Good morning. My name is Lisa, and I will be your conference operator today. At this time, I would like to welcome everyone to the Travere Therapeutics Top-Line Interim Results from phase III DUPLEX Study of sparsentan in FSGS Conference Call. All lines have been placed on mute to prevent any background noise. I would now like to turn the call over to Mr. Chris Cline. Please go ahead, sir. Great. Thank you, Lisa. Good morning, and thank you all for joining us on short notice today to talk about the top-line interim results from our ongoing phase III DUPLEX study of sparsentan in FSGS. A copy of the press release announcing the results are available on the investor section of our website. Today's call will be led by Chief Executive Officer, Dr. Eric Dube. Eric will be joined for the prepared remarks by Dr. Noah Rosenberg, our Chief Medical Officer. Dr. Bill Rote, Senior Vice President of Research and Development, will join us for 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 performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the Risk Factors section of our Forms 10-Q, 10-K filed with the SEC. In addition, any forward-looking statements represent our view only as of the date such statements are made, February 2nd, 2021, and Travere Therapeutics specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. With that, let me now turn the call over to Eric. Eric? Thank you, Chris, and good morning, everyone. Thank you for joining us today to talk about the promising top-line interim results from the ongoing DUPLEX study released earlier today. First and foremost, I would like to thank the patients and their caregivers, patient advocacy organizations, and investigators and site staff for their ongoing commitment to our study, particularly in light of the ongoing COVID-19 pandemic. Collectively, they have enabled DUPLEX to become the largest interventional study in FSGS to date, and their continued participation has been instrumental in getting us to this important milestone today. There has been a lack of innovation in rare kidney disorders for decades, and new treatment options are desperately needed to slow the progression to end-stage kidney disease, transplant, and dialysis. For the more than 40,000 patients with FSGS in each of the U.S. and in Europe, there are no approved medicines indicated for their condition. Physicians treating people living with FSGS rely on therapeutic strategies that are limited to ACE inhibitors, ARBs, calcineurin inhibitors, and steroids, and they are often not enough, either due to limited efficacy or long-term safety issues. People with FSGS live every day coping with the fear of seeing their proteinuria increase, signaling progression towards dialysis. It is estimated that 30%-60% of people living with FSGS progress to end-stage kidney disease within 5-10 years, and 50% of patients with severe FSGS progress to kidney failure within 1,000 days of diagnosis. This is why we have made our sparsentan investigational programs the highest development priority at Travere over the last several years. Today, I am pleased to report that our phase III DUPLEX study of sparsentan achieved a statistically significant response on the clinically meaningful interim proteinuria endpoint compared to irbesartan after 36 weeks of treatment. Based on the data from the interim analysis, we intend to pursue submissions for accelerated approval of sparsentan for FSGS. We will continue our engagements with regulators in the first half of 2021, with the objective of sharing additional details from the ongoing study and establishing next steps for filing with the available data set. In tandem, we plan to continue our NDA and CMA preparations, as well as commercial and medical readiness activities to prepare to bring this important treatment to people living with FSGS if approved. Before I turn the call over to Noah, I'd like to remind everyone that DUPLEX is an ongoing study, and as we previously guided, we can provide only limited detail from this interim readout in order to maintain the trial integrity for the full study out to 108 weeks of treatment. Now I'll turn it over to Noah. Noah? Thank you, Eric. Good morning to you all. I'd like to start by repeating Eric's gratitude for all those participating in our DUPLEX study. As you'll recall, the ultimate goal of our sparsentan programs is to deliver the first novel non-immune suppressive medicine indicated for people living with FSGS and IgA nephropathy. The ongoing DUPLEX study in FSGS is a landmark trial and one of the first of its kind. We believe that it has the potential to not only support eventual approval of sparsentan, but to also significantly advance the understanding of FSGS for the nephrology community. It has been informed and designed with the key learnings from the prior successful DUET study of sparsentan in FSGS, and data from more than 600 subjects in aggregate from the program's clinical