Hello, ladies and gentlemen, thank you for standing by. Welcome to the Travere Therapeutics Corporate Update Call. I would now like to turn the call over to your host, Naomi Eichenbaum, Vice President of Investor Relations. Ms. Eichenbaum, please go ahead. Thank you, Marjorie, thank you all for joining us today. Earlier today, we issued a press release covering the top-line results from the phase 3 DUPLEX study evaluating sparsentan for the treatment of focal segmental glomerulosclerosis, or FSGS. A copy of the press release, along with the slides that we will be reviewing on today's call, are available on our website. Today's call will be led by our Chief Executive Officer, Dr. Eric Dube. Joining Eric will be our Chief Medical Officer, Dr. Jula Inrig, and our SVP of Research and Development, Dr. Bill Rote, will be available during the Q&A session. Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of future performance. They involve known and unknown risks, uncertainties, and assumptions that may cause our actual results, performance, and achievements to differ materially from those expressed or implied by such statements. Please refer to today's press release and accompanying slide deck, as well as risk factors and sections of our annual report on Form 10-K filed with the SEC. In addition, any forward-looking statements represent our views as of today, May 1st, 2023, and we specifically disclaim any obligation to update such statements to reflect future information, events, or circumstances. With that, let me now turn the call over to our Chief Executive Officer, Dr. Eric Dube. Eric? Thank you, Naomi, and thank you everyone for joining today's call on such short notice. First off, I would like to thank everyone who contributed to getting us here today. In particular, I would like to recognize the patients, their families and caregivers, the physicians and research teams participating in this study, as well as the clinical trial site staff, all whose participation has led to the ongoing development of sparsentan for FSGS. I would also like to thank our employees, all of whom have been dedicated to advancing the DUPLEX study over the past five years, as it has certainly been a meaningful accomplishment completing the double-blind portion of the trial, which is the largest interventional active controlled clinical study in FSGS to date. Our dedication has been driven by a deep commitment to FSGS because we know that as a leading glomerular cause of kidney failure, there is a substantial impact on patients and their families. FSGS is an exceptionally complex, rare disease that rapidly progresses to kidney failure and dialysis. Even with a kidney transplant, 40% of FSGS patients experience disease recurrence. With no FDA-approved medicines and a growing incidence, the unmet need in FSGS is incredibly high. Today, we are disappointed to share the news that the DUPLEX study did not achieve the pre-specified primary efficacy endpoint of eGFR total or chronic slope following 108 weeks of treatment. We are encouraged by the fact that all secondary and top-line exploratory endpoints trended favorably. Notably, we observed a durable reduction of proteinuria with sparsentan compared to irbesartan out to 108 weeks of treatment, including a continuation of the benefit in FPRE measurement that was achieved at the interim analysis. These data show consistent activity of sparsentan, including a sustained 50% reduction in proteinuria and could be indicative of a long-term benefit with sparsentan in FSGS. Importantly, treatment with sparsentan in the DUPLEX study was well-tolerated, appeared consistent with the previously observed safety profile and comparable to irbesartan. These findings are particularly noteworthy as sparsentan was evaluated in the DUPLEX study at 800 milligrams, a dose 2x higher than the dose in the PROTECT study in IgAN and over the two-year period, building upon the existing known profile observed across all clinical experience to date. While the data did not achieve statistical significance on the eGFR slopes, we believe there is strong rationale to engage with regulators to understand if there is a path to enabling sparsentan to have a role in treating FSGS. In particular, we believe that the trends on eGFR slope and the sustained proteinuria reduction paired with the well-tolerated safety profile observed in the study give us reasons to present the totality of the sparsentan data and explore a potential path to registration. As a next step, we will be engaging as soon as possible with the FDA. We will also be working with our collaborator, CSL Vifor, to engage with the EMA for guidance in Europe. Lastly, I would like to highlight that the DUPLEX study is the largest and most robust clinical trial in FSGS, and it was incredibly well run. This is not a small feat given the complex nature of FSGS, the global footprint of the study, and the five years in duration. The investigators and site staff focused on supporting patients throughout the trial and enabled a very high-quality readout. This is just the top-line data set, so we will be somewhat limited in what we can answer today. Once we have time to do more analyses, we