All right, I think we're ready to get started. So, thanks everyone for joining us for this year's Biotech Summit here at Guggenheim. I'm Vamil Divan, one of the biopharma analysts here. Next up in this room, we have the Travere Therapeutics team. Next to me, Eric Dube, the President and CEO, and then Chris Cline, the CFO. Thanks so much for joining us. And, maybe just to start it off, Eric, it's obviously been a busy time at the company, a lot of different moving parts. Maybe just give an overview of where things stand with the company, and then we'll go into the questions.
Sure. Well, thanks so much for hosting us. You can find this and more information as well as our forward-looking statements on our website. Travere is in a really exciting place as we look at really transforming the outlook for many rare disease communities. We're focused exclusively on rare disease, and we have been focusing our efforts on three in particular: IgA nephropathy, a rare kidney disease; FSGS, and even rare and one of the most severe rare kidney diseases; and then a rare metabolic condition called homocystinuria, or HCU. And last year, we made incredible progress on all three of those programs.
This is now. We're ending our third year of launch of FILSPARI in IgA nephropathy, and we are really making great strides in becoming the new foundational care and replacing the traditional role that RAS inhibitors and ARBs have played in that treatment paradigm. We've closed last year very strongly with our strongest quarter to date in our commercial performance. We also have an sNDA under review with FDA for our FSGS program with FILSPARI. We recently announced an extension of that PDUFA date as FDA requested additional information from us, which we have provided. So we're eagerly anticipating that approval. And that could put FILSPARI as the first medicine ever approved for this condition, a community we've been working with for over 10 years who really is in an urgent state to have something approved for their condition.
Then finally, with HCU, we worked on addressing some of the manufacturing scale-up challenges we faced over a year ago. Those have been resolved, and we're now in a position to restart our phase III HARMONY study this quarter. Incredible execution from our teams and really well poised to have another strong year in 2026.
Okay, great. Thanks. So a lot to cover in 20-something minutes here. Let's start with FSGS, because I think that's where most of the focus is. You mentioned the extension, came in January and now the PDUFA date in April. So, maybe you can just I think a lot of the questions we've been getting is sort of what led to that, you know, the extension, there was some back-and-forth information requests from the FDA right before the PDUFA date, and then your level of confidence going into the April PDUFA.
Yeah. Well, let me start with the last question. Our level of confidence remains very high in the approvability of sparsentan and FSGS, not just because of the unmet need, but because of the consistent, strong results that came out of the only pivotal study ever done and it with a strong rigor as a head-to-head study demonstrating superiority in proteinuria reduction versus a known nephroprotective therapy, irbesartan. With regard to your first question of, you know, what led to the extension, you know, the extension was a result of some of the additional information that FDA requested. Those information requests that came in December when we were expecting to have draft labeling, those information requests came in. We don't really know why they came in at that time. What we can say is that the questions themselves were quite straightforward.
If we would have received those earlier in the review, we wouldn't have batted an eye. But it was really the coming so late in the review. It's hard to say why they came in at that point. You know, our teams, however, did come together very quickly. We believe we've answered all of those questions, and we're now in a position to wait for draft labeling and potential approval on April 13th.
Okay. And one thing, obviously, just with the nature of things at the FDA right now, a lot of turnover in personnel, anything along those lines that I don't know how much you would even know, but just in terms of changes in people reviewing it, new people getting involved, anything there that could have maybe played a role at all?
Yeah, it certainly can be. I mean, we have seen the same headlines around staff reductions at the agency. We have seen a number of new reviewers during those questions that we received in December. But because we don't have—because it's an sNDA and we do not have formal meetings like a mid-cycle review meeting or a late-cycle review meeting, it's near impossible for us to be able to estimate, you know, the degree of personnel changes and whether they were, you know, what led to some of those late questions. I think what's important is that we continue to have strong engagement with the FDA. The Director of Cardiorenal, who's been involved in our program for over 10 years, is still there.
And importantly, as we take a step back, you know, we believe that we have the data as well as the strong external support, including from the PARASOL Initiative, you know, really showing why proteinuria is a should be a validated endpoint in this disease, really gives us strength going into this PDUFA.
And then one last on the regulatory side, what we should expect from the company going forward between here and April 13th? Last time you sort of went into a quiet period, you know, should we expect a similar sort of approach? And what's the kind of plan from a communication perspective?
Yeah, that's right. So you can expect that we'll go into a quiet period, you know, in over a month, before the PDUFA date, so sometime in early March after our earnings coming up, that we'll go silent, until the PDUFA date or until we have, you know, other meaningful written correspondence from the FDA.