history. The DUPLEX study is a global, randomized, multi-center, double-blind, parallel arm, active control phase III clinical trial assessing the efficacy and safety of sparsentan in 371 patients ages 8 to 75 years with primary FSGS. After a two-week washout period, patients are randomized 1-to-1 to receive either sparsentan or irbesartan, the active control, and a representative RAS blocker, which is considered standard of care in the absence of an approved medicine for FSGS. Patients are dose-titrated over a two-week period to the maximum dose of 800 mg of sparsentan or 300 mg of irbesartan as tolerated. Overall, we continue to be pleased with the conduct in the study and the commitment of the investigators and site staff. Because the trial is ongoing, we must remain vigilant in the conduct of the trial to ensure a high-quality completion. This means that we will focus on maintaining strong patient retention and minimize any chance of biasing or inadvertent unblinding of the trial. As such, today, we will not be able to provide data beyond the planned interim proteinuria assessment. The DUPLEX study protocol provides for an unblind analysis of at least 190 patients to be performed after 36 weeks of treatment to evaluate the interim efficacy endpoint, which is the proportion of patients achieving an FPRE or FSGS partial remission of proteinuria endpoint, defined as a UPC or urine protein to creatinine ratio of less than or equal to 1.5 gram per gram and a 40% reduction in UPC from baseline at week 36. Complete or partial remission of proteinuria is widely regarded as beneficial in the slowing of progression of FSGS and is recognized as a treatment goal amongst nephrologists. Achieving FPRE has been shown to be a clinically meaningful and robust correlate of kidney survival in patients with primary FSGS. This has been demonstrated across five independent cohorts from clinical trials in the field. As Eric mentioned, the DUPLEX study met its interim FPRE endpoint. After 36 weeks of treatment, 42% of patients receiving sparsentan achieved FPRE compared to 26% of irbesartan-treated patients, and the results were statistically significant with a P value of 0.0094. To date, sparsentan has performed in line with our expectations for FPRE response and consistent with the findings from the phase II DUET study. The confirmatory primary endpoint of the DUPLEX study to support full regulatory approval is the rate of change in eGFR over 108 weeks of treatment. As of the time of the interim analyses, available long-term eGFR data for the confirmatory endpoint were limited, given the long-term nature of this endpoint. Consistent with the DUPLEX study protocol, patients will continue in a blinded manner to assess the treatment effect on eGFR slope over 108 weeks. From a safety perspective, we are very pleased with the interim results, which indicate sparsentan has been generally well-tolerated and that the safety profiles in the study to date have been generally comparable between treatment groups. Of note, the independent data monitoring committee recently completed their fifth scheduled meeting to assess safety in both DUPLEX and PROTECT study in IgA nephropathy, and I am pleased to report that the DMC recommended both studies proceed as planned based upon their safety review. We will not be able to provide further data on efficacy or safety because this is an ongoing trial, and we must do all we can to protect the blind and full completion of the trial to ultimately support full approval. I would like to commend our internal biostatistics and medical teams for achieving an expeditious and high-quality readout. These interim results build upon the foundational evidence generated by the phase II DUET study. We believe these data provide further support for the potential of sparsentan, an innovative product candidate combining selective endothelin A receptor and angiotensin receptor blockade to treat the high unmet need in rare kidney disorders, if approved. I would like to again thank the patients, their caregivers, investigators, and site staff whose continued commitment is critical to reaching this milestone and to ultimately completing this important study for those living with FSGS. As Eric mentioned earlier, we look forward to meeting with regulators in the coming months to share the available data set and establish next steps for potential accelerated approval. I'll now turn the call back over to Eric for his closing comments. Eric? Thanks, Noah. There is a clear unmet need in FSGS, and we are very encouraged by the data released from the DUPLEX study today. We believe this interim analysis brings us another step closer to realizing our goal of delivering a new treatment standard for people living with FSGS. Moving ahead, we look forward to engaging with the FDA and EMA with the available data set from DUPLEX, as well as the robust and supportive data from our previous phase II