will provide further information in the appropriate forums. With that, let me turn the call now over to Jula to walk through the data. Jula? Thanks, Eric. Good afternoon to everyone. I'd also like to start by thanking the patients, their families, caregivers, investigators, and site staff, as well as patient advocacy groups and our research partners, all of whom have been critical to completing the double-blinded portion of the DUPLEX study. We are incredibly grateful for the many years of dedication and commitment from so many people which has led us to where we are today. While FSGS is a histopathologic lesion, the disease and its manifestations can be quite severe, causing significantly impaired quality of life and progression to kidney failure within five to 10 years. In FSGS, endothelin-1 and angiotensin II are key mediators of damage and act in tandem via the ETA and AT1 receptors to exacerbate podocyte pathology and drive podocyte damage, inflammation and sclerosis, and heavy proteinuria. Elevated proteinuria increases the risk of FSGS disease progression, one of the treatment goals for patients is proteinuria reduction and remission, which correlates with kidney survival. This was the efficacy objective of the phase 3 DUPLEX study, which explored the long-term antiproteinuric effect and nephroprotective potential of sparsentan. The DUPLEX study is a global, multicenter, double-blind, parallel-arm, active-control trial evaluating the safety and efficacy of sparsentan in 371 pediatric and adult patients with FSGS, ages eight to 75 in the U.S. and the U.K., and adults ages 18 to 75 in the rest of the world. At screening, patients were required to have greater than or equal to 1.5 grams per gram of proteinuria, an eGFR greater than or equal to 30, and biopsy or genetic-confirmed FSGS. Of note, the DUPLEX study design is different from our PROTECT study for IgA nephropathy in that patients in the DUPLEX study were not required to be on a max tolerated dose of an ACE inhibitor or ARB for 12 weeks prior to screening. Following screening in DUPLEX, patients stopped ACE inhibitors and/or ARB therapy during a two-week washout period and then were randomized one-to-one to receive initial doses of 400 milligrams of sparsentan or 150 milligrams of irbesartan. Patients were titrated up to the maximum dose of 800 milligrams of sparsentan or 300 milligrams of irbesartan as tolerated over a two-week period. Demographic characteristics in the DUPLEX study were generally representative of primary and genetic FSGS, with enrollment of nearly 10% pediatric patients. Importantly, baseline characteristics were well-balanced between arms. RAS inhibitor background therapy had been used in nearly 80% of patients prior to the required two-week washout. The primary efficacy endpoint in DUPLEX was the slope of eGFR over two years. The slope of eGFR following the initiation of randomized treatment from day one to week 108 is referred to as the eGFR total slope. The slope of eGFR following the initial acute effect of randomized treatment from week six to week 108 is referred to as chronic slope. While both the eGFR total and chronic slopes are estimated using all on-treatment data from baseline up to week 108, the model for chronic slope specifies an inflection point at week six to account for the known acute effect of sparsentan on eGFR. For the two-year analysis, the pre-specified statistical analysis plan called for a hierarchical assessment of the primary endpoint, beginning with total slope for the U.S. regulators and beginning with chronic slope for Europe. When evaluating the primary efficacy endpoint of eGFR slope following 108 weeks of treatment, the annualized treatment difference in total slopes was 0.3 mL per minute per year in favor of sparsentan, which was not statistically significant compared to the active control irbesartan. The annualized treatment difference in chronic eGFR slopes was 0.9 mL per minute per year in favor of sparsentan, which is in the range of what has been considered clinically meaningful but was not statistically significant compared to the active control irbesartan. Here, patients treated with sparsentan showed a slope decline of - 4.8 mLs per minute per year as compared to - 5.7 mLs per minute per year for those receiving irbesartan. When looking at the difference between total and chronic slope, an important element is the acute effect on eGFR seen at the beginning of treatment with sparsentan. This is a known effect of sparsentan's mechanism of action and is well-documented, albeit with smaller magnitudes of effect with nephroprotective therapies such as SGLT2 inhibitors and RAS inhibitors. During the first six weeks of treatment, patients treated with sparsentan on average experienced a 3.3 mLs per minute greater acute decline in eGFR when compared to patients treated with irbesartan. This difference was likely exacerbated by the two-week washout period prior to randomization. Given the clear correlation between persistently elevated proteinuria, greater risk of FSGS disease progression, as well as lower quality of life and disease symptoms, we also looked at the durability of effect on proteinuria as part of