Oh, okay. All righty. Let's go ahead and get started. Welcome everyone to the 42nd annual J.P. Morgan Healthcare Conference. My name's Anupam Rama. I'm one of the senior biotech analysts here at J.P. Morgan. I'm joined by my squad, Priyanka Grover, Laraya Hall, and Malcolm Kuno. Our next presenting company is Travere, and presenting on behalf of the company, we have Eric Dube. Thank you very much, Anupam, and thank you, J.P. Morgan, for hosting us. I'm Eric Dube, President and CEO of Travere Therapeutics. I will start with the formal information. Our forward-looking statements you can find on our website, as well as additional information about our company and our pipeline. We're a company that is focused exclusively in rare disease, and we focus on developing and delivering medicines for communities in the rare community that have very little to no options, therapeutically. We're very pleased to be able to provide hope for patients, particularly within the rare kidney and metabolic arena. In fact, we aim to be able to help in providing hope to tens of thousands of patients that we believe are addressable in the U.S. within two diseases alone. The first is a rare kidney disorder called IgA nephropathy that afflicts about 30,000-50,000, that we believe are addressable with our medicine, FILSPARI or sparsentan. Then we have a pipeline asset that just went into phase 3 for the treatment of classical homocystinuria or HCU, which afflicts several thousand, over 10,000 patients in the U.S. We believe that there are at least 3,000-5,000 patients that are addressable. Together, we believe reflect over $10 billion of market opportunity within those diseases. We also have the opportunity within another rare kidney disease called FSGS or focal segmental glomerulosclerosis, that represents another several tens of thousands of patients for whom there is nothing approved, and we are aiming to change that with our medicine, FILSPARI. This is a snapshot of our portfolio. We have three medicines that are currently approved by FDA. FILSPARI, that was recently approved last year under accelerated approval, and then two therapies, Thiola and Thiola EC, that have been around for a number of years, but are considered the standard of care for the treatment of cystinuria. We have, as I mentioned, another program, FSGS, that was completed phase three, which I will speak about. And then we have a pegtibatinase in HCU that last month just moved into phase three. We'll start with FILSPARI, which again, was available very recently. This is a single oral molecule that dually inhibits both angiotensin and endothelin, a very unique profile within the space. A little bit about IgA nephropathy. This is a rare condition and is considered one of the most difficult to treat based on nephrologists who rate the unmet need in both IgA nephropathy and FSGS as highest. One of the most devastating aspects of IgA nephropathy or IgAN is that patients are often diagnosed in the prime of their life. The typical patient with IgAN is diagnosed in their 20s, just as they're thinking about starting a career or starting a family, and they're told that maybe in the next 10 years on average, they're going to face kidney failure, hopefully a transplant, if they're lucky, and if not, a lifetime of dialysis. This is essentially the outlook for patients with IgA nephropathy up until now, and I think with a lot of innovation from Travere, but also from many other companies that have now invested, we believe that we're changing that. And so we're hopeful that we'll be able to change what has been a very difficult outlook for a large group of young adults. I want to talk just a little bit more about what this prognosis looks like. This is an analysis from the RaDaR registry. This is the largest registry of IgAN patients, and it's out of the U.K. This was looking at a segment of those patients that represent largely those that are enrolled in the phase 3 IgAN program. What you can see is that for a typical patient that does not have any improvement in their proteinuria, they face, on average, time to kidney failure of about eight years. Now, proteinuria is really important for two reasons. One is it's a hallmark of this condition. Patients oftentimes present with elevated proteinuria that progresses and gets worse over time, but it also is a modifiable factor of this disease. If you can reduce proteinuria, you're able to improve the prognosis and ultimately slow and hopefully prevent these patients entering into kidney failure. And in fact, with this analysis, what you can see is that for those patients that are able to get their proteinuria level down to 40%, you're giving them an extra 6.5 years out of kidney failure. And if you're able to do what has been seemingly impossible and get these patients' proteinuria cut in half, you're able to extend that by 8.5 years. Now, I'll talk a little bit about how these patients have been treated with all of the off-label therapies that physicians have thrown at them. But essentially, what we believe with sparsentan is the single greatest reduction in proteinuria that we've seen with an agent. We believe that we'll have the opportunity