Travere Therapeutics, Inc. ($TVTX)

All right. Well, great. Thanks, everyone, for being here. I'm Christina Yun. I'm a Vice President in the Healthcare Investment Banking team at Goldman Sachs. And I'm very pleased to be here with Eric Dube, who is the President and CEO of Travere Therapeutics. Eric, welcome. It's a beautiful morning. Ready to dive in if you are.

Great. Thank you very much for hosting us.

Yes. So for investors who may be a little bit newer to the story, could you provide a brief background on Travere and overview of your program?

Sure. So Travere Therapeutics is a rare disease company based in San Diego. And we have a commercial footprint focused on rare kidney disease, particularly with FILSPARI, which is now approved for 2 rare kidney diseases, IgA nephropathy and then the recent approval for the first medicine ever approved for FSGS. We also have a Phase III program in homocystinuria, a rare genetic metabolic disease. And then we recently announced an in-licensing deal of a BTK inhibitor that we intend after close of that deal to develop in immune-driven rare kidney diseases.

Yes. And so that announcement, the in-licensing, you only did that -- you did that just last week. Could you share the strategic rationale for the transaction and how you think it will fit into your broader portfolio?

Absolutely. So over a number of years, we have really built a strong infrastructure and particularly development programs within the rare kidney space. And so as we now have success both in IgA nephropathy with FSGS, we were really eager to be able to apply a lot of the expertise and the know-how that we've developed to other rare kidney disease communities that don't yet have an approved therapy. And we believe that we, in many ways, are uniquely positioned to develop something like [ evobrutinib ] in this space. So for us, it was a very natural fit for us. It really provides now a second molecule and complementary to the work that we've been doing in -- with FILSPARI.

So turning to FSGS. You presented last week on the ongoing DUPLEX open-label extension. What were the key takeaways from that data?

Yes. So DUPLEX is really a landmark study that we completed, that was the pivotal study in FSGS that obviously served as for the recent approval. We study these patients in the double-blind here 2 years. We also then had an open-label extension that followed patients out to beyond 5 years for many patients. And so this was really the first look at the efficacy and safety long term beyond the double-blind period. And what I'd say is that there are 3 major conclusions. The first is for those patients that continued on FILSPARI for that 5-year period, we saw a durable effect on the reduction of proteinuria. The second is for those patients that were initially randomized to irbesartan for 2 years. The experience of those patients switching from irbesartan to FILSPARI for that open -- the -- sorry, the OLE [indiscernible]. We saw that those patients -- those patients really responded to -- from switching from irbesartan to sparsentan. And really what's important is that the addition of endothelin blockade on top of RASP inhibition really confirmed better efficacy. And then the third conclusion is that we saw a safety profile, it was very consistent over 5 years, consistent with what we saw in the first 2 years of treatment. So very reassuring for a medicine that we foresee is the new foundational treatment for patients with FSGS.

And so far, we recently gained approval for FSGS in patients without nephrotic syndrome. I mean it's the first approval in that indication, right? But what does the label mean in terms of treatment benefit for patients?

Well, I think it's very easy to see how important this approval is given the unmet need that we see within FSGS. I mean so many of these patients or find themselves in dialysis. And unfortunately, even for those patients transplant over half of them have recurrent disease because the transplant just does not solve their issues with FSGS. So really having the first medicine approved is a profound shift forward for the rare kidney disease community. I'd say the 2 aspects of -- or 3 actually of this label. One is that this is one of the first medicines in kidney disease that actually from the start study pediatric patients. So we are approved for patients 8 years and older. I really believe that this should not only help those patients that are diagnosed with FSGS as kids, but also serves as a model for other companies that they shouldn't have to wait or be resistant to studying kids. That's a really unmet need in this space. The second is that this is a broad indication statement across all etiologies or all types of FSGS which really is important because the unmet need is consistent regardless of what your cause of FSGS is. And then the third, Christie, as you point out, is that this is indicated for patients that are not in active nephrotic syndrome. These are patients with nephrotic syndrome oftentimes present in a very unique manner with very high proteinuria as well as very low serum albumin levels and edema. So those patients oftentimes and based on the current treatment algorithm, really require immunosuppression, most often with steroids. So those patients, we really do see should be treated with immunosuppression once they're out of that state and they have -- they're outside of nephrotic syndrome, that's really where the role of FILSPARI comes in play.

