Travere Therapeutics, Inc. (TVTX) Earnings Call Transcript & Summary

All right. I think we are live. Good afternoon, everyone. Thanks for joining us on the second day of our Fifth Annual Guggenheim Genomic Medicine and Rare Disease Day. I'm Vamil Divan, one of the senior analysts here at Guggenheim, joining -- Arseniy is also on the line from the Guggenheim side. And we've got the full team here from the Travere Therapeutics side for our next session. Thanks so much to all of you for joining us. We have Eric Dube, who's the President and CEO. We have Chris Cline, the CFO; and Peter Heerma, the CCO, along with Naomi Eichenbaum from Investor Relations. And obviously, a lot to get to, so I'm just going to jump right in. But before I do that, for those of you listening in, if you have any questions that you want me to ask, please feel free to e-mail me at [email protected] and I'll work them into the conversation.

But I thought what we could start. We obviously this weekend just had some additional data released at WCN. So maybe if you guys just want to share, I guess I'll turn this to Eric, if you want to share your thoughts on the Lancet publication, key takeaways that you took from the data and the confidence that provides you as you, as we wait for the 2-year data in the fourth quarter of this year.

Sure. Well, Vamil, thanks to you and to Guggenheim for hosting us today. We certainly are excited about the information that we have thus far in the year, which is a very important year for us at Travere, but more importantly for the rare -- kidney community. And with the World Congress of Nephrology just completing, we were very excited to be able to provide some additional data from our ongoing PROTECT trial as well as a simultaneous publication in The Lancet. And I think I'll certainly caveat this that this is an ongoing trial. This is an interim look at the data. But what we've seen so far and what was published really does give us further encouragement and confidence in what we expect and hope to see at the 2-year m end point of this important trial. Certainly, what we saw was a very rapid and sustained improvement in proteinuria for these patients, and that really is reflected in our FILSPARI label. But we also were able to provide some additional information in that response of proteinuria reduction. For example, partial remission, over 70% of patients on sparsentan were able to achieve partial remission of less than 1 gram per day compared to about 44% of patients on an active control irbesartan, and that difference was highly significant. We also saw a more rigorous measurement of remission -- complete remission. Those patients that were able to achieve less than 0.3 grams per day of proteinuria, 21% of patients on sparsentan compared to 8% on irbesartan. So this also was very exciting to be able to see this early in the trial and really a sustained reduction in proteinuria at least up until the point of this analysis. We also were very encouraged to see early trends in outcomes, hard outcomes for these patients, which we know are very important for nephrologists. These are get preliminary numbers, but we did see a numeric difference in the reduction of eGFR kidney failure mortality compared to active control irbesartan. One of the other -- that I think the response at the -- the early response at the meeting was very positive from the nephrology KOLs and community. One of the questions that we've received quite a bit around the mechanism of action for sparsentan is -- are the benefits that we see on proteinuria really tied to a reduction in blood pressure. We are pleased to be able to show the blood pressure data, and there was a very small difference between groups. But essentially, it doesn't what we believe explain the difference in proteinuria, meaning that it's not just hemodynamic alone. It's likely well beyond that. And our hypothesis based on some of the preclinical data is that it really is based on structural changes that are going on in the kidney. So more to come there, but really, directionally confidence building. And then finally, really around safety. It's important to be able to demonstrate that the safety, especially with a known mechanism like endothelin blockade that has for other agents been associated with edema, heart failure or hepatotoxicity. And we continue to see a profile emerge with sparsentan, where there are levels of edema, but no cases of severe edema, no cases of heart failure, no cases of hepatotoxicity or edema-related discontinuations. And so -- and we also were able to provide some body weight change data in this presentation and manuscript. So I think it provides further information in this ongoing trial, and we're well poised and eager to be able to complete the trial this year and provide additional information at the 2-year measurement of safety and efficacy in the fourth quarter of this year.

Okay. That's great. And then you touched on some of the early feedback on the data. It kind of ties into my next question just sort of the early feedback on the launch because you got the approval about 6 weeks ago. And so maybe you can just sort of share your latest thoughts on how the launch is progressing. I know obviously, you guys commented how you got your first script filled pretty quickly after the approval. But how are things sort of 6 weeks out? And what's the feedback been from physicians and patients both on the sort of process to go on therapy, but also just in the efficacy and safety of the product.

Yes. I think certainly, Peter can cover all of those questions. To give a high-level overview, we've been very pleased with the launch performance to date. I've been very impressed with how Peter's team has been able to execute on all levels to ensure that we get out very quickly. We know that these patients have been waiting for very long. We know that time matters for these patients. And every launch, really, is founded in strong execution, and I think Peter's team has been able to demonstrate that from not just day 1 but hour 1. Peter, do you want to talk about the early response so far?