through this and through other therapies in development to really change the life and the disease course for IgAN. As I mentioned, FILSPARI was approved under accelerated approval in February of last year. This is an oral, non-immunosuppressive therapy that's taken once a day with a target dose of 400 milligrams. The adverse event profile is very well characterized, given that the two mechanisms of action—angiotensin receptor blockade and endothelin blockade—are well characterized. Largely, the adverse events that are most common, dizziness, hypotension, that oftentimes present early but then resolve. I want to talk a little bit about how these patients are treated up until now. It's really been a two-prong approach to address the overactivation and the injury that occurs in the kidney, and then upstream to reduce additional injury by reducing or immunosuppressing the patient. And the way that physicians have been able to do that to date is in the off-label use of ACEs and ARBs to reduce that overactivation of angiotensin, but unfortunately, that is often not enough, and these patients progress despite being on ACE or ARB. The second prong is really in immunosuppression, which has largely been in the use of steroids. Now we know that it should be low-dose steroids to be able to slow the progression or to reduce further injury within the kidney. We believe, based on the data that we have thus far, and I'll share a high-level overview of our two-year data, that we have head-to-head data to show superiority over traditional ACEs and ARBs, which has been the foundational therapy for treating these patients. We believe that with these data, that FILSPARI is uniquely positioned to become the new foundational therapy and ultimately replace the role that ACEs and ARBs have played in the overwhelming majority of patients that with IgAN that are treated. As we look to the future with all of the exciting innovation that's now currently in development, there's going to be a lot of options, but fundamentally, those two treatment prongs are going to remain the same. You want to address nephroprotection by reducing overactivation within the kidney and preventing further, inflammation, further scarring. The best way to do that is going to be FILSPARI. Essentially, physicians are going to have the option of ACE or ARB or FILSPARI, in addition to SGLT2s, which have been increasing based on some of the broader CKD trials that reported out. We don't believe that that option is going to change with regard to, you know, the foreseeable future. The second prong is really whether there's going to be additional treatment options for physicians. How do you reduce further upstream injury? That could be complement inhibitors, it could be B-cell, APRIL/BLyS, it could be targeted steroids. All of those really play a very different role in the treatment algorithm to address that upstream injury, very different than the role that FILSPARI is playing and will play for the future treatment algorithm. As we look at the first 10 months of launch, we've been incredibly pleased with the progress that we've made thus far. We have very good access through payers. We ended the year with about 69% of lives covered with very high-quality coverage, meaning that there is very limited barriers for patients to get FILSPARI. We also have been able to access over 5,700 out of the 6,000 nephrologists. That is no small feat, given that most of these nephrologists are community-based, very busy, very difficult to access, and traditionally, quite a conservative specialty. Despite that, what we've been able to generate is quarter-over-quarter growth in new patient start forms. This is the first rare kidney launch that has been able to show in the first year of launch, incremental growth in new patient start forms every single quarter. We ended last year in the fourth quarter with 459 new patients, and I think we saw an acceleration in the number of new patients as well as the breadth of new prescribers after the ASN meeting or Kidney Week in early November, where there was a lot of buzz and two simultaneous publications and presentations with our sparsentan data. So we believe that there is going to be incrementally greater momentum as we move forward with this launch. And what we've seen is we've been able to pull through a lot of that demand with a significant inflection in our revenue of $15 million in the fourth quarter. As we look to the year ahead, we believe that there are several important factors that will drive further growth, both in demand as well as revenue. I want to highlight what those are on this slide. The first is we have a very established commercial team. They are operating and execute incredibly well. We believe that not just through the additional education of nephrologists about the importance of dual blockade, that will help in continuing to grow the prescriber base, but also peer-to-peer experience. One of the most compelling things that we've heard over the first year of launch is just how compelling and consistent the clinical experience is for patients. They're seeing within the first month of getting their labs and their proteinuria, a