STIFEL 2026 HEALTHCARE CONFERENCE - TRAVERE THERAPEUTICS INC

Good afternoon, everyone. I'm Alex Thompson with Biotech Annals here at Sequel. I'm very happy to have CEO Eric Dubé here from Travere Therapeutics for a fireside chat this afternoon. Maybe I'll kick it over to Eric for a brief overview of the company, and then we'll get into a Q&A. Yeah, great. Alex, thanks so much for hosting us. It's been a great day. And so I'm Eric, and Travere is a San Diego-based rare disease company. We are both commercial stage as well as development with our pipeline. We have been leading in many ways within the emerging rare kidney disease space, launching first within IG nephropathy and now the first medicine approved for focal segmental glomerulosclerosis or FSGS. Our focus has been very much within rare kidney diseases and we also have branched out into rare metabolic disease and our focus has in those areas that are of highest unmet need where we believe that the emerging science allows us to translate that into hope and commercialization of our medicines. Great. Yeah, so I've lost track of time, but you've recently reported three Q earnings. You know, the second quarter now of FSGS, a continuation of IGAN for Phil Sparry as well. Can you sort of talk at a high level about the quarter and some of the underlying dynamics there? Yeah, absolutely. So we're very proud to have another strong quarter. we had $200 million in revenue posted, and I think it reflects not just the underlying demand, but also a very strong base of continuing patients, particularly with IG nephropathy. In the quarter, we received 1,932 new patient start forms. And I think it's easy for us to lose sight of the numbers. I think if we take a step back and say, We have a medicine that is reaching nearly 2,000 patients in a quarter, when just a number of years ago, there was nothing for these communities. So we're really proud of the impact that we've had. When we look at some of the underlying dynamics, and that can probably fill the remaining time that we have, I'll cover the highlights. The first is a very strong level of demand. The second is that we anticipated and talked about the summer seasonality that we've seen each year within the rare kidney disease space, particularly with an IgG nephropathy. And we saw nearly identical rate of decrement in patient start forms, small low percentage in Q3 versus Q2, which is reflective of the lower number of patient visits to nephrologists that we see in audited chart data for patient visits. And that was the same that we saw in 2025 as well as 2024. There was some slight adjustments around that for FSGS, where we saw numerically more versus Q2. And in IG nephropathy, we saw slightly less than what we saw in Q2, but largely a very, very strong quarter of demand. So maybe starting with IGAN, as you alluded to, you saw the seasonality last year. But I think one of the questions that folks are trying to wrestle with here, and I think you talked about this on the call as well, is with the ongoing launches of ciboprenolamab and atacicep, there's this question around, is this truly a seasonality, or is this a shift in the way that nephrologists are thinking about treating IGAN now that we have these other drugs? So how are you thinking about that as an underlying trend? Yeah, so what I would say is that in large part, this is about seasonality. I think if we look at what the data and the patterns actually show, it's more seasonality. Now, we do not see any evidence in the data, in the market research, or in the prescriptions that we see where there is a tradeoff that physicians are making to say, I'm going to now shift away from filspary and to the emerging B cell class. What we are seeing, however, are nephrologists now having six, seven new companies talk to them, which is a limitation on their time, a limitation on their attention. And we do fully expect to see continued positioning and strength of Phil Spari. And that's exactly what we're hearing from nephrogists when we meet with them around our advisory work as well as market research. So there is going to be a lot of dynamism. But I see dynamism as a real lead measure of growth in this market as we see more patients being treated earlier. Yeah, and can you talk a little about, I guess, the Kidigui online specifically and how, like, is there a path for you to sort of really, you know, cement PhilSparry as a combination drug on top of or with a BathApril? Like, how is that going to play out and how are you working towards getting that to playout? Yeah, so two years ago, we saw the Cadego guidelines publish a new framework for prescribing as well as new treatment goals. And when we look at the treatment goals, they're rather aggressive. And I think that that was a real testament to the authors of the Cdego saying, we can do better. You know, if we think about these patients traditionally have been prescribed off-label generic medicine, steroids and RAS inhibitors, this is really a step change. And before this, it was thought that it's really difficult to get most patients into complete remission or to stabilize their EGFR. That now is the goal, to say, if a patient has proteinuria above 0.5, they need to be treated, they needs to be treated aggressively, and the goal should be complete remition and stabilized EGF-R. That's really important because oftentimes patients with IG nephropathy are young, they're otherwise healthy, and we now have the tools to be able to achieve what essentially will be long-term benefit for them. What they say in terms of the treatment framework is that these patients should address two components of the disease. They need to address the underlying immune overactivation. We now know that there are complement inhibitors, B-cell therapies, as well as the traditional steroids. We believe that's now