Good day, and welcome to the Travere Therapeutics Corporate Update Call. Today's conference is being recorded. At this time, I would like to turn the conference over to Chief Financial Officer, Chris Cline. Please go ahead, sir. Thank you. Great. Thank you, Cynthia. Good afternoon, and thank you all for joining us on short notice today. We'll be covering a regulatory update for sparsentan and IgA nephropathy. A copy of the press release announcing the update is available on our website. Today's call will be led by our Chief Executive Officer, Dr. Eric Dube, and our Chief Medical Officer, Dr. Jula Inrig. Our Senior Vice President of Research and Development, Dr. William Rote, will also join us for the Q&A session. Before we begin, I would 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 on our forms 10Q and 10K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, October 13, 2022, and Travere specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. Let me now turn the call over to Eric. Eric? Thank you, Chris, and good afternoon, everyone. Earlier this year, our new drug application, or NDA, for accelerated approval of sparsentan in IgA nephropathy was accepted for priority review and granted a PDUFA target action date of November 17, 2022. This update is meant to provide insight into the late-cycle review interactions that were recently completed as part of the NDA process. As you might expect, given where we are in the review process, the details that we'll be able to provide today is going to be somewhat limited because the dialogue with FDA is ongoing. We will do our best to give you the latest insight into the process and how we plan to move forward. I would like to first highlight that we are continuing to make good progress with the NDA review and have received a draft label. As part of the late-cycle review interactions, however, the FDA requested that we update our proposed Risk Evaluation Mitigation Strategy, or REMS, to include liver monitoring for sparsentan, consistent with some of the other products in the endothelin receptor antagonist class. We have planned for REMS to monitor the risk of teratogenicity as this is universal across endothelin receptor antagonists, but the requirements for liver monitoring among endothelin receptor antagonists vary, and our safety profile has been consistent in not showing liver injury to date. Jula will go into a bit more detail on this shortly. While this request for a broader REMS came unexpectedly, and we now anticipate a three-month extension of our PDUFA date, our confidence in the potential for sparsentan to be approved and to become a new treatment standard for people living with IgA nephropathy remains high. Most importantly, the strong data supporting the clinical profile of sparsentan is unchanged, and the significant need for effective non-immunosuppressive treatments remains. Let me now turn the call over to Jula for a bit more detail on the interactions. Jula? Thank you, Eric, and good afternoon, everyone. I'll add as much context as I can within the bounds of not being able to share specific data from the ongoing blinded studies of sparsentan. Building on what Eric mentioned, based upon few cases of asymptomatic ALT, AST elevations in the program's history, the agency has determined that drug-induced liver injury is a potential risk for sparsentan. The agency has acknowledged that there have been no cases of sparsentan-related liver injury in the clinical program. However, the FDA indicated that because serious drug-induced liver injury has been seen with other members of the ERA class and sparsentan's database is currently limited to what is available via the accelerated approval pathway, a REMS to monitor liver function is warranted. The FDA has also noted in our interactions that there's added caution given this is the first time nephrologists would be using this class of medicines. Our studies include more than 1,200 participants who've received sparsentan, including some who've been on therapy for nearly seven years. As is common in most studies, abnormal liver tests are an adverse event of interest, and these are monitored closely by us and our Data Safety Monitoring Committee. We've been regularly assessing this in our studies. Importantly, to date, in our sparsentan program, we have not seen elevations in bilirubin. There have been no reported clinical diagnoses of sparsentan-related liver injury. In the few cases with asymptomatic AST, ALT elevations, there's been no evidence of abnormal liver function. We have not experienced any cases of Hy's Law, and there's no evidence suggesting a dose-related effect of AST, ALT elevations with the higher dosing levels in the DUET and DUPLEX studies in FSGS. Importantly, our adverse events of interest related to ALT, AST elevations in both our phase III studies, spanning nearly 800 participants at the time of the data analyses, were comparable between sparsentan and irbesartan. As a result, we believe that the profile of sparsentan remains well suited to address the unmet need for people living with IgA nephropathy. And notably, the agency also indicated that they'd be open to modifying the REMS if occurring data from the program support doing so. We hear