profound reduction. Now, if you think about the mindset of many of these patients, they've been using off-label therapy, and despite that, these patients see their proteinuria creep up every time they do labs. So to be able to see a 50% or sometimes greater reduction in their proteinuria within a matter of a month or two, it is a profound relief for these patients. Their physicians are excited about it and talk to other nephrologists, but importantly, it also leads to very high levels of compliance with these patients in the first year of launch. We also expect to see further updates to the guidelines. We are in the up-to-date guidelines that reflects that if patients are not controlled on ACE or ARB, that they should be switched to FILSPARI. The KDIGO guidelines are the global kidney guidelines. We expect those to be updated later this year to include FILSPARI, but we also importantly expect that the KDIGO guidelines are going to talk about the need to treat earlier, given a lot of the literature that we've helped to support and the evidence that we've helped to generate, showing that even in patients that are below one gram, which is typically considered low risk of progression…. These patients oftentimes have a high risk of progression to kidney failure within ten years. So we believe that there's going to be a greater urgency to treat early, as well as greater aggressiveness in combination therapy as we move forward. We also expect to file an sNDA with FDA this quarter, and assuming priority review, we would expect to get full approval in the third quarter, which would allow for potentially a broadening of our indication statement and additional clinical data to be able to help in establishing FILSPARI as that new foundational therapy. Finally, we have other trials that are ongoing to be able to help in supporting and really staying ahead of other therapies that could be coming to market with the only trial looking at treatment-naive patients in a first-line setting, that's the SPARTAN Study, as well as two studies looking at the combination of FILSPARI plus SGLT2s as two once-a-day oral nephroprotective therapies, which we hear from nephrologists is the combination that they expect to be most common in the future. So with that, I'd like to just give a high-level overview of our protect data. This is our phase 3 study that was conducted. We see that over a two-year period, there is a very rapid and durable reduction in proteinuria. This is the first time that we've been able to see this magnitude of proteinuria reduction over time, and it is sustained. This is unlike what you see with ACE inhibitors. This is a head-to-head trial. In fact, it's the only phase 3 trial being done in this space that includes an active comparator, this an ARB irbesartan. And you can see that whereas at nine months, which was the primary endpoint, you see 15% reduction, you lose about two-thirds of that benefit out to two years because you are not also tamping down the overactivation of endothelin. There is a feedback loop within the kidney that if you do not block both of those, you could continue to see the disease progress. So this is a very compelling profile that we hear from nephrologists. With the most rigorous measure of proteinuria, that is complete remission, that is getting patients below 0.3 grams of protein, we were able to get 2.5 times greater patients to complete remission with sparsentan compared to active control irbesartan. Now, how that translates into long-term kidney function, which is measured by eGFR, you can see that on the bar chart, that patients that were very well controlled on irbesartan, this is a very different type of trial design, where patients were actively managed up to target dose. Patients still lost over 9 milliliters per minute over that two-year period, compared to sparsentan, where patients lost 5.8 milliliters per minute, or a difference of 3.7. That is very clinically meaningful, and I'll show you in a moment what that looks like in terms of projecting time to kidney failure. What you can also see is our measures of eGFR slope. These were the confirmatory endpoints, and we were statistically significant on chronic slope. We were not on we barely missed on eGFR total slope, but there is, I think, recognition amongst the nephrology community that eGFR slope is not an ideal measure for clinical trials, and in fact, there is a movement away from it. So as we look at the totality and every other measure of kidney function, we see a compelling measure of longer-term slowing of disease process. And that 1 milliliter per minute per year difference on eGFR slope is clinically meaningful. If you use that and you project that out using the RaDaR data, you can see that for the purple line or the gray line, that these are patients that you can project out on standard care. This is real-world use of ACE or ARB, where most patients are not optimized on their dose. They're probably not fully compliant. These patients are going to be in kidney failure on average in eight years. For patients that are optimized on their RAAS blockade, you can see that that is extended out to 11 years. This is really essentially