the top-line analyses. Here, we observed favorable results with sparsentan on proteinuria reduction compared to irbesartan. After 108 weeks of treatment, patients receiving sparsentan achieved a mean reduction in proteinuria from baseline of 50%, compared to a mean reduction in proteinuria from baseline of 32% for irbesartan-treated patients. As complete remission of proteinuria to less than 0.3 grams per gram is an important clinical indicator and quite difficult to achieve in FSGS, we also assessed the rates of complete remission during the two-year period. Importantly, patients on sparsentan were 2 x more likely to achieve complete remission compared to patients on irbesartan. We've also evaluated the combined hard endpoints of confirmed both 40% and 50% reduction in eGFR, end-stage renal disease or death, they're trending in favor of sparsentan. These data build upon the previously reported statistically significant interim efficacy analysis on the FPRE endpoint conducted at 36 weeks, where we observed that 42% of patients receiving sparsentan achieved a urinary protein to creatinine ratio of less than or equal to 1.5 grams per gram and greater than 40% reduction from baseline, compared to 26% of patients receiving irbesartan, representing that patients receiving sparsentan had a 60% greater chance of achieving FPRE compared to irbesartan. Overall in the two-year efficacy results from DUPLEX, we saw clear activity with sparsentan that was consistent with its performance throughout development. Unfortunately, the acute decline in eGFR observed with sparsentan and the magnitude of treatment effect compared to the active comparator in this study likely prevented us from achieving statistical significance on the primary endpoints. Important to note is the heterogeneity in FSGS disease progression, which can contribute to variability. Switching to safety, results from the two-year analysis demonstrated that sparsentan was well-tolerated and has shown a comparable safety profile to irbesartan. The adverse event of interest of AST or ALT of three times upper limit of normal was comparable between sparsentan and irbesartan. It is important to highlight that in this study, we evaluated a higher dose than in IgAN, and we have more than two years of follow-up. We did not see any cases of Hy’s law or drug induced liver injury with sparsentan. We also did not observe any serious adverse events due to congestive heart failure in the double-blind period, and the rates of AEs and SAEs due to edema were directionally lower with sparsentan than irbesartan. These findings build on earlier reported trial results suggesting that sparsentan is generally safe and well-tolerated. It is noteworthy to reiterate the complexity of FSGS, the value of the DUPLEX study as the largest interventional active controlled trial to date, and the importance these trial results will provide for the broader FSGS community. While we are disappointed that the DUPLEX study did not achieve the primary efficacy endpoint, we remain encouraged that the data support the primary scientific hypothesis for sparsentan. Specifically, the inhibition of both endothelin-1 and angiotensin II is important for glomerular disease, as evidenced by the directional trend of sparsentan on eGFR chronic slope and the sustained reduction in proteinuria. We are also impressed with the well-tolerated safety profile that continues to support our confidence in the overall profile of sparsentan. While we have only shared the top-line results today, we'll be working diligently to complete our additional planned analyses to provide further insights into the efficacy and safety of sparsentan as a potential treatment for FSGS. We look forward to sharing these data with regulators in the U.S. and Europe with the goal of exploring a potential regulatory path forward. I'd like to turn the call back over to Eric for next steps and closing remarks. Thanks, Jula. FSGS is a challenging heterogeneous disease, and the DUPLEX study represents a significant step forward in the field of FSGS research. While we are disappointed to not achieve the total and chronic slope endpoints, especially for patients with FSGS who were looking for a clear outcome for sparsentan, we remain encouraged by the eGFR and proteinuria trends seen over two years and a well-tolerated safety profile. These data further support our conviction in the approach of dual antagonism for rare glomerular nephropathies. We will continue to evaluate the data beyond the top-line analysis to further inform our understanding of sparsentan. In the near term, we will engage with the FDA and EMA to explore the potential for future submissions. Once that is complete, we plan to provide an update regarding next steps for the FSGS program. While we encountered complexities in exploring the efficacy of sparsentan in FSGS, our confidence in sparsentan for IgAN remains unchanged. The treatment effect of sparsentan demonstrated in the PROTECT study in IgAN at the interim analysis could not be more clear. As we have seen with other molecules like SGLT2 inhibitors, FSGS is a more difficult disease to show a treatment effect. It is also important to highlight