shifting to B-cells in terms of at least what we're seeing in the uptake, but you cannot ignore the damage that's going on in the kidney. And that is where Filspari plays, and that is the combination of Filspari plus SGLT2s, where we have two data sets, two studies showing an additive benefit of that combination. So our view is that's gonna be the kidney-directed combination, and then they will add in their immune targeted therapy, what we're now seeing oftentimes is B-cell therapies. We do not have data on that combination, but we're certainly eager to continue to explore that opportunity with those companies as we move forward. I think more of the companies will probably generate data with Phil Sparry as a background therapy too, yeah. And how are payers digesting this dynamic? Obviously, the April Bath Aprils have been priced quite a bit higher than Phil at this point? Yeah, so I think the payers are being very thoughtful. We've been impressed with our engagements with payers where they're paying attention to the Cadego guidelines. I think they're seeing that there is an opportunity for us to really make a difference in the patient's lives as well as ultimately what payers have been funding in terms of the long-term care of these patients because these patients will ultimately end up in a dialysis chair or renal transplantation if they are not treated aggressively early so we have seen receptivity to combination certainly you know with uh phil spari sglt2s etc as you know we look at the emerging immune targeted therapies we are also seeing receptivity there and i think they're trying to figure this out you want to see how the nephrologists are prescribing them we are seeing uh payers pay for b cell therapies or complement inhibitors on top of filspari we are seeing relatively broad access at this point and we are also seeing some payers introduce step edits where in order to get access to these immune targeted therapies the patient needs to be on filspare yep we do not see the opposite i think we need to continue to see how uh payers start to to manage this but at this point we've been impressed with the access that we've continued to to receive do you have a sense at all about sort of how much PhilSpar use there is on top of other branded agents at this point, or is that not data that you have that you'll share? So it's difficult to be able to look at that. We do look at audited chart data, so we are starting to look AT that. I would say it's still early, and there is a lag time to look At those data sources, but we have been encouraged that nephrologists are starting To adopt what the Cadego guidelines are recommending, and again, you know, when they prescribe, we are saying that payers are paying for them. So then maybe let's shift over to FSGS. As you said, second quarter, you saw an incremental increase in demand. So I think this conversation around bolus seems like maybe that might not be the case. But maybe the question is, how sustainable is this trajectory from here in FSGS? What are you seeing and how might that look over the balance of the year? Yeah, so we agree we do not see evidence of a bolus. What we anticipated for the FSGS uptake was a very different uptake curve. And the reason we we assumed that it would be a different uptake curve is because this is, we were entering into a market that has a high awareness of Phil Sparry given the approval in IGAN. Very broad clinical use of Phil SPARRY in IGAn. And the foundational elements were already in place. We have, you know, we received full approval, broad indication statement. We assumed payers would be able to adopt payer policies quickly because they already had policies for IGAN in place And the REMS was already modified to quarterly, which is aligning to the frequency that most FSGS patients are seeing by a nephrologist. And so we assumed that there would be a rapid acceleration of uptake that then would be sustained over time. Now, we're only two quarters into the launch, but what we've seen is very much aligned to that expectation. Quite different from what we saw with IG nephropathy, which was a step up every time we saw one of those catalysts in the launch. Yep. And then can you talk a little about prescriber overlap, maybe some differences in terms of populations, maybe more of the pediatric use? What do those trends look like so far? Yeah. So we cover between 6,000 and 7,000 nephrologists. That's where about 85%, 90% of the patients with IgG nephropathy and FSGS are seen. There is a specific subset of nephrogists for FSGS only, and that's pediatric nephrologists, since we do not have the pediatric indication for IGAN. So there's a very large overlap. Now, there may be some differences in terms of the number of patients with IGAN versus FSGS that a practice may see, but largely there's a large overlap? The other aspect that's important to call out is just the addressable population for IGAN patients is larger. It's more than two times the size that we see the FSGS addressable population today. So they're seeing IGAN patients more often in their practice, but the sense of urgency to treat FSGS is higher. Yep. And then, you know, obviously the one element of the label here in FSGS is this exclusion of nephrotic syndrome patients. Can you talk a little about whether, is there any material impact on the way that physicians are thinking about using Filspare here? How has that sort of played out in the real world? Yeah, I'd say overall we've been very pleased with how nephrologists understand our prescribing information in our indication statement they are using it broadly across the different types of fsgs and they understand what nephrotic syndrome is active nephronic syndrome and are able to really address the more you know acute need that those patients have with other treatment modalities and you know