our control arm in PROTECT. Compared to those patients on FILSPARI that had a 1 milliliter per minute per year difference, that projects out to over 15 years delay to kidney failure, which is an incredibly compelling picture, not just to patients, but certainly to their treating nephrologists. This is really what we believe should compel continued growth in FILSPARI and essentially replacing the role that ACEs and ARBs play with the majority of patients that are treated with that regimen. Moving on to FSGS, which is an even more devastating and rapidly progressing disease, the hallmark symptom is not just proteinuria, but oftentimes these patients present with nephrotic range, very high levels of protein in their urine, and oftentimes these patients will progress to kidney failure in fivtwo-10 years. It is a devastating disease, and there is no pharmacotherapies that are currently approved. When we look at the picture of what we have from our phase 2 DUPLEX Study that was completed early last year, you can see a very similar pattern of reduction in proteinuria compared to active control irbesartan. Patients are able to reduce, within a matter of weeks, their protein in their urine by 50%, which is sustained out to two years. And a very similar picture when you look at the most rigorous measure of protein, proteinuria, complete remission. Again, 2.5 times greater patients on sparsentan are able to achieve complete remission. Unfortunately, for this, confirmatory endpoint of eGFR, we were not able to show a statistically significant difference, even though the difference of 0.9 milliliters per minute per year is considered by many nephrologists as clinically meaningful. This is a disease that is highly heterogeneous and oftentimes is relapsing and remitting.... So in a measure, to be able to look at a difference and, and to find the signal from the noise is incredibly challenging. And there is now a movement, since we announced these data, amongst the nephrology community and regulators, to reevaluate what is an appropriate endpoint for FSGS. And I think there's very clear recognition, and possibly there will be alignment, that eGFR is not the right measure, just given how variable this is. Even within a patient, their measure of eGFR can vary from visit to visit. So we've got to come up with a better measure, and certainly, as we can see here, sparsentan, we believe, has a profound reduction and improvement in proteinuria. So we will, we will be meeting with FDA later this year to assess whether there is a regulatory path. They're open for us coming back with additional data to see what possibly could be a benefit for sparsentan with an sNDA. I want to turn to pegtibatinase briefly. This is a pegylated humanized enzyme replacement therapy that has just moved into phase 3 for the treatment of HCU. HCU is a genetic disease that essentially affects the CBS enzyme. The CBS enzyme is responsible for metabolizing homocysteine. Homocysteine and methionine we get from protein in our diet, and unfortunately, these patients, because of a defect in their CBS enzyme, have a toxic accumulation over their lifetime of homocysteine that oftentimes can lead to ocular lens dislocation in childhood, and many of these patients have thrombotic events by the time they're in early adulthood. It's a devastating disease, not just because of clinical outcomes, but from the stories that we hear from these patients, they share with us the difficulty of what is currently the standard of care. You take vitamin B6, which is a cofactor for any remnant of CBS enzyme that the patient may have, but the mainstay of these patients is a phenomenally strict diet, essentially little to no protein in their diet, and they have to take a horribly tasting, very expensive medicine, betaine, to be able to supplement what is still inadequate. The number one need that these patients have is just to eat like their friends, their family, or to sit at a family gathering and to be able to feel part of it, and not to feel that every time they go to a gathering, a grocery store, a restaurant, that they are isolated and reminded that they have this, this disease. So our goal is to change that. Our focus is to make sure, first, that we're able to do a better job as a society in reaching these patients. Because it's a genetic disease and it's been understood for a long period of time, it's actually part of newborn screening. Despite it being part of newborn screening, half of newborns are missed. We've got to do a better job, and there is the technology already available to be able to be more effective in finding these patients. We believe that through those efforts, we'll be able to reach and identify and diagnose more of these patients, diagnose them earlier. Because there's essentially no effective therapies for many of these patients, many of these patients just are lost to follow-up, and they don't go to their physician because the physician's going to say: What are you doing with your diet? No one wants to hear that. So we believe that over time, what is a current addressable population of about 3,500 should grow to well over 5,000, representing a significant