All right. Hello, everyone. My name is Prakhar Agrawal. I'm a Biotech Analyst at Cantor. Welcome to day two of Cantor's Global Healthcare Conference. For the next session, we are very excited to host the team of Travere Therapeutics. Representing Travere, we have Eric Dube, President and CEO, and Peter Heerma, Chief Commercial Officer. Gentlemen, thank you for coming. Thanks for having us. Obviously, a lot going on at Travere right now. We'll go into the specifics, but maybe just to level-set expectations, why don't you start with an overview of the key priorities right now for the company? Sure. This is indeed an exciting year for Travere and the role that we look to play within the rare kidney and broader rare disease space. Our number one priority for this year is to continue the success of the launch of FILSPARI in IgA nephropathy. We've been very pleased with the performance for the first half of the year, and we've got some very exciting updates to continue that success in the back half of this year, including the recent modification of the liver monitoring REMS and the removal of the pregnancy testing REMS, which makes it that much simpler for patients to access. The second priority is the ongoing work with FDA for the potential approval in FSGS. This would be a transformational approval for that community that's been waiting far too long and has nothing approved for them. In the background, we have continued the work on our pegtibatinase program in classical homocystinuria, or HCU. That progress has gone according to plan, and we're on track to reinitiate enrollment in our phase III next year. Yesterday, we presented at the Inborn Errors of Metabolism Conference in Japan the data one year from our phase I/II that shows a long duration of effect for those results for patients in the open label extension, giving further excitement to that community for something that really addresses the direct cause of the disease. OK. Maybe let's start with the FSGS side of things for FILSPARI. Just start with a brief overview of the PARASOL initiative and the FDA's involvement throughout the process. Sure. For background, P ARASOL was formed in the fall of 2023. It's a public-private partnership from thought leaders within the FSGS space, the patient advocacy organizations, as well as global regulators, including the FDA. We have been able to observe some of the workshops that were done, but we are not directly involved within that PARASOL work. It was formed really with the intent, much like the Kidney Health Initiative, to use evidence in that disease to best identify and define clinical endpoints for clinical trial development within that space. Whereas there was a limited literature that helped us to define both the potential for partial remission and eGFR for approval, certainly with a readout of our phase III DUPLEX trial, we showed that we were able to show a profound reduction in proteinuria that did not translate into a statistically significant effect in eGFR. PARASOL really started with that premise and said, what is it about this disease that we need to better understand to identify clinical endpoints? They really came away with three conclusions. Those conclusions were based on an analysis of 26 different real-world registries of patients with FSGS with long-term follow-up. The first conclusion was that eGFR, of course, is important to any kidney disease, but it's not a feasible endpoint in a trial design for FSGS because it is highly variable. It's highly variable for two reasons. The first is that FSGS is a heterogeneous disease. The second is that patients' individual eGFR can vary significantly over time, contributing to a lot of variability within a two-year clinical trial. You would need to have nearly 1,000 patients per treatment arm in order to show a statistically significant difference for the magnitude of treatment effect that sparsentan showed over an active comparator. The conclusion was eGFR is important but not feasible. The second conclusion was we need to look at what is the biologic plausibility of another clinical endpoint. When you look across the different types of FSGS, there's one commonality, and that is the podocyte. This is the filtering cell within the nephrons. This is really what helps to keep protein within the blood. Unfortunately, with patients with FSGS, those podocytes begin to slough off. That leads to proteinuria. That proteinuria actually directly causes further injury to healthy podocytes, which leads to this vicious cycle of proteinuria increase over time. That really led to the third conclusion, which is, can proteinuria independent of eGFR predict a patient's risk of kidney failure? That's what they found, that if you can reduce proteinuria at one to two years, you're able to substantially reduce a patient's risk of kidney failure at seven years. It sets us up to then have a discussion in our phase III data of what does this mean for the potential of sparsentan in FSGS. Got it. You have the upcoming AdCom for the FSGS indication. What's the latest thinking on the topics for the AdCom? Sure. We don't yet have insight from FDA about the specific questions. We assume that's going to come much closer to them announcing the date of an advisory committee publicly and on the public register. We do have some insight into how they would be thinking about our file. After PARASOL initiative reported out, we had a type C meeting with the FDA to ask whether they would be open to us filing this SNDA. They agreed, and they said that this review is largely going to focus on understanding your clinical data in the context of PARASOL. We've obviously been very focused on making sure that we can articulate what is the clinical benefit of this proteinuria reduction and the superior proteinuria benefit that we