Awesome! Thank you very much for joining us today. Again, my name is Mohit Bansal. I'm one of the biopharma analysts here at Wells Fargo, and I'm very happy to have Travere management team today with us. We have Eric Dube, the CEO of the company, and we have Peter Heerma, the Chief Commercial Officer of the company. Thank you, Eric and Peter, for joining us today. Thank you for having us. Great. So maybe, we can begin with brief intro, what have you, what have you been doing, and obviously the deal you recently struck and, and the launch. So can you just briefly touch upon that, and then we get into Q&A? Sure. Well, certainly I would encourage everyone to take a look at our filings on SEC for any forward-looking statements. We've got a lot going on with the company. So at Travere, we're focused on rare disease. We're based in San Diego, and we're a commercial stage as well as a pipeline asset that will. W e expect to go into phase III later this year. This has been a really pivotal year for us, as we started the year with the accelerated approval of Filspari, or sparsentan in IgA nephropathy. And we are on track to report later this quarter, early next quarter, the confirmatory endpoint from our phase III in IgA nephropathy. We're also on track to provide an update on our regulatory engagement with FSGS in sparsentan this fall. As I mentioned, our phase III program that we expect to start later this year is our pegtibatinase program in homocystinuria or HCU. So I think, you know, very, very busy and critical year for us. We've been very pleased with the progress we've made so far, particularly in the launch, but also in our pipeline programs. And as you alluded to, we've earlier this week announced the closure of a divestiture of our bio asset portfolio to Mirum Pharmaceuticals, where we believe this really is a win-win, where they're focused on rare hepatic disease. And, you know, we're able to realize substantial value for these assets that we were able to grow over a number of years. So I think it really positions us from a financial standpoint to really invest in what would be a very exciting future growth for Travere, both with Filspari in rare kidney disease, as well as the potential to be the leader within HCU with our pegtibatinase program. So that's sort of a high-level overview of the company and this year. Great. Thank you very much for this. And maybe let's just dive right into the Filspari launch so far, and I'm glad, Peter, you are here as well, so that all the questions are not directed to Eric only. So what has been the initial feedback so far? And obviously, you have sales there as well. So in terms of KOL feedback, in terms of how it is performing compared to a standard of care at this point? Yeah. Well, thanks. Good morning, everybody, and thanks for having us, Mohit, today. Before going there, maybe it's good to highlight, like, what has been our focus so far. And I think it's fundamental for a launch, especially in the first 9-12 months, is really generate demand, making sure there is broad access to the product, and then ensuring, like, a first positive experience. If I think about generating demand, to your question, like, what is the thought leader feedback? I think there is a good recognition and awareness of Filspari. I think it's rapidly increasing, and also the intention to prescribe is very high. It was 90% prior to launch, and that remains 90%. I saw actually a market research earlier this week that it was 100%. I've been involved in launches for quite some time. I never saw a 100% intention to prescribe. So I think that speaks to the desire of this product and what it means for patients that have a high unmet need. I think the, to your point on the thought leaders, the mode of action, the mechanism of Filspari, I think is increasing to understand. Angiotensin was well understood by thought leaders in the past. I think the role of endothelin is gaining understanding as well. And the translation in that into, like, behavioral change and prescribing Filspari and seeing the first results is really encouraging. I mean, if I hear what physicians see in real-world evidence today, is very consistent to what we saw in the study. Rapid and sustained proteinuria reduction in patients that have been unable to manage to target levels, and also patients that are in remission, which you hardly saw before. So that's with regards to key opinion leaders. I think the other part of your question was: What are you hearing from patients? It's actually quite remarkable that we have patients that reach out to us directly, that have been on the product. And some of those patients actually, with the worst prognosis, like crescentic proteinuria, that were actually in proteinuria remission and are reaching out to us, because they're willing to advocate for the brand. So I think early indicators but very positive feedback from both key opinion leaders as well as patients on what they have seen with efficacy so far. Great. Great, and how about the safety side of it? I know you—like, again, there is a monitoring requirement there. So how has been the feedback so far, and do physicians find it a bit onerous or are they comfortable with that? Yeah, it's a great question, and maybe it's good to peel that a little bit in different pieces. You talked about the safety profile. If you look at the safety profile of Filspari, it's similar to irbesartan. Mm-hmm. We do have a REMS. I think that's what the nature of your question