DUET study. To establish next steps in our intent to pursue accelerated approval. Additionally, we will remain focused on maintaining excellent study conduct and integrity in DUPLEX to enable a high-quality readout of the confirmatory eGFR endpoint. Finally, we are looking forward to the upcoming readout of the PROTECT study of sparsentan in IgA nephropathy. PROTECT remains on track to deliver top-line interim results from its 36-week proteinuria endpoint in the third quarter of this year, and if successful, could serve as the basis for accelerated approval submissions of sparsentan in IgA nephropathy as well. Let me now turn the call back over to Chris for Q&A. Chris? Great. Thanks, Eric. Lisa, can we go ahead and open up the line for Q&A, please? At this time I would like to inform everyone, if you would like to ask a question please press star and then number one on your telephone keypad. Your first question comes from the line of Maury Raycroft with Jefferies. Hi, everyone. Good morning, and much congrats on the update today. Thanks for taking my questions. On your 3Q 2020 call, you implied that it might be important to see a positive trend in eGFR at week 36. I'm not necessarily asking for data on this because it seems like you're not providing much more data, but just asking if there was a positive trend in eGFR at week 36 you can comment on. Yeah. Thank you, Maury, for the question. You're right. As we mentioned, we're going to be very limited in the information that we share. Certainly, we will be looking at data that are going to be critical for our submissions to regulators. Evaluation of the early read of eGFR will certainly be part of that, along with other measures of efficacy and safety. Noah, is there anything else that you'd like to add to Maury's question? Yeah. I think eGFR is a long-term endpoint that really is measurable at 108 weeks, so any look right now would not be fully mature. I think to your point, if we were to speak about it, we would potentially introduce biases to the trial. We need to keep those patients in the study long-term. This is aligned with the regulatory view and in the best interest of the study conduct. I think you covered it well, Eric. Got it. Thank you. I'm also wondering if you can talk more about the correlation between FPRE and predicting eGFR in FSGS. If FDA extrapolates and predicts based on your FPRE results, can we assume the extrapolation will indicate eGFR falls into the approvable scenario, or what else could influence that prediction? Sure. Maybe I'll have Noah talk a bit about some of the existing data and those cohorts that he mentioned to support the development of FPRE. I would say that from a regulatory perspective, we're going to need to continue to meet with them and make sure that we understand what their needs are for data, understanding that they will be looking at FPRE, looking at longer-term eGFR, and certainly assuming that they will evaluate the totality of the data. As Noah mentioned, the eGFR data at this point is not a mature endpoint. It's a 108-week endpoint that is meant to serve the basis for the confirmatory approval. Noah, do you want to share a little bit more about how we're thinking, or maybe Bill, on the way that regulators might be looking at eGFR? I can go ahead and get started, Bill, if you want to follow in. Just, FPRE, as you alluded to, is really a very relevant endpoint given its clinical meaningfulness to kidney survival. It's been linked in databases in a number of studies to improvement in outcomes and stabilization or improvement in eGFR. It's something that across renal diseases has been shown, but also within FSGS. Bill, maybe I'll turn it to you for the regulatory perspective. Certainly. Thanks, Noah. We believe that the FDA is very engaged in the glomerulonephropathy space at looking at the linkage between proteinuria and effects on eGFR, preservation of eGFR based on a reduction in proteinuria. This is evidence based on their interaction with joint workshops with EMA and the National Kidney Foundation and publications that they have participated in. I think that the field as a whole is on the same page here and is enthusiastic about this as a way to provide a tractable development path for innovative therapies in nephrology. Got it. Okay. Thank you very much for taking my questions, and congrats again. I'll hop back into queue. Thank you, Maury. Your next question comes from the line of Michelle Gilson with Canaccord Genuity. Hi. Congratulations, and thank you so much for taking my question. You indicated that you're intending to pursue an accelerated approval submission. Is it safe to assume that results are generally in line with what you've previously discussed with the FDA? Are your plans to reengage regulators to discuss anything specific in the data set that you've observed? Good morning, Michelle, and thanks for your question. We are confident in the interim proteinuria