three key differences between the clinical programs that support our expectations for a successful outcome with the PROTECT study. First is that IgAN is a more homogeneous disease with more consistent presentation and progress compared to FSGS. As you can see from the baseline characteristics that have been reported from the two studies, we expect variability in eGFR to be lower in the PROTECT study compared to DUPLEX. While we cannot go into specific interim data from PROTECT at this time, the magnitude of acute difference in eGFR should not be the same as what we observed in DUPLEX. A key component of this is the fact that patients in PROTECT were required to be on max-tolerated ACE or ARB therapy leading into the study, and there was no washout period. Perhaps most importantly, we saw a greater relative effect size on proteinuria with sparsentan versus irbesartan in PROTECT at the interim assessment. In PROTECT, we observed a magnitude of difference in proteinuria reduction in favor of sparsentan that was roughly two times larger than DUPLEX. The robust literature, recent precedent studies, and eGFR trends that were observed at the interim all support that we should expect a clinically meaningful benefit on eGFR at two years. Taking these differences into account, we remain highly confident in the expected benefit with sparsentan on eGFR in IgAN at two years, we are on track to report these results in the fourth quarter of this year. While we have work to do to further analyze the data from DUPLEX and engaging with regulators to explore potential paths forward for sparsentan and FSGS, our future remains very bright. In our upcoming first quarter earnings call on Thursday, we look forward to sharing an update on our commercial progress for the ongoing launch in IgAN and highlighting progress towards our additional clinical and regulatory milestones still to come this year. With that, I'd like to turn the call back over to the operator to take your questions. Operator? Thank you very much, sir. Ladies and gentlemen, if you would like to ask a question, please press star one on your telephone keypads. If you're using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, that is star one to ask a question. We will now take a moment to assemble that queue. We'll take our first question from Joseph Schwartz from SVB Securities. Hi. Thanks very much. My condolences on the outcomes here. I was wondering, now that you have these results, Well, really, I was hoping if you could tell us how they compare to your powering assumptions for DUPLEX so we can understand why the proteinuria benefits shown by the drug did not translate into a stat sig benefit on eGFR. Thank you. Thanks, Joe, and I'll turn that question over to Jula. Thanks, Joe, for the question. You see, we did see a consistent and durable improvement in proteinuria with sparsentan, which importantly is consistent across all tri-trials, and we saw a trend toward improved eGFR. To your point, we were powered based on the magnitude of treatment effect that we saw in DUET at eight weeks, and we had little data to know how irbesartan would do over a longer period of time in FSGS. However, irbesartan, as you can see, performed better than we anticipated and with a more durable response than anticipated. I'd point out a couple of other notable things. We had an acute hemodynamic effect to overcome. We had a wide range of eGFRs and stages of FSGS, including disease severity. FSGS has kind of a variable disease progression, which can be relapsing and remitting and unpredictable. These and other factors we're going to need to explore because we believe they added to the variability and impacted our ability to achieve statistical significance, even if we saw trends in the right direction. Okay. What kind of analyses will you be doing and bringing to the FDA to see if they resonate enough that you can still file on this? Well, we're going to do a number of sensitivity analysis around our primary. Then of course, we're going to do additional subgroups analysis. We still have to complete our primary analysis set as well. Okay. Thanks. I'll get back in the queue. Thanks, Joe. Thank you very much. We'll take our next question from Maury Raycroft from Jefferies. Please go ahead. Hi. Thanks for taking my questions. Just wondering if you'd talk a little bit more about scenarios for next steps in respects to a conversation with FDA and what timing could look like for that FDA meeting and public update? Based on your prior conversations with regulators, can you talk more about how FDA is weighing the data? Do you think they'll ask for an additional study? If so, what could the size and scope of that study look like? Maury, thanks for the questions, and I'll turn that over to Bill. Yeah, thanks. Thanks, Maury. I think that, you know, as Jula just noted, we've got top-line data now. We have a fair amount of analysis for the full two-year data set to complete, and there's some specific subgroup analyses that we want to put together before we engage with the agency. We, as you can imagine, have a sense of urgency around doing that. Your, to your question around timing, we need to complete some analysis