opportunity. But we also believe that we have an opportunity with pegtibatinase because it's the only therapy currently in development that really, we believe, addresses the fundamental defect in this disease and can be disease-modifying. It's a pegylated enzyme that essentially replaces the role that native CBS enzyme does in metabolizing homocysteine. All of the data that we have thus far in animal models, as well as humans, reflects that it acts and behaves very similar to the CBS enzyme. It's administered subcutaneously twice a week at our target dose, and we have FDA breakthrough therapy designation, rare pediatric designation, we have orphan designation in U.S. and Europe, and we have fast track. We've really been able to leverage the breakthrough designation, have very collaborative discussions in helping to work with the FDA to come up with what we believe is now a very innovative phase 3 design that should address not just the needs of regulators, but also of patients. And that was really based on our phase 2 COMPOSE study. You can see the top-line data here in the reduction of homocysteine levels at the target dose of 2.5 mg per kg, 67% average reduction in total homocysteine versus essentially zero on placebo. 100% of the patients are able to get below the guideline level of 100 micromolar. Half of the patients were able to get below 50, which is essentially how physicians think about whether they will be able to introduce some kind of protein into their diet. One patient in our target dose was able to be normalized. Incredibly encouraging and one that we believe just really gives a lot of wind at our back and a lot of excitement amongst the HCU community. So when we look at our phase 3 HARMONY program, which was initiated last month, and we expect to have top-line data in 2026, it's innovative for a couple of different ways. One is we want to make sure that we're able to address what does FDA need? Reduction in total homocysteine levels. That's our primary endpoint, which is the measure, the average reduction in total homocysteine between weeks six and 12, averaged during that time period. Secondary endpoint is looking at durability of that over 24 weeks. There's about a six- to 10-week screening period to be able to stabilize their diet so that we can minimize any variability or, within the double-blind period to make sure, given that diet is such a critical part of how a patient's homocysteine level behaves. And then we have an ENSEMBLE, open-label extension that really is going to be looking not just at longer-term safety and efficacy, but perhaps for the first time in our knowledge, is to protocolize a diet as an endpoint. Being able to look at how these patients are able to increase protein intake and really start to normalize diet, diet in many ways, which we believe is going to be very exciting. So we're, we're excited, about the opportunity now we have with pegtibatinase. Financial snapshot. We ended last year, this is unaudited, preliminary of $567 million in cash on the balance sheet. Our cash runway gets us into 2028, so we're well-capitalized to invest in both our FILSPARI launch as well as the continued development of pegtibatinase. And we have net product sales of $40 million, $40 million in the fourth quarter, again, 15 of which is from FILSPARI. And then just to end, we've got an exciting year ahead. Really, it's a year of execution, both of the launch and our clinical development program. And along the way, we have two very important regulatory updates. The first is for full approval in the U.S. for IgAN. We will be submitting our sNDA this quarter. We expect to have in the second half, if we get prior review, it'll be third quarter, and then we expect to hear opinion from CHMP for the approval in Europe, this quarter, with potential approval, 67 days thereafter. So, and along the way, clinical data from our ongoing programs. So with that, thank you for the time, and Anupam, I'll take any questions. Yeah. Thanks, Eric. So many of you have heard this before, but there are three ways to ask a question. If you old school way, just raise your hand and I'll call on you. There's the new school way, where if you have access to the portal, submit your question, it'll show up on the iPad. I'll ask it anonymously, or you can just email me, and I'll do the same thing. So I will start, and then we'll see if there's any questions from the audience. So what are the final gating factors to getting that two-year PROTECT data submitted for FILSPARI this quarter? Well, essentially, there's nothing further gating other than our teams writing the rest of the sNDA. We've had a very productive pre-NDA meeting last year, where FDA essentially said, "We agree with your plans to submit for full approval. What we want to see is additional sensitivity analyses, given that we're all learning, they're learning about, you know, the measure of eGFR over time." They've also asked for some additional cuts of the data to be able to look at how we would expand the indication statement to show consistency of benefit across different subcuts of baseline characteristics. Those are the things that FDA asked for. Those are the