Yes, absolutely. And thanks for hosting us today. A couple of things, you already referenced that early prescription that we got like basically was in 8 hours after the approval. I think that speaks to the unmet need, but also the amount of patients that are being seen by nephrologists. And I think the team that we have put in place, and we have already a foundation -- commercial foundation in nephrology with our cystinuria product, THIOLA, which we have expanded. So we have over 800 commercial people in the field right now that have a very good understanding of nephrology that knows nephrology very well. Our initial focus is to be consistently targeting 6000 nephrologists that cover about 85% of the rapid progressing IgA nephropathy. And to Eric's point, like the early indicators of how the launch is going, we're very pleased with the initial feedback and receptivity of the market. We see scripts coming in. We see repeat scripts. We see awareness from the payer to cover us. I cannot go into numbers today, but we will be covering that at the next earnings call, where we will provide additional color on what we are seeing with regards to patients thought forms, net revenue as well as progress we're making with the payers with regards to covering FILSPARI so far. One of the questions that we had a lot of initial response from the investor community was like, well, what does the REMS mean for initial uptake I think having been in the market now for 6 weeks, what we have the opportunity to really sit down with the nephrologist and talk about the efficacy data as well as the safety data, often the question we're getting is like why do you have a REMS program in the first place? And once the physicians understand like what the implication of REMS are and what the burden workload is for them, and that's basically attestation, that burden kind of like falls away. So far, we don't really see too much of a burden from the REMS implication Yes, I think overall, the receptivity has been very solid from the nephrology community. Patients are there. The unmet need is being acknowledged and our field force has a good understanding to have the connectivity with the nephrologists.

Okay. That's great. So maybe one quick follow-up on that is just in terms of the patients that are starting therapy, can you talk about sort of, I assume they're all sort of ACE and ARBs has been discussed before getting on FILSPARI, but most of them are also on SGLT2s, and also maybe if you can touch on Tarpeyo. Are they -- have they already tried Tarpeyo? Just a sense of kind of where the patients are coming from.

Yes, it's a great question. First of all, like all of the -- we are focusing on the nephrologists. All those patients are under the care of the nephrologists have had the confirmatory biopsy as well. All those patients have been on ACE and ARBs and that's like 90% of the patient population in the first place. I would say even higher. SGLT2 is an interesting one. I mean, certainly, we see an increase in uptake of SGLT2. It depends on what position you're talking with. It's -- FILSPARI is certainly seen as the potential for a new foundational care. It has the ARB component, but it adds then also the endothelin component. So it bought 2 bad actors in the pathophysiology of the disease. So physicians understand like where FILSPARI is, more early up-front in the treatment paradigm earlier than, for example, steroids like, for example, Tarpeyo. SGLT2, as to what I mentioned earlier, you see a more rapid uptake over the last year to 1.5 years with SGLT2. And physicians see the combination of FILSPARI with SGLT2 as the new standard of care because it allows for a non-immunosuppressive treatment paradigm to those patients to regress the progression of disease and stabilize those patients. So I don't have insights yet on like how many patients are on or not on SGLT2 through the building the evidence as well in our open-label extension trial, where we allow for SGLT2, but so far, very pleased with where FILSPARI sits and how physicians react on where they see the positioning of FILSPARI, which is kind of like up-front in the treatment paradigm.

Okay. That's great. And what about on the payer side? And maybe you can just talk a little bit on what the sort of initial reaction has been on this for a few weeks from -- in terms of getting patients reimbursed for the therapy.

Yes, absolutely. And at the earnings call, we already highlighted that we have had substantial interaction with payer already prior to launch. We -- and we had a field force -- an account of management field force that were active in the field already 6 months prior to launch to really educate payers with regards to costs associated with disease, IgA nephropathy to make that more up-front in their understanding as well as the humanistic burden of IgA nephropathy. And now we're building upon those interactions with the actual data and the label. As we are in the process to get to the calendar of the [indiscernible] agendas, and inclusion in the policies and the formulary, right now, it's mainly on a medical exemption, and we're seeing good progress so far. I mean I was talking about early script initially. We see a repeat script as well. And we see claims coming through to the payer. So, so far, early days, but very pleased with the initial feedback that we're receiving from the payers and the actions they are taking.

Okay. So one question I got as a quick follow-up here, and you touched on the SGLT2s and is there -- just when would we see sort of more formal presentation of safety data for the combination? I don't know what's the latest you've said there?

