[Eric Dube] 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. Eric?
Yeah, great. Alex, thanks so much for hosting us. It's been a great day. 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 IgA nephropathy and now the first medicine approved for focal segmental glomerulosclerosis, or FSGS. Our focus has been very much within rare kidney disease, and we also have branched out into rare metabolic disease. Our focus has been 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, I've lost track of time, but you've recently reported 3Q earnings, the second quarter now of FSGS, and continuation of IgAN for FILSPARI as well. Can you sort of talk at a high level about the quarter and some of the underlying dynamics there?
Yeah, absolutely. 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 IgA 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. 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-
Sure.
remaining time that we have.
Yeah.
I will 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 have seen each year within the rare kidney disease space, particularly within IgA 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 were some slight adjustments around that for FSGS, where we saw numerically more-
Sure.
versus Q2, and in IgA 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 sibeprenlimab and atacicept, there is 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?
Yeah.
How are you thinking about that as an underlying trend?
Yeah. What I would say is that in large part, this is about seasonality.
Yep.
I think that 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 trade-off that physicians are making to say, "I'm going to now shift away from FILSPARI 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 FILSPARI, and that's exactly what we're hearing from nephrologists when we meet with them around our advisory work as well as market research. There is going to be a lot of dynamism.
Yeah.
But I see dynamism as a real lead measure of growth in this market as we see more patients being treated-
Yeah.
more patients being treated earlier.
Yeah. Can you talk a little about, I guess, the KDIGO guidelines specifically and how is there a path for you to sort of really cement FILSPARI as a combination drug on top of or with a BAFF/APRIL? How is that going to play out, and how are you working towards getting that to play out?
Yeah. So two years ago, we saw the KDIGO guidelines publish a new framework for prescribing as well as new treatment goals. When we look at the treatment goals, they are rather aggressive. I think that that was a real testament to the authors of the KDIGO saying, "We can do better. If we think about these patients traditionally have been prescribed off-label generic medicine, steroids, and RAS inhibitors.
Yep.
This is really a step change. 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 need to be treated aggressively, and the goal should be complete remission and stabilized eGFR. That's really important because oftentimes patients with IgA 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. You cannot ignore the damage that's going on in the kidney.
Yeah.
That is where FILSPARI plays, and that is where the combination of FILSPARI plus SGLT2s, where we have two data sets, two studies showing an additive benefit of that combination.
Yep.
Our view is that is going to be the kidney-directed combination, and then they will add in their immune-targeted therapy, what we are now seeing oftentimes is B-cell therapies.
Yeah.
We do not have data on that combination.
Yep.
But we are 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 FILSPARI as a background therapy too.
Yeah.
How are payers digesting this dynamic? Obviously, the BAFF/APRILs have been priced quite a bit higher than FILSPARI at this point.
I think the payers are being very thoughtful. We have been impressed with our engagements with payers where they are paying attention to the KDIGO guidelines. I think they are seeing that there is an opportunity for us to really make a difference in the patients' 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-
Yeah
renal transplantation if they are not treated aggressively early. We have seen receptivity to combination, certainly with FILSPARI, SGLT2s, et cetera. As we look at the emerging immune-targeted therapies, we are also seeing receptivity there, and I think they are trying to figure this out.
Yeah.
They want to see how nephrologists are prescribing them. We are seeing 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 FILSPARI.
Yep.
We do not see the opposite. I think we need to continue to see how payers start to manage this, but at this point, we have been impressed with the access that we have continued to receive.
Do you have a sense at all about sort of how much FILSPARI use there is on top of other branded agents at this point, or is that not data that you have or that you will share?
It is difficult to be able to look at that.
Yeah. Okay.
We do look at audited chart data, so we are starting to look at that. I would say it is still early.
Yep.
There is a lag time to look at those data sources, but we have been encouraged that nephrologists are starting to adopt what the KDIGO guidelines are recommending. Again, when they prescribe, we are seeing that payers are paying for them.
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. 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 assumed that it would be a different uptake curve is because we were entering into a market that has a high awareness of FILSPARI given the approval in IgAN, very broad clinical use of FILSPARI in IgAN, and the foundational elements were already in place. 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 seen by a nephrologist. We assumed that there would be a rapid acceleration of uptake that then would be sustained over time. Now, we are only two quarters into the launch, but what we have seen is very much aligned to that expectation. Quite different from what we saw with IgA nephropathy, which was a step-up every time we saw one of those catalysts in the launch.