things that we're now including in the sNDA, but we are on track to submit this quarter. And have US regulators noted anything particular about reassessing the black box warnings of hepatotoxicity as part of the sNDA review process? Well, when they first told us that they were going to require a REMS for liver monitoring and potential hepatotoxicity, they did indicate that this was out of an abundance of caution, given that this is through accelerated approval and other endothelin antagonists have had it, although not all. They did say that they are open with additional data to reevaluating the need for REMS. We did not have that as part of the discussion with our pre-NDA, but we do plan with two opportunities this year. The first is with the integrated safety database that we will be submitting. We not only have the two-year data from PROTECT, but we have the two-year data from DUPLEX and FSGS, which is studied at double the dose. So we believe that there is a robust safety data set now. We also have the required one-year safety update that will be submitted this quarter, given that we had approval in February. So that really is the first opportunity, and as we look to discuss and evaluate labeling through this sNDA process, that's the point at which we will be requesting, you know, changes of removal of the REMS. Question from the audience? I think your oral explanation in EU was in December, right? So you should be hearing from CHMP probably this month, right? So we would expect to hear this quarter. Now, we were a possible topic for oral explanation, but maybe I can provide a little bit of context for that process because it, I think, is quite unique for us. We were put onto the agenda as a potential topic because we didn't have all of our questions answered at that time. And that was primarily because we had submitted the two-year confirmatory data during the review. Now, in many ways, that's very reassuring, we would imagine, for regulators, because they now have the confirmatory endpoint, which was positive for EMA, while they're reviewing the application for conditional marketing authorization. We've realized in that process that we've answered all the questions, and they took us off the agenda, so there was no need for us to have an oral explanation. So essentially, what they've done is they've said, "Let's have a clock stop," so that they can have time to more fully evaluate the two-year data, and that now puts us on track for the opinion this quarter. Questions from the audience? Yeah. On average, how long do you expect patients to be on treatment? This would be a chronic treatment. As we look at patients with IgA nephropathy, essentially, they're going to have a disease process within their kidney and overactivation of the RAS system as well as endothelin, you know, as long as there is evidence of disease. And so like patients that are currently treated on ACE and ARB, it's a chronic condition, a chronic treatment. You said that it is the disease was trying? ... So pegtibatinase for homocystinuria would be disease-modifying, as we see that we essentially are replacing the enzyme, the native enzyme. And, you know, what we've seen evidence of, you know, thus far in animal models would be disease modifying. Thanks. Yeah, Sean? Back there. I believe you've communicated that your base case for sparsentan IP is into the 2030s. Can you speak to potential actions you could take to continue shoring up the IP position, and if we should expect any updates on that this year? Sure. Our assumption is into 2033 for the U.S., and certainly with two landmark studies that were reported last year, as well as a very you know, number of innovative studies that we're doing, we continue to assess whether there are additional avenues for IP. But until things are granted, we wouldn't be able to provide any further updates beyond 2033 at this point. On patient start forms, where are you seeing that growth from? Is it from new prescribers or from more repeat prescribers? So as someone who's launched many therapies and spent most of my career in commercial, this is one that I obsess over. And I am very pleased that we are seeing that continued expansion of new prescribers, as well as a very steady trend in repeat prescriptions. And we did see a trend break in the fourth quarter, where we saw a significant inflection in new prescribers, and that really was correlated with the ASN meeting. And in fact, after the ASN meeting, we saw an uptick in the number of thought leaders or KOLs that we track prescribing. In fact, we now have the majority of KOLs in the U.S. prescribing FILSPARI. And then, with regard to repeat prescriptions, this really is one where I think is an amazing story, where physicians are seeing very early on the benefit in their patients, which just fuels them looking for additional patients in their practice to treat. Keep in mind, this is still a rare disease, so it's not as if they see an IgAN patient every day or every week. There's on average about five IgAN patients per nephrologist, so, you know, they're typically seen every three months. So it does take time to get through that process, but we have been very