now more than ever that physicians need new non-immunosuppressive treatment for their patients who continue to have significant proteinuria and progressive loss of kidney function while living with IgA nephropathy. And sparsentan is the only non-immunosuppressive molecule to date to demonstrate a nearly 50% reduction in proteinuria with a consistent safety profile in a well-controlled pivotal study. We continue to expect nephrologists to ultimately utilize sparsentan as a new treatment standard for their patients with IgA nephropathy, if approved. Our teams are working diligently on the updated REMS, and we expect to submit that to the FDA in the coming days. As Eric highlighted, the FDA has communicated to us that procedurally, the updated REMS submission is likely to result in a major amendment to the NDA and that we should therefore expect a three month extension for their review. We estimate that the new PDUFA target action date will be on or around February 17, 2023. We anticipate receiving confirmation of this date after we submit the updated REMS, and it's been reviewed by the agency. Finally, I will highlight that there have been no requests for additional clinical data or studies as part of the application review process, and this update to the PDUFA timing is solely related to the modification to the REMS requirement. We will continue working collaboratively with the FDA on the updated REMS and in parallel on the draft label that we seek. Let me now hand the call back over to Eric for his closing comments. Eric? Thank you, Jula. While this unexpected extension of three months is disappointing, especially for the IgA nephropathy community, it ultimately does not change the strength of the clinical data that supports sparsentan or our ambition to deliver a new treatment standard to patients facing a progression of IgA nephropathy with no currently approved non-immunosuppressive treatments available. We remain steadfast in our confidence in sparsentan. We know the path in rare disease is rarely straightforward, and we are well positioned to absorb this extension. Our financial foundation remains strong. We plan to report our third quarter earnings at the end of the month, but we currently expect to continue managing the balance sheet such that there is no change in our previously guided cash runway into 2024. And I'm proud of the progress our organization has made over the course of the year to be well-positioned for the originally planned launch next month. And we have an experienced and talented team that will utilize the extra time to be even more prepared for the expected successful launch of sparsentan in the beginning of next year. Now let me turn the call over to Chris for Q&A. Chris? Thanks, Eric. Cynthia, can we go ahead and open up the lines for Q&A, please? Thank you. If you would like to ask a question, please signal by pressing star one on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. In order to allow time for additional analysts to ask their questions, we ask that you please limit yourself to one question and one follow-up before reentering the queue. Again, press star one to ask a question. We'll pause for just a moment to allow everyone the opportunity to signal for questions. We will take our first question from Carter Gould from Barclays. Carter, your line is now open. Great. Good afternoon. Thanks for taking the question. I guess for Eric and Jula, I know you probably don't want to comment on specifics of what the REMS may include, but I guess just looking at some of the other products, monthly liver monitoring doesn't seem like too big of a leap. Can you just talk about how that monitoring may disrupt, I guess, how these patients are cared for today, what additional ask that might be for patients in their current kind of regular interactions with their nephrologists? Any insight on that front would be helpful. Yeah. Carter, thank you for the question. I'll provide some overview, and then I'll ask Jula to provide anything further. I think it's important first to point out that the discussions about the REMS elements are continuing, and so we're in the midst of that, so we wouldn't be in a position to be able to describe specifically what our REMS will look like. I think we'll be able to provide that upon approval. What I can say is that the team has done a really thorough job to assess what are the elements of other REMS both within the class of endothelin receptor antagonists as well as others within the rare renal or similar disease areas. There is variability, and I'll ask Jula to speak a little bit about that. Fundamentally, one of the things that we see is that it hasn't impeded the demand in many ways for an effective therapy, particularly where there's a high unmet need. We believe, and it further reinforces our confidence, through some of these analogs, that we can have a successful launch with sparsentan. I think there are gonna be key elements that we need to think about in the design and implementation of this that are going to be very seamless for both the patients as well as their clinicians. Jula, do you wanna add anything further? Yeah. There are different elements to the REMS which we are negotiating, as Eric mentioned, and