results, and that they can support accelerated approval. As we have been, we'll continue to engage with regulators to make sure that we understand what data analyses they would want to see from this trial, given that it's ongoing and that the evidence we have now is based on a surrogate marker for the longer-term endpoint. We will look to understand and meet their expectations in our file. Certainly, those would be planned meetings that we have in the first half of this year. Okay. If I could, just one more. It looks like the placebo arm outperformed some investor expectations. I'm just curious if what you saw in these results on the proteinuria changes or evolves the way that you think about the study in IgA nephropathy at all. Yeah. Michelle, that's right. The one thing that I will say is that it was an active control, so irbesartan, not placebo. I'll ask Noah to give his perspective on how it performed. Thanks, Michelle. As we've shared previously, we knew there was limited data for irbesartan in FSGS, and this is the first long-term study that includes irbesartan in FSGS. We're learning about this and sparsentan over time. Having said that, we accounted for this level of response in FPRE. Notably, despite the increase in FPRE in the irbesartan arm, we saw a clear difference between arms, and sparsentan showed a statistically significant response. FPRE is a clinically meaningful endpoint, and we are encouraged by the 42% response for patients treated with sparsentan after 36 weeks. Thank you. Congratulations again. Thank you. Thanks. Your next question comes from the line of Joseph Schwartz with SVB Leerink. Good morning. Congratulations on the positive data. I was wondering if you've had the opportunity to look at the proportion of patients that were able to get to other remission thresholds, like complete remission, and tied in with that, if you've been able to analyze the impact of or the benefit of higher doses towards achieving that or FPRE. Joe, good morning. Thank you for your questions. I'm going to reinforce that we're just not going to be able to comment on any of the additional analyses that have or will be conducted in this interim analysis. We really want to ensure that we're not introducing any bias to the trial. I recognize that we're asking for your patience in this, but certainly, we will be looking at a number of different measures of efficacy in this study. Importantly, much of that will be once the study is fully completed. Noah, anything further that you would like to add? I think the key here really is we're charged with the 36-week FPR endpoint, and that's what we've reported out. Obviously, we'll continue to look at additional analyses potentially for the submission. At this time, that's what we're comfortable with. We don't want to do anything, as we said earlier, to impute or bias the results and want to make sure to maintain integrity of the study out to the full 108 weeks. Right. That's very understandable. I appreciate that. Thanks. Then just based on your prior discussions with the FDA, how much of a trend towards showing a positive eGFR benefit do you think that they want to see in order to grant the go-ahead to file for accelerated approval? How strong does the trend need to be? Is it sufficient, do you think, if as long as it doesn't go against the drug in a more neutral scenario? Do you think that they would like to see any degree of positive impact on GFR, given the limited amount of data that's going to be available? Thanks, Joe. Let me put it perhaps this way, that we will continue to understand how they want to see these data as they are limited and an interim based on a longer-term measurement. I would say there's not a specific threshold at an interim look at this endpoint. Again, this is part of why we want to make sure we continue to have dialogue with FDA and EMA to understand what data they would like to see in the submissions. Makes sense. Congrats again. Thanks, Joe. Our next question comes from the line of Tim Lugo with William Blair. Congratulations on the impressive results, especially around managing this trial through COVID. It's very impressive. One question, though. Can you discuss maybe the slope of effect at earlier time points, such as week eight, 16, 24, and if those earlier time points were in line with what we saw with DUET in the OLE? Thanks, Tim. Good morning. Maybe I'll ask Noah to talk a bit about that, but let me just reinforce that we're not going to be able to share any further data from this trial other than the week 36 analysis on FPRE. Again, we want to make sure that no patient can look at their individual data and unintentionally blind themselves. Noah, anything further you'd want to add? And perhaps, inferences from DUET rather than DUPLEX. Yeah. That's where I was going, Eric. Let me start. We're encouraged by what we've seen in the first six-week analysis. We can't speak to specific trends in