Hi, everyone. My name is Maury Raycroft. I am one of the biotech analysts at Jefferies. It's with great pleasure that I'd like to welcome Eric Dube, the CEO of Travere, and Peter Heerma, the Chief Commercial Officer of Travere. Thanks so much for joining us today. All right, Maury, thank you and Jefferies for hosting us. And we're going to do fireside chat format. So maybe for those who are new to the story, if you want to provide a one-minute intro to Travere. Sure. So Travere Therapeutics is a commercial stage rare disease biotech company that's based in San Diego. We are exclusively focused in rare disease and are very pleased to have a commercial stage medicine, FILSPARI or sparsentan, that is now fully approved for IgA nephropathy, both in the U.S. and in Europe. We're very pleased with the commercial performance to date and see FILSPARI as a potential new foundational therapy for the treatment of IgA nephropathy, given its non-immunosuppressive and very consistent profile. We also are leaders within the broader rare kidney disease space and are hoping to be able to bring sparsentan to the FSGS community, which has nothing approved for them and is one of the most rapidly progressing and proteinuric of the rare kidney diseases. And we have a phase three program for pegtibatinase in classical homocystinuria, or HCU. So a very exciting profile. We've had an exciting year and certainly hope to be able to bring our medicines to even more patients as we look to next year. Got it. Yeah, it's a great intro and overview. And you mentioned FSGS, nothing approved for these patients right now. Maybe let's talk about that a little bit and the setup there. For those who may be unfamiliar with recent developments in this space, can you talk about the PARASOL workshop and the joint initiative with involvement from FDA, KHI, NKF, and academic collaborators as well? How did this group come about? What did they discuss and conclude the last six weeks or so? And how does this relate to your FSGS phase three DUPLEX study? Sure. Well, let me go back a little bit further. Over the last decade, there have been public-private partnerships to better understand what are the endpoints that are going to help in driving innovation and investment within the rare glomerular space. These are some of the most progressive of the rare kidney diseases, FSGS being one of them. And that work really led to the focus on eGFR as a measure of kidney function as a validated surrogate endpoint. And with that work, we were successful in completing two of the only programs that have been conducted in FSGS, our phase two DUET program, which showed about a 50% reduction in proteinuria for these patients compared to max dose irbesartan as an active control. Those results were replicated in our phase 3 DUPLEX study, which is the largest study conducted in FSGS, again showing about a 50% reduction and a two and a half times greater proportion of patients that were able to achieve the most rigorous endpoint of proteinuria that is complete remission of proteinuria. And when we looked at the two-year data and the confirmatory endpoint of eGFR, we were disappointed that while we saw a clinically meaningful treatment effect on eGFR of just under one milliliter per minute per year, which is clinically meaningful for these patients and could delay their progression to kidney failure, we were unable to overcome the variability in this trial. This is a very heterogeneous population. These patients oftentimes relapse and remit. And this trial included pediatric patients where you see even greater variability in kidney function over time. And so, just to bring you to the PARASOL group, that was formed about this time last year when we presented the complete two-year data at the ASN and the Late Breaker and a simultaneous publication in the New England Journal of Medicine alongside our two-year PROTECT data in IgA nephropathy. Both of those trials showing about a 50% reduction that is sustained over time in proteinuria and a clinically meaningful treatment effect in eGFR around one milliliter per minute per year. We saw benefit in IgAN, but we did not see that significance in FSGS. And the community very quickly looked at this and said, it's the variability, which they all know in FSGS. And so this PARASOL group, which really was, I think, an evolution from the KHI initiative, formed very quickly and said, we need to figure out what are the right endpoints that are feasible in a clinical trial setting, a two-year clinical trial setting, which is pretty much the longest you can do in this population. And the PARASOL group is formed by the patient advocacy organization NephCure, as well as leading thought leaders from the U.S. and Europe and Asia, as well as FDA. And over the last year, they were able to amass a number of different databases looking at patients with FSGS. And they first looked at, is eGFR a feasible endpoint? Was the data that we saw from DUPLEX really just by chance, or was it truly not effective? What they were able to determine is that in order to have eGFR as an endpoint, you'd need to have about