Okay. Now maybe shifting to the commercial side. You mentioned severe condition, rarer than IgAN and no approved therapies. How are you thinking about the sort of potential uptake, assuming you do get good news in April?
Yeah. So we will be ready. We've been ready, and that's because we know that time matters for these families. I've had the opportunity to meet many families and many parents whose children are affected by FSGS, and to say that there is a desperation for a therapy is probably an understatement. So we take that to heart and we'll execute like we never have. And we believe that there is going to be a rapid uptake, not just because of the sense of urgency, but also because of the strong execution and because there is a level of experience and awareness that nephrologists have with FILSPARI and IgA nephropathy. The strong success that we've had in IgA nephropathy really should confer stronger confidence in an uptake.
It's really our ambition to have the strongest uptake that we've ever seen within kidney disease because this is what the patients deserve.
What do you need to do in terms of just your infrastructure, your strategy? I think there's quite a bit of overlap in terms of the doctors, but maybe you can talk about similarities or, or new areas you need to think about investing in.
That's right. So we did invest in an expansion of our field team in the fall to get ready for the January PDUFA date. So those teams are in, and I am just incredibly impressed with the level of expertise and experience, not just in rare disease, but in nephrology that they bring. And I think that in large part was one of the reasons why we saw our strongest quarter in IgA nephropathy last quarter, because they really started out strongly. And I think that's just a taste of what you can expect to see in terms of our execution in FSGS. In terms of the overlap of prescribers, there's a very high degree of overlap, about 90% overlap between physicians that treat patients with IgA N and those that treat FSGS. Really, the primary difference is pediatric nephrologists.
So our label currently is for adult patients with IgA nephropathy. We would expect with FSGS to be approved also for pediatric patients. So part of our expansion is also to be ready to reach pediatric nephrologists as well.
Okay. Maybe just one more on the commercial side here. We're hearing a lot more about FSGS at this conference and, you know, from other companies. How are you just thinking about the sort of competitive landscape in FSGS?
Yeah, I mean, I would not expect or I would not be surprised that others follow suit. You know, we've helped to lay the pathway for what can be done in FSGS. And, you know, we've seen with FDA and with PARASOL an evolution of the regulatory pathway. And so I would absolutely expect that there will be others that follow suit. What I would say is that this is a condition that nothing that we see and no mechanism that we see potentially would be curative. And therefore, patients are probably going to need multiple treatment options and likely combination therapy. And so the things that we see in development are likely to be complementary.
We don't see anything in development that we would consider a competitor to ours or a, you know, treatment option of the same mechanism. So we would fully expect that there will be folks that follow suit, but it will be a number of years before anything is commercially available in our estimation.
Okay. So why don't we switch over to IgAN ? We'll do it on the time if we have time to come back to FSGS. But IgAN, you mentioned sort of record performance you showed in the, you know, in the recent quarter. We have seen some new competition come into play. Maybe you can just talk about the dynamics you're seeing in the market in terms of continuing to roll out FILSPARI, new guidelines supporting more aggressive treatment of these patients, but also more competition.
Yeah. So we certainly are seeing a lot of a lot more treatment options come to patients with IgA nephropathy. And I think that's going to be incredibly welcomed by the community. And really, we hope that there's a future in the next five years when these are all available, that patients will have access to multiple therapies and that no patient would have to face kidney failure. That really, we believe, is on the horizon. But that is going to require much more aggressive, earlier treatment of these patients, and it's going to require combination therapy. We're starting to see evidence of that. We're seeing use of FILSPARI in earlier patients, less severe patients. And we believe that that's not just because we have full approval and we've got a data set to support that use, but also the guidelines really call for earlier treatment.
If a patient is not at goal, which is essentially complete remission, they need to be treated, and they need to be treated with combination therapy. And we are seeing with the, the emergence of some of the newer therapies, combination with FILSPARI. It's early, and it's anecdotal, but we are seeing that physicians are wanting to align to the KDIGO treatment guidelines around, combination. So it'll be interesting to see how that evolves, but we've been predicting that that's, that's the way of the future as we move forward. And really, we have not seen evidence that it will, dampen the growth opportunity of FILSPARI. In fact, as new therapies come out, we're seeing our performance continue to strengthen. And it's likely because that's growing the awareness of the need to treat. It's growing the market, and patients are being more effectively treated.