see over a nephroprotective medicine, irbesartan, and then see whether there is a consistent pattern of results with what PARASOL saw in these registries. If you had to nitpick the PARASOL analysis, the database included a lot of observational data. Has the robustness of the PARASOL data or the sample size really come into the conversations with the FDA? We've not had discussions with FDA about PARASOL or the robustness. What I can say is this is not just typical of rare disease. This is actually a fantastic example in rare disease where oftentimes you have academic physicians that are reluctant to donate their data. This is a proprietary data set for them. We were amazed to see how eager these nephrologists were to donate their data. Twenty-six different registries across the globe gave sufficient power to really look at longitudinal data that is robust. We would love to be able to have clinical trial data to aggregate and do a meta-analysis or pooled analysis, much like was done in IgA nephropathy years ago. Unfortunately, those trials just don't exist. Our DUET and DUPLEX trials are really the only interventional trials that were done in FSGS. OK. Those trials were not part of the PARASOL foundation. Is that something that could be part of the data updates that we see in the foreseeable future? Yes, it's a great question. We were very intentional not to contribute our data for that initial analysis in PARASOL. We wanted to maintain the independence so that any type of endpoint recommendation that comes out of PARASOL is not dependent on what we see with sparsentan. We don't bias those results. We think that maintains a high level of integrity with the PARASOL recommendations. Certainly, we'd be open to contributing that later if there is a strong rationale. We think that where we stand going into a review shows that our clinical trial evidence actually is consistent with what PARASOL showed in a real-world setting. Right. Do you have a sense of endpoints that the FDA could focus on regarding approval? I know you mentioned proteinuria-based endpoints. Any specific threshold, time frame, anything that you can add? What I would say is reflecting what was discussed at the PARASOL workshop when the committee, including the FDA, was asked. That is that those recommendations are going to be based on—they're going to be up to the sponsor, to the company, to recommend. There was an important reason why. That is because what threshold or what endpoint or measure of proteinuria may be dependent upon the types of patients that you enroll. Pediatric patients are different. More advanced patients have more scarring, and you may only be able to show certain types of reductions in proteinuria compared to earlier patients. I think it was wise that the PARASOL panel said they're going to leave it up to the company. What's important within our data set is every single threshold that we pre-specified shows a meaningful difference in superiority over active control irbesartan. I want to be cautious that most of those at two years are nominally significant. All of them are nominally significant. We do have alpha protection showing statistical significance at nine months with our partial remission endpoint because that was the primary endpoint in our trial. OK. We still get some lingering questions on the level of eGFR data that could be required here. Will there be a focus on eGFR on the FSGS regulatory side? It's hard to know at this point what level of detail will be the focus at an advisory committee. What I would say is in that type of meeting that we had with the FDA, there was no discussion of eGFR. It was really understanding our data in the context of PARASOL. Of course, we will be absolutely prepared to talk about the eGFR data, which was all about the slope of eGFR. We saw that there was a numeric benefit of sparsentan on the slope of eGFR over time compared to irbesartan, and that there was no evidence of harm on eGFR or on kidney function. I don't believe if you assume and accept the results of PARASOL, then the role of eGFR becomes less important in assessing the benefit, is what I would assume. Right. It's been a few months since the recent FDA changes. Anything you can comment on based on your interactions with the regulatory agency, specifically in the Cardiorenal Division? Sure. We've been very pleased with the level of engagement. We see the same types of changes within FDA broadly. The Cardiorenal team has been consistent. The only change that I would say of note is that the longstanding Director of Cardiorenal, Norm Stockbridge, retired earlier this year. Aliza Thompson, who was the lead nephrology reviewer and the Deputy Director, is now the Director of Cardiorenal. She's been actively involved in rare kidney disease endpoints through the Kidney Health Initiative and PARASOL. We've been not only pleased with the stability of staffing there, the level of engagement. Keep in mind that we've had another SNDA on our REMS modification with the FDA, and they approved that not just on time, but a day early. We've been very pleased with the level of engagement. Because this is an SNDA, will Aliza Thompson be the ultimate sign-off on the? That's our understanding. For an SNDA, the Division Director is responsible. OK. Any latest thinking on the timing of the AdCom? The typical advisory committees are held four to eight weeks before the PDUFA date. That would put us in the November, December time frame. They're typically announced in the public register anywhere from two weeks to six weeks before. I think we can expect to hear in the next month or so. OK. I did want to touch on the commercial side for FSGS as well. I guess once FILSPARI gets approved, let's talk about the strategy there in terms of the launch, the addressable market that you