one milliliter per minute per year as a significant treatment effect. You'd have to have over 900 patients per arm in order to show a significant, really not feasible in a rare disease like FSGS. They then shifted their attention and said, if eGFR is not going to work, can proteinuria reductions be used as an independent validated surrogate endpoint? That's, in fact, what they saw. Last month, they presented the findings and a consensus came out of that showing that if you're able to reduce proteinuria over a two-year period, you're able to substantially reduce a patient's chances of progression to kidney failure over about a seven- to eight-year period. Those magnitudes of risk reduction were upwards of 90%. On the same level as you would see for eGFR, and that was independent of kidney function. We now are at a point where PARASOL has recommended that reductions in proteinuria are a feasible endpoint and can be used as a validated surrogate endpoint in clinical trials for FSGS. A profound shift over the last year, really spurred by the work that we've done with Sparsentan and FSGS. Got it. Yeah, I think that's a great overview and background on PARASOL. And Eric, you've already scheduled a Type C meeting with FDA. Maybe talk about next steps there. What are the key objectives and can you walk us through potential outcomes? Sure. I think what's most important is that we are confident in the profile of sparsentan in FSGS. So although we had discordance on our endpoints, we saw a significant benefit, statistically significant benefit on proteinuria. We did not see that on eGFR and the study is completed. We had a meeting with FDA over a year ago, a pre-NDA meeting, where at that point they said, based on the eGFR data, we don't believe you should file an sNDA for this indication right now. But with additional work, come back and talk to us. With the work that PARASOL has done recommending proteinuria as an endpoint in this disease, we are going to reengage with FDA to see if they're open. This is what the topic is for the Type C meeting. We have that coming up very shortly. We expect to provide an outcome from that meeting by our next earnings call, so sometime around the February timeframe, and the outcomes could be, look, you can file and it will be a review decision. They may say no, which I think is not likely given the urgency to treat these patients and there's nothing else approved or on the near-term horizon, or they could say do some additional analyses that may be more akin to how PARASOL analyzed proteinuria over time. Not all that different from what we did in our trial, but they may want to look at things differently. Our team will be ready. We're in parallel writing the sNDA now so that we can move very quickly if FDA does suggest that we can submit an sNDA. So in many of those scenarios, with assuming a six-month review, we could have the first medicine approved for FSGS by the end of next year. Got it. Interesting. What data from your FSGS program are the most important and what will you be submitting to FDA? We will be submitting our complete study report, which shows a consistent benefit in proteinuria all the way down to complete remission. While complete remission is an approvable endpoint by FDA, it is so difficult to achieve that very few companies pre-specify that. That is going to be very important as well as other thresholds that all show a statistically significant benefit over an active comparator. We also will submit our eGFR data because we believe that they're informative and they do show a benefit over time, even though we were not able to overcome the variability, as well as hard endpoints and safety, so it's very difficult to power a study on hard endpoints, and yet in this study, we were able to show a numeric benefit in patients that were reaching kidney failure within a two-year period. So we think it's the totality of those data that are going to be very important in elucidating the profile of sparsentan in this disease. But fundamentally, we think that the argument from a regulatory standpoint are the data on proteinuria based on the PARASOL findings. Right. Yeah, makes sense. And your study and the proteinuria analyses in your study was run prospectively, which is something that FDA wants as well. And so that should all check that box. And there was also focus on the 0.7 gram per gram threshold recommendation, a newly contemplated threshold that wouldn't have been included in the statistical plans. Talk about the rationale behind that threshold and how do you weigh your pre-specified analyses with 0.3, 0.5, 1, and 1.5 gram per gram thresholds? Sure. Well, you can look at the data that were published in the New England Journal as well as the supplement for the New England Journal showing a very consistent benefit at the pre-specified thresholds of 1.5, 1, 0.5, and 0.3. And in fact, the more rigorous that threshold, the stronger the relative risk reduction is with sparsentan versus irbesartan. As you point out, there was a new threshold of 0.7 that was recommended. This is new within the area of FSGS. But the rationale