Ready to go. We're live. Okay, welcome to HealthCONx. My name is Liisa Bayko. I'm one of the analysts here at Evercore ISI, and I'm joined by Travere Therapeutics, which is a company I've been following and getting to know these guys over a long period of time. Eric Dube, CEO, is here with me. We have Chris in the room too, if there's any financial questions. But let's start with a company overview, and then we can take it from there. Sure. Well, thank you for hosting us. Of course. Travere Therapeutics is a company based in San Diego that is exclusively focused in rare disease. We are both commercial and clinical stage. We are one of the leaders within the rare kidney space with a medicine, sparsentan or Filspari, that's been approved recently fully by the FDA for the treatment of IgA nephropathy. We have a longstanding history within the rare kidney space with an older medicine, Thiola, for cystinuria, as well as the groundbreaking work that we've been doing over the last 10 years in FSGS. We have a program that was completed, the only phase III ever done and completed within FSGS, which I'm sure we'll talk about, as well as a phase III program, pegtibatinase for classical homocystinuria. So a really exciting time for the company, and we're making incredible progress both on the commercial front as well as bringing new innovation to patients that really have no other approved therapies within the diseases I just mentioned. So there's been a lot of chatter lately about FSGS. Let's just set that aside for a second. I first want to talk about IgA nephropathy. Tell us how the launch there is going from your perspective, and what do you see as, I mean, I feel like there's been a lot sort of maybe lifted, and there's some nice tailwinds behind you now with guidance and label change and all those kinds of things, so guidelines, I mean. Yep. So talk to us about kind of where you see this going from here? Sure. Well, we've been incredibly pleased with the performance that we've had since Filspari was launched under accelerated approval last February. We saw some of the strongest uptake and the best performance of a rare renal launch in recent years, and that was all with a limited label under accelerated approval. What we've seen since September, when we received full approval and a broader label for the treatment of IgA nephropathy, as well as the draft KDIGO guidelines that really demonstrate that Filspari is a superior therapy to the longstanding use of ACEs and ARBs that are used in about 90% of patients that are diagnosed with IgA nephropathy, we've seen exactly what we were planning for and hoping for, which is a strong inflection in uptake. Most of these patients that are treated with IgA nephropathy, they have two diseases. They have an immune overactivation as well as damage directly in the kidney, and that's where ACEs and ARBs have traditionally played. But we know that ACEs and ARBs are insufficient, particularly over the long term. And so we are really pleased that with a broader label with KDIGO, that particularly community nephrologists, where most of these patients are being treated, are really starting to replace the role of ACEs and ARBs and see Filspari as we've positioned it as the new foundational treatment for IgA. One sort of, in a way, I think headwind that you still have is the REMS program. Can you talk about how much of a headwind that has actually been? What's the feedback, and what are you doing to sort of alleviate that? Sure. Well, the REMS really is for liver monitoring. This is one where there is a history of potential liver damage within the endothelin class. That risk is variable, but under the abundance of caution, and because we were approved under accelerated approval, the FDA gave us a REMS for liver monitoring, even though we don't have cases of drug-induced liver injury. And so patients in the first year of treatment need to have their liver function test every month and then quarterly thereafter. We've not really seen that as a headwind. I mean, it is definitely something that needed to be worked through, particularly for the first patient that a practice treats Filspari with. But because these patients are seeing their clinician quite regularly, it hasn't been a major barrier. In fact, we see continued growth quarter- over- quarter and some of the strongest performance of a rare renal launch compared to others that don't have a REMS. So I would say it's not been a headwind. What I would characterize it as we look forward is that modifying the REMS to less frequent, potentially every quarter, would allow us to reach those patients more broadly, those that may be earlier in their disease, those that may not see their nephrologist as frequently. And so if we are able to modify the REMS and we have an SNDA submitted to the FDA to do just that, I think the aperture for us to be able to reach more patients now with this broader label would allow for further acceleration. How is your payer access and sort of the tiering and what patients have to go through to really get on drug? Yeah. I mean, this is one that I'm very proud of our team. We have really great expertise within the payer engagement. And I worked in this space for a number of years at another company. And I think the evidence package that we have for payers really has been critical to us having some of the best access that I've seen within rare disease. 