have. Yeah. Yeah, great question. Maybe it's good to talk first on how we see the opportunity for FSGS. We think FSGS is an even bigger opportunity for FILSPARI than IgA nephropathy. I think both have the potential to be blockbuster indications. The reason why I'm so confident about FSGS is the unmet need is very well established. Every nephrologist has FSGS patients top of mind, as this is the most rapidly progressive glomerular disease. Patients are often symptomatic. With IgA nephropathy, we really had to establish the urgency to intervene earlier. That's not the case for FSGS. On top of that, this is basically the same prescriber base. Physicians have a strong brand awareness for FILSPARI. Many of them have already experienced. From a payer perspective, we are already in formularies and payer plans. All the heavy uplift that you do normally in the first 12 to 18 months prior to launch is already established. I'm expecting an even bigger opportunity for FSGS, but also a more rapid uptake. OK. How much is the overlap with the current prescribers we face? Yeah, it's over 80%. Basically, every physician that is treating IgA nephropathy is also treating FSGS patients. The only target physician that we haven't targeted so far is the pediatric nephrologist. We anticipate that we will get an indication including pediatric, and that's a new call point. Overall, very consistent and similar to IgA nephropathy. Right. For the FSGS launch, how much of an incremental sales force expansion will you need? Yes, we will be expanding our field force to the point that I just made, given the high overlap. It's not like a full new field team that you have to add, but it's still incremental sizing that we are doing because we want to make sure that we remain competitive in IgA nephropathy and really take the opportunity. We are on a very strong trajectory, that we can continue that trajectory, but that we also have the uptake that I was just talking about in FSGS. OK. You mentioned about access that's already there for the IgAN market. Does that help ramp up the coverage of FSGS, or do you have to sort of renegotiate the contracts and the policies with them? You still have to add the indication. We have the value proposition in place, and our account team is already actively having conversations with payers for them to understand that indication. To your point, once you are in the formulary as a product, it's much easier to do an add-on for an additional indication. Got it. What's the latest thinking on pricing for the FSGS indication? It is linear pricing. It is the same price. For FSGS, since it is a sicker patient population spilling more protein, it is double the dose for the adult patient population. You expect linear pricing based on that? That's right. Yeah. If we take a step back from the dosing, our strategy for pricing across both IgAN and FSGS is really based on the position that we think it will play in the treatment algorithm, which is broad foundational therapy longer term. We've done a lot of work over the years to understand for both indications, what is that price that's going to be delivering the right value proposition? That really is established for this chronic condition of foundational therapy. We're very pleased that we're able to provide strong access so far in IgAN. We would expect that we would see that same broad access with this pricing in FSGS. This is a therapy that patients should be able to get access to. OK. How many diagnosed FSGS patients could be out there? How does it compare versus IgAN? Yeah, we have done quite some research on it over the past. We anticipate that it's about 30,000 addressable patients for FSGS at launch, and that could increase over time when you see more biopsies and earlier biopsies. To Eric's earlier point, there are no approved therapies for FSGS. We don't anticipate there is anything else in the foreseeable future. OK. Longer term, do you see FSGS as a bigger opportunity than IgAN? We see IgAN as a blockbuster opportunity, but we see FSGS as an even greater opportunity. OK. Got it. It's a good segue to IgAN. 2Q, great quarter. We were doing some analysis where it seems that within the IgAN market, a lot of the products have started to see some sort of hockey stick growth, including FILSPARI in 2Q. Let's just talk about the market dynamics that you're seeing. Yeah, there is definitely a lot of dynamic in a rare disease market, very uncommon in rare disease. To your point, I think we are on a very strong trajectory. When I think about the launch so far, it's basically two phases. The first phase was within accelerated approval. We were at about 400, 500 new patient start forms per quarter. After we had full approval last year in September, we grew that basically with 40%. We have been stable around 700 new patient start forms per quarter Q4, Q1, and Q2. That's on top of a very strong compliance and persistence for patients that are already on the drug. Right. You had some recent updates to the label with the removal of REMS for pregnancy and reduction in liver monitoring frequency. Is there a way to quantify the impact there in terms of new patient starts? Yeah, the opportunity that I really see for the REMS program modification is twofold. One, it's broadening the patient population because physicians often have a certain patient profile in mind that would be compliant to monthly monitoring. Quarterly monitoring will broaden that patient base. The second part is the competitiveness. You spoke earlier about the dynamic. You have more entrants coming to this market, and we want to make sure that FILSPARI remains competitive. This is an angle that the competition was focusing on. I think that this takes part of the wind out of their sails. What will be the next step for the REMS removal completely? Yeah, so