is that they wanted to have a threshold that was not just predictive of reducing the risk of kidney failure, but also was rigorous enough that you're not going to simply enroll patients above 1.5, which was the entry criteria for a number of trials, and if you can just simply get them below 1.5 or 1, which may not be clinically meaningful from a percent reduction. And so 0.7 reflects not just that threshold analysis, but also at least a 50% reduction from baseline, which also is considered meaningful and independently predictive of reduced risk. Got it. Okay. And another recommendation from the PARASOL group was to use a landmark time point. How do you think your proteinuria response rates would look if they were done at a year or two years potentially? Sure. Well, we pre-specified nine months and then looking at proteinuria at two years, both of which showed a consistent benefit. But as you point out, there were different time points for the PARASOL group. That's something that we certainly can do. We're not going to be running a bunch of post-hoc analyses before we meet with FDA. That I don't think would be looked upon well from any statistician. But we're confident in the data because when you look at the analyses that were pre-specified and published in the New England Journal, you can see the Kaplan-Meier curve. There was a very, very early separation between the two groups showing a benefit, including the most rigorous of complete remission. And that benefit is sustained over time. And most patients were able to stay below their baseline threshold. It's particularly important given that this is a relapsing and remitting disease. The thing we know about sparsentan across all of the studies that we've conducted, that benefit on proteinuria happens early. It is sustained over time and it's consistent across different subgroups. I think those analyses, while we haven't done all of them that you could, we're confident that we should show a benefit there. Got it. And at ASN, you reported some interesting data on a subgroup from DUPLEX with genetic mutations that had better eGFR responses. Are there any additional learnings from particular FSGS subgroups that may be helpful? We were very pleased in both our IgAN and FSGS trials to show consistency across subgroups. I think probably the most meaningful for us was that group of genetic FSGS. FSGS isn't one disease. It's a heterogeneous disease of scarring within the kidney that progresses over time. For those that have a genetic subtype, these are often pediatric patients, as you would assume for a genetic disease. They are often more rapidly progressing, and perhaps the worst part about it is these patients are often resistant to any type of other treatment, including steroids, chemotherapy, et cetera. We were incredibly pleased to see in this subgroup that you had a consistent benefit with Sparsentan and a consistent safety profile, so we're very pleased to be able to, if approved, be able to reach patients that really had little hope and few options. Got it. And for sequence of events going forward, you typically wait for meeting minutes from FDA. But assuming you have alignment, how quickly can you file the sNDA and what are expectations for review timeline? Yeah, so we look to provide an update once we receive minutes from that Type C meeting. As I mentioned, we're writing the sNDA in parallel. We don't want to waste any time. These patients have been waiting for years, and so we want to move quickly. A lot of this will be contingent on whether FDA asks for any additional analyses. But again, under those circumstances, even with a request for additional analyses of data we have, we expect we can get a file in quickly and be able to hopefully be approved by the end of next year. Got it. Okay. And let's talk about the market opportunity. So as we mentioned earlier, there's nothing approved for FSGS and little in development for the broader FSGS population. How many patients are out there that could be addressable at launch and what proportion of them are primary versus secondary FSGS? Yeah. Happy to tell you that, Maury. So we think that the market opportunity for FSGS for FILSPARI is at least the size of IgA nephropathy. There are about 30,000 addressable patients for FILSPARI today. This is mainly primary and genetic FSGS to Eric's earlier point. And there's a high unmet need with basically no approved therapies and basically nothing in the foreseeable future for these patients as well. Got it. Okay. And similar market size, is that based on primarily number of patients or also based on how the dosing works too? It's a combination of the amount of patients, the dosing, and the competitor space. Yeah, I think maybe just to clarify, the size of the population is about half that addressable for IgA nephropathy. But as we think about the value size of that population, it's, as Peter pointed out, much larger as we see than IgA nephropathy, not just because the dosing is double the target dose, but also because for the foreseeable future, we don't see other treatment options coming to this market for a number of