Yes, we also -- Go ahead, Peter.

Go ahead.

Yes. No, we have provided information from a drug-drug interaction study in healthy volunteers that we believe now demonstrates that it is safe to combine sparsentan and SGLT2s. That really allows us to now look at the combination of sparsentan and SGLT2. We have initiated their 2 studies that will be going on this year, and we'll have data next year. And that will be looking at the addition of an SGLT2 on top of those patients in an open-label extension for PROTECT trial so on top of sparsentan. And then we're doing a separate study looking at the opposite where we're looking at what the benefit and the safety is of looking at the addition of sparsentan on top of those patients that are on stable SGLT2. And we believe that, that's going to be important looking at it both ways because we know that there are a segment of patients that are already on SGLT2 or will be referred to a nephrologist already being treated with an SGLT2. So you can really expect to see more of these data sometime next year when we complete those 2 studies.

Okay. Great. So do you want to talk a little bit more about the competitive landscape. We touched on Tarpeyo briefly there, but there's obviously atrasentan in development as another ERA and then other mechanisms, the APRIL, BLISS approaches and others. So maybe you can just talk about how you see this sort of field evolving. We've seen some great progress in the last couple of years with 2 approvals. But what do you see the role of ERAs and sparsentan specifically say, do we look out 2, 3 years from now or maybe 4 years from now when there might be a couple of other players in the space?

Yes, Peter.

Yes, I think it's a very exciting time in particular for patients. These are the patient population that is on a rapid path on progression that basically have seen no innovation in the last 30, 40 years. So I think the patient really wins with like all the new mobilities that are in development. To my earlier point where we see FILSPARI is really like up-front in the treatment paradigm. It blocks angiotensin as well endothelin. Both are known as bad actors in the progression of disease and in the public physiology. I think all new modalities that come to market is complementary to FILSPARI. So, we -- and I think the 2 -- at least 2 year window that we have before new modalities come to the market, allows us to create the foundational space that I think we are able to capture based on the mechanistic approach and new modalities could then bring patients to proteinuria levels even lower than what...

Okay. All right. Great. So just kind of conscious of the time, there's obviously a lot more we could discuss on the launch and on IgAN, but a lot of focus from investors on FSGS also with data coming here pretty soon. So the first question is that one, which we're getting. I don't know if you can comment any further beyond the second quarter in terms of the eGFR data from FSGS? Or where do you stand in terms of the process of releasing that? And then the other question we've gone along those lines and what should we sort of expect in the top line release when it comes?

Sure. Well, we are on track to be able to provide the 2-year confirmatory end point data this quarter. So we've not narrowed down more specifically within the quarter, but we are on track to be able to provide that. You can expect that we would issue a release to announce the top line data that, that should include enough of the eGFR data at 2 years as well as some high-level statement around safety to be able to give a good enough view around the confirmatory end point as well as what that means for regulatory pathway. We will evaluate what level of detail for additional results, but I would not expect that we will go into much detail in a release. We do believe that this is a very important and highly anticipated trial. It really is the largest controlled trial done in FSGS. And so we do want to make sure that we reserve enough of the results to be able to have a top-tier journal as well as to present this information at a medical meeting. So our goal is to be able to provide clarity on the results and clarity on the regulatory pathway and timing. We'll look to do that. We recognize that it's a large data set. This is a complex disease or disorder, and we'll look to be able to provide that information very quickly in a medical setting.

Okay. I have one quick follow-up. I don't know if you can answer this, because I was asking if you can talk about sort of last patient visit or anything along those lines to give people a better sense on timing. I don't know if you...

Yes, we've completed that. So we're well beyond the Last Patient Last Visit, and that was obviously, a very important one for us to be able to now collect the data, clean up the data, QC, QA and start the analysis, but nothing further in terms of what that would mean for timing this quarter.

Okay. And then just in terms of -- so we had a panel yesterday as part of this conference on the renal market with a couple of KOLs and talking about sort of what level of eGFR benefit would be needed in FSGS. Maybe can you just talk about those or what do you think you need to show in this trial, either from a statistical perspective or -- and/or a clinical perspective to have really sort of meaningful data in this indication?

