At the Guggenheim Healthcare Innovation Conference. It's been a productive first day, I think, for most people, so I appreciate everyone being here. I'm Vamil Divan, for those of you who don't know me. I'm one of the biopharma analysts here, joined with Arseniy Shabashv ili on the Guggenheim side, and next up in this room, we have Travere Therapeutics, and we have Christopher Cline, the CFO of the company, joining us up here. A little fireside chat format here. Obviously, a lot going on in the company. So let me just turn to you first, if you want to make any sort of opening comments, and then we'll go into Q&A from there.
Sure. Thanks, first and foremost, to you and Guggenheim for hosting us. The obligatory forward-looking statements. We will be making forward-looking statements, so please reference all of our full disclosures in Form 10-Q and Form 10-K. But at Travere, just overall, we are a company that's exclusively focused on identifying, developing, and delivering life-changing therapies for people living with rare disease. And like you said, we've had a very busy year, but even especially the last few months. And that's really been led by the continuing advancement of sparsentan, which is, or FILSPARI, that's approved for IgA nephropathy. And here we've been doing a great job of continuing on our launch from accelerated approval and now gaining full approval recently in September. And we've got some exciting developments in the FSGS pathway and the potential path forward there as well.
We also have another program in development, pegtibatinase, which is an enzyme replacement therapy for classical homocystinuria, or HCU. That's another program that we're very excited about because right now there's really nothing that is disease-modifying for patients with HCU. We've got some very promising phase I/II data and the start of a phase III program that we can talk more about. That's, in a nutshell, where we're at as a company and very exciting times as we end the year and go into 2025.
OK. All right, great. Let me turn to Arseniy, actually, ask a few questions on the FSGS side first, and then we'll swing back to IgA nephra .
Yeah, so starting with the PARASOL committee and their findings, we see it as a very big shift in how the nephrology community views approval endpoints in this condition. But for those in the audience who are less familiar with PARASOL and kind of less familiar with Travere's path in FSGS, maybe you could briefly recap what is this initiative, how it came about, and what were the key findings?
Sure. So I think the most helpful thing to do is sort of start with the context in which we were all, as sponsors, thinking about the pathway in FSGS historically. Really, through our discussions with FDA and how the overall field had evolved, you had to design a study that was going to show a benefit on proteinuria that then was confirmed on eGFR in FSGS. What we found in our phase III DUPLEX study, which is the largest study that's been run in a pivotal setting in FSGS, we saw that with sparsentan, we had a statistically significant difference on proteinuria. This is both at week 36 and at two years. We saw that that translated into benefits in both partial and complete remission that were statistically significant. When you look at eGFR, we saw a clinically meaningful difference on chronic slope, for example.
But there was too much variability in our endpoints for us to be able to reach statistical significance. And so it created this sort of discussion or thought process of, well, if you can't hit stats on eGFR in one of the largest run studies in FSGS, how can you? And so around the time of us coming out with the two-year data and this sort of developing more into the community, we saw that the PARASOL group came together. And the PARASOL group is a consortium of patient advocacy. And so you've got the foremost leaders in rare kidney and in FSGS. You've got FDA. And in FDA, you've got very key personnel alongside the kidney team and also statisticians. You've also got all the thought leaders in FSGS and glomerular disease more broadly that all came together over the course of the last year.
And what they did was they were able to, and this is quite amazing, actually, they pulled together, I think it's almost 30 databases' worth of FSGS data and 1,600 patients' worth of data was what they were able to sort of analyze in a very rigorous way. And they've gone through with the goal of identifying other endpoints outside of just eGFR potentially for a regulatory pathway in FSGS. And so what this all culminated in was the most recent public workshop that was held in early October and then the corresponding presentation at ASN, where the PARASOL group had a number of very important findings. First, very similar to what we saw in our study, they saw that there's a lot of variability in eGFR. And so that isn't a feasible endpoint for FSGS.
There was very clear alignment with all in the group and the community on that. The next thing that they sort of went through and really aligned on was the use of proteinuria for FSGS and the importance of proteinuria, and specifically at a year or two years, predicting being able to delay kidney failure. They looked at it in a number of different ways and came to various different thresholds that very clearly aligned to that. The other thing that they talked about was biologic plausibility and making sure that any sponsor that comes in any drug that you want to develop in the space, you need to have a clear rationale mechanistically as to why it works. I think that the most important thing leaving the PARASOL sessions was this alignment that proteinuria-based endpoints should be used in FSGS.
So it's been about a year or so worth of work. You've seen a group that's come together, an independent group that's come together, and really come quite a ways in a very short period of time. It's very exciting for patients with FSGS.