years. So we do see, much like in IgA nephropathy, FILSPARI, if approved, becoming the new standard of care within FSGS. Got it. Okay, and do you believe the data support a broad label in line with DUPLEX inclusion-exclusion criteria at launch or could it look differently from that? For our assumption, it would be comparable to what we study. That's typically going in. I mean, certainly it's part of the discussions with regulators, but our assumption is, particularly given the unmet need and the consistency of benefit, we would look to have a label that reflects the broad population that we studied in DUPLEX. In fact, DUPLEX is one of the few studies that have been conducted in rare kidney disease that included pediatric patients as well. Got it. Okay. And let's shift gears and talk about the FILSPARI launch in IgA nephropathy. You now have a broad label there as well as more favorable draft KDIGO guidelines, which can create some tailwinds. What are you seeing in fourth quarter on FILSPARI starts and how are you setting commercial expectations for FILSPARI heading into 2025? Peter, you want to take it? Yeah, absolutely. So really good progress for those of you who are not familiar. FILSPARI was approved in February 2023 based on accelerated approval. We recently had the full approval September 5th. And since then, we have seen a meaningful uptake and acceleration of demand. Really pleased with that progress. And I think that sets us up nicely to end the year very strong and also start 2025 at a strong pace. Got it. Okay, and can you give us a sense of how many PSFs have converted and how many patients are on therapy and what proportion of the patients are on free drug program pending reimbursement? Yeah, I think the best reflection on progress we have been making on fulfillment and the efficiencies is the growth that we had in revenue in the third quarter. We reported over 30% revenue growth, which is a good reflection on the progress we have made on our fulfillment process. As you would expect, as you are longer in the launch, we're now 20, 21 months into the launch, your amount of free product is diminishing over time. So the majority is now paid product. We're very pleased also with the strong coverage rate that we have with payers. It's covered in 96% of the patients that have access to FILSPARI paid product. And that's what we see reflected also in our payer approval rates for FILSPARI. So we're really pleased with that progress. Now, in particular, with the full approval, we also see payers already adopting the full guidance. Some of the payers already are deleting the proteinuria levels. Very much in line with our thinking with the potential of FILSPARI. Got it. Okay. And can you talk about what you're seeing in respect to how FILSPARI is being used in the real-world setting? What proportion of IgAN patients are being treated with SGLT2 inhibitors? And are you getting a sense of trends or dynamics as it relates to Tarpeo treated as well as Fabhalta use as well? Yeah, as you would expect, early in the launch, you have the patient is being treated where the physician is most worried about. So basically lower eGFR levels, higher proteinuria levels. And over time, you see eGFR levels going up, proteinuria levels going down. That's exactly what we are seeing right now as well. And we have now the evidence as well to treat patients in lower proteinuria levels. We had at the recent ASN meeting the effect of FILSPARI in patients that start with proteinuria level below 1. You You see basically the same efficacy rates that we saw in the full patient population. And we also presented the sparsentan data for patients with naïve, treatment-naïve, RAS inhibition. We saw like a 70% reduction in proteinuria. So as we grow into the market space, we also have now data for different patient segments. That's where the growth opportunity for FILSPARI is. With regards to SGLT2, I would say overall it's about half of the patients that are on FILSPARI are also on SGLT2. With regards to steroids and now Fabhalta, complement inhibitor that was recently approved as well, sits in a different category. I think it's important to realize patients with IgA nephropathy basically have two diseases. They have a kidney disease and they have like an immune-mediated disease. You need to target both of those targets. FILSPARI sits really in that foundational category where you want to target the kidney and minimize the kidney damage. The other products that you're talking about, the steroids and Fabhalta, that's more in the immune-suppressive therapies. Got it. Okay. Makes sense. And for getting patients to adjust how they're using ACEs or ARBs or switch off of those to go on to FILSPARI, can you just talk about how the switch conversation goes with doctors and payers? And are there some payers requiring step edits? Yeah, I mean, it's a very easy process because you can stop ACE and ARBs today and start FILSPARI tomorrow. That's an easy switch. From a payer perspective, there are some plans that have step through edits through ACE inhibitors and ARBs. We haven't seen that as an issue