is. Sure. But that's really focused on, the endothelin receptor antagonist in pulmonary arterial hypertension, the initial ERAs, did have, liver toxicity. So within that context, FDA said to us, like, We want you to make sure that, physicians are aware of that, especially since this is a new, prescribing physician that hasn't had the experience with ERAs. So it's more from an educational perspective rather than from a safety perspective. But it's an important point to clarify, because the safety profile of Filspari is similar to irbesartan. Well, Peter, I think that's a great overview. Why don't you share a little bit about what we're hearing from nephrologists now that we are actually able to- Yeah communicate about the product? Great point. I mean, if we have the opportunity to really sit down with physicians and talk about the efficacy and the safety profile, and I think the advantage of our study is that it's a head-to-head comparison- Mm-hmm ... contrary to other studies, being done in IgA nephropathy. You can also do that head-to-head comparison from a safety perspective. Right. And so if we sit down with the physician, and we show them head-to-head what the safety profile of Filspari is relative to Irbesartan, the question we often get is like: Well, why do you have a REMS in the first place? Exactly. Yeah. Got it. That completely makes sense. So I think that brings me to the next question, which is like, again, with the full data set, is there an opportunity to make it a little bit less frequent over time? Well, I think that certainly is the intent, and that was the suggestion of FDA. You know, the rationale, again, maybe bridging off of the feedback that we hear from nephrologists of, "Why do you have a REMS in the first place?" I mean, certainly the REMS for teratogenicity, that is a known class effect within endothelin. But the real question was around liver safety, and I think when we look at the actual data from our head-to-head trial, where you see no issues and no cases of liver damage, but you do see elevation in AST, ALT, but it's quite comparable to Irbesartan. So 2.5% with sparsentan, 2% with Irbesartan, and actually in the completed DUPLEX trial, again, at double the dose, you see comparable rates as well. You know, when FDA late in the review cycle said that they wanted to have a REMS for liver monitoring, they indicated that that was because it is approved under accelerated approval. Right. We don't yet have the full safety data set, and we don't have the full benefit from the two-year confirmatory. What they did say is that they will commit to relooking and evaluating what the need for REMS is longer term, once we have more data. So our strategy is to be able to provide those safety updates along the way. Certainly, with the completion of the DUPLEX trial earlier this year, where, again, at double the dose, you see a comparable safety profile and still no cases of liver damage. Later this year, we'll have the completion of the PROTECT trial. Again, two-year data. We'll have open label data. We'll have real-world data from now that we are available commercially. All of that information we will be able to provide along the way, requesting perhaps not just reducing the frequency of liver monitoring, which is once a month in the first year, every three months thereafter, but potentially removal of the REMS. There is precedent within the endothelin class, and FDA acknowledged that with additional data, that, that you could potentially remove the REMS. We will take every opportunity we can to do that, but we're very encouraged by the reception of nephrologists once they actually see the clinical data, rather than what we believe is FDA's abundance of caution in how they've labeled. Right. And when you talk about the precedent, you're talking about ambrisentan from Gilead, right? That's right. Do we know what was the, like, can you remind us what was the case again? Sure. So, you know, there are three commercially available, endothelin, antagonists within PAH. And, you know, one of those, ambrisentan, was launched with a boxed warning and a REMS. The company did, a study that was quite unique to that situation because there were other therapies on the market where they looked at a switch of those patients that had elevated AST, ALT and switched from another endothelin blocker to ambrisentan, showing that upon rechallenge, they did not have, an elevation of ALT, AST. That's not something we would be able to do because there are not other therapies- Right ... available in IgA nephropathy within this class. And so we're looking at, you know... They were approved under full traditional approval, not under accelerated. So we believe the opportunity we have is looking at the two-year longer-term data, looking at what happens in open label extension, including those patients that were on irbesartan during the first two years and switched in open label to sparsentan. So I think we have plenty of opportunity in clinical trial data as well as real-world data to support the removal of the REMS. Great. No, this is super helpful. Maybe let's just talk about the launch once again, and then, how, when you think about 2023, rest of the year, and then going into 2024, when you think about, like, how, how should we think about the expectations there? And, do you think consensus is at the level where you are comfortable with at this point? Yeah, maybe I'll start with the last part- Sure ... and I'll have Peter talk about the outlook. I