Okay. I guess one question that comes up a lot because there's so many so many new therapies, branded therapies, expensive therapies, how, how are payers reacting to combination use? I don't know if you've seen anything in the hasn't been that long, but, you know, in the last year or so, have you seen any changes in how payers are adopting these?
Yeah, it, it's still early. We are seeing that payers are covering these therapies. We have seen, again, anecdotally, that payers are allowing combination on top of FILSPARI. Again, I want to caution because you see one payer, you see one payer. And we would imagine that as more options come out, that, you know, payers are going to have choice. I think for our view, we are quite confident both in the unique positioning that we have within the treatment guidelines as unique versus the immune-targeted therapies, but also the health economic evidence that we have. We're the only company that went head-to-head against an active competitor. So essentially, for us, we are seeing that physicians should adopt us versus an ACE or an ARB. That's really the treatment choice that we're asking physicians and payers to make.
We've got the superiority data to be able to support that.
Okay. And then maybe one question that comes up sometimes too, now that you've been on the market for some time, is how long patients are staying on these therapies. Maybe you can just comment on what you've seen sort of in the market in terms of, persistence.
Yeah, we've been very pleased by the compliance and persistence. The refill rates continue to be some of the highest I've seen in my career for chronic therapy. And I think that's in large part because, one, the simplicity. It is, you know, a once-a-day pill. And also, patients see the benefit. You know, these are patients that oftentimes are seeing their lab values worsen each time they visit their nephrologist. And for the first time with FILSPARI, they're seeing their numbers go in the right direction. And that's incredibly encouraging for a patient to want to stay on therapy.
Okay. And what about the REMS program? I know you got it sort of eased up a little bit, you know, last year. What's the sort of next steps to potentially have that modified or lessened?
Yeah, I mean, I think, you know, the, the modification that we saw in the fall last year really was one of the key contributors to our strong performance. You know, physicians that may have been waiting to prescribe FILSPARI or reluctant to prescribe in, in some patients that may not have the ability or interest in getting their, their tests done every month, now are able to do that once a quarter, which aligns largely with how patients are being seen by their nephrologist. So a really, meaningful, contributor to our, our performance. But I think there's an important role that the REMS has. I mean, it helps to, to maintain awareness around the profile, but it also ensures that patients have their lab values, including for their kidney, kidney function, every three months.
So I think, you know, we're really at a spot where we're quite pleased. We will continue to look at amassing our safety data set to eventually look at removal of the REMS. As part of last fall's change, we did have the pregnancy monitoring REMS removed. But that's going to just take more information. We've wanted to wait until after an FSGS approval to be able to have those conversations with the FDA just to maintain a focus on ultimately getting FSGS approved.
It's one thing we've been saying, at least from our side, on FSGS as it comes out, because of the REMS sort of familiarity with it now, familiarity with the product overall, we'd expect much more rapid adoption relative to what we saw in IgAN. Does that seem reasonable to you? How are you sort of thinking about the uptake with FSGS relative to what we've seen over these first couple of years?
Yeah, we, we absolutely would expect a faster uptake in FSGS for a couple of reasons. You know, if we look at when we were approved in IgA nephropathy, it was under accelerated approval. We had nine-month data, and we had a REMS that required monthly testing. And, also, you know, we were working through the, the payer access and our, patient services. All of that has shifted. So assuming that we get approved on April 13th, it would be for full approval. The REMS would be quarterly. We have a strong base of payer access, but also we have familiarity and clinical experience by many nephrologists, which, you know, makes it that much easier to be able to, to decide to, to prescribe, for FSGS. But I think the other aspect that probably will drive above all of that is the sense of urgency.
We had to really generate the evidence to show that patients with certain levels of proteinuria in IgA nephropathy, while they may be stable, they're still at high risk of kidney failure over 10 years. So there was quite a bit of time to be able to really educate nephrologists around IgA nephropathy, you know, to address how they were educated in medical school that IgA nephropathy is a slowly progressing, lower-risk disease. In FSGS, we don't need to do that. Nephrologists and patients know that they are at very high risk and are often seeing these patients progress. So the sense of urgency to want to adopt a therapy like FILSPARI, we believe, will be quite rapid.
Okay. So why don't we shift over to pegtibatinase?
Okay.
I feel like he's been a little bit behind this, under the radar. Everyone's focused on FILSPARI, but I feel like that might change later this year, assuming we get through the FSGS approval. So maybe you can just talk a little bit about that market, and kind of frame what the unmet need is, how are these patients with homocystinuria currently managed, and what do you see as sort of the market opportunity, both U.S., ex-U.S.?