because like 90% of the patients have been treated with RAS inhibition. Half of those patients already come to the nephrologist with a RAS inhibitor. And even before diagnosis, what the nephrologist usually is doing, kidney damage, prescribing a RAS inhibitor till you have the confirmatory biopsy. That's the moment that FILSPARI comes in. Got it. Makes sense. And you've submitted the sNDA to reduce the REMS monitoring from monthly to quarterly. How did this conversation with the FDA evolve? And then what would be needed to completely remove the REMS requirement? Maybe talk about that. Sure. Well, in the discussions with FDA for the accelerated approval early last year, FDA indicated that they wanted to have liver monitoring REMS for FILSPARI for several reasons. One is that there has been some variable risk within the broader endothelin class. And this being under accelerated approval, there was not a full data package for not just safety, but also for the benefit of FILSPARI. What they indicated is that with broader exposure data, they would look to discuss whether a REMS would be needed moving forward and reference the precedent of removing a REMS within the ERA class in pulmonary disease. And so we've been working diligently on not just the pharmacovigilance to ensure that patient safety is overseen. And to date, we've seen no cases of drug-induced liver injury with FILSPARI, both in our clinical trials and in commercial exposure. And we recently met with FDA to review this updated information and gauge their interest in, at this point, reviewing a modification of REMS. Just for background, patients that are on FILSPARI, they will be checking their liver functions every month for the first year and then quarterly after. And what we've requested is that moving forward in this sNDA, that patients would be checking their liver function tests every quarter, every three months. What's important about this, and while it's not been a barrier for patients, and we hear really positive feedback from patients about the experience they have and the very high compliance persistence rates, but as we grow FILSPARI into earlier patients, as Peter alluded to, we want to reflect how frequently these patients are seeing their nephrologists. And so these are typically younger, very busy patients. We don't want this to be a barrier to them receiving effective care. And so that's where we believe quarterly would fit. We expect to hear from FDA next year. And our next step is with broader exposure at some point to be able to request full removal of the REMS. We see that time point on the horizon, but our first priority is to get this modified in frequency. Got it. All makes sense. And we're almost out of time. So I'm going to ask kind of a three-part question for the last one. Novartis, they had atrasentan and pivotal data at ASN last month. Why don't you talk about how you view that program as a competitor? And then also provide an update on pegtibatinase in HCU. And then just talk about pipeline expansion and BD opportunities this year to close out. Sure. Peter, do you want to take the first one? Yeah, absolutely. Well, first of all, I think it's great to have validation of the endothelin pathway. And so second endothelin inhibitor, I think, is good for the market potential. I think it's also good to realize that FILSPARI is a different profile compared to other endothelins. Sparsentan, FILSPARI is inhibiting both receptors of angiotensin as well as endothelin. And why is that important? Those are the two bad actors in increasing kidney injury. And FILSPARI consistently inhibits both receptors. If you inhibit that consistently, you see that translating into efficacy as well as convenience for the patient because it's only one pill. And that's exactly what we are seeing in the data so far. We're very comfortable with the efficacy profile of 50% after nine months for FILSPARI that is sustained over time. Even after two years, you still saw 40% reduction in proteinuria that translated into year-over-year preservation of kidney function. That's a very important element. In particular for this audience, like nephrologists are relatively conservative and very evidence-driven. To have that full data set and how proteinuria reduction translates into kidney preservation that is growing year-over-year is a very important aspect. That's why we also see the uptake that we have seen since the full approval. Just very briefly on the last two questions, pegtibatinase and HCU, we're very excited about the opportunity for it to become a disease-modifying therapy for the HCU community. Our focus right now is on commercial manufacturing scale-up. No new updates since our last progress. With the success we've had in rare kidney disease and assuming continued success next year with the potential approval of FSGS, we certainly will be focusing our business development efforts to be able to bring all of those experiences that we have in clinical development, commercialization, and RKD to other communities that have no approved therapies. Got it. Thanks so much for joining us today. Great. Thank you.