think we're. You know, if we look at consensus, that is largely in line with what we've seen first-year sales for other rare kidney therapy launches. And so I think that that's quite reasonable for us to achieve. And while we have a higher ambition than those other rare renal launches, the profile of Filspari, we believe, is very strong. The first year of any launch, particularly, a specialty product like those that we mentioned, you know, there are some very similar dynamics. You've got to educate nephrologists, and this is a specialty that is not really accustomed to innovation. They don't have the same type of infrastructure and habit for continuing education around new clinical data.... that's really starting to emerge. It takes time to get full payer coverage and reimbursement, and it also takes practices time to be able to work, you know, have that workflow, you know, for working with specialty pharmacy, et cetera. So largely, that's why we believe we see the first-year sales pretty tight in terms of how they occur. So we are comfortable with where that is. Our outlook, however, is to show a differentiation in the launch uptake after this year. We believe that the pro-clinical profile, our infrastructure and expertise in the area, we believe, will differentiate us. But Peter, why don't you talk in more detail about how we think we're gonna be able to show that differentiation? Yeah, no, absolutely. I think there's a couple of dynamics that you have to take into consideration, specifically for Filspari. The first one that I wanna outline is, since this product was approved through accelerated approval, there is a limitation in the first 100 days, how you can talk and communicate and educate physicians. Now we are past that window. We have a broader opportunity to educate physicians. We have an opportunity to start, like, peer-to-peer programs, speaker programs, and I think that gives us more leverage. So that's one. I think the second piece is where Eric was alluding to, our payer coverage is increasing, and in the last earnings call, we outlined that 54% of the payer plans is now including Filspari. That continues to grow, so that makes it easier for physicians then to prescribe and get patients on product as well. The third one is, a little bit in line with my earlier point. Physicians start to see the efficacy of Filspari right now and they, they start to see that they can manage patients to target levels that they couldn't do before, and that by itself encourages further prescriptions. So I would say based on those three dynamics, I would see continued growth in the H2 of the year. To your other part of the question, like, how, what is your anticipation then for 2024? I think there's a couple of dynamics. We outlined the PROTECT confirmatory data we expect by the end of Q3, early Q4. I think having that in the public domain will further help us to broaden the prescriber base. But we also expect that the KDIGO guidelines will be updated either late this year or early next year. That provides another opportunity, and then we will have additional data with SGLT in combination with SGLT2 next year as well. So I think it's almost like a rolling launch. Right. You start with, like, minimal communication, educational tools, but we are ramping that up, and I think into 2024 and during 2024, you will see that continued growth that we anticipate. That makes sense, and that's a nice, perfect segue into the PROTECT trial. So, let's just talk a little bit about your confidence level here. What do you think would be the good data in your mind? And then, of course, I mean, there was FSGS trial. It's... So what are the differences, why we should not worry about this trial because of the FSGS trial? Maybe I'll take that one, and I'll start with how rigorously the PROTECT trial was designed. Right. This is the most rigorous trial design in the IgA space. The reason I say that is really twofold. The first is it's the only head-to-head trial- Right ... where we have an active control, Irbesartan. The second is that all patients before randomization are managed up to an effective and tolerated dose, based on blood pressure, so that they are randomized at really essentially, you know, optimal RAS blockade, and then randomized. So we're truly looking at what is the benefit of Filspari on top of what is the current standard of care, ACEs or ARBs. And when we looked at the primary endpoint at the 36-week period, we saw a profound improvement, a rapid and profound improvement in proteinuria, 50% reduction versus 15%, so over a threefold increase in proteinuria reduction with Filspari compared to active control. I think that really surprised the field in a positive way. The other aspect that gives us great confidence is when we look at the IgA nephropathy literature; it has very well characterized the relationship and the predictive value of proteinuria reduction to longer-term kidney function, specifically eGFR. So when we look at the 35% relative reduction in, you know, benefit of Filspari over Irbesartan on that proteinuria, that should translate, based on the literature, based on the Inker meta-analysis and that model, to a clinically meaningful benefit in kidney function. What we're looking at is annual slope of eGFR. That's how we measure that longer-term kidney function. So that's how, you know, we are looking at it and gives us great confidence. But we've also mentioned, and our Chief Medical Officer mentioned on our most recent call