Sure. So HCU or homocystinuria is a genetic metabolic disease. So patients are born with a defect in their CBS enzyme, which is responsible for metabolizing an amino acid in our diet called methionine. What happens is with that, you have an accumulation of homocysteine, as a result of that enzymatic defect. That homocysteine levels and methionine levels accumulate over time and become toxic. What happens if a patient is not really aggressively maintaining their homocysteine levels is that they will start to see cognitive and psychiatric defects. They'll see eye problems with their lens dislocating. About 25% of these kids will have an ischemic event before they're a teenager. Half of them will have an ischemic event or multiple events before they turn 30. So there's a whole constellation of symptoms that occur as a result of homocysteine elevations.
The mainstay of treatment is really an aggressive diet in restricting their protein levels, which is the source of methionine in our diet. We'll have to replace that with a really foul-tasting medical protein. They also, for any kind of remaining CBS enzyme that a patient may have, they'll use vitamin B6, which about half of patients are responsive to. We look at the number of patients that are diagnosed. There's about 10,000 patients in the U.S., and about 3,500 that are actively under the care and are not at goal. We think that that is a really significant underestimate because half of the patients are not diagnosed, even though HCU is part of newborn screening. So there's real efforts to be able to help in better methods for newborn screening and being able to reach patients that may have been lost to follow-up.
So in many ways, this is similar to PKU, but I want to be respectful of the HCU community that it's not a direct, not a direct comparison to, to PKU. There's nothing really approved that directly addresses the defect of this disease. So we really believe that pegtibatinase could be the, the new standard of care if approved.
You're in the process of getting the phase III restarted. Can you just give us some sense how you think it'll progress here in terms of enrolling that trial? How long should it take? Execute?
Sure. Yeah. So, so in parallel to some of the manufacturing scale-up that we've done over the last year, we've been actively engaging with the HCU community to get ready for the enrollment. So there are many patients that are eager to be screened. We've been working on identifying the sites. We typically will provide guidance on the timeline for top-line data once we've got the first patient dosed. So, you know, that will be in the future that we'll provide that information. But we do expect that this will enroll quickly. The one thing that I would want to point out that is quite unique for this trial is one of the key factors and risks that we want to manage is variability within this trial. Because the diet can impact homocysteine levels, we want to really manage the stabilization of the diet.
So there's an extensive screening period for this trial, over eight weeks to stabilize the patient's diet. So there will be that factor, but we believe that this will be very quick to enroll.
Okay. And then in terms of the competitive landscape here, it looks pretty open from what we've seen and anything you're seeing.
We don't see anything in clinical development. So we do want to still move very quickly, but we don't see anything in development for HCU.
Okay. So in the last few minutes, I just want to talk more longer-term now. One, we still get a lot of questions around the patent estate around FILSPARI. So maybe your latest thinking is there. And then beyond FILSPARI, kind of how are you thinking about the longer-term outlook for the company in terms of bringing in other assets, you know, further development of things in your own maybe internal pipeline? How do you think about that?
Chris, I'm going to bring you in to answer these questions.
Sure. So from the patent perspective, our base case is 2033. So that's really grounded in not only our Orange Book listed patent with the patent term extension, but then also orphan drug exclusivity that we would have for each individual indication. We also have some additional work that is currently underway with PTO review that can extend that beyond the 2033 timeframe. And then on the business development front, that's something that we're certainly interested in pursuing post-FSGS. What we want to make sure we're doing is getting through the FSGS process, ensuring that we have the internal capacity. And then, you know, at that point, we would look to bring in additional assets that we believe really have clear synergies with either our, you know, mid to late stage development expertise and commercial expertise ultimately.
There's certainly the, you know, the aspiration to continue building the company for that next phase of growth beyond FILSPARI and pegtibatinase.
Okay. And just in terms of your current capital position, kind of maybe just a reminder on where things stand at the end of the year?
Yeah. So at the end of the year, we had $323 million in cash. From a, you know, support of the overall business perspective, there's no near-term need for capital. We believe that we can utilize that to support the three priorities that Eric has been talking through, you know, really driving the continued momentum in IgA nephropathy, getting through approval and successful launch in FSGS, and then, advancing pegtibatinase to date and ultimately to a commercial launch there. So we're in a very good shape from a financial perspective.
Okay. Great. So obviously, all eyes on April 13th. Best of luck as we approach that date. Then obviously, the continued progress in IgA N and HCU as well. Congrats on the progress and look forward to seeing it continue.
Thank you. All right. Thanks so much.
All right. Thank you.
Thanks.