for the rest of the patients or when a patient is not in nephritic syndrome they do see the clear role that phil spari plays yep so we actually we talked a lot about um you know igan in the competitive landscape here there's there's you were the first here in fsgs but there's competitors on the horizon too more in the genetics side april one you're you're thinking about that with your btk inhibitor which we'll get to as well and then there's also some data from fanerino and some of these other broader ckd drugs how are you thinking about you know how fsg as a market might you know evolve over the next few years yeah i i think we'll we'll continue to see very strong uptake of phil spari uh let's see what the cadigo guidelines say but we we know that they've met our anticipation is that phil sparry will play an important role in the treatment algorithm there we do hear that physicians are continuing to use sglt2s even though you know the data in fsgs was less clear than in ig nephropathy but you know we know that these patients really need you know multiple therapies to be able to get their proteinuria down down. With Phenerenone, I think that's also one that, like SGLT2s, is going to be used broadly in chronic kidney disease, including FSGS, but we believe more in combination. This is a class of medicines that nephrologists have been using for many, many years. I think in terms of the emerging therapies that are in development, there are very few, perhaps only one, that could be used across different subtypes of FSGS. are some that are focused on specific genotypes, like APOA1. There are others that are looking to be studied in immune-driven FSGS. But those mechanisms, we believe, would be complementary to filspari as the foundational therapy in this condition. And maybe one more question on the FSGS side. I guess with this titration to the higher dose in FSGS, where are you at on average in terms of net price? Are you at a stable run rate, would you say, on net price, sort of double IGAN, or are you still on that sort of upward trajectory of net price? Yeah, I would say we're still on that trajectory because we're still bringing in new patients, and every new patient, let's assume adult patients for a moment, because pediatrics are at half the dose. The first two weeks is at 400, and then titrating up to 800. What we are seeing is very, very strong adherence to that up titration. we have a patient services hub that helps the practices and the patients through that step, and it's very consistent with that up titration with IGAN. So there's every reason to believe that the majority of patients will get to the target dose and will stay at the target dose. And our assumption is that not every patient will get there or will need to get there. Okay. Maybe let's talk about the pipeline a little bit. Where would you like to start? Peg to badness or siglorabrutinib? Let you choose your own adventure. Just stick with kidney and go with SIVO. Oh, yeah. So SIVOR, you want to talk about why you did that deal and how that fits in your pipeline. Yeah. Well, I think there is a real renaissance going on within rare kidney disease. And that really was driven by FDA looking at the evidence and saying, we need to do better with regard to evidence and endpoints to be able to spur innovation. Clearly, we're seeing that. I mean, we've got now seven medicines approved for IG nephropathy, which I think is just a true testament to the agency and the community of physicians and patients. And so for us, looking at other modalities that would be complementary to what we have already with PhilSparry is where we wanted to focus. This particular asset we saw with BTK, it's the ability to be able to focus on B cells, but not in a way that completely depletes them. And what we saw with the proof of concept data in primary membranous nephropathy gave us real excitement around the rapidity of the response, as well as the mechanistic rationale of reducing lipoprotein A to R and its relationship to very robust reductions in proteinuria. So, what we saw from an efficacy standpoint, we believe could be meaningful for this community. And also, we're optimistic that there will be very clear pathways since there are other programs using proteinuria. I think the other aspect is for a rare kidney disease, you're going to need to look at a profile that is amenable to long-term chronic use. What attracted us also was the potential for differential safety and tolerability long- term given the reversible binding nature, as well as the real specificity for BTK, rather than some of the other targets. Yeah, I think that's kind of the big question here is just, you know, how comfortable are you with the safety database so far? How many patients have been dosed? What kind of duration do we have? Yeah, so what we have seen is over 150 patients that have been treated with SIVO. And, you Know, some of those were in healthy volunteers, someof those in PMN patients. Everest Medicines is continuing with the basket study more broadly to get exposure. I think what we've seen has been really encouraging and aligned with our hypothesis and our expectation for a strong profile. It's something we're going to need to continue to study. Yep. So then what are the next steps here in terms of you moving into your own studies? So the first goal is to submit an IND to the FDA this year. We're on track to do so. We also want to make sure that we do some additional enabling work, looking at PKPD work, as well as some additional dosing work to make sure that as we go into later stage development, we're really confident in what that dose is, particularly in a broader global population, as well a data set that would be amenable for FDA. That's the near-term work. We're also working on what are the different trial designs, what are endpoints, where