on our side and put together a briefing book and a request for the agency. We're, we're probably looking at a summertime meeting and then a month later having minutes from that. I think that, you know, your, part of your question was around the FDA's perspective. We won't know that until we speak to them. Really, I can't speak for the agency at this point, but we are interested in engaging with them because they've maintained throughout our conversations, an alignment with us that this is a rare disease that has a very high unmet medical need. There's no approved therapies for these patients. They, they've also commented in the past that this is a difficult disease to study and difficult space to run clinical trials. You know, I'm anxious to have that conversation with them. We just need to do the work to prepare to have those conversations. I think lastly, you asked about a subsequent trial. I think it's premature to discuss a potential next trial. I think we've got to get through, those conversations, and go over the study data with the agency in some detail before I would have a perspective on that. Got it. That makes sense. Maybe one other question for the subgroups? I think Jula mentioned the range of severity for FSGS and also eGFRs. Are there certain subgroups where you're seeing a stat sig difference? Is there any more that you're saying about the subgroup analyses? At this point in time, we're just talking about the top-line data. We've just unblinded the study and put together the top line. We need to do the work to understand the different subgroups and how they performed. We're not prepared to discuss that today. Got it. Okay, thanks for taking my questions. Thanks, Maury. Certainly. Thank you. Our next question comes from Greg Harrison from Bank of America. Please go ahead. Hi, thanks for taking the question. What does this data set mean for your confidence heading into the confirmatory endpoint for IgAN? Understood that FSGS is a more heterogeneous disease, but is there a concern that maybe irbesartan provides a more difficult comparison in that trial as well? Greg, thanks for the question. I think, you know, we remain highly confident in PROTECT and, you know, what our assumptions are for eGFR. I'll ask Jula to comment on how irbesartan has performed and why we see a difference between these two trials in that regard. Thanks for the question, Greg. I'd start with saying that the diseases are quite different. FSGS is a relapsing-remitting disease, versus IgAN is continuously progressive disease with regards to eGFR, so different with regards to the heterogeneity. The other thing I'll point out with regards to the potential for an acute hemodynamic effect, in FSGS, you have hyperfiltration similar to diabetic kidney disease, which has a greater potential for an acute hemodynamic effect, which we don't expect to see in IgAN. The study designs were also different. We had a washout in DUPLEX, which again, can contribute to that acute hemodynamic effect, which we didn't do in PROTECT. We don't expect to see that in PROTECT. The other thing I'll point out is the magnitude of treatment effect and difference that we saw in PROTECT versus DUPLEX. We saw a consistent treatment effect of 50% reduction with sparsentan in PROTECT and in DUPLEX. The irbesartan arm was significantly greater in DUPLEX versus in PROTECT. We saw a 15% reduction in PROTECT. We didn't see that magnitude. We saw a much greater magnitude in DUPLEX. I'd also like to point out, we see something similar with the SGLT2 inhibitor trials. We've seen this pattern. Much less ability to show a treatment effect on eGFR in FSGS versus an IgAN in the SGLT2 inhibitor trials. Okay. That's really helpful. Then maybe one more quick one. How did the hemodynamic effect for irbesartan compare with your expectations? Jula? Yeah, I'd say it was in line with what I would expect. Okay. Thanks for taking the question. Thanks, Greg. Thank you very much. Our next question comes from Tim Lugo from William Blair. Thanks for taking my question. Can you comment at all on the differences you see in the baseline data within DUPLEX? You know, maybe not between trials, but within DUPLEX, which may have clouded results? I guess as I was looking through it, I'm wondering if that 76% of patients in the irbesartan arm that had been had prior RAS use, maybe was that kinda maybe a little lower than expected versus the sparsentan arm, and maybe that complicated results a bit? Yeah, I would say, you know, largely we're seeing consistency across the two groups in DUPLEX. I don't know that there's anything that we've seen that would help in explaining the results. I think you do see numeric imbalance there. Julie, I don't know if you wanna talk about that, but at this point there's, you know... We'll continue to explore whether there were any subgroups that drove a differential effect. At this point, I think that the study is well-balanced across treatment arms. Jula, anything further that you'd want to add? No, nothing further. We haven't explored those subgroup analysis yet to be able to speak with further clarity. Okay. Thank you. Thanks, Tim. Thank you. Our next question comes from Vamil Divan