we've had over the years a strategy of two steps to be able to first modify the REMS. We're very pleased to be able to now achieve that. The second step would be removal of the REMS. That would take additional exposure data. Again, assuming that we continue to see no cases of Hy’s Law, which we've not, we'll continue to work with FDA on the level of exposure that they would want to see. We have a post-marketing requirement for 3,000 patients for two years. We'll continue to see whether the amount of information we have is sufficient, given that they've recently approved another therapy in the class without a liver monitoring REMS. Right. With that therapy's approval, do you think there might be more flexibility in terms of the safety exposure database that's required? It's hard to say. Certainly, that's a question we'd like to explore with the agency. I wouldn't be able to speak for them at this point on that. OK. Maybe if you can comment on the competitive dynamics here, Novartis' Vanrafia was recently launched. What are you seeing in the market in terms of the impact? Yeah, still early days. They were approved about five months ago, so early in April. The second quarter was the first full quarter that we were competing against them. It was our strongest quarter. The initial signal is positive. I think it's also good to realize that the biggest challenge that we had in the launch was really to establish the urgency to intervene earlier. I was talking about it earlier. When you have more competition coming into the market, they kind of reinforce that message. The second part is with Novartis now also having an endothelin inhibitor, it's also reinforcing the importance of endothelin inhibition as part of foundational therapy. In that respect, it will help us to establish the class. Within the class, then you're competing. We have the long-term data, the broad label. We're well established in the mindset of the physicians and the payers. I think we have a strong position. Also, given the differentiated profile, FILSPARI is a dual mode of action. It provides that consistent nephroprotection with the long-term superior data versus a maximal tolerated RAS inhibitor. I think we are in a very strong position there. In terms of the impact, any impact in terms of the new patient starts? Is it like the market is just growing? It's hard to say because Novartis is not disclosing their patient start forms. The first quarter that they were in the market was a strong quarter for us from a new patient start form perspective. OK. Some physicians have highlighted the ease of new patients that can get on Vanrafia because you don't have to discontinue any medication. Please speak to how you are managing that dynamic in the market. Yeah, it's an interesting one. I've occasionally heard that. I often hear the opposite side, that physicians actually are pleased that they can stop a medication for IgA nephropathy. In particular, when you think about this, this is a patient population that on average takes about five different medications. Historically, there were no approved medications for IgA nephropathy. What we are hearing from physicians is that patients are saying, for the first time, we feel we are winning. For the first time, we hear from the nephrologist, you are doing well. You're hitting the target levels, and you can actually stop a medication. It's the way you look at this. I think in this dynamic market where you will have different modes of action and different modalities, it will be adding and adding and adding. FILSPARI is taking away a treatment. I think that's a positive rather than a negative. Yeah, we've not heard one patient say, oh, I'd rather add another medication rather than stop and get to a medication that was actually designed for them. OK. Maybe on the other competitor that's upcoming, Otsuka's anti-APRIL drug will be launched in 4Q. There will be a lot of B cell modulating agents launching in the next one to two years. Just talk about the dynamics there. Yeah, we actually don't see that class of medicines as a competition. We see the B cell therapies as complementary and another treatment option. I think if we take a step back to how this disease historically has been treated and how it's characterized in the global KDIGO guidelines, it gives a very clear sense that there is an important role that both FILSPARI plays as well as immune-targeted therapies like B cells. Patients with IgA nephropathy have essentially an overactive immune system that damages the kidney. By the time every patient is diagnosed, they already have kidney damage. They have kidney disease that is demonstrated based on their biopsy. The guidelines really are recommending that every patient with proteinuria with IgAN is on combination therapy. A nephroprotective foundational regimen, we believe that the best option is FILSPARI plus SGLT2s. We now have really exciting data to demonstrate the additive benefit of FILSPARI plus SGLT2. Addressing the overactivation of the immune system, historically, that's been steroids. There's been a shift away from steroids in this space because of the safety tolerability aspects. We believe that the B cell therapies, when they come, like Otsuka's launch potentially soon, will help to be able to shift for more patients to be on that regimen. Those are all being studied on top of foundational nephroprotective therapies. I think the evolution is going to be increased combination. Patients are essentially going to be treated better. I really hope that in the years to come, we have a future where no patient with IgAN will ever have to see kidney failure. Whereas five years ago, every single patient with IgAN was modeled to have kidney failure within a 10 to 12-year period. I am really optimistic that we're going to see