would we want to focus in these different different diseases and then working with regulators on the path forward i guess like on that on that latter point like i think the thing that has struck me the most here is just you know watching how you know parasol changed sort of the nature of fsgs and they're looking at membranous nephropathy now i guess if you had to sort of compare and contrast sort of where parasol was with the data and sort of at the progression fsg s to where we are with membranious nephthropathy like what's similar and what's different right now i think what's similar is that they're looking at what are the endpoints that can be measured much more quickly than EGFR or kidney outcomes. I think what's important and what I believe the work in membranous nephropathy is that they're collecting those data sets to be able to do a larger meta-analysis of what is the right endpoint, is it proteinuria? Is it LPA reductions? And at what timeframe would it be predictive of longer-term kidney function and kidney benefit? So it does feel like a solid framework that they're applying the learnings from FSGS. I think what we need to do is see what the outcomes of those analyses are with PMN. So does that, you know, does that sort of renal database like we had with FSGS exist yet for MN? I believe that that's what they're compiling now. I mean, I with fsgs what we saw was all of that work was done uh within a year i don't know what the time frame is for pmn but i think you know what i think has been encouraging and the feedback we received from the nephrology community is that their efforts to donate their data donate their time work on all this actually led to a meaningful outcome the first medicine approved for fsga so it does feel like it will be a worthy endeavor i think we just need to see what the what the outcome is we're doing our own work independent and in parallel to make sure that we can move our program forward you know i guess sort of the sort of question is do you have a sense of whether or not you'll be in a position to sort of learn from uh parasol in this context before moving into your next study or is are those two things independent as it stands right now i'd say at this point it's independent we don't see the readout of that as gating i think if there does have if there is a readout yeah that drives uh you know an earlier endpoint uh et cetera we'd obviously take that into account but i don't know that us waiting to make sense particularly given that there are other therapies that are in development in dmn okay um and then beyond memory isopropathy sort of how are you thinking about staging beyond beyond that and other renal indications yeah what we've said is that we do plan to go into multiple indications two of which would be immune-driven FSGS as well as minimal change disease there's high unmet need and I think if we just look at our indication with FSGS we do not have an indication for patients with nephrotic syndrome that is an a high unmet needs we also believe that this mechanism is complementary to what Phil Sparey offers and so you know that is going to be our next area focus we've not discussed the the timing or anything further on the the trial design but it is definitely an area that we will be focusing on. Okay. So maybe shifting gears to bait to bat mace. Okay. Let's talk about maybe kind of the data that you generated to date here and the progress on phase three. So we've been very pleased with the consistent benefit that we've demonstrated in our phase one, two study, where we were able to show in the target dose that 67% reduction in total homocysteine, and that's across a broad range of baseline values, albeit small numbers. And then we saw that consistently when patients were up titrated from the other dose cohorts. These patients have also, many of them have been followed for five to seven years. And so we do see a very meaningful, albeit again, small numbers, safety and tolerability profile as well. That gave us great confidence going into phase three. The other aspect that I think is particularly important all of that you know that i mentioned for safety and efficacy for regulatory purposes from a clinical perspective and a patient perspective what does that mean in our phase two study we were able to get 100 of the patients on peg to baton ace below the guideline target of 100 micromolars of total homocysteine that threshold is really important because that's what the guidelines say below which a patient is a much lower risk of the clinical outcomes Outcomes such as an ischemic event, vision issues and a lens dislocation, cognitive and psychiatric issues. So we do believe that the impact could be clinically meaningful for these patients. As we look to phase three, we're looking to replicate those findings in a very similar trial design. The duration would be the average total homocysteine reduction between week six and 12. The phase two was out to week 12, so we do belief that there's consistency. and we're doing a lot of work to make sure that we're managing a stable diet during the double blind period because these patients' intake of protein is one of the greatest variables in total homocysteine. We will follow those patients out to 24 weeks to make sure we've got some additional durability data and longer-term safety tolerability, and we are well on track with that program. So taking a step back here, you had some manufacturing delays when you were originally going to start this study. There was a pause for a little while. You're back on track. Is there any impact to the integrity of the study as we think about data next year that we should think about at all? So we continue. Any patient that was dosed in our Harmony study, they were able to continue. And so we do not believe that there's any issue. There was no dose interruption. And