there's different frequency in which you might monitor patients. I will add the way in which we monitored within our clinical trials was consistent with clinical practice, which is every three months. And there's different preferences for how you monitor in other REMS, and there's been successful uptake of other molecules within the rare kidney disease space, which has more frequent monitoring. We've seen that within rare kidney disease settings. And we do believe that there is such an unmet need for these patients that it shouldn't impede uptake. We've seen such a great magnitude of proteinuria reduction. There's such a high unmet need, and we believe that with implementation of the REMS and the frequency of monitoring, we believe that there's still gonna be a significant need for the therapy. We will take the next question from the line of Joseph Schwartz with SVB Securities. Joseph, your line is open. Great. Thanks so much. I was wondering if you can share any thoughts on how your REMS might work at an operational level in terms of the systems and processes that are required for this to function and determine whether patients are able to be dispensed medication. Do you know how to set up the systems and processes or how you might do that and just to perform all these operations? And does the three-month PDUFA delay give you enough time to do so that way when sparsentan is launched, hopefully patients, physicians and pharmacies have a, you know, seamless experience? Yeah. Let me add two things, and then I'll ask Jula to provide her perspective because her team has been working, as you can imagine, on a lot of these details. The first is that we've been planning to implement a REMS, as we know all ERAs, or all medicines approved in the endothelin receptor class, have a REMS for teratogenicity. This is something that we've been planning from day one. Those elements, those vendors, those processes are already in place. This is simply an addition to it. We need to make sure, and Jula can speak to, you know, what that might mean from a nephrologist perspective and from a liver monitoring perspective. The thing that I would also add is, you know, this is going to require some additional education for our field-based team once approved. We do recognize that that's gonna lead to a more gradual uptake in many practices as they become familiar with this. But again, we do have the benefit of learning from others that have REMS, particularly within rare renal, to know what works and what feedback nephrologists would have, that they like or would see improvements upon. Jula, do you wanna do further? Well, I'll just echo what Eric said. We have the benefit of we've known that we're gonna have a teratogenicity monitoring REMS and have been doing that education to make it as simple as possible with regards to educating the physicians for their initial sign-up and then working with the pharmacists for the continued monitoring and to make it as simple a process as we possibly can. We have that added benefit, and so adding this, it's just an additional monitoring aspect of it. And we're learning as much as we can from others who've gone before us to make sure that we don't add additional burden to the physicians and their providers and to patients with regards to making sure we have the systems in place for education and monitoring without adding additional burden. That's very helpful. Thanks, Jula. We will take the next question from the line of Greg Harrison from Bank of America. Greg, your line is now open. Hi, guys. Thanks for taking the question. Are you able to give any maybe broader comments on the draft label? You know, without going into specifics, just is it in line with what your expectations or hopes would have been going into the review process? Greg, thanks for the question. I would say it's gonna be challenging for us to comment on any specifics of the label given that it is draft and we still are in discussions with FDA. You know, certainly we'll be in a position to provide all of that upon approval. I think what we can do is maybe have Will share a little bit about some of the insights we've gleaned from the agency through the late cycle meeting and how they're thinking about labeling and approval. I think, again, I'll reiterate that we were very pleased to receive a draft label on schedule from the FDA. Will? Yeah, certainly. Again, without going into specifics, we've been encouraged by the energy and the collaboration on the other side of the table, the engagement and the dialogue. I think that I can share that the agency's perspective keeps in mind and keeps in focus that this is accelerated approval and that it's a partial dataset on which they are basing their decision-making. I think that shapes some of their stance in this space, and I think the REMS may be part of that as well. Happy with the progress, happy with the interaction and the pace on the other side and the continued collaboration from the agency. Yeah. There've been no surprises, I think, fundamentally. I think what we're sharing with you today is the aspect that really does have a material impact on our timing. Great. Thanks for taking the question. Thanks, Greg. We will take the next question from