preference, I think it all comes down to the heterogeneity of the disease, as Dave has mentioned. But generally, you know, when patients given the option to use a twice-daily oral therapy, or to use a sub-Q pump patch twice a week, I mean, that's a clear preference, particularly in this younger population, right? And we're very encouraged to see as well the high degree of persistency and adherence that we've seen with Fabhalta in PNH, which can potentially be used as a proxy as well of what we could see, right? So it's one of the elements, of course, that will play into decision making. Others, you know, as Shreeram pointed out, will be our ability to support patients, activate patients and HCPs commercially, which we're well poised to do. And then from a therapeutic standpoint, Dave, I will pass it over to you to Yeah. - Respond to the first question. Yeah. Thanks, Victor. Yeah, thanks, Emmanuel. So I think your question related to what baseline characteristics were different in APPEAR between treated and placebo group. And the answer is that there were the population in the iptacopan-treated group was slightly younger, which is consistent with the fact that a lot of them had dense deposit disease at baseline. This is a more severe, typically a more severe phenotype, and so when you actually split that eGFR curve, the historical eGFR curve, you actually see a more precipitous decline in the iptacopan treated population. So I think that's consistent with the fact that, you know, what we see is some heterogeneity in the study, which is, you know, can happen in these relatively small phase three trials. However, the important thing is that we, as Shreeram said, is we see stabilization of eGFR in the population that's treated with iptacopan, which is the critical thing. Because, you know, most of these patients are gonna end up on dialysis or requiring a kidney transplant. And then, of course, after a kidney transplant with C3G, you don't get rid of the disease. And in fact, a lot of patients have recurrence of C3G after they have a transplant. So, you know, having an oral therapy that could, you know, impact favorably on protection of renal function is a big benefit to patients. Thank you for that, and apologies if I was not clear. I was actually referring to differences in the baseline characteristics between VALIANT and APPEAR on a cross-trial basis. Thank you. Yeah, but I think, Emmanuel, as you know, the mix. VALIANT had IC-MP GN patients, some post-transplant patients. Our population got incoming baseline GFR was about eight or nine mLs higher. So our interpretation of the data for us is that we enrolled a population that was a little bit earlier in their disease state. We had a different mix of C3G and subsets of C3G, like dense deposit. And I think therefore, with these high double-digit number of patient populations, comparisons of directly looking at proteinuria reduction comparisons across trials starts getting complicated, which is partly why we then zero in on the fact of, well, what are we achieving in terms of GFR? I hope that makes sense. Thanks. Next question, operator. Thank you. Thank you. Our next question comes from the line of Kerry Holford from Berenberg. Please go ahead, your line is open. Oh, hi, thank you for taking my question. I'm just thinking about sort of bigger picture here with regard to the approval process in some of these rare kidney disease areas, accelerated versus full. Do you expect the reduction in proteinuria to continue to enable accelerated approval for a number of these rare diseases, or is that route likely to become more limited as the competition increases? And then, I guess, associated with that, how confident are you that reduction in proteinuria will remain the primary focus for the regulators? Is there a risk that eGFR stabilization or any benefit around time becomes increasingly important for getting that initial approval? Thank you. Thanks, Kerry. It's Shreeram. You're indeed correct, that I think that the purpose for approving drugs on the basis of proteinuria reduction was based on the not having to wait long, when there were no therapies available. We fully expect that as drugs get approved, additional drugs getting approved on the basis of proteinuria reduction alone will need to defend why they are an advantage over what is an approved standard of care. So we fully expect that, that to happen over time. When that happens, then I fully expect that regulators will focus in on the primary purpose and efficacy of renal function assessment and demonstrating a benefit on slowing of decline, in, you know, which is the basis for confirmatory approval now. But I think the answer to your question is, we indeed expect that to happen over time. And Dave, do you want to add something? Yeah, yeah, just add something really quickly. I mean, I think you know what we've seen with IgA nephropathy is really an explosion of therapeutic options in that field. That partially has resulted from the fact that proteinuria reduction became a validated surrogate for approval in the U.S. So I think the academic community is certainly interested in pushing for more validated, you know, more indications where UPCR could be a validated surrogate. And we've seen, you know, ongoing work, especially with the PARASOL Group and FSGS to try to, you know, extend some of that thinking and try to bring therapies to patients more quickly. So I think the IgA sets a great framework for accelerated approval and how you actually get that done, but it's gonna have to play out in a lot of these other diseases. Mm-hmm. Thank you. Thank you. Operator, next question? Our next question comes from the line of Christopher Uhlén from SEB. Please go ahead. Your line is open. Christopher Uhlén, from SEB. Thank you very much for taking my questions. It's focusing on C3G. So I wondered if you could tell us how you obviously have a skew in your baseline on, with respect to, dense deposit disease. How did the data look in, the non-DDD only patients? And then, you know, in terms of the protocol, you've got, you know, a requirement that patients be on maximally tolerated, RAS blockade. What proportion of patients were treated at or above that target, dose? And, you know, why did you go for a maximally tolerated RAS blockade? Was this an FDA or EMA suggestion or requirement? Noting that your competitor's trial, was only for optimal RAS blockade. And if I could just squeeze in another one on that. So competitor is showing C3G staining post-treatment and a big reduction. You guys haven't shown that data. How does it look in your data set? And I guess the last thing would be sort of with respect to the proteinuria and eGFR. So we have six-month eGFR follow-up. Did FDA and EMA at any time specifically say that would be sufficient? I mean, I realize that you needed to end up showing twelve-month follow-up for at least the FDA, but why not longer? Why not design the trial with a longer eGFR follow-up before crossover, given that I mean, you already have proteinuria as a surrogate endpoint? What's the point if six months was supposed to be okay? Thank you very much. Yeah, thanks, Christopher. I'll apologize if I don't get every one of the points that you raised, but let me go through those that I captured in order, and