Yes. And what is the awareness about the disease and what do you think is required to further educate the providers on how to treat this disease?

Yes. If we first start with who is -- who's seeing these patients? These patients are being seen across the broad academic and community setting. And so there is a high level of awareness of FSGS even though it is a rare disease. And that's typically because these patients are actively progressing. They're oftentimes younger than patients that nephrologists treat in late-stage kidney failure or late-stage kidney disease. So there is a high awareness and there is a high sense of urgency to treat. With that said, there are a couple of areas that our team is really focusing on educating the nephrology community. The first is a lot of the work that we've done over the last 3 years to really understand the unique role that proteinuria plays as a modifiable risk factor and also for one that portends the rate of progression to kidney failure unique in FSGS. So a lot of the work that came out of PARASOL. The second is to address the label and make sure that physicians understand that nephrotic syndrome is not the same thing as nephrotic range proteinuria. Nephrotic syndrome really is a constellation of several clinical and lab findings. And then the third is that the dosing within FSGS is different than our indication in IgA nephropathy. So there's some work that needs to be done to educate on the unique dosing regimen within FSGS. All 3 of those things we believe are easily addressed, but we do want to make sure that we're diligent in educating nephrology community.

Yes. And recognizing it's still early in the launch, but I'm sure everyone will want to hear how things are going.

Yes. So we are -- we've been very eager to launch FSGS. Our teams were trained that day of approval, and we're in the field meeting with nephrologists that morning. We were very happy to see that the first prescriptions came in the same day as approval, and that was really reflective of, I think, the sense of urgency that we had as well as the anticipation within the nephrology community. Things have been going very well. I think there's a high level of awareness, not just to the disease I just discussed, but also with FILSPARI, given that we are approved in IgA nephropathy. Many nephrologists already have experiences treating their patients with IgA nephropathy with FILSPARI. So we do believe that there should be a faster uptake than what we saw in our initial approval in IgA nephropathy. And what we've seen, not just with the nephrologists, but within the payer realm is that the first half approvals of patients that are prescribed FILSPARI with FSGS is even higher than what our early experience is in with IgA nephropathy, I think reflecting the work that our teams have done, but also recognition that payers have of just a high unmet need and the cost burden of patients with FSGS.

Yes. So that seems to be synergies in the efforts between the 2 indications. So -- and if we look towards the future and any other assets that are in development for FSGS, how do you see FILSPARI sitting in that treatment continuum?

Yes. So we see FILSPARI really playing a foundational role in the treatment of FSGS, much like we see within IgA nephropathy. FILSPARI acts on both the endothelin and [ angiotensin ] systems within the kidney. And those are fundamental in slowing the disease process that really affects the main filtering cell, the podocyte that leads to progressive scarring and increased proteinuria. So being able to address both of those really helps to address what is actually going on in the kidney and offering nephroprotection and reduction in proteinuria over time. So we believe that FILSPARI will play a fundamental role long term in the treatment algorithm for both diseases. When we look at FSGS specifically, there's really nothing in the near term that we see coming to this community. And so we really see an obligation to make sure that we can get FILSPARI used quite broadly for these patients that need more than just the off-label therapies and immunosuppressants that had been used to date. As therapies now become studied within FSGS, we see the classes of medicines that are being studied really complementary to the role that FILSPARI plays. And much like we see within IgA nephropathy, we believe that the future treatment landscape is going to be about not only reaching these patients earlier in their disease to preserve as much of the kidney as possible, but using combination therapy with different mechanisms of action. One great example, which reflects what we were excited about in our recently announced acquisition is targeting some of the immune activation for immune-driven FSGS, particularly the role that B cells play within the pathophysiology of immune-driven FSGS. So more to come. I think it's going to be a number of years before we see anything else come to the FSGS community. But in the meantime, we really have a -- we see a clear role that FILSPARI will play, and we're going to execute incredibly strongly to make sure that we reach those patients.