the line of Liisa Bayko from Evercore ISI. Liisa, your line is now open. Hi, this is just top pick sparsentan. Can you maybe talk about, you know, where you are with kind of the hiring of sales force and kind of like the commercial ramp and like how much spend can we push out, you know, given this delay? Just curious kind of where you are with that. Yeah. Liisa, thank you for the question. What I can characterize is that our plans to be ready for an approval on November 17th were absolutely on track, and that meant the hiring of our field force team to be ready. They are ready, they are trained, and I think what we wanna do is make sure that we use this additional three months to further prepare them. They are very experienced. Most of them have rare and nephrology experience. You know, it's about continuing to build their expertise and their relationships. With regard to spends that could be pushed out, I'll ask Chris to share that, but that certainly is an exercise that we're looking at for variable spend that you would imagine would be associated with the launch. Chris? Yeah. Happy to do that, Eric, and thanks for the question, Liisa. I would say it's a little early for me to go into any kind of specifics on that. There will be, of course, some variable spend that just goes with the timing of launch and investment in certain activities that go along with that will be shifted out a few months. And e'll likely be able to go into a bit more detail on that when we report our third quarter earnings later on this month. Happy to go into more detail then. Okay, thanks. What about any inspections or anything along those lines? Are you done with most of the manufacturing facilities with the CMC inspections? Has anything come up there that you can [crosstalk] Oh, sorry, Liisa. William, would you like to take that? Sure. Without getting into specifics, we have had some of our inspections that are complete and behind us. I don't think I'm in a position where I can characterize what remains or what the outcome of those are. That'd be inappropriate at this stage of the game, but that process continues. Okay. Thank you. Thank you, Liisa. We will take the next question from the line of Maury Raycroft with Jefferies. Maury, your line is open. Please go ahead. Hi. Great. Thanks for taking my question. I was just wondering if you can clarify if there were any liver monitoring data in your prior REMS submission. And are you providing more specifics on proportion of patients with liver enzyme elevations in PROTECT? And what do you have to show in the confirmatory data to get the REMS removed? I'll ask Jula to take those. The question, I think, Maury, if I'm understanding it correctly, is what did we put in our draft label with regard to liver monitoring? What were the rates in PROTECT and anything else that we had shared or can share with regard to liver safety. Is that correct? That's correct. Okay. Okay. Jula? Thanks. Maury, when we looked at our data at our initial data submission, as I said, we looked at adverse events of interest, of AST, ALT elevation. We planned that prospectively due to the known class effect, and as you know, most therapies you want to plan that so you can have a comparison. We saw similar rates across sparsentan and irbesartan, and we did not have this in our label that we submitted to the FDA because we didn't see it as a concern. When they came back to us, they recommended this to be added as a potential risk due to the class effect and then raised this as an issue at the late cycle meeting with regards to the level of monitoring being a consideration to have in the REMS. That is when the first time that this was brought to that level of a monitoring to avoid potential risk and how we can manage it that way. With regards to rates, I can't give you the numbers, but as you can imagine, due to the low numbers that we saw and the similarity, we didn't raise it as a concern that we felt like needed to be monitored, at the level and rigor that it would require to be a risk within our label. Thanks, Jula. I think, Maury, the only thing that I would add is that hopefully will be helpful here beyond, you know, what we show as rates of ALT, AST elevation is the insight from the agency that, you know, they are taking this cautiously given that this is an evolving data set since it is accelerated approval, and trials ongoing and, you know, maybe in their perspective, characterized as a limited data set. I think that's the aspect that might be useful to understand why, you know, now they are asking for this additional element of the REMS. Got it. If you maintain the status quo in the final data set, there's potential for the REMS to get removed. That's correct. Yeah. I think that's right. I wouldn't necessarily characterize it definitively as, you know, with the final data set, but I think with additional data, and I think that's part of what we will need to align upon final approval. Yeah. Got it. Cool. Yeah. Realize the REMS gives you a process for monitoring. It gives you a system in place where there will be a set amount of time in which patients need to be monitored and a process for recording of adverse events. We can see, is it consistent with what we've seen