Clearly, in order for this to happen, everyone involved had to be very motivated. Can you talk a little about FSGS as a condition? Maybe we think a lot of people are familiar with IgAN , maybe not as many investors are familiar with FSGS. How is it different from IgA N in terms of prognosis, unmet need, other approved treatments for FSGS? Can you comment on that?
Sure. So FSGS is certainly more progressive than IgA nephropathy. And there's a far greater unmet need. And that's driven in large part by the fact that there are no treatments available in FSGS. Right now in IgA, we're in the early innings of a sort of renaissance, if you will, and we're seeing more and more therapies come to fruition, which is great for IgA patients. FSGS right now is a very different story. And so to your point, I think that's a large driving factor for why you see PARASOL able to move and really they're driven to move that quickly. When you think about the overall sort of dynamics of FSGS, you have patients that are many of them within 5- 10 years are going into transplant or dialysis. So again, it's more rapid of a progression versus IgA nephropathy.
Just from an overall population size, in IgA, you've got about 70,000 patients that we look at with FILSPARI, at least, and think of it as being addressable, and in FSGS, it's about 15,000-30,000 patients that we would look to as being addressable, so it's a little bit of a smaller number, a little less than half, but at the same time, you're talking about a community that desperately needs something because patients are looking at losing kidneys, and there's no approved treatment options, and there's nothing really else out there on the horizon that has a lot of potential to come to market anytime soon, so I think that there's a big drive from the community and certainly from our organization. We want to get to patients as quickly as we can.
Then in terms of this endorsement or recommendation that PARASOL gave for proteinuria, and I think they recommended a few different endpoints or a few different thresholds of proteinuria that are meaningful in terms of reducing the downstream risk of kidney failure. My question is, what does this mean for Travere in the context of your prior clinical findings and your overall clinical program for FSGS?
Sure. I think the interesting thing from the PARASOL work and the analyses that they went through is the consistency in which our data line up to what their conclusions were. And you highlighted the proteinuria thresholds. And there was talk of everywhere from 1.5 down to complete remission at 0.3. And there was a lot of discussion around 0.7. And that's all driven by the data that they went through, right? They took a very data-driven approach of the 1,600 patients to find the strongest signal. And what we're encouraged by is within our data set, what we see not only in DUET, which was our phase II study, and there we've shown that complete remission really does tie well to better outcomes from a kidney standpoint. But in DUPLEX, we see in every which way we cut the data that you have a better response on proteinuria, right?
So when I mentioned this earlier, you have 36 weeks and two years' absolute difference in proteinuria reduction. For patients in partial remission of proteinuria, you have a 1.6 greater likelihood of being able to achieve partial remission on sparsentan, and you have a 2 and 1/2 times better likelihood of achieving complete remission on sparsentan. So those ladder into the analyses well. But when we look at the actual thresholds that you highlighted, if we started our pre-specified endpoints 1.5, getting patients below 1.5, below 1 gram, below 0.5, and then below 0.3 grams, then we see a very clear response across all of those. And it's pretty much linear. And the important thing there is you gain strength in the signal, and they're all statistically significantly different in favor of sparsentan.
Those data really line up well to the analyses that were presented as part of PARASOL and what we'll look to engage with FDA on.
And so you now have the Type C meeting on the books to discuss this. And I believe you said you expect to update on the outcome of that meeting by the 4Q earnings call. Can you talk a little about your strategy of discussing the clinical data that you have with the FDA or how you're going to present it during the Type C meeting?
Yeah, it goes back to what I just talked about, right? The thresholds that PARASOL outlined, I think very clearly, they're very clearly aligned to our data and consistent with everything that we've seen. And so our goal is to go in and have a discussion with FDA. And as you mentioned, it's a Type C meeting that we have currently on the books. We'll have that discussion. And then once we're in a position to be able to provide an update, which will be by our earnings call, we'll certainly do that. And in parallel, our plan is we're going to be working on the SNDA. So we're going to be doing that in parallel so that if we have a path forward, as we hope to, then we're going to be able to submit very quickly.
Our goal there would be to have a potential approval by next year.
So last, in terms of the commercial opportunity you see in FSGS, we touched on the number of patients, the competitive landscape. Can you also talk about price or how you see pricing, future pricing in that market?
Yeah, we're not in a position where we can talk specifically about pricing yet. But I think the two things that I would point to are one would be we've always looked at making sure that we prioritize access, right? And so we did that with our IgAN market and making sure that we priced that in a way that patients had access, we had strong reimbursement. So that's certainly top of mind. And then the other piece is just making sure that we take into account any differentials in dosing, right? So for FSGS, it's 800. In IgA, it's 400. And those will be the things that we're thinking about.