Moving on to IgAN, it's a different competitive dynamic here. We see a lot more assets in the space. But FILSPARI is still showing a lot of momentum. What do you think is driving that uptake? And where do you see areas worth further the penetration?

Sure. I mean, certainly, it's an exciting time within IgA nephropathy, and we do hope that for that community, they have many options and hopefully see a day where no patient with IgA nephropathy ever has to face kidney failure and dialysis. I think that's going to require nephrologists to adopt innovation earlier, which we are seeing but also to adopt combination therapies earlier, which is what the treatment guidelines recommend. And we see a very sustained role that FILSPARI is playing and will play in the future, becoming the new foundational treatment. If we look historically at how IgA nephropathy has been treated, it really has been treated with off-label ACE inhibitors and ARBs to be able to address the over activation in the kidney, and then in combination with steroids to address the over activation of the immune system. Really what we're seeing with all of the innovation coming to IgA nephropathy is just a better tools but the same strategy, that two-pronged strategy. So FILSPARI really is meant to replace the role that ACEs and ARBs play and the superior data that we have in our head-to-head study and the reflection in the KDIGO guidelines really shows the role that FILSPARI will play. And essentially 90% of patients with IgA nephropathy are treated with [indiscernible]. So really what we're asking physicians to do is to upgrade that foundational therapy from RAS inhibitors to FILSPARI. As we see new classes of therapies like B-cell therapies, complement inhibitors come through FDA. Those are really meant to play a role on top of foundational therapy by reducing the immune overactivation and slowing the deposition of immune complexes in the kidney to address further future damage. And so as we look to the future, it is going to be about combination. And really, FILSPARI will continue to play that role. And we've been very excited, Christy, as you alluded to, the strong performance that we've had with FILSPARI even in the face of new treatment options coming through FDA and approved, we've seen our strongest quarters of demand after the approval of April Bliss or April -- into April therapies. And that's really, I think, because of the growing recognition of nephrologists as more companies educate the nephrology community about reaching these patients earlier and initiating combination therapy earlier. And so we do see a sustainable source of growth for FILSPARI in the years to come.

And coming out of ERA, we saw some data updates for a number of medicines in the space. How does that impact your thinking of how the landscape will develop over time?

Yes. So our thinking has really reflected all of this activity a number of years. So what we've seen, not just this last weekend, but what we anticipate over the next year really doesn't change our view of this landscape. I mean it's because our view is really based on the fundamentals of this disease. It is a combination of an immune disease and a kidney disease. And so every patient really is going to require 2 pillars of their -- of their therapy. And for every single patient who is diagnosed with IgAN, they have a kidney condition and damage in their kidneys that requires a foundational therapy like FILSPARI. So as companies present their data on B-cell therapies, it really doesn't change the role that FILSPARI plays. And so everything that we saw coming forces our review of future and in fact, is reflective of what the thought leaders and what the guidelines say is best for these patients.

Pivoting to the topic of patent, there was a new patent allowed for IgAN for FILSPARI, how should we think about the IP with this recent update?

Yes. So we were very pleased to see the notice of allowance. Once that is granted, we will quickly submit that for Orange Book listing, which would give certain methods of use in IgA nephropathy out to October of 2037. So we do see this as a positive update. We'll continue to provide updates once additional patents are approved. We have been working on something similar in FSGS to reflect a lot of the work that we've been doing to best understand the role that sparsentan plays in these diseases.

So you've guided to a total peak sales opportunity on FSGS. What are the building blocks behind that assumption?