when asked about the powering to show that benefit at two years. FDA asked during the review for us to look at conditional power based on our actual data at 36 weeks. And when we looked at that, we saw a very high level of conditional power to be able to demonstrate that treatment effect on eGFR at two years. So when we look at it, whether it's external validation or the actual data from the trial, we're in a very good spot. We powered the trial to show a 30% difference in proteinuria at 36 weeks. We saw greater than that, 35%. So we believe that, you know, assuming, you know, consistent effect, which we saw in DUPLEX, consistent effect on proteinuria, over time, that that should translate into a meaningful treatment effect at two years. And I think the other, the final aspect is the variability or the heterogeneity within IgA nephropathy is much tighter- Right. than you would expect in FSGS. So we do believe that, you know, when you think about its treatment effect and variability that leads to a clinically and statistically significant effect, we feel very good where we are right now, and we're on track to report those end of this quarter, beginning of next. Also, the incremental benefit over irbesartan is higher in IgAN versus FSGS. Is that correct for proteinuria? That's correct. So as I mentioned, we were positively surprised that the treatment effect on proteinuria was greater than we powered. Mm-hmm. That's different than what we saw in FSGS, where while we saw statistically significant and meaningful difference on proteinuria versus irbesartan, it was actually less than what we had assumed, which made it more difficult to overcome that at two years. I think we're sitting in a very different position when we look at IgA nephropathy and PROTECT. Got it. And then I think there's a difference between how EMA looks at the endpoint versus FDA looks at the endpoint. Can you talk a little bit about that for those who don't, like- Sure. Understand it? Yeah, so there is a slight but important difference in how FDA and EMA look at this. For both of them, the primary endpoint for this trial is proteinuria reduction to 36 weeks. And, you know, we very handily were able to show superiority versus irbesartan at 36 weeks. At the 2-year confirmatory, EMA looks at the chronic slope. So that is the measure of kidney function after you account for that acute reduction in eGFR based on the lowering of blood pressure in the kidney. That is actually a good thing for patients. Right. There's a well characterized effect in the literature showing that for those patients that show a reduction in blood pressure in the kidney, 'cause most of these patients actually have hypertension systemically and in the kidney, you actually, you know, lower the pressure and the potential damage in the kidney. And EMA and the nephrology community at large certainly recognize that, and that's why chronic slope at 2 years is the primary endpoint. In fact, that's what the endpoint was in the SGLT2 trials that showed a benefit in eGFR long term. For FDA, we believe, I can't speak for them, but we believe that they want to have consistency across all of the trials in IgAN coming, where they're looking at total slope, and that's the slope from baseline to 2 years. And so there is a slight difference in terms of which measure of eGFR kidney function is there for the secondary endpoint, the confirmatory endpoint. But we're confident that we'll be able to show a benefit there. And, you know, whereas we do expect, and we have seen an acute reduction in eGFR with Filspari, that trial design difference that I mentioned, how robust it is that we optimize patients before randomization, should mitigate any of some of that acute reduction in the IgA nephropathy trial. So while there might be, we think that there should be a less of a difference between chronic and total slope. Got it. I think initially your question was, like, how will it help your commercial launch as well, once you have the PROTECT data and the confirmatory eGFR data? I would say three aspects I would like to call out. One, I think it helps us in broadening the prescriber base. You have now the prescribers that are excited about the proteinuria benefit, and so are early adopting the product. But you also have physicians that are on the fence. They say, like, "Well, you know what? We're excited about the profile. That's why we have, like, 90%-100% intention to prescribe, but I want to see the confirmatory data." So I think it allows us to broaden the prescriber base. I think it also allows us, to my earlier point, to be included in the guidelines and build further confidence on the brand. But I think ultimately it will also help us in, broadening the label, and deepening the prescriptions per prescriber. So I think it is an exciting opportunity for us to continue that commercialization in 2024. Got it. That is very helpful. Thank you for this. And then maybe talk a little bit about once you have the data, what are the gating factors to file it? And then, I mean, how should we think about the timelines for the traditional approval? And is it really important? Because this community reads a lot, so I mean, like, you'll have the data out there anyway, so- Mm. So. Yeah, I mean, we certainly know that there is a high level of expectation within the nephrology community for these data. I think particularly after we published the interim results in The Lancet. Right ... where we showed not only the profound reduction