Let me turn it back to.
Yeah, so why don't we shift back to IgAN? I think FSGS is driving the stock right now, but IgAN driving the sales. So strong third quarter you guys had following the full approval. Maybe you can just talk a couple more weeks into the next quarter or two now. The impact the full approval has had on what your sales force have been able to talk to us about and the impact of that, and also around the same time, the clinical guidelines, how is the message sort of evolving and resonating with doctors?
Yeah, great. So first on 3Q, just before we even get to full approval, very pleased with the commercial team's performance and the continued uptake of FILSPARI. So we had 505 new patients start forms and being above 500 in a quarter where you typically see some seasonality around the summer months. Just like most products out there, you have patients and physicians who are taking some time off around the summers and traveling and everything else. There are just fewer visits. And when you take that into account, plus when we brought the field team out of the field force to be trained on the full approval and the new label and materials for a week, very pleased with the demand there, even leading into full approval, right? So the fundamentals are all there and all trending in the right direction.
And then when you add on full approval, and what we've seen since is the inflection that we had hoped to see, right? We expected and have been guiding everybody to the fact that the full approval label, the ability to talk to two years' worth of data in eGFR and safety, et cetera, as well as the draft kidney guidelines, should serve as a nice tailwind for the product. And that's certainly coming through so far with what we're seeing post full approval. You asked specifically about the kidney guidelines and how they're being talked about or utilized. And this is more anecdotal, but especially because it's early days here. They haven't been out for that long. But it was interesting to see just at ASN, for example, you have a lot of physicians who are engaging with people either within our organization or in other places.
And there's already a lot of reference to them, which I take as a good sign, right? Because you're getting important leaders that are thinking about it and talking about it. And there's a lot of good that came out of those kidney guidelines that we're looking forward to seeing come out in the community.
OK, maybe we can talk about the competitive landscape. So there's two other products approved now for IgA N, TARPEYO, iptacopan, others clearly coming from Novartis and others. So just kind of how is FILSPARI being integrated right now relative to the other options that are available? And then how do you see that maybe evolving over the next year or few years as other treatment centers?
Sure. The IgA N landscape is evolving a lot like how we expected it to. Now we're seeing more and more data come out, which is great. But ever since the outset of the IgA N program, we had always looked at FILSPARI as being combination use going forward. And so as a bigger picture view, I think everything is sort of playing out very close to what we would have expected. And the interesting thing is there's a lot of focus right now on showing proteinuria reductions and stability of eGFR. And we actually, in our SPARTAN data, it's quite interesting. At ASN, this is a small study of about 12 patients that we did repeat biopsies in treatment-naive patients. And we show there that you have, with treatment and sparsentan, 70% reduction in stable eGFR.
We're continuing to generate new data that helps position FILSPARI in the right light among the evolving paradigm. I think I'd go back to the draft kidney guidelines because there's a few things in there that are going to sort of shape the overall dynamics. The first is they've put in there lowering the treatment threshold to 0.5 or potentially 0.3 for patients. That's critical because if you go back a year, you'd have a number of physicians who were saying, OK, well, if my patient is at a gram, they're probably OK. But what the data now tells us is that those patients are at risk of kidney failure. You need to be treating them earlier. You need to be treating them more ambitiously.
So we're going to see more and more patients treated, which is great for the IgAN community and obviously as us as people developing therapies for IgA. The other piece of it is very clearly in the kidney guidelines, they highlighted the fact that you have to address both aspects of disease. So this is the overactivation in the kidney, and it's the overactivation in the immune system. And what we know from everything that's out there is nothing in development or commercially available that will take everybody into complete remission and address both of those things. So that was very clear in the kidney guidelines and why they're driving towards the use of combination therapy going forward, right? And so our placement really is in the overactivation in the kidney where we think we're positioning FILSPARI to take over that space and really be foundational care.
When you think about what we're able to show with FILSPARI and the fact that it's a non-immunosuppressant, really positions us well to be able to do that. More to come. Everything so far is shaping up in a way that we think that we have a great position to be able to be foundational care in the future. It will be used in combination with other medicines. We're seeing the early signs of that with some of the other medicines that are out there, such as SGLT2s or TARPEYO. We expect that to continue.
So one important update you guys gave on the earnings call is this filing of an sNDA around the liver monitoring something. Maybe you can just talk about that, what your hope is here. Sounds like moving more to maybe quarterly. And then what will be the steps to potentially getting it removed altogether? And then commercially, how important is that to kind of get some of that sort of update to come through?