That estimate of peak year sales of $3 billion was before this recent patent notice of allowance and really is reflective of the current addressable population that is just over 100,000 patients across IgA nephropathy and FSGS. We do expect that with greater awareness and earlier diagnosis that the addressable population will grow. We also believe that FILSPARI will continue to play a foundational role in IgA nephropathy. And as other therapies come through FDA and are approved for that condition, it does not change the unique role that FILSPARI will play. With regard to FSGS, we're just getting started, and we believe that FILSPARI is the only medicine that's approved for that condition and nothing really in the foreseeable future that will come to this community, we see a very strong opportunity for us. And the rest is really up to execution. And I can say that we have an incredibly experienced and well-respected field-based team. And it's really going to come down to execution of making sure that not only are we reaching these patients and getting them through the payers to get reimbursed medicine, but a lot of our patient services and helping to maintain patients on therapy really are fundamental to the growth of FILSPARI moving forward.

Great. Moving on to your pipeline, pegtibatinase [indiscernible]. What is the latest status of this program?

Yes. So we are -- our HARMONY study, which is our Phase III program with pegtibatinase, it is currently enrolling. Two years ago, we paused enrollment as we work on some of the manufacturing scale-up for pegtibatinase. We've resolved that. And we now are on track for top line data readout in the second half of next year.

And could you help us paint the opportunity in HCU? What is the addressable market there?

Yes. I think if we first start with what is classical homocystinuria, it is a genetic disorder that is part of newborn screening. Patients are born with a defect in their CBS enzyme, which is responsible for metabolizing an amino acid methionine in our protein in our diet. These patients, as a result, have an accumulation of homocystine over time in their blood that leads to toxic levels that can lead to things like ischemic events oftentimes in childhood or teenage years, eye problems, cognitive problems, bone malformation, a whole constellation of outcomes. And unfortunately, there really has not been much innovation within HCU. In many ways, it's similar to PKU as we think about that condition and the evolution of that treatment paradigm. And so really, our goal is to make sure that we can reach these patients early in their disease before some of these symptoms start to occur. So not only do we want to make sure that we get pegtibatinase through our trial and through FDA, but we want to do a lot of the work, which we have started already in helping to improve diagnostic techniques and reaching these patients before they have things like an ischemic event that leads them to a diagnosis.

And could you remind us of the Phase I/II data and what we're hoping to see in the Phase III?

Yes. So what we're looking to do is essentially 2 things. The first is to reduce a patient's total homocystine levels. And what we saw in our Phase I/II study at the target dose is about a 67% mean reduction in total homocystine. I think that is a profound reduction for these patients. But I think what's most telling is when you look at where the patients ended up, 100% of those patients got their homocystine levels below the current target in guidelines of 100 micromole and half of those patients got to below 50 micromolars, which really should confer longer-term reduction in the patient's risk profile. When you talk to these patients, they actually ask for something even more, which is not just to reduce their risk. But the common -- the most common way that patients are managing their condition is through a very restrictive diet. Most patients are only allowed to have maybe 10 grams of protein, imagine the world that we're living in, where everything is about added protein and increase your protein, this is a really difficult disease for people to manage, especially for teenagers and adults. And so what patients are asking for is to be able to not only have a medicine that can lower their total homocystine but how can they do it in a way that actually allows them to introduce more protein into their diet. And that's exactly what we're looking to do is to take the work that we've done in Phase I/II, but then replicate that in Phase III, but we also have a sub study for those patients that are able to reach their goal of managing homocysteine levels. How can we do this and protocolize protein intake in a way that meets patients and really what they're looking for.

We're looking forward to that data. Just to wrap up, because you outline what investors should be focused on for the next 12 to 18 months?

Sure. Well, it's certainly a busy and exciting time for Travere. The first and foremost is to, we'll provide on our quarterly earnings calls further details on the performance in IgA nephropathy and FSGS with FILSPARI, and we'll look to provide a bit more context and qualitative information about how the treatment dynamics are evolving within both of those diseases. You can expect next year to have top line data from our pivotal study HCU with pegtibatinase. And then we expect to have our recently announced deal with the BTK inhibitor [ seboribrutinib ] for Everest Medicines close next quarter. Our first step is to meet with FDA to align on a development program across multiple immune-mediated rare kidney diseases. So more detail to come on those trials, on those programs and the time lines. But certainly, we've got a lot to -- a lot of innovation to bring to these rare disease communities.

Yes, great. Really exciting time. Thank you very much for discussion.

Thank you, Christie.