then you can let me know what I missed. But with respect to the heterogeneity in the baseline characteristics in the population, what we see is we see consistent effects across all subpopulations within APPEAR. And you know, as we said, the overall results, I think, support a beneficial treatment effect on UPCR and stabilization of GFR in the entire population. I think the second question you had to do. Well, a question that you had was about staining. We did show results from a C3 deposition score at ASN, showing a statistically significant reduction in C3 deposition score in APPEAR. I don't have an image to show you that looks like the one that you saw from the competitor, but I think that tells you that iptacopan reduces deposition score in the disease. I think importantly, also from other indications, what we see is when you administer iptacopan systemically, you very effectively reduce Factor B alternative pathway activation by biomarker using Wieslab and other measures of complement activation. So we know that the disease is sort of turned off at its core by reducing alternative pathway activation. And then I think the other question had to do with the connection between UPCR and GFR at six months. I mean, I think whenever we design a trial, you know, you have to take into consideration that patients are going to, you know, be able to tolerate placebo control for a certain period of time. In some situations, when you go longer than a certain timeframe, individuals are not willing to be exposed to placebo any longer. So you have to balance these sort of pragmatic aspects to a trial design versus a scientific, you know, testing your scientific hypothesis. What we showed at six months is we have the effects that we were looking for, so both in terms of UPCR reduction and GFR stabilization. Then continuing the study out, we have the power of the crossover, where you see in the individuals who had been treated with placebo before and then were treated with iptacopan, you see a confirmation of that UPCR reduction effect in the placebo-treated group and stabilization of GFR across the entire population. So I think it actually, you know, APPLAUSE gives us very compelling results at the end of the day, at the twelve-month time point. Yeah, and I think if I had to add, I think, Dave, when we were designing APPEAR, APPEAR was the first study of its nature in a randomized controlled setting with a placebo control for a disease that affects young people and is known to be pretty aggressive. So I think that it was very clear that the opportunity, the ability to keep a person on placebo for longer than six months was simply considered unrealistic. And frankly, while our trial actually enrolled patients that were at a slightly earlier stage of their disease, with incoming GFRs that were higher than what was seen with our competitor, what is noteworthy is that in the competitor trial, over a course of six months, there was a nearly just under eight mL per minute drop in GFR. So the fact that this population can behave in ways that is pretty aggressive is very clear. And so the ingoing design was based on that patient-centric, if you will, principle. But I think the fact that we could then reconfirm the benefits on proteinuria through the placebo to active control conversion, as well as the sustained benefits of eGFR stabilization, allow us to make the case for substantial evidence of efficacy. So thanks, Christopher. I think if we can go to the next question, my kind request is to please limit your question to one question so that we can get done with the few that are still in line. Our next question comes from the line of Seamus Fernandez from Guggenheim Securities. Please go ahead. Your line is open. Thanks very much for the question. So, we just had one question on the historical data for zigakibart. I think there were two cases in the earlier dataset that had some SAEs. Just hoping that you could maybe cover those SAEs and explain to us if it was specific to the patients in those earlier datasets, or if perhaps it was reflected, you know, with an issue with the product. Thanks. Yeah, I mean, I'll try to give you some clarity on that, Seamus. So I mean, first of all, there were no AEs in the trial that led to treatment discontinuation. So I think that's the important thing. You know, in any small size trial, especially with individuals who have, you know, a significant disease, especially when you don't have a placebo control, you know, you might have events that happen in the study. We had one event that occurred that was a serious listed as a serious adverse event that was not treatment related. I think as of right now, as I said during the presentation, we're very confident in zigakibart's safety profile, based on the year-and-a-half data follow-up we have with this drug. You know, I think the specificity of the mechanism of action is also an important sort of attribute, where you know, targeting APRIL in isolation, I think gives us an opportunity to be very specific about how we address the disease, the root cause of the disease. Just to clarify, the hypogammaglobulinemia cases were deemed not due to study drug? There was one, I believe. I'm not sure. I can't say specifically what the attribution was, but one did occur after the treatment period, and they were both in individuals who were on corticosteroids, so there were, you know, potentially confounding situations going on with those individuals. Okay, great. Thank you. Thanks. Thanks, Seamus. Next question? Our next question comes from the line of Steven Scala from TD Cowen. Please go ahead, your line is open. Oh, thank you. Just one brief question. Industry-wide, how big do you think the IgAN market could become? For instance, do you think it could total more than $10 billion, more than $20 billion, and what portion of that would Novartis capture? Thank you. Steven, thank you very much for your question. I mean, I would revert back to the data that we've shared in terms of prevalence, right? And then reflect on the drivers that will give us that will lead us there. About a hundred and eighty-five thousand patients that are prevalent, and today, probably the biggest opportunity for this market to expand is to increase diagnosed prevalent rate. And that, that's gonna be a key driver of the market. And that today is a little bit challenging because it requires a biopsy. But what we do know is that, you know, as we have more entrants in the space, you know, the market will continue to develop, and we will expect an increase there. So what we have said, or what we can guide to, is that we do expect both atrasentan and zigakibart to become blockbusters on their own, right? And that we've guided iptacopan to be a $3 billion plus, you know, across indications. So we do expect the market to be a very significant one, and of course, we're deploying a portfolio strategy and a commercial strategy to take a leading place into this portfolio. So thank you very much, Steven. Okay. So with that, I think I thank you for joining us this morning for our renal-focused call. Look forward to many of you joining our quarterly call tomorrow. Thank you very much. This concludes today's conference call. Thank you for participating. You may now disconnect. Speakers, please stand by.