from Guggenheim Securities. Oh, his line disconnected. Vamil, if you can hear me, if you would re-queue, please. In the meantime, we'll go next to Mohit Bansal from Wells Fargo. Hi, this is Adam on for Mohit. Thanks for taking our question. When the FDA reviews the data and sees the difference versus irbesartan on proteinuria, do you think that there's potential they see that favorably despite that it didn't translate to an eGFR benefit based on past meta-analysis data? Adam, thank you for the question. Maybe I'll provide an overview and I'll ask for Bill to provide any further. I think it's difficult for us to speak for FDA. You know, our assessment is that the consistent benefit that we see on proteinuria from week 36 and beyond is meaningful for these patients. We do know that proteinuria is a marker of damage, but also can be directly damaging itself for persistent proteinuria. It is what we believe is part of the totality of the data and again, is certainly consistent across all of our trials to date. Bill, Jula, anything further that you would like to add to Adam's question? Yeah. Let me just add that it is important, and from a patient perspective, the reduction of proteinuria can have a benefit with regards to the symptomatology over time, and we did see trends toward lower rates of edema. We will be looking at quality of life over time, and I do think that's important. To add to Eric's point, I would say that the rate of eGFR decline within the patients on the irbesartan arm of -5.7 mL per minute is lower than what you would anticipate in this disease course of patients who are rapidly progressing. I do think that they saw a benefit on eGFR better than what we would expect for historical control, where we would anticipate that they would be progressing 7 mL-10 mL per minute per year. I think the totality of the data needs to be taken into consideration and all taken into context. We'll next go to Vamil Divan from Guggenheim Securities. Can you hear me now? Yes, we can hear you, Vamil. Okay. Okay, sorry about that. Not sure what happened. I just had one question. Maybe if you can just remind us, obviously, the key difference here between this one and PROTECT is the fact that people did not have to be on optimized ARB therapy in the washout. Can you just remind us why the difference between the two studies was set up the way it was? Sure. I think we can certainly speak to the rationale at the time being that there is a variability in how patients are treated with FSGS compared to for IgA nephropathy. In order to get a consistent evaluation across treatment arms, patients were washed out to ensure that there is consistent effect from randomization. That is quite different from the trial design in PROTECT and also in how patients are treated, where, you know, the overwhelming majority of these patients are on ACE or ARB. We'll be evaluating, you know, what, if any effect that washout period might have had in the higher response that we saw with irbesartan. Okay. Appreciate your comment on the next steps with the agencies in terms of presentation of the data. Do you think some of this may be available for presentation next month at ERA, or is it more like second half of the year before we see more details publicly? Jula, would you like to take that? The ERA late breaker has passed before we got our top line results, so I wouldn't anticipate we would be able to at ERA, so anticipate at a later meeting this year. We would like to be able to present the totality of the data. Again, as we just have scratched the surface on our understanding, we'd like to be able to complete more of our analysis before we are able to present it at a congress. Okay. Thank you. Thank you. We'll take our next question from Carter Gould from Barclays. Good afternoon. Sorry for the outcome here. Maybe following on the prior question for a second, maybe just talk about sort of, I guess, your commitment to share any subgroup analyses that you will go to FDA with prior to going with FDA. I mean, can investors expect to see that before you, I guess, meet with FDA? Acknowledging all the nuances and differences between the indications, Eric, maybe just talk about, you know, any impact you see here relative, you know, on the launch. Again, I know you guys have talked in the past around this being a data-dependent community. This clearly is a negative, you know, data point. Just how you see that impacting the launch, if at all. Thank you. Yeah, thank you for the questions, Carter. I'll take the first one. Sorry, I'll take the second one first, which is the potential impact on launch. I think, you know, it's certainly early days. We are continuing, you know, to execute on our launch. We'll share more details about how that is going on our earnings call on Thursday. As we look forward, I think it's really important for us to educate nephrologists about the data that we have with PROTECT. I think we're very proud of the quality of data that we've seen at the interim. That is certainly reflected in the high-quality publication recently in The Lancet, where we are able to share a bit of information about the profile of sparsentan and the very robust treatment