in proteinuria, but a trend to actual hard endpoints of kidney failure. So that was very encouraging to the nephrology community. We are operating at a sense of urgency, not only in getting the trial reported out, but also the trial published, because, you know, the- we believe that, that within the nephrology community, the published literature really is going to drive the right conversation and the right behavior change. That's also the basis for KDIGO to make any updates. They will not make-- They will not include your data unless it's in a peer-reviewed journal. So there is a real drive to get that published. There's no assurance that they're going to reflect that or... but it's definitely a major driver for us. And then we have indicated that we will put a file in in the H1 of next year. We are well on track to be ready once we have the trial completed to finish that SNDA. With regard to the timing for review, you know, we certainly can expect to see an accelerated review period versus a traditional review period, but those are typically granted once the SNDA- Right -is accepted. And I think as we saw from another company in this space that just recently submitted, they were granted that accelerated or priority review timeline. So it's all operating assumption, but we won't know that until we actually submit. For an SNDA, priority is what? 4 months? ... 4-6 months- 4-6 is what you can typically say. Got it. Completely makes sense. And then before we move on to pipeline, I think, let's just talk a little bit about those complement inhibitors that are being developed. And then I think, obviously, Novartis buying Chinook, like, they have their own factor. How do you see those and APRIL inhibitors as a competitor, or do you think they are more complementary at this point? Hmm, yeah. Well, we truly believe that, that Filspari will be the foundational therapy, replacing the traditional role that ACEs and ARBs have played as the first line of therapy, because you have to address the damage that's going on in the kidney. And we now know, based on pre-clinical and clinical data, that there is a crosstalk between activation of the angiotensin system and endothelin. And if you don't tamp down both, you're going to see that disease process continue within the kidney. So we do believe, and I think nephrologists understand that you, you know, there is a very critical role that Filspari can play. Everything else we believe that would be working upstream is complementary to Filspari. And, and Peter, you've been in this space for quite a long time. What are you hearing? Yeah, I think it's... I mean, first of all, I think it's a very exciting time- Right First of all, for patients. That's what the doctors are saying. For a long time, there was, like, nothing available. I mean, 40 years ago, you had, like, steroids that started being used for IgA nephropathy, and then in the nineties, you had ACE inhibitors and then ARBs, and then basically there was nothing until recently. And so I think this is a good thing for patients. If you—I think your question was, do you see it as a competition or- Complement. I see this as complementary. Complements? Yeah. Inhibitors are complementary to Filspari. Yeah. Because you have to realize, I, I made the point before, we're the only product that actually had an active comparative study. All the other mechanisms are being studied on top of standard of care. Standard of care is RAS inhibition, and since Filspari has an ARB component, angiotensin receptor blocking component, it has the ability to replace RAS inhibition. So I think we are well-positioned there. I think we have an opportunity to reestablish Filspari as the foundational care. But given the way other complement inhibitors in the APRIL B-cell are being studied, it's on top of standard of care, and Filspari is replacing the standard of care. So I feel it's complementary to what we are establishing. Got it. This is super helpful, Peter. Maybe... Excuse me once again. Sorry about this. Maybe let's just move on to pipeline for last few minutes. Can we talk a little bit about, pegtibatinase? I just cannot pronounce it. We call it pegty. Pegty, okay. Yeah. Thank you very much for this. Pegty, again, compared to other enzyme replacement therapies and, and the addressable population with homocystinuria here. Sure. Peter, would you like to take that? Yeah, so we, we did quite some research already in, in claims data to see, like, well, what is the, the current patient population that is identified in, in the US and in Europe. We anticipate it's about 3,500 patients diagnosed with disease right now, and that are addressable for pegtibatinase in the US and, and a similar patient population in Europe. But we expect that, that we will continue to grow that, because this is a rare disease. With our legacy product portfolio, the bioasset portfolio, but also Thiola, it is one of the core capabilities is to identify new patients. Right. This is a more rare disease compared to IgA nephropathy. Those patients have a long process before they are being diagnosed with the actual disease. And by educating physicians and having a broader call point, I think we will be able to diagnose and identify more patients. And that's why in our last earnings goals, we also said, like, we anticipate that we should be able to increase that patient population with 50%. Got it. And then, like, there are so many rare diseases with enzyme replacement therapy. So is there an example