DUPLEX, but I think, Tim, to redirect you back to DUET, I think we've got a pretty good idea of how this drug behaves. It's well-characterized. We've gone out to six years, and we published the recent 42.5-month median analysis. I think I would just earn your attention there. That's not unexpected for us in DUPLEX, but I can't speak directly to the data. As I said earlier, the top priority is really to maintain conduct and outliers. Understood. Thank you for the color. Can you maybe speak a little bit of just generalizations around the side effect profile and the PR interim safety looked to be comparable, but could you talk maybe about some of the serious side effects that came up, and were those relatively balanced between arms? Yeah, I can take that one. Tim, again, for the reasons we cited, won't be speaking to specific AEs, but looked across a number of different avenues, including some of those that you mentioned. We are encouraged by these interim results from the study to date indicating that sparsentan has a comparable safety profile at this current time in this ongoing study to the comparators, irbesartan. I'll also add that we just completed a fifth data monitoring committee meeting. They of course, have access to unblinded data. They gave us the green light to proceed as planned. We're of course monitoring adverse events, serious adverse events, AESIs, carefully as we continue on with the study. All right. Thank you for that. Again, congratulations. Thank you, Tim. Thanks, Tim. Your next question comes from the line of Liisa Bayko with Evercore ISI. Hi. Congratulations on the data. Couple additional questions from me. First of all, can you speak to the balance and use of background meds like steroids and immunosuppressants? Are you comfortable with how they look at baseline? Noah, why don't you take that one? We're not guiding, as we said, to any specifics on baseline, but we can say that in general, we've published this 36-week with the knowledge that the groups were balanced in general at baseline between groups with regard to demographics and background treatments. Of course, we'll do a much deeper dive for the NDA, but we're encouraged by the results, and I think we're seeing that balance between groups. Okay. In the DUET study, there seemed like there was a greater treatment differential over irbesartan in the more mild patients. What are you seeing here with respect to kind of the above three grams versus below three grams in terms of kind of treatment benefit? Is it pretty much the same despite severity, or are there some nuances there in terms of? Yeah. What I can say is we're not going to be guiding to specifics and specific subgroups, but we did mention on a previous call that the baseline characteristics in DUPLEX were similar to DUET with regard to UPC. I'll just say that we're very pleased with the 42% achievement of response for FPRE with the baseline close to DUET. Imagine there would be a significant number of patients above and below that threshold, so that contributes to that overall effect. Okay. Did you actually just to ask a little bit more about eGFR, and I know you can't comment, but did you look at it yourselves at this interim? Just trying to get a sense of if there was alpha spend on this interim in terms of eGFR. As we discussed previously, the statistics were hierarchical. Maybe I'll ask Bill to talk a bit about that. Certainly. The way the interim is structured in the statistical analysis plan with positive data on FPRE, that is statistical significance, which we've achieved in this interim look, all of the alpha now flows to the confirmatory endpoint of eGFR slope at 108 weeks. We don't have an alpha spend penalty for taking the interim analysis. Okay. Interesting. I guess what I was trying to understand is did you actually take a look at eGFR on an unblinded basis at this interim? Even though I know you're not going to disclose it because you want to keep the study blinded, I understand that. I'm just wondering if that's something you took a look at. Liisa, our focus at this point was the 36 week FPRE endpoint and key safety data, and we will continue to assess the interim data in line with expectations from regulators. Much of what we will be doing in the coming months is precisely that, and that will also be informed by the planned meetings that we have with regulators. Okay. Can you maybe talk about your timelines to file here? As you file, will you be filing on data that's kind of maturing over time, and so the kind of future readouts may be different than today, and maybe you could talk about then trends you're seeing on proteinuria and such. Thanks. Sure. Bill, would you like to take that? Certainly. Well, we believe that the agency is very engaged and interested in bringing these new treatment options to patients, and we're in a good position to engage and have planned interactions, as we've stated, in the coming months. From