96% of patients have a path to approval for Filspari. And when we think about the path to approval, it's typically what you would expect for a rare disease medicine where it's typically prior auth. We've actually seen since full approval loosening of the criteria for many patients, including loosening proteinuria levels, loosening eGFR levels, which now reflect both the broader label and the KDIGO guidelines, really driving for more aggressive therapy within IgA nephropathy. But we've also seen in some instances removal of step edits. Now, the step edits for us are predominantly patients that are treated on ACE and ARB. And because 90% of these patients are already on ACE and ARB, it's not really a barrier. But I think it reflects the fact that payers really value the head-to-head data demonstrating that we're replacing a therapy, and we're really pleased and excited about what we have moving forward. How are you preparing for the launch of atrasentan? So we are preparing, I mean, I think this is twofold. On the one hand, having another medicine with a somewhat similar mechanism of an endothelin receptor antagonist is only going to help in driving greater shift away from traditional ACEs and ARBs into this combination. So I think that there's going to be further dynamism and growth there. That's going to help, and it's going to help in also articulating what we've been saying for many, many years. These patients need combination therapy. You need a kidney-directed therapy and an immune-directed therapy. So having not just us and the KDIGO guidelines saying that, but another company is going to help. With that said, obviously, physicians are going to have a choice. Do they keep them on ACE and ARB? Do they move them to Filspari? Or do they add another medicine like atrasentan? And I think the data is going to speak for itself. I mean, we have been very pleased with the clinical profile that we have, the convenience. I'd say the best quote is what we hear from patients themselves. For the first time, these patients feel like they're winning. They see it in their labs, and they're able to stop, quote unquote, in their words, their blood pressure medicine. We're the only ones who are able to actually replace a medicine that patients have been on and to be able to show that they can do better. So I think we're going to be in a really good place and certainly welcome the innovation that's coming to IgAN. And what's your expectation for atrasentan in terms of a REMS? And does that have any ultimate implications on how people think about these two drugs side by side? Yeah. I mean, certainly, as you would imagine, we're preparing for any scenario. Our assumption has been that they are under accelerated approval and they are an ERA, so they should have the same REMS, just as they're likely to have the same label and indication statement under accelerated approval, limited for those patients at highest risk of progression. That said, the FDA may not be consistent and grant them accelerated approval without a REMS. We'll be prepared anyway. And if you think about it, we now have a broader label. We're able to talk about eGFR. We're able to talk about the full two-year benefits, whereas any of the medicines that will be following for a period of time are going to have to focus on a narrower set of patients with a narrower set of proteinuria-only data. So I think we'll be able to compete both on the benefits that we have, but also potentially alleviating the frequency of REMS potentially next year could minimize any potential difference if they do launch without one. Next year, we're going to have some of the B-cell modulators sharing their data finally, and maybe coming to market is probably in the 2026 timeframe. How do you see things evolving with the introduction of B-cell modulators? One thing that's very notable there is it seems like they can keep eGFR relatively flat. In that context, where do you see the role for Filspari with B-cell modulators coming to market? Yeah. So our view hasn't changed over the last six to eight years. These patients need combination therapy. If you look at how the trials are designed, they're all designed as combination therapy. You have an immune-directed therapy, and you have a kidney-directed therapy. And they're all being studied, whether it's APRIL/BLyS, B-cell, they're all studied on top of foundational therapy. Most of it is ACE/ARB, but some of them now include ERA as that foundational therapy. And the KDIGO guidelines, the draft guidelines that came out, really the framework of looking at those two different targets and really demanding that physicians have simultaneous combination. I think the message is very clear that patients need to have both. This is not a winner takes all where you can have a monotherapy and be able to resolve that. That potential for a flattening of eGFR is on top of background therapy. Now, what I think is really exciting as we move forward is that you're going to have therapies that are going to be replacing the traditional role of steroids that have targeted the immune system, and that's potentially where B-cell and complement could go because no patient wants to be on a steroid that I've ever spoken with, but we also are going to have superior therapies like Filspari replacing the role of ACEs and ARBs. And the KDIGO guidelines reflect that the largest study ever done of ACEs and ARBs in IgAN was our PROTECT study. And it showed that over two years, even with max tolerated ACE and ARB, nearly 90% of the benefit on proteinuria is lost if you're only targeting angiotensin, so dual inhibition really is important. I think that's going to be the future. When you look at our study, SPARTAN study, where patients, the first study that's been conducted in a treatment-naive, early, recently diagnosed IgAN setting, you see a very similar profile when patients are on sparsentan alone, where you got 70% reduction of proteinuria, nearly two-thirds of patients in complete remission, and a stabilization of eGFR. I think that the future for IgAN treatment is incredibly bright, given that we'll have not just options, but a real push within the field for combination therapy with more modern treatments like phosphory plus potentially B-cell. Do you think these agents will all be used initially together, or will there be some like you start on this and then you move to this and then you move to that? How do you think it's going to be? Yeah, it's a good question. I mean, KDIGO makes it very clear to say if a patient is above 0.5 when they're diagnosed and they have biopsy-proven IgAN, start on simultaneous therapy. That said, we know that nephrologists are typically conservative, and so payers may not want that. I think it remains to be seen. What we do know is that for a patient with proteinuria at diagnosis, they already have kidney disease, and the KDIGO guidelines make it very clear that the only short-term modifiable biomarker that should guide treatment is proteinuria, and so physicians will be using foundational kidney-directed therapy maybe first. I think we need to see what the evidence shows