Well, great. Thanks everyone for being here. I'm Christina Yoon. I'm a Vice President in the healthcare investment banking team at Goldman Sachs. I'm very pleased to be here with Eric Dube, who's 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.
Yeah. For investors who may be a little bit newer to the story, could you provide a brief background on Travere and overview of your programs?
Sure. Travere Therapeutics is a rare disease company based in San Diego, and w e have a commercial footprint focused on rare kidney disease, particularly with FILSPARI, which is now approved for two rare kidney diseases, IgA nephropathy, and 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.
Yeah. So, that announcement, the in-licensing, 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. Over a number of years, we have really built a strong infrastructure and particularly, development programs within the rare kidney space. As we now have success both in IgA nephropathy and 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. We believe that we, in many ways, are uniquely positioned to develop something like civorebrutinib in this space. 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 with FILSPARI.
Turning to FSGS, you presented last week on the ongoing DUPLEX open-label extension. What were the key takeaways from that data?
Yeah. DUPLEX is really a landmark study that we completed. That was the pivotal study in FSGS that obviously served for the recent approval. We studied these patients in the double-blind period for two years. We also then had an open-label extension that followed patients out to beyond five years for many patients. This was really the first look at the efficacy and safety long-term beyond the double-blind period. What I'd say is that there are three major conclusions. The first is for those patients that continued on FILSPARI for that five-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 two years, the experience of those patients switching from irbesartan to FILSPARI for the OLE period.
We saw that those patients saw a further improvement in their proteinuria, where the majority of those patients really responded to, from switching from irbesartan to sparsentan. Really, what's important is that the addition of endothelin blockade on top of RAS inhibition really conferred better efficacy. Then the third conclusion is that we saw a safety profile that was very consistent over five years, consistent with what we saw in the first two years of treatment. Very reassuring for a medicine that we foresee is the new foundational treatment for patients with FSGS.
FILSPARI recently gained approval for FSGS in patients without nephrotic syndrome. I mean, it's the first approval in that indication, right? 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 find themselves in dialysis, and unfortunately, even for those patients [audio distortion] transplant, over half of them have recurrent disease because the transplant just does not solve their issues with FSGS. Really, having the first medicine approved is a profound shift forward for the rare kidney disease community. I'd say the two aspects, or three actually, of this label, o ne is that this is one of the first medicines in kidney disease that actually from the start studied pediatric patients. We are approved for patients eight years and older.
We 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. 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.
Those patients oftentimes, and based on the current treatment algorithm, really require immunosuppression, most often with steroids. Those patients we really do see should be treated with immunosuppression. Once they're out of that state and they're outside of nephrotic syndrome, that's really where the role of FILSPARI comes into play.
Yeah. 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?
If we first start with who's seeing these patients. These patients are being seen across the broad academic and community setting. There is a high level of awareness of FSGS, even though it is a rare disease. 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. 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 was done over the last three 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.
A lot of the work that came out of PARASOL. The second is to address the label and to 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. The third is that the dosing within FSGS is different than our indication in IgA nephropathy. There's some work that needs to be done to educate on the unique dosing regimen within FSGS. All three of those things we believe are easily addressed, but we do want to make sure that we're diligent in educating the nephrology community.
Yeah. Recognizing it's still early in the launch, but I'm sure everyone will want to hear how things are going.
Yeah. We've been very eager to launch FSGS. Our teams were trained that day of approval and were 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 of 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. We do believe that there should be a faster uptake than what we saw in our initial approval in IgA nephropathy.
What we've seen, not just with the nephrologists, but within the payer realm, is that the first-pass approvals of patients that are prescribed FILSPARI with FSGS is even higher than what our early experiences in with IgA nephropathy, I think reflecting the work that our teams have done, but also a recognition that payers have of just the high unmet need and the cost burden of patients with FSGS.
Yeah. There certainly seems to be synergies in the efforts between the two indications. If we look towards the future and any other assets that are in development for FSGS, how do you see FILSPARI fitting in that treatment continuum?
Yeah. 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. 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. 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 have 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. 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 see a clear role that FILSPARI will play, and we're going to execute incredibly strongly to make sure that we reach those patients.
Mm-hmm. Moving on to IgAN, it's a different competitive dynamic here. We see a lot more assets in this space, but FILSPARI is still showing a lot of momentum. What do you think is driving that uptake, and where do you see areas for further penetration?
Sure. Certainly, it's an exciting time within IgA nephropathy, and w e 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. 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 overactivation in the kidney, and then in combination with steroids to address the overactivation of the immune system.
Really, what we're seeing with all of the innovation coming to IgA nephropathy is just better tools, but the same strategy, that two-pronged strategy. 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. Essentially, 90% of patients with IgA nephropathy are treated with ACE/ARB, so r eally, what we're asking physicians to do is to upgrade that foundational therapy from RAAS 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.
As we look to the future, it is going to be about combination, and really, FILSPARI will continue to play that role. We've been very excited, Christie, as you allude 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 therapies. 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. We do see a sustainable source of growth for FILSPARI in the years to come.
Mm-hmm. 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?
Our thinking has really reflected all of this activity for a number of years. 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. 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, so every patient really is going to require two pillars of their therapy. 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. As companies present their data on B-cell therapies, it really doesn't change the role that FILSPARI plays.
Everything that we saw coming [audio distortion] forces our view of the 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?
Yeah. 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. 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.
You've guided to a total peak sales opportunity [audio distortion] IgAN and FSGS. What are the building blocks behind that estimate?
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. 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.
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 in HCU. What is the latest status of this program?
Yeah. Our HARMONY study, which is our phase III program with pegtibatinase, it is currently enrolling. Two years ago, we paused enrollment as we worked on some of the manufacturing scale-up for pegtibatinase. We've resolved that, we now are on track for top-line data readout in the second half of next year.
Could you help us paint the opportunity in HCU?
Yeah.
What is the addressable market there?
Yeah, 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 homocysteine 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. 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.
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. 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.
Could you remind us of the phase I and II data and what we're hoping to see in the phase III?
What we're looking to do is essentially two things. The first is to reduce a patient's total homocysteine levels. What we saw in our phase I/II study at the target dose is about a 67% mean reduction in total homocysteine. I think that is a profound reduction for these patients. I think what's most telling is when you look at where the patients ended up, 100% of those patients got their homocysteine levels below the current target in guidelines of 100 µmol , and half of those patients got to below 50 µM , which really should confer a 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 most common way that patients are managing their condition is through a very restrictive diet.
Most patients are only allowed to have maybe 10 g of protein. Imagine the world that we're living in, where everything is about added protein and increase your protein, t his is a really difficult disease for people to manage, especially for teenagers, young adults. What patients are asking for is to be able to not only have a medicine that can lower their total homocysteine, but how can they do it in a way that actually allows them to introduce more protein into their diet? 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. 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 in really what they're looking for?
We're looking forward to that data. Just to wrap up, could you outline what investors should be focused on for the next 12- 18 months?
Sure. Well, it's certainly a busy and exciting time for Travere. The first and foremost is we'll provide on our quarterly earnings call 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 in HCU with pegtibatinase, and we expect to have our recently announced deal with the BTK inhibitor, civorebrutinib from 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. More detail to come on those trials, on those programs, and the timelines. Certainly, we've got a lot of innovation to bring to these rare disease communities.
Yeah, great. Really exciting times.
Great.
Thank you very much for the discussion.
Thank you, Christie.