you can use for this? Yeah, I think the best example is probably PKU. Right. In Palynziq of BioMarin. I think that is a good comparison of an enzyme replacement therapy in this field. Got it. That's super helpful. And then this is a... This is more of a Chris question, but Chris is not on the podium. But let's just talk about the cash profile of the company, especially after the sale of bioasset products, and how much more runway does it give you? Certainly. So we ended last quarter with $491 million. Mm-hmm. That does not account for the upfront payment in the divestiture that we recently did of $210 million. We believe that, that, you know, before the divestiture, that our cash runway got us beyond 2025. We'll look to provide further updates on our next earnings call, but, you know, certainly we believe that we're well capitalized, and, and really are in a good position to continue to fund the launch of Filspari. That's our number one priority, is to make sure that we are continuing to be successful with that launch, particularly to ensure that leadership position and that lead time that we have relative to any other potential treatment options that come. Also, the very exciting opportunity we have with pegtibatinase going into phase III and preparing to launch that to again be a leader within HCU. So we believe that we have the right cash runway, and certainly we, you know, will continue to be very disciplined in, you know, how we spend, as well as, you know, whether and when and how we would tap capital markets, but we don't see any short-term need for that. ... Got it. It's very clear that with this divestiture, you are focusing squarely on the Filspari launch at this point, and obviously the pipeline. So do you see, like, do you see any room for or any opportunity for some kind of BD to bring assets in, which could be complementary to these efforts? Yeah, we certainly do. I mean, business development has been a very important part of how we've grown the company. I think we're very pleased with what we've done, both with pegtibatinase and then recently in divesting some of our older assets, that should allow us not only to support these two pillars of sparsentan and pegtibatinase, but also it's a really exciting time within rare disease. And I think we have the capabilities for clinical development as well as commercialization, to be able to look. And certainly, rare kidney disease is an area of focus for us, but it's not the only area. Right. If we look at something like pegtibatinase, this was one that was really underappreciated. Mm-hmm. It was an area that really has not had any innovation for decades, and, you know, we were able to bring that in, and I think we'll be leaders within the space. That's exactly the kind of deal that we'd be looking for. You know, and we want to make sure we get through this year with the launch, the phase III readout, the phase restart. But certainly, we're going to be very eager to look at where might we be able to add value and grow our company in the years to come. Awesome. Thank you very much for this. And one last, my favorite question. September 2024, we are sitting here, you and... I hope I am here. You, I hope you are here, too. So the question is, at that point, what would make you feel good about the, the prior year? And then you'll be like- Mm. Yeah, we accomplished something here. Yeah, it's a great question. I'll start, and Peter certainly can add. You know, we are at such, as I started, a very critical juncture for this company. We believe that we're off to a great start with the launch of Filspari. As we look at one year from now, we will have over a year and a half of launch progress, and we'll have hopefully, you know, either full approval or near full. You know, near being close to full approval for that product, being able to unequivocally say that we are going to be the foundational therapy. I think, you know, we still have the opportunity, and we'll provide an update in the fall around FSGS. This is one that we believe is such a high unmet need. It's the highest area of unmet need, and what we've heard from nephrologists is that, you know, the profile coming out of the DUPLEX trial with sparsentan is really meaningful for this disease. And so, you know, hopefully, we'll be able to move the needle quite significantly a year from now, and we'll be well on our way in the phase III with HCU. So for three major opportunities, we believe that this next year is really about continuing to build that leadership position and continue to be a leader within rare disease. Got it. Peter, you have anything to add? No, I think that's right. I mean, most rewarding is the feedback that I was talking about earlier- Right ... like, patients directly reaching out to us, and especially in a patient population that has been underserved for so long. I'm really excited for the opportunity it represents for those patients that can finally slow the progression of their disease. So I think we really have that opportunity to become foundational therapy. I think all the early indicators right now, both from physicians as well as from patients, are indicating that we are on the right trajectory, and I hope that further materializes when we come here one year from now and we see that uptake that is consistent to our ambition. Exciting times. Yeah. Good luck with everything. Thank you very much for joining us today, Eric and Peter. Thank you very much. Thank you, everyone, for being here. Thank you.