encouraged by the steady trend on both new and repeat prescriptions. Yep. Are all patients eligible or depending on the disease stage? Yes, it's a great question. So our current indication is for patients that are at risk of rapid progression. There are a number of different factors that do put a patient at that risk. The most commonly understood is proteinuria, but there are others based on biopsy, based on ethnicity. Patients of East Asian descent are at greater risk of rapid progression. So there are a number of things that the physicians consider. And what we've seen with regard to payer access is that, you know, it is very aligned with our label, and they are open to the different risk factors that patients may present with. There are biomarkers that can show the progression of the disease or if they are responding, et cetera? That's right. And that's really where proteinuria, which is such a commonly used measure- Um. -that's the biomarker, as well as a measure of response. Okay. Yes. Yeah. I was just wondering if you could talk a little bit about the way you see the competitive environment evolving over the next three-five years with competitors like TARPEYO and then iptacopan coming? Yeah. I think I'll go back to the two-prong approach that we see. Addressing nephroprotection in the kidney and addressing, you know, preventing further injury more upstream through immunosuppression. Largely, we don't believe that there is any direct competitor other than another endothelin blockade because it's half of the mechanism that we have with sparsentan. So essentially, what we see, for example, with TARPEYO, is they're addressing the, you know, prevention of further upstream injury, and we address the overactivation in the kidney and are nephroprotective. So we believe, and as we've seen in the fourth quarter, there was a step change in the expansion of the dynamic market of new patients that are being treated with either FILSPARI or with TARPEYO. We think that that's only going to continue with greater awareness and guideline changes. As we look, you know, several years out, as there are new modalities that could come to the market, largely, I think most of the competition is going to be for that upstream. There's very few treatment options other than generic ACEs and ARBs to address the nephroprotection within the kidney. So we think that we're very uniquely positioned, and again, we're the only trial designed to be able to show superiority over the current standard of care, which we think FILSPARI should now become the foundation upon which you can add other immunosuppressants or other treatment modalities. I think it's really important to keep in mind that FILSPARI is non-immunosuppressive, which really allows it for longer-term use. I think there will be lots of questions about what is the longer-term benefit of some of these other treatment modalities. Other questions from the audience? Maybe I could squeeze a couple in on pegtibatinase. Sure. Yes, please. Where are you in terms of, like, site initiation, and how's the geographies for the sites going to break down? Well, first of all, thank you for asking about pegtibatinase, because we think it's an underappreciated opportunity and one we are very excited to talk about. We have already initiated sites as the trial was initiated last month. We are starting first with sites in the U.S., and then we'll look to move to other geographies. You'll see that many of the patients are in U.S., Europe, and Middle East, and that's really largely where we look to have our clinical trial footprint. We will look to expand the number of sites, but we're going to start in a very measured way to make sure that we have a great experience for these patients so that we can really, you know, accelerate from there. But we're well on track with those first sites. Have U.S. and E.U. regulators noted anything about correlating reduction in homocysteine levels to functional outcomes for an approval? That was definitely part of our discussions, and this is where, again, having breakthrough therapy designation has helped because we've had very regular discussions to help in educating the agency around this disease. And they certainly recognize that if we were to look at any clinical outcomes in a 24-week or any foreseeable time frame, it'd be incredibly difficult because the time course of these, like an ischemic event, is variable, and it would be very difficult to power a study within a disease prevalence such as this. We do have a natural history study that we've used to be able to correlate total homocysteine levels with measures such as neurocognitive symptoms, and I think FDA was very comfortable with the package that we have. I think one of the very exciting things about this program is that they also are encouraged by looking at diet and protein modification in our Phase 3 program as not only a PRO, but also a clinical endpoint, all of which we believe will help in bolstering the program. But fundamentally, we have agreement to use total homocysteine as the endpoint, as a biomarker for full approval. Great. If there are no other questions, thank you, Eric. Okay. Thank you very much.