a timing perspective, we're continuing to work on preparing the NDA and CMA applications in parallel, and we expect to submit those in the second half of the year, pending regulatory interactions to really align on how they want the data presented. We're committed to providing update following those regulatory interactions, which is our custom. Okay. I guess when you file, will you be filing on data that's evolving or just exactly the cut you saw today? If it's data evolving, can you maybe talk about any trends you're seeing on proteinuria as you look at out at patients who've gone out farther? Thanks. That's my final question. Yeah. No, I understand the question. Taking the first half of the question, we'll be presenting analysis of pretty much all of the data, and we'll be working with the agencies on how they want that presented. As far as trends, I'm not going to speak to trends today on what we're seeing for the reasons we've stated. Just to add one thing, Bill. Liisa, to your question. We did get an immature early look at eGFR, and as Bill alluded to, the data's not mature yet enough to really analyze to just ensure there was nothing concerning in terms of any safety trends or any concerns along those lines, and I think we're confident there. As to Bill's point, as we evolve that data grows in its information fraction, I think we'll be more comfortable commenting. It's part of obviously the full data set. That's why we're not discussing to ensure we don't bias and to keep patients in the study and ensure the integrity of the study. Okay, good. That's great. Thank you for that clarity and congratulations again. Thank you, Liisa. Your next question comes from the line of Geoff Meacham with Bank of America. Hey, guys. Congrats on the data and thanks a lot for taking the question. Just had a quick one. If you look at the patients that were maybe non-responders or even hyper-responders, are there any themes that you can tease out among that? I'm just trying to think of things that could interfere with the effect, like background therapy or disease progression or things of that nature. Noah, do you want to take that one? Sure. Geoff, it's a good question. I think in the frame of we can't really discuss any more specifics, I'll just say that if you look at DUET, I think we did publish some data then that showed that regardless of background steroid therapy, above and below UPC and a number of other factors, race, et cetera, demographics, we were able to see results in those populations, pediatric, et cetera. I think the drug does appear based on the DUET, we've got that long-term data set to demonstrate an effect in a broad population. Specific to DUPLEX, we just can't comment any further. Okay. Just last one, I know you guys are going to have a discussion with FDA and with regulators. Maybe just help us with going into the interim, was there any sort of metric or effect size that they prospectively had discussed, or was it just the interim based on your protocol? Bill, I'll have you take that one. Certainly. The interim analysis has been based on the achievement of FPRE, and that's been the agreement for what we will be bringing in our submission for accelerated approval, both for the U.S. FDA and for the EU. There isn't, I think, as you describe it, a specific metric or effect size that's been delineated. Ultimately, it needs to be, and I think we've covered this some in the past, really a look at the totality of the data. You have a surrogate endpoint that's predicting or thought to predict ultimate effect in the confirmatory endpoint, and the regulatory agencies want to have confidence that the effect that they are seeing is reasonably likely to predict success at the outcome. They will be looking at all available data to assess that question. Geoff, let me add that we believe that FDA understands the unmet need in this space, and we are confident based on the proteinuria results that we have to date and our ongoing dialogue that accelerated approval can be supported by these data. Of course, we want to make sure that our ongoing dialogue. Reflects their thinking and their expectations. We believe that we'll be able to get this across the line and we'll continue to prepare for those files and we believe, based on any regulator's desire to see the full study completed, maintain, as Noah says, the high focus on the quality and completeness of the study. Okay. Great. Thanks a lot guys, and congrats again. Thanks, Geoff. Thanks, Geoff. Your next question comes on the line of Laura Chico with Wedbush Securities. Hey, good morning, guys. Congrats on the data. Thank you for taking the question. I guess I just wanted to follow up. I'm sorry to continue on this line. We're getting a lot of questions, obviously, related to the eGFR data. I guess I just wanted to clarify. If the accelerated approval filing submission is largely based on FPRE, I guess what is giving you confidence