effect versus irbesartan in that trial. We will continue to make sure that we articulate the differences. I think the differences between these two diseases is well understood by many nephrologists. I think our focus is to continue to make sure that we can educate and ensure that the IgAN community is able to benefit from FILSPARI. We'll also continue to engage to understand how the results that we've announced just now are understood and the reaction from the nephrology community. Julie, anything further that you'd wanna answer on that question as well as take the question on whether we'll share subgroup analyses before the FDA? I don't anticipate sharing before we go to the FDA. I think we'd want to have greater clarity. We're gonna take a little bit more time to do some of these analyses and then be able to present them in a high-quality congress as well as journal. Just give us a little bit more time on that. Understood. Thank you. Thank you. We'll take our next question from Liisa Bayko from Evercore. Please go ahead. Hi. Just a couple questions for me. First, I know you looked at four weeks post-treatment. Do you have that data yet that you can discuss? Thanks, Liisa. Jula, would you like to take that? Everything trended in a positive direction with regards to the secondary endpoints. We did not put that in our press release. We'll be releasing that at a future time. Okay. Just as it relates to PROTECT, I see the acute effect differential here is minus, you know, 3.3 sparsentan versus irbesartan. Is that the right magnitude to think about, like, if you were, you know, in the scenario of PROTECT where you're sort of on max tolerated headed into the study, that you'd still have around a three-point differential for sparsentan? Is that the right way to think about it? Jula? I wouldn't expect to see that magnitude of a differential effect between sparsentan and irbesartan in IgAN. Because patients are fully optimized and on a high dose, you wouldn't expect to see as great of a differential. The other thing that I'll point out, I would predict less of an acute decline in IgAN because they don't have hyperfiltration at baseline. That's the other thing that would make me anticipate the less of an acute hemodynamic effect. It's a different disease and pathophysiology than FSGS and from diabetic kidney disease. Two things to point out for why I don't anticipate as large of a delta. Okay. Let's see here. I think that's it for me. Thank you so much. Thank you, Lisa. Thank you. Our next question comes from Laura Chico from Wedbush Securities. Please go ahead. Hi, thank you very much. I guess one question in terms of the renal outcomes endpoints. I'm just curious if you can comment in terms of was this the overall event rate, was this lower or in line with your expectations? Laura, thanks for the great question. Jula, would you like to take that? I would say FSGS, as we've said before, is a rapidly progressive disease and we enrolled a wide range of eGFR. Some of the patients had lower eGFR at baseline, so we had a fair number of events. I would say it was relatively in line with our expectation with regards to the number of patients who hit kidney failure, and, you know, eGFR confirmed less than 15%. As you see, we looked at the 40% reduction in eGFR, which when you have patients in the high range and are declining, which that's potentially a beneficial thing, sometimes that can add noise. That's why we also looked at the 50% reduction in eGFR. I would say the take-home message is this is the largest conducted trial in FSGS with the greatest number of endpoints in a well-designed trial. I think this adds a significant amount of benefit to the field with regards to this. Importantly, all the endpoints trended in the right direction, favoring sparsentan versus irbesartan. Okay, that's helpful. I guess maybe one follow-up, and I'll ask this a little bit differently than was asked previously, but just given the body of work here from DUPLEX and the learnings that you're getting out of this, what is your appetite for conducting another clinical trial in FSGS if that's ultimately necessary? Do you feel like you can identify appropriate subgroups and have a better fix on certain elements here? Thank you. Yeah, Laura, maybe I'll take that. I think we have a lot to learn from what we would consider a landmark trial within this space. I mean, this is the largest study ever conducted within FSGS. I think we have just started to understand, you know, what the disease as well as what this mechanism with sparsentan can do. I think it would be premature for us to talk about whether there's a need to do a second study and also how we might go about that. We definitely want to make sure that we're contributing to our understanding of FSGS and certainly, you know, have discussions with regulators before commenting further on a potential path. Thanks very much. Thank you. Thank you. Our next question comes from Alex Thompson from Stifel. Please go ahead. Hey, guys. Pat Culliton for Alex. I guess, building on Greg's question earlier on PROTECT, do you guys expect UPCR to remain flat in IgAN after 36 weeks? You know, in the active control arm with only a 