the patients will be in a consistent type of product. So we do believe that there is a consistency there. While we did pause, we're now back on track as we went from clinical stage manufacturing to commercial scale manufacturing. All of that now is on track. And then in terms of your primary endpoint here of total homocysteine, you had agreement with the FDA on that back when you started the study. Historically, a lot of ERTs have had functional primary endpoints for approval. How confident are you that total homocysteine remains you know, the bar here for approval and sort of what other functional data might you be able to generate? Yeah. So FDA has agreed. We have a breakthrough therapy designation. So we've had a number of interactions with the agency. They have agreed to this biomarker endpoint of reduction in homocysteine. That has been a regulatory endpoint before with betaine, albeit that was some time ago, but there is precedent and there is sufficient evidence that we have to be able to show that that's a meaningful endpoint for full approval. We will be measuring functional endpoints and clinical endpoints. FDA has not stated that that is a requirement. One of the most important that we are measuring is protein intake. When we talk to the patient community, one of the important things other than avoiding outcomes like ischemic events is, can I actually eat more protein? The average patient is taking in about 10 grams of protein on a daily basis with medical protein as a supplement. It's a really difficult one, particularly when you're interacting with family and friends. So we are doing a sub-study looking at whether patients who gain control of their total homocysteine are able to, in a protocolized manner increase their protein. FDA has stated that that could be a functional benefit if we are able to demonstrate that. It's not required for approval, but they've applauded our team for thinking about what the voice of the patient is. And we believe for the first time having a pivotal trial that actually includes diet as an endpoint. Will you have those data at the top line as well? We will have some of those. We do have some patients in that sub-study as well, but we will not have the full data set by the time we report top line. That will be when we complete double blind. But we'll be able to get into more of when those data will be available, whether for top line or for the BLA next year. So then, you know, thinking about the market opportunity and pricing in particular, you know historically there's a pretty narrow band for ERTs, but then more recently Denali's ERT was priced quite a bit higher. So is that a trajectory for ERTs that we should be thinking about here or sort of the historical sort of Fabre-type band? Does that make more sense? Yeah, I think we're going to be looking at a broad range of pricing. I think will continue to look at what is the value that PEG to Batenase brings. I think want to be able to see the clinical data from our phase three before we start to refine some of those. But we do believe that there is a broad range of opportunity for us to be able to price this while most importantly making sure that we have broad access for patients this is the only medicine that really would would be addressing the core defect of the disease so we want to make sure that uh as many patients are able to uh to access pectivatinase if approved makes sense um thinking about thinking about sort of spend trajectory and and everything next year um with sevorabrutinib you know with you know this trial wrapping up how should we think about spend next year. Is there a path to near-term profitability at Travere? What I would say is that there's definitely a path of profitability. We're very excited about what we're seeing in terms of the success with Phil Spari. With regard to spend for next year, we're in the midst of our budgeting cycle. So it's hard to say with specificity until we're done with that. What I would say isthat there will be an increase in SG&A as we will have a full year with FSGS and IG nephropathy. And we are looking to advance pegdabatinase as well as the work that we're doing on sivorabrutinib. Obviously, the timing of that program will drive when that investment starts. But you can expect to see some increase in both of those. But that does not negate the real strong opportunity that we have with profitability. Do you expect to share any filspary guidance? Or are you still sort of keeping to the demand guidance that you've been giving, at least quarterly demand metrics? Yeah. So what I would say is that we are certainly evaluating as we are at a pivot point in particularly IGAN launch where most of the value moving forward is about continuing patients. FSGS, we're only two quarters in, and I think we've got to see what that trajectory looks like. But that's a question I think is going to be most important for the incoming CEO, Bradley Campbell, who's going to be thinking about how does he want to set the vision and guidance. And I think if we take a step back, we are seeing a lot of excitement around what we are seeing with Phil Sparry overall, certainly the phenomenal performance that we've posted to date, particularly recently with FSGS. But what I'd say has been really interesting as we look to next year is the focus on Peg de Battenace. I think this today alone with some of the meetings, we've had a number of investors focus all or nearly all of the meeting really starting to do work on what the opportunity is with Peg de Battene and HCU. So I think we'll see where where bradley goes but next year is going to be a really exciting year not just for phil spari but i think the the incredible opportunity we have to change the lives of people living with hcu great well eric always a pleasure thank you all right thank you so much alex