to move forward with that submission? Are there other elements beyond eGFR that are really more important here to focus on? I guess I'm just trying to understand basically what gives you confidence that things are trending in the right direction at this point. Thank you, Laura, for the question. Yes, we are confident that the data that we have from the interim proteinuria results can support accelerated approval. As we discussed previously, we do recognize that regulators are going to be looking not just at those data, but also in the totality of evidence, particularly given that FPRE is a surrogate marker of longer-term endpoints, and that longer-term endpoint of eGFR isn't yet mature. We think that regulators recognize that, and that's why we believe this engagement with regulators is so important, so that we understand how they want to see the data, what type of data they see, and that we ultimately can meet their expectations for the interim data and ultimately in the confirmatory endpoint. I think that we are in a good position. We've got to continue to see this study through, and that I think is going to be a high priority for regulators as well. Of course, there's no guarantee, but it's going to come down to the quality of the file and ultimately ensuring that we have a study that is conducted with the highest level of integrity, and then it'll come down to a review decision. What we see today, we're confident in our path forward. Okay. Thank you, Eric. That's helpful. I guess one last follow-up. Can you just remind us at this point how many more DMC assessments we should be expecting for DUPLEX? In terms of what would constitute a safety event that would warrant pausing the study or pausing dosing, could you give us an example of an event that would necessitate having that trigger occur? Thanks. Noah, do you want to take that? I can answer that. I just want to follow on to the previous question, too, to just say that what's also important, I think it ties into your question, is the safety data. I think we've seen balance between groups, which is very encouraging for us. It's a well-characterized mechanism. You can see, again, back to the data out to six years in DUET, the long-term follow-up. We know how the drug works. We understand their AESIs, and we're following those very carefully. Patients are tolerating the drug quite well. Physicians are comfortable. I think that's the key. Just point out that this is a heavily proteinuria disease. Physicians, when they target an approach in practice, they will try to treat proteinuria down as low as they can get because they realize that proteinuria is directly toxic to the kidneys. That's really the basis of the FPRE, right? Is that the proteinuria endpoint itself is clinically meaningful. There really aren't good options out there. I think Eric alluded to that in his opening. There are drugs that are either limited in their efficacy or they've got long-term side effects with the IST. Having a non-IST achieve a 42% reduction, just to summarize, in a disease with a high unmet need, a proteinuria disease where half these patients on average are going to dialysis within 10 years, I think it's pretty important data in light of seeing a drug that is safe and we will continue to follow these patients long term. To your question about the DMC, we don't typically guide and they're driven per protocol, but I think it's encouraging that we had this fifth meeting. They see completely unblinded data, and they've given us the green light to move forward. I think we'll continue to follow the study. Your question about what event would occur, that's really a DMC question. That's the type of information that they're evaluating. If you're asking me as a clinician, I would say if you saw some very surprising event that came in with some frequency, either something very serious or a frequency that was unexpected, it would have to be looked at carefully. I think we're in a really good place. I think, again, I point to DUET out to six years. We published all that data. We're in a unique position in having that long-term data set to point to 600+ patients, again, well characterized. Hopefully that addresses to some degree your question. Yeah, it does, Noah. Thank you, guys. Congrats. Thank you, Laura. Thank you. Your next question comes from the line of Do Kim with BMO Capital Markets. Hi. Good morning. Thanks for taking my questions. Congrats on the data. I guess my first question is, when you look at the FPRE results at this interim analysis, how do you think about the assumptions that you made for the eGFR confirmatory endpoint and the statistical powering around that? Did you account for this level of difference in FPRE? Yes. Do, good morning, and thanks for the question. These results are consistent with our assumptions and our powering. We were pleased to see the results thus far, and I think our focus is that eGFR will also play out