15% change in baseline UPCR at week 36, is there opportunity for that to materially increase over time? Any concern that that effect size could shrink? Thanks. Thank you for the question. Jula, would you like to take that? I would point you to what we've seen in the DUPLEX trial with regard to the magnitude of effect on UPC. Even though it's a different disease, we had a durable treatment effect on the UPC over time, and we also saw that in DUET. With regards to in PROTECT, I would say it's a continuously progressive disease, and I would anticipate to have a continued magnitude on proteinuria over time. There's nothing that makes me believe within IgAN nephropathy that we would lose efficacy over time. I actually think that we might gain efficacy over time as we continue to have remodeling within the kidney and have beneficial effects rather than the kind of more the relapsing remitting in FSGS. Whether or not you're going to see much additional benefit in irbesartan, I don't think we're going to have an incremental benefit over time. If so, it's going to be negligible because remember, these patients were already optimized. They had whatever benefit they would have gained from treatment would have already been accrued over time in the period prior to coming in to PROTECT. The only reason I actually think we get that 15% additional benefit with irbesartan is because we made patients take every single pill, and we counted them. You're seeing that adherence rate that is 100%, and that's where we're seeing that incremental gain. In addition, we didn't have everyone optimized prior to coming in. It's really those two things. You know, we had about 65-ish% on the max dose. Now we've got almost everyone on max dose in PROTECT. It's quite different. Yeah. I think taking a step back to your question, I think we would expect that treatment effect on UPC to be sustained if we see a similar pattern of results from DUPLEX. I think the one thing that we also are seeing now across our three clinical programs is a very consistent profile of sparsentan in proteinuria. I think that gives us confidence that we will see that treatment effect at the end of two years. Great. Thanks, guys. Thank you. Thank you. Our last question in the queue comes from Ed Arce from H.C. Wainwright. Hi, good afternoon, everyone. This is Thomas Yip asking a couple of questions for Ed. First, trying to tease out the regulatory thought dialogue that's ahead of us sometime in the summer. What are some possibility between the FDA and the EMA, specifically regarding sparsentan's positive efficacy in UPCR, PRE and remission rate over irbesartan? Any major differences that you anticipate between the two regulatory agencies? Yeah, thank you for the question. I think it's, we certainly will be presenting, we will plan to present the data from, you know, proteinuria, these endpoints, as well as eGFR to both FDA and EMA. I think it's, we're not in a position to be able to comment on what they might be looking for, but I'll turn it over to Bill to see if he has any comments, further. Yeah. No, I think it's, until we interact and get their feedback, it's hard to handicap them. I will add that, you know, we have two separate filings in the U.S., so we can go FDA. For the EMA, we can engage with them, but we can't submit until after they've made a decision on IgA nephropathy, which we expect later this year, and which would allow the submission. They're a little different procedurally, but we need to have those conversations. Got it. Thank you for the clarification. Perhaps one final question from us. Just trying to narrow down the timeframe of the data set, once you would expect to see it. It sounds like it will be after regulatory discussions, sometime in the mid-year. Perhaps sometimes in the fall timeframe, or what are some possible conferences that we can expect? Yeah, you know, we'll continue to work on what the right opportunity is for us to present any further data. I think our priority right now is to make sure that we complete the primary analyses to ensure a submission to regulators. You know, as we typically do, we will make sure that we provide, you know, an announcement upon, you know, major meetings such as we recently did with ERA or, you know, in the future with ASN as the two major meetings. I think right now we're gonna focus on the analyses for regulators and we'll. You know, if we're in a position to provide any further update on timing for additional analyses, we'll certainly do so. Got it. Thank you so much for the kind of questions. Thank you. Thank you. As a reminder, ladies and gentlemen, that is star one to ask a question. We'll pause for just a moment. With that, we have no further questions. I'd like to turn the call back to Ms. Eichenbaum. Please go ahead. Thank you, Marjorie. Thank you all for joining us on short notice to discuss the update for our sparsentan program in FSGS. We look forward to speaking with you later in the week as we provide our first quarter 2023 results and earnings. Thank you again, have a good night. Thank you. Ladies and gentlemen, that does conclude today's conference. We appreciate your participation, and have a wonderful day.