historically, giving more patients over time who get exposed? Remember, some of these events are very rare. As Eric mentioned, you know, we may not have seen them because we don't have as many patients exposed. We're in rare disease. How do we monitor patients over time and show what our true rates are over a longer period of time so we can give more confidence about what the true potential risk can be over a longer period of time? That might be able to modify the REMS monitoring requirements in the future. Got it. Makes sense. Thank you very much. We will take the next question from the line of Tim Lugo from William Blair. Tim, your line is now open. Hey, guys. This is Lachlan on for Tim. Thanks for taking the question. So you know, you mentioned that the FDA want to be conservative given its accelerated approval and a limited data set and so on, which makes sense. But did they give you any reasons as to why they've only just raised this now and not earlier? I mean, the fact that it's an accelerated approval and a limited data set hasn't exactly changed during the review. Bill, would you like to take that? Yeah. I can only speculate. The review team reviewed the data, but then also for this specific question, the agency has a specific group of people with expertise that they bring in for questions relating to specific topics. In this case, they brought in their hepatic experts who look at this across different drug platforms. I think some of this may be, you know, the heart of your question is why didn't they do this earlier? Why wasn't this raised earlier? It may be just based on when that team was triggered to do their review and when they completed that work as part of the overall process leading up to the late cycle review. Got it. Thanks. Mm-hmm. Thanks a lot, Eric. We will take the next question from the line of Do Kim from Piper Sandler. Do, your line is now open. Hi. Thanks for taking my question. I was wondering, since the FDA is taking this class approach for the REMS, is there any expectation for the label to have black box warnings for teratogenicity and possibly for liver toxicity like the other ERAs? Was that ever a consideration? Do, thank you for the question. Yes. Jula, would you like to take that? Yes. We knew that there was gonna be a box warning for teratogenicity. There was a possibility that they just said, "Okay, put a box warning around liver injury, but don't have it as the level of a REMS," yes, we will have both, with the addition of the REMS. And you still think that the commercial impact will be limited even with black box warnings? Yes, that's correct, Do. I think, you know, first, with regard to teratogenicity, this has been a planning assumption that we've had all along, based on the very consistent labeling across endothelin receptor antagonist. And so you know, that certainly has been part of the work that Jula's team as well as Peter's team have been doing for launch planning. With regard to liver monitoring, this again I think has been part of our early assessment of other medicines with a REMS and box warning for liver safety. You know, as I mentioned in my prepared remarks that we have seen an opportunity. The opportunity is there. We believe that the demand will still be there. What we have to do is make sure that, you know, we really understand what is going to be the required education and what will that gradual uptake be once we launch. It certainly is something that we have a good handle on. We're gonna continue to do work over the next couple of months to make sure that we absolutely understand what are the elements that are gonna help us to properly educate nephrologists and also make sure that the elements of our REMS are very efficient for nephrology offices and for patients. I think more to come with regard to any potential impact, but it doesn't change our ambition. You know, we certainly, you know, need a little bit more time to understand what those impacts are because our planning assumption to date has not been that we would have a REMS or a box warning for liver function. Okay. Thank you. Thank you, Do. We will take the next question from Laura Chico from Wedbush Securities. Laura, your line is now open. Thanks very much. I had one just kind of as a follow-up to that last one. Would there be any contraindications as a part of the label, or the REMS? So specifically, are there going to be any limitations on patient populations? Understand there's gonna be the black box warning, but would there be specific carve-outs in terms of certain utilization? And then the commentary earlier from Jula was really helpful with respect to the prior history of sparsentan and liver enzyme elevations. Can you remind us, is there any sort of pattern in which these occur? Is this more common when additional agents are on board, so concomitant therapy or something along those lines? Thanks. Laura, thank you for your questions. I'll take the first one in just saying that, you know, we won't be able to comment on any specific elements of the label until it's finalized since we're mid-process with that. There's nothing at this point that we would say would be new with regard to our view of contraindications. But, Jula, I'll turn it over to you to