Sure. Well, let's start first with what is clinically meaningful for these patients. And if we think about FSGS as the most rapidly progressing of the glomerular diseases. It is, as Peter mentioned, a rare disease with high unmet need. For us to be able to look at how we can slow the progression of these patients to delay their progression to kidney failure, really, what we see is that it should be around 1 milliliter per minute per year difference than active control. We have designed and powered the trial to be able to demonstrate at the 90% level power, a low single-digit difference in annual slope. So we would well be -- if we achieve that, we certainly would have a clinically meaningful benefit that then would translate into a slowing of the progression to kidney failure. That really is consistent with what we hear from nephrologists that's consistent largely with how guidelines reflect eGFR slope. And we believe that in demonstrating a difference and of a magnitude of 1 or above that, that should be aligned with what regulators would be looking for. That's really what we would expect. We'll look to be able to provide that information later this quarter.

Okay. All right. Great. And then maybe just on the commercial side, I think maybe because of some of the other developments in IgAN, there's been a lot more focus on the commercial opportunity there. But Eric or Peter, when you can just -- how do you see the sort of commercial opportunity in FSGS, either just on its own or relative to what we're seeing in IgAN?

Peter, would you like to take that?

Yes, absolutely. While FSGS clearly has a very high unmet need as well. I mean it's an even faster progressing patient population. I was just seeing a market research last night that over 70% of those patients have higher proteinuria levels than1.5 gram per gram. So a very sick patient population, more fast path of progression and less competitive as well. We're speaking about the new modalities development in IgA nephropathy. We see less of clinical development in IgAN -- in FSGS. And given that it's a sicker patient population, we also have a higher dose. It's a more proteinuric disease in general. So there's a dosing difference as well in FSGS. So overall, we see that as a very significant patient population, high unmet need and certainly a strong opportunity for FILSPARI to penetrate as well.

Okay. We have a couple of minutes left. So I just don't want to ignore pegtibatinase where you also have some data coming up here. So a similar sort of question, I think a couple of questions on this. One, sort of what should we expect with the update in the middle of the year here? And then kind of maybe you can just sort of frame some sense of the commercial potential. Again, I think it's an area where maybe there's been a little bit less work done in terms of how to think about the market opportunity.

Sure. We're also very excited about the opportunity with pegtibatinase, and this is a community -- the HCU community that has also a high unmet need for better therapies. And as a pegylated enzyme replacement therapy, we believe pegtibatinase is well poised to be able to really become the new standard of care for these patients. We would expect that in the middle of this year, we'll be able to provide an update on the highest dose cohort in our ongoing COMPOSE study, which is Phase I/II. So we'll look to provide information on there. We obviously have had positive data from Cohort 5. We want to be able to see what incremental benefit we could have at a higher dose. We'll also look to provide regulatory clarity given that we're in the midst of engaging with regulators around the design of a Phase III. We -- based on what -- where we are today, we're still in a position to be able to start that Phase III later this year. And those are the types of updates that we'll look to provide in the middle of this year is really what does that Phase III look like. And with regard to the population and the opportunity, we believe that based on conservative estimates, there are about 3,500 patients in the U.S. and similar numbers in Europe that are addressable. There are [ pockets ] of patients with classical homocystinuria in other parts of the world. But this is, I would say, a conservative estimate for U.S. and Europe based on what we know now, but we do know that many patients go undiagnosed or undetected despite newborn screening. There has been quite a bit of research in the last few years that reflects that there may be a broader number of patients. And so we will continue to explore how we might be able to better define and reach those patients. But conservatively, the 3,500 addressable population, we believe that this is meaningful. And again, we would expect that pegtibatinase would become the new standard of care based on the profile that we've seen thus far.

Okay. All right. Great. So then just in out last minute, I guess, maybe we can get Chris in here for just a second ow 2. You did the raise earlier this year. If you can just talk about sort of your current cash -- financial position and your cash runway going forward here?

Yes, sure. Thanks for the question, Vamil. And really, I would say that we're in a very strong position from a financial perspective. And we ended the year with $450 million in cash and equivalents on the balance sheet. And then as you highlighted, we did a recent equity offering, which had gross proceeds of $230 million. And so when we look at that in aggregate, we believe that, that can support our operations into 2025. And when you think about that, it includes a number of these great milestones we've been talking about today. So that includes the FILSPARI launch that's ongoing in IgA nephropathy potentially European approval for IgA nephropathy as well as the DUPLEX Study data, potential U.S. approval and European approvals there as well and investing in the launch and then moving pegtibatinase in the Phase III. So we're really in a great position to continue to support these growth opportunities.

Okay. Great. Unfortunately, we're at the end of the 25 minutes here goes quick, but I definitely appreciate all of you joining us for the conference. Hope it's been a productive conference. And I'm sure we'll be in touch soon with all this data and information coming in the next few weeks here.

Thank you Vamil.

Thanks so much.

Thank you very much.

Thank you.

Thanks.