Sure. So we did file an sNDA to have the liver monitoring adjusted to quarterly. Currently, it's monthly. And then after one year, it goes to quarterly. So this would just make it quarterly the whole way through. And I think what it does is it's probably a little bit less about a barrier that's in place right now. It's more about making it easier for patients and really having patients that are, if they're busy in their day-to-day lives, going to work, going to school, whatever it is, making things more convenient than that factor. And really, with the quarterly REMS, what we'd be doing is aligning it to their normal cadence of getting labs with their docs, right? So it just makes it a seamless process. So that sNDA is in place or it's been submitted. We will hear from FDA on the timeline for review.
And then at some point in the future, once we've generated a bit more data, then we would look to also have it potentially removed. But we've got to generate some more data to do that. But so far, all things are going in the direction that we had hoped to for that and more to come.
All right, great. So maybe we talked a lot about the U.S. side. Maybe we can talk also ex-U.S., sort of how you see the potential there. I know you have some partnerships already, but just in terms of the IgA N, and then also FSGS. And maybe with FSGS specifically around the PARASOL, there's some questions around FDA versus the MEA, sort of how bought in the MEA is on the proteinuria endpoints. Maybe you can touch on that also in terms of the ex-U.S. opportunity.
Sure. So first off, we've got great partners in Europe and Japan. CSL Vifor is our partner in Europe. And they've done very well navigating the regulatory path. And now they've gotten approvals in Germany, Austria, and just got one in Switzerland. So they're operating very well. They've got launches now that are in their very early stages in Germany, Austria. But everything that we hear, things are moving well. And we're excited to see what they'll be able to do with FILSPARI over in those countries. And they haven't provided guidance yet or anything of that nature. But we'll certainly provide updates as we have it. But it's going to be an important medicine in Europe. From an FSGS standpoint, things are probably a little bit further behind the U.S. in that regard. And you touched on FDA being a critical component in PARASOL.
EMA wasn't as active in it, but they were still involved in it. And so we'll see how that evolves over time. We'll be working with Vifor, who has been the regulatory lead for Europe, to see what the right appropriate next steps would be. And we'll provide an update when we can.
OK. All the positive progress on IgA, FSGS, pegtibatinase did have a little bit of a setback. Maybe you can just talk through that, the manufacturing update there. Sort of, when should we expect to hear more in terms of the progress you're making in resolving that?
Sure. So with pegtibatinase, we remain very excited about this program because there really is nothing that's available for patients with HCU. In our phase I/II data, 67% reduction in total homocysteine levels is very encouraging, and so that's something that we continue to have a lot of hope for. As you mentioned, we did recently announce that we were pausing enrollment in our phase III study, and that's driven by the need to insert a process improvement for our commercial manufacturing scale, and you may recall that we started the study while scaling up for both enabling further enrollment but also commercial use, and there's some work there that needs to be done, but what we see, we believe that we can solve, and it's really just about time and a little bit of investment to improving the process.
But our goal is to have enrollment started back up in 2026. And the good thing about all of our work with the community has been there's a lot of interest in the study. And there continues to be interest in the study and support from the patient community as we work through this. So we're looking forward to getting going as soon as we can.
All right. And maybe last couple obligatory questions. One, we mentioned at the beginning, a lot going on. Just if you can lay out the sort of catalysts here as you look out over the next 12-18 months?
Sure. So we talked a little bit about the commercial side of things. So you should expect the normal updates as we go through each quarter and update on our IgA N progress and how things are shaping up post full approval. We're excited about what we're seeing so far. We will have the update between now and our next earnings call. So we typically report in the February time frame. But we'll have the update for FSGS by then. So that's going to be something that we're excited to share once we get to the right point. And then assuming we have a path forward, we would be moving very quickly for an sNDA submission there and working through the regulatory process. So if we have that path forward with FDA, then you'll be hearing more about that process and a potential approval sometime next year.
So I think those are probably the key elements. And if there's something with pegtibatinase that we can communicate on the process improvements and where things are going in phase III, then we would certainly look to do that as well and more updates coming from Europe.
OK. And maybe just last question. I know you guys just announced the filing last week. So maybe a limited, what you can say, but just around cash position, your current runway, the latest comments you can make there?
Sure. What I can point to are back to our comments on our Q3 call where we had $277 million in cash, and that was runway into 2028, and what I would say about the recent financing is it provides additional flexibility for us to be able to invest in some of the activities that we need to do right now for FSGS in order to be prepared going forward.