Yep. Can you talk a little about sort of prescriber overlap, maybe sort of some differences in terms of populations, maybe some 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 IgA nephropathy and FSGS are seen. There is a specific subset of nephrologists 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.
Yeah.
It's more than two times the size that we see the FSGS addressable population today. They're seeing IgAN patients more often in their practice, but the sense of urgency to treat FSGS is higher.
Yep. Then, obviously, the one element of the label here in FSGS is this exclusion of nephrotic syndrome patients. Can you talk a little about whether there is any material impact on the way that physicians are thinking about using FILSPARI 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 and our indication statement. They are using it broadly across the different types of FSGS, and they understand what nephrotic syndrome is active nephrotic syndrome, and are able to really address the more acute need that those patients have with other treatment modalities. For the rest of the patients, or when a patient is not in nephrotic syndrome, they do see the clear role that FILSPARI plays.
Yep. We obviously, we talked a lot about IgAN and the competitive landscape here. You were the first here in FSGS, but there's competitors on the horizon too, more in the genetic side, APOL1. You're thinking about that with your BTK inhibitor, which we'll get to as well. And then there's also some data from finerenone and some of these other broader CKD drugs. How are you thinking about how FSGS as a market might evolve over the next few years?
Yeah, I think we'll continue to see very strong uptake of FILSPARI. Let's see what the KDIGO guidelines say. But we know that they've met. Our anticipation is that FILSPARI will play an important role in the treatment algorithm there. We do hear that physicians are continuing to use SGLT2s-
Yeah
even though the data in FSGS was less clear than in IgA nephropathy. But we know that these patients really need multiple therapies to be able to get their proteinuria down. With finerenone, 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 years.
Yeah.
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. There are some that are focused on specific genotypes-
Sure
like APOL1. 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. Every new patient, let's assume adult patients for a moment, because pediatrics are at-
Yeah
half the dose. The first two weeks is at 400, and then titrating up to 800. What we are seeing is very strong adherence to that uptitration. We have a patient services hub that helps the practices and the patients through that step, and it's very consistent with that uptitration with IgAN. So, there is 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? pegtibatinase or civorebrutinib?
Oh.
Let you choose your own adventure.
Let's stick with kidney and-
Okay
stick with civo.
Oh, yeah. So, civorebrutinib, 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.
Yeah.
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 IgA nephropathy-
Yeah
which I think is just a true testament to the agency and the community of physicians and patients. For us, looking at other modalities that would be complementary to what we have already with FILSPARI is where we wanted to focus.
Yeah.
This particular asset we saw with BTK, it is the ability to be able to focus on B-cells, but not in a way that completely depletes them.
Yeah.
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 anti-PLA2R and its relationship to very robust reductions in proteinuria. What we saw from an efficacy standpoint, we believe could be meaningful for this community, and also, we are optimistic that there will be very clear pathways-
Sure
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.
Yeah.
What attracted us also was the potential for differential safety and-
Yeah.
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, how comfortable are you with the safety database so far? How many patients have been dosed, and sort of what kind of duration do we have?
Yeah, so what we have seen is over 150 patients that have been treated with civo, and some of those were in healthy volunteers, some of those in PMN patients. Everest Medicines is continuing with a 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-
Yeah.
to study.
Yep. What are the next steps here in terms of you moving into your own studies?
The first goal is to submit an IND to the FDA this year.
Yeah.
We are on track to do so. We also want to make sure that we do some additional enabling work, looking at PK/PD work, as well as some additional dosing work to make sure that as we go into later-stage development, we are really confident in what that dose is, particularly in a broader global population. As well as a data set that would be amenable for FDA. That is the near-term work. We are also working on what are the different trial designs, what are the endpoints, where would we want to focus in these different diseases, and then working with regulators on -
Yeah
the path forward.
I guess, on that latter point, I think the thing that has struck me the most here is just watching how PARASOL changed sort of the nature of FSGS.
Yeah.
Now they are looking at primary membranous nephropathy. I guess if you had to sort of compare and contrast sort of where PARASOL was with the data and sort of the progression of FSGS to where we are with primary membranous nephropathy, what is similar and what is different right now?
I think what is similar is that they are looking at what are the endpoints that can be measured much more quickly-
Yeah.
than eGFR or kidney outcomes. I think what is important, and what I believe the work in primary membranous nephropathy is that they are collecting those datasets to be able to-
Yeah.
do a larger meta-analysis of what is the right endpoint? Is it proteinuria? Is it anti-PLA2R reductions? And at what timeframe would that be predictive of longer-term kidney function-
Yeah.
and kidney benefit? 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.