see if there's anything that you'd want to add or to answer the question about the pattern of effects. No, I can't comment on the pattern. As I've mentioned previously, there, we just have a few cases of asymptomatic AST, ALT elevations, and as you can imagine, you do like to look to see if there's any trends in this. Of course, that'd be something we're interested in because that impacts how you monitor. Do you see them early? Do you see them late? At which point? Because then you could change the monitoring. Of course, this is something that we look into, and we'll share it at some point in time, but not today. We will take the next question from Ed Arce from H.C. Wainwright & Co. Ed, your line is now open. Great. Thanks for taking my questions. I have a couple. First, as you mentioned, expectations for a bit more gradual uptake in some of the practices due to the extra physician education. I was just wondering what that operationally entails. I would imagine, for example, that liver monitoring, whether it's three months or some other interval, would initially just be a simple blood draw and evaluate that to see if there's any elevations, and it may rise to more if there is. I'm just wondering if that's, you know, if that seems correct. Ed, thank you for the questions. I think, you know, first, let me caveat to say that, you know, we won't be able to speak to elements of our REMS program because we're still in the process of aligning with FDA on that. What we can speak to, and I'll have Jula speak to sort of how this might be administered within a physician's office. There are some elements, if you look at other REMS programs where, for example, physicians need to register as part of the REMS. The pharma, the dispensing pharmacy needs to register. There needs to be a proper education of the physician and pharmacy before they can be registered, so that they are well aware of the safety profile and label. There's typically an education component for patients. So these are all elements that are common in most, if not all, REMS. I think with regard to frequency and how it's done, there is some variability, and I'll ask Jula to speak to your question about how liver function may be assessed. Yeah. Eric Dube got to the key points around education, and there'll be a description for the physician materials, for the pharmacist, and the patient with regards to how frequent you measure, and then what you do thereafter, in fact. The implementation of it as far as signing up and the education at the beginning, and how to get those measurements done and how that occurs will all be part of our process for what happens under the REMS. More on how it's gonna be implemented. Okay, great. Just a variation on, I guess, a question that's been asked before. Given that this clearly, this impetus for liver monitoring is clearly based on the precedent with the class effect, and the fact that other drugs in the class have consistently required liver monitoring as part of their REMS, I'm just wondering what was your perspective or what specific data led you to leave it out, given this is, you know, fairly short-term data? Thank you. Ed, thank you for that. Let me first say that we would not characterize the assessment of liver monitoring as consistent across the endothelin receptor class. I think that's an important point to note as we, you know, went into our discussions and NDA and draft label with the assumption that it would reflect the data that we've collected on the program to date. Jula or Bill, would you like to add anything more specific on this question? Yeah. Let me add a little more clarification around it. If you're familiar with those ERAs, when they became available to the market, they had a box warning and a REMS with monthly liver monitoring and continue to do so. As additional newer agents came to market, if you're familiar with ambrisentan, when this came out, they did warning and liver monitoring, but that's subsequently been removed with additional data. They no longer have a warning since the last section. Similarly, macitentan when they became available, they didn't have a box warning with REMS. It has historically been the data decisions and with, you know, prescriptions within a prescriber base that now commingle with this class of agent. I will give the caveat, though, that those things were approved under full. I do see that some distinction with us that were under accelerated approval and don't have our full data set. There is a consistency with regards to requirements and the monitoring, and so we made a data-driven decision, i.e., didn't believe that we needed to have the level of monitoring or warning. Okay. Thank you. That was helpful. That concludes today's question and answer session. Mr. Cline, at this time, I will turn the conference back to you for any additional or closing remarks. Thank you, Cynthia. And thank you all for joining us on short notice to talk about the update for sparsentan and IgA. We look forward to talking with you here later on this month as we move to the third quarter earnings call and report our operating results. Thank you again, and have a good night. This concludes today's call. Thank you for your participation. You may now disconnect.