and is well powered. That is a longer-term endpoint. That's why you'll hear us continue to repeat that we've got to make sure that we maintain the blind and keep these patients in for that full 108-week measurement. Great. Thank you. As we think about the IgA nephropathy data the third quarter, are there any takeaways that we could look at the FSGS proteinuria data and apply it to the upcoming IgAN trial? I'd say that we're encouraged by the statistically significant response in FPRE with DUPLEX, and we think that it supports the hypothesis that sparsentan can meaningfully reduce proteinuria for patients with rare kidney disorders. We think it does build further confidence that sparsentan can be effective in IgA nephropathy. I want to point out that these are different trials. They are different diseases. Our focus is making sure that we conduct that trial well and reinforce that the mechanism addresses a common pathway between the diseases. We're confident, but we've got to wait until quarter three to see those results. Okay. Last question. Could you comment on how the dose titration worked in this study? Did it go and prevent the dose interruptions and reductions that you saw in the phase II? Noah, why don't you take that one? Yeah. Good question, Do. We had looked at that in a blind manner previous to unblinding, and I think we had reported that the two-week titration was allowing patients to get to that higher dose. No reason to change that statement. Again, we'll continue to analyze the data and follow these patients, but we feel confident that titration step was an important change between DUET and DUPLEX given the blood pressure-related side effects that we saw in DUET. Got it. Congrats again, thanks for taking my questions. Thank you, Do. Thanks. Your next question comes from the line of Liisa Bayko with Evercore ISI. Hi. Thanks for taking the follow-up question. I just wanted to ask, in your conversations with FDA, does it seem like FDA is well-informed with kind of a temporary dip due to initiation of therapy, a temporary dip in eGFR, which is actually seemed to be a good thing, versus a sort of change in slope over time that can be an indication of kidney worsening. A change of slope in eGFR versus a kind of temporary dip due to initiation of therapy. Is that something that kind of FDA is aware of? Can you maybe speak to how informed and educated they are on this point? It's a point that was kind of well-articulated with a KOL call we hosted earlier this week, and so that's why I'm just following up to ask. Thanks. Sure. Thank you for the follow-up question, Liisa. I'll provide my comments and ask Bill to provide anything further. I think that the acute hemodynamic effect is well understood for these classes of medicines, and I think we would imagine, I certainly don't want to speak for the FDA, but that it would be well understood that the blood pressure-lowering effect of sparsentan could be associated, much like we saw in DUET, with that acute hemodynamic effect. There are other classes of drugs that don't have that acute effect. I think as you point out, our understanding and the broad nephrology community's understanding is that it's well understood, and it is not deleterious to the long-term renal health of the patient. Bill, I'll ask you to speak anything further with regard to the regulatory perspective. Certainly. It's a great question, Liisa. The folks on the other side of the table, both at the U.S. regulatory agencies and in Europe, are really very well-versed in nephrology as well as trial design, and they do understand the physiology of drugs that present with a reduction in blood pressure and then the concomitant transient reduction in eGFR. They understand the nature of it. They're well-versed in this. It's been a focus of some of their work externally with the National Kidney Foundation and with academic groups studying just how do you run trials when you have a physiology or a pharmacology of the drug that creates an intermittent confounder to the overall confirmatory variable. I think part of the reflection of that is the duration of the study. A two-year endpoint allows for what a readout that would be immature at 36 weeks to mature and to allow things to stabilize and get a true read on the comparison of the efficacy of the agents. I think that is reflected in the study design and those discussions that we've had for quite a while. Great. Thanks for that. There are no further questions at this time. Great. Thank you, Lisa, and thank you all for joining us on short notice this morning and appreciate the quick pulling together to talk about the promising results from the DUPLEX study. We look forward to speaking with you in the near future as we continue to make our progress and also when we report full-year results later on this month. Thank you again, and have a great rest of the day. This concludes today's conference. You may now disconnect.