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.
Okay.
And I think with FSGS, what we saw was all of that work was done within a year.
Yeah.
I don't know what the timeframe is for PMN, but I think what I think has been encouraging in the feedback we received from the nephrology community is that their efforts to donate their data, donate their time work on all of this, actually led to a meaningful outcome, the first medicine approved for FSGS.
Sure.
So, it does feel like it will be a worthy endeavor. I think we just need to see what the outcome is. We're doing our own work-
Yeah.
independent and in parallel to make sure that we can move our program forward.
Yeah, and I guess 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 PARASOL in this context before moving into your next study? Or 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.
Yeah
I think if there is a readout that drives an earlier endpoint, et cetera, we'd obviously take that into account. But I don't know that us waiting-
Sure.
makes sense, particularly given that there are other therapies that are in development in PMN.
Okay. Beyond membranous nephropathy, how are you thinking about staging beyond that and other renal indications?
What we've said is that we do plan to go into multiple indications, two of which would be immune-driven FSGS-
Yeah.
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 a high unmet need. We also believe that this mechanism is complementary to what FILSPARI offers. That is going to be our next area of focus. We have not discussed the timing or anything further on the trial design, but it is definitely an area that we will be focusing on.
Okay. Maybe shifting gears to pegtibatinase.
Okay.
Yeah, let us talk about maybe kind of the data that you generated to date here and the progress on phase III.
We have been very pleased with the consistent benefit that we have demonstrated in our phase I/II study, where we were able to show in the target dose that 67% reduction in total homocysteine, and that is across a broad range of baseline values, albeit small numbers. Then we saw that consistently when patients were uptitrated from the other dose cohorts. These patients have also, many of them have been followed for five to seven years.
Yeah.
We do see a very meaningful, albeit again, small numbers, safety and tolerability profile as well. That gave us great confidence going into phase III. The other aspect that I think is particularly important, all of 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 II study, we were able to get 100% of the patients on pegtibatinase 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 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 III, we're looking to replicate those findings in a very similar trial design. The duration would be the average total homocysteine reduction between week 6 and 12. The phase II was out to week 12, so we do believe 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're 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?
We continue Any patient that was dosed-
Yeah
in our HARMONY Study, they were able to continue. We do not believe that there's any issue. There was no dose interruption.
Okay.
The patients will be in a consistent type of product. We do believe that there is a consistency there. While we did pause, we are now back on track as we went from clinical stage manufacturing to commercial scale manufacturing. All of that now is on track.
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 the bar here for approval, and what other functional data might you be able to generate?
Yeah, so FDA has agreed. We have breakthrough therapy designation, so we have 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-
Yeah
some time ago. There is precedent, and there is sufficient evidence that we have to be able to show that that is 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.
Yeah.
When we talk to the patient community, one of the most 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 is a really difficult one, particularly when you are interacting with family and friends. 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.
Okay.
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.
Yeah.
That will be when we complete double-blind. We will be able to get into more of when those data will be available, whether for top line or for the BLA next year.
Then, thinking about the market opportunity and pricing in particular, historically, there is a pretty narrow band for ERTs, but then more recently, Denali's ERT was priced quite a bit higher. Is that a trajectory for ERTs that we should be thinking about here, or sort of the historical sort of Fabry-type band? Does that make more sense?
Yeah, I think we are going to be looking at a broad range of pricing. I think we will continue to look at what is the value that pegtibatinase brings. I think we want to be able to see the clinical data from our phase III 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 be addressing the core defect of the disease. So we want to make sure that as many patients are able to access pegtibatinase if approved.
Makes sense. Thinking about sort of spend trajectory and everything next year, with civorebrutinib, with 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 to profitability. We're very excited about what we're seeing in terms of the success with FILSPARI. 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 is that there will be an increase in SG&A as we will have a full year with FSGS and IgA nephropathy. We are looking to advance pegtibatinase as well as the work that we're doing on civorebrutinib.
Yeah.
Obviously, the timing of that program will drive when that investment starts. 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 FILSPARI guidance, or are you still sort of keeping to the demand guidance that you've been giving, at least quarterly demand metrics?
Yeah, 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.
Yeah.
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-
Sure.
Bradley Campbell, who's going to be thinking about how does he want to set the vision and guidance. I think if we take a step back, we're seeing a lot of excitement around what we're seeing with FILSPARI 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 pegtibatinase. 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 pegtibatinase and HCU. I think we'll see where Bradley goes, but next year is going to be a really exciting year, not just for FILSPARI, but I think 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.