that combination in that future that's best for these patients. Is that data something that you guys can generate in terms of the combination? We're certainly eager to. We're eager to. We're open to. I would suspect that those types of studies would only happen once those therapies are approved. I think that's what makes most sense for development. As we've done with the two studies we've completed with SGLT2 combination, we'd be very open to looking at combinations with B cell modulators as well. Right. Maybe on the market, I think one thing that is interesting is the duration of therapy for these drugs. I think we've been trying to do some work around that. Are you able to put numbers on what you are seeing as the average duration of therapy, given the drug has been launched for a couple of years now, more than a year, a couple of years? Yeah, to Eric's earlier point, I mean, FILSPARI is really focused on protecting the remaining nephrons. You want to do that in a chronic way. FILSPARI is used chronically. What we have seen so far is that both the compliance as well as the persistence has been incredibly high, much higher than I was anticipating beforehand based on historical data on chronic, often non-symptomatic disease. I think the high compliance and persistence speaks to, one, the efficacy of the drug, but also the patient services support that we are giving that is well appreciated and allows for long-term protection of the nephron that Eric was talking about. OK. As we look forward to the second half of 2025, what are some of the headwinds and tailwinds that the street should be focusing on? Yeah, I think the remainder of 2025 and then moving into 2026, some of the things that we talked about already, one is the modification of the REMS program. Second component that we didn't talk about is the KDIGO, the global guideline final publication. The draft publication was disclosed a year ago. We do anticipate the full publication this year. That helps us with three points. One is that the treatment target will be more aggressive. Historically, that was g/day. What the draft guideline indicated was 0.5 g/day or preferably 0.3 g/day. Much more aggressive treatment target, number one. Second one is what Eric was just talking about. This is basically two diseases. You want to protect the kidney, but you also want to impact the immune over-suppression. FILSPARI is positioned in a certain way. The third one is FILSPARI in the draft was called out as the only drug that has shown superiority versus a maximally tolerated RAS inhibitor. I think that will further help us as well. That's the second part. The third one is really in preparation for FSGS. We will be expanding our field force. I think once you have the FSGS approval, there will be a halo effect from FSGS on IgA and vice versa. OK. Yeah, if you can talk about that, like once FSGS is approved, because it's the same prescriber base, how does it help you competitively? How does the FSGS approval help you in terms of the competitive dynamics in IgAN? Yeah, because the physician will see a broader utility for this medicine that other products don't have. Rather than have different products in different indications, it further reinforces the utilization for FILSPARI. Right. Given the KDIGO guidelines, the draft guidelines have been there for about a year, are you seeing more physicians treating earlier in the disease, like in terms of the proteinuria baseline that you're seeing? Yeah, we certainly see that. I think it also is indicative a little bit to the hockey stick that you were talking about earlier on. I see it more in the thought leader community and the academic hospitals. I think there's an opportunity to really educate the broader community nephrologists. That's where the majority of the patients reside. I think that's where really I see the opportunity. Take in mind, we see this IgA nephropathy as an addressable market of about 70,000 patients. In my opinion, we only scratched the surface so far. Got it. Maybe just longer term, because the street is probably not there at blockbuster sales. What's the long-term sort of opportunity for FILSPARI and just IgAN indication? Yeah, I mean, I would say it starts with what is the role in the treatment algorithm. 90% of the patients with IgA nephropathy are on an ACE inhibitor or an ARB. If we look at the new treatment guidelines of ideally getting these patients into complete remission, only 10% of patients on a RAS inhibitor are in complete remission. They're essentially non-responders to that degree and really can do better with FILSPARI. This is a very broad opportunity for us to be able to reach. As we're seeing in the data, in the guidelines, and in the KOL opinions, a combination of RAS inhibitor, ERA, SGLT2, and immune-targeted is the way of the future. We're going to play a very important role for continued growth that will help us to be able to reach that status. Maybe just last question, we don't have to bring Chris on the stage for that. On the cash runway, what does it cover, especially in the context of you preparing for the launch of FILSPARI and FSGS? Yeah, what we've said is that we've got cash into 2028, potentially beyond. That's based on the growing revenues and the net income of milestone payments. That really covers the continued support of the IgA nephropathy launch, preparation for the FSGS launch, and really fully supporting that opportunity, and all of the ongoing work that we have with pegtibatinase going into phase III next year. We're very well positioned from a capital standpoint to really invest in these three very important community opportunities. All right. That's all the time we have today. Thank you to the Travere team for joining us, and thank you to the audience for listening in. Thank you. Thank you.