for these other therapies. We don't yet have any evidence, but the real question is going to be, are they chronic therapies? They are immune-mediated, so they are going to be immune-suppressive. And so I think that's going to be a real question about how they're used in that sequencing. But we do know ultimately patients are going to need that two-prong approach. Okay. Great. Let's talk about FSGS. So I think this has been a really exciting time, obviously, with the PARASOL data. So where do you stand now in terms of meeting with the FDA and sort of next steps to really sort of get the wheels in motion to have a proper review of your data? Sure. Well, I think just for background, the PARASOL group was formed last fall just after the ASN when our DUPLEX phase III trial read out showing a consistent benefit at two years on proteinuria, a treatment effect on eGFR that was clinically meaningful, but the variability was so great that we couldn't overcome that statistically. And so this group was formed to look at what are the endpoints that should be used and can feasibly be used in FSGS. And they've recently recommended, and the consensus shows that proteinuria should be used as a validated surrogate endpoint. What that means is that we're able to go back to the FDA. We have a meeting scheduled, a Type C meeting, and this is a follow-up to our pre-NDA meeting where they said, based on the eGFR data, we don't think you should submit now. But with further work, let's come back and have the conversation. I think now with PARASOL out and this consensus, we have the opportunity to go in and say, does our evidence, the only phase III ever done showing a profound and robust benefit on proteinuria, are they okay with us submitting an SNDA? When is the meeting? So the meeting is coming up. It is on the books. And we will provide an update by the time of our Q4 earnings announcement. Okay, so no date reveal? No date. Yeah. We have a practice of not revealing the dates, and we wait typically until we have minutes because those things can change, and we want to be certain. How long after the meeting? Usually 30 days. Okay. Yeah. So we don't have to wait too long. And even with a scenario where they want us to do some additional analyses based on PARASOL, that can be done rather quickly. We could potentially file next year and also potentially be approved by the end of next year. I do get investor questions on whether another study would be needed, or can you use the existing data? I mean, it seems logical using existing data. Is that your expectation, or would you be willing to do another study? Yeah, it is our expectation. I mean, we have a phase II and a phase III that very clearly show a consistent and robust benefit, not just on proteinuria, but also its relationship to eGFR and to hard endpoints, so I think it could be that they ask, but the FDA has stated previously, and we're prepared to talk about how difficult it would be to enroll, and the ethics around randomizing a patient to what demonstrate that sparsentan reduces proteinuria. We know that, so I think we're well positioned and prepared to go in and make the argument that we have the data to be able to move forward, and this is a patient community that has been waiting far too long, and we know that hundreds, if not thousands, of patients lose their kidney with FSGS every single year. In the PARASOL review that they did at the recent Kidney Week meeting, they did talk about some thresholds, and they want to be pretty aggressive about it to make sure there's really a substantial benefit in proteinuria, and you have the data. It's just not cut that way. When might you share that? Yeah. So we do have pre-specified cuts below 1.5, 1.5, and 0.3. As part of PARASOL, they looked at what would be the highest level to be able to show something meaningful, but low enough that it's not spurious, like a 1.5 might be done by chance. And so they said 0.7 is one, but it's not hard and fast that the only. They want to give some flexibility. So what we want to do and go in and say, we have very clear, in fact, the strongest relative risk reduction is at 0.5 and 0.3. If they want us to cut at 0.7, we certainly will do that. We don't want to start messing with the data before we meet with them. We want to focus on the strength of our pre-specified endpoints. But we'll be able to do that rather quickly. We would provide that if we do need to analyze it. We'll provide that at the appropriate time. Okay. Are you going to do any pre-announcement of data and give 2025 guidance? Our standard practice is to provide an early preview in January. So you can expect that. In terms of guidance, we want to make sure that we have a very clear read on the uptake from the full approval in KDIGO. That said, I've been incredibly pleased with the performance. But we do want to make sure that the guidance we provide is robust, and we'll do that at the appropriate time. That may be early next year, but it may be a little bit longer just to understand the trends here. Okay. And then cash position and sort of pathway to some profitability? Yeah. We have a strong balance sheet. We had a recent financing, a very modest one recently that allows us to have the flexibility within our capital structure as well as to make some early investments in FSGS and to continue the strength of our investments in IgAN. Our previous guidance was into 2028. That remains the same, and we'll provide an update early next year. But that said, we are in a really good place and certainly could see a path that way. FSGS is going to be a very important variable that we want to have before we start to make any definitive guidance there. Okay, and then just finally, as we wrap up, give us a preview into 2025. This has been a fantastic year. We're set up for an even stronger year next year with the full approval in IgAN and continue to reach even more patients. We're making really good progress on pegtibatinase and the manufacturing challenge we set there, as well as a potential approval in FSGS, and then also the potential for REMS modification. So a very strong year. We're well financed, and we're executing on all fronts to be able to reach as many patients as we can in 2025. Excellent. Thanks, Eric. Thanks, Lisa.