Travere Therapeutics Inc Aktie

All right. 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. And 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.

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 then particularly development programs within the rare kidney space. And so 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. And we believe that we, in many ways, are uniquely positioned to develop something like sevobrutinib 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 a pivotal study in FSGS that obviously served as for the recent approval. We studied these patients in the double-blind period for 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 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. And really what's important is that the addition of endothelin blockade on top of RAS inhibition really confirmed better efficacy.

And then the third conclusion is that we saw a safety profile that 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 are -- 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, Christy, 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 into 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 our -- 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 was 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 the 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 of the disease I just discussed, but also with FILSPARI, given that we are approved in IgA nephropathy, many nephrologists already have experience 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-pass 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 the high unmet need and the cost burden of patients with FSGS.

Yes. There certainly 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 nephro protection and reduction of 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 has 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 for further 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 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 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 ACE, ARB. 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 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 [indiscernible] 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 for a number of years. So what we've seen not just 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 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 reinforces our view 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 in HCU. 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 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.

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 homocysteine 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 homocysteine levels below the current target in guidelines of 100 micromoles and half of those patients got to below 50 micromoles, 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, young adults.

And so 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. 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 substudy 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, could 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 in HCU with pegtibatinase. And then we expect to have our recently announced deal with the BTK inhibitor sevobrutinib 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. 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, Christy.

Good morning, and welcome to Travere Therapeutics Business Update Call. Today's call is being recorded. At this time, I would like to turn the conference over to Nivi Nehra, Vice President of Corporate Communications and Investor Relations. Please go ahead, Nivi.

Thank you, operator. Good morning, and thank you all for joining us to discuss Travere Therapeutics' exclusive licensing and collaboration agreement with Everest Medicines. Today's call will be led by Dr. Eric Dube, our President and Chief Executive Officer. Eric will be joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer. Chris Cline, our Chief Financial Officer, will join us for the Q&A.

Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today as well as Risk Factors section in our forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, June 2, 2026 and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances. With that, let me now turn the call over to Eric. Eric?

Thank you, Nivi. Good morning, and thank you all for joining us. Earlier this morning, we were very pleased to announce that Travere has entered into an exclusive licensing and collaboration agreement with Everest Medicines for civorebrutinib, also known as EVER001, a potential best-in-class reversible BTK inhibitor. Under the agreement, Travere will receive development and commercialization rights to civorebrutinib in global markets outside of China and certain countries in East and Southeast Asia. This is an exciting and strategic transaction for Travere. We've been engaged on this program for some time. And now we are entering into this agreement from a position of strength with the ability to execute on these development programs quickly once the deal closes.

Notably, the transaction brings a potential best-in-class product candidate into our rare kidney portfolio with proof-of-concept clinical evidence in primary membranous nephropathy or PMN, and a compelling mechanistic rationale across several immune-mediated rare kidney diseases, including immune-mediated FSGS, minimal change disease or MCD and potentially others. While civorebrutinib is initially anchored in PMN, a disease with no approved medicines today, its multi-indication potential is an important part of what makes this transaction strategically compelling and why we view it as a potential pipeline in a product.

Importantly, civorebrutinib will bring a distinct immune-mediated mechanism to our portfolio alongside FILSPARI's nephroprotective role. In immune-mediated FSGS, FILSPARI and civorebrutinib would give Travere 2 distinct medicines with complementary profiles, and we see that as an important opportunity to further address unmet need in FSGS over time. Civorebrutinib will also provide further long-term growth potential and diversification alongside and beyond FILSPARI and pegtibatinase while remaining closely aligned with the areas where Travere has the greatest expertise and ability to execute.

With this transaction, we are building on the momentum of our current portfolio, including recent strong performance in FSGS and IgA nephropathy. Travere has built its leadership by advancing medicines for rare diseases with significant unmet need and limited treatment options. With FILSPARI, the first medicine ever approved in FSGS and the first non-immunosuppressive medicine approved in IgA nephropathy, we have demonstrated our team's ability to successfully advance a rare kidney medicine from clinical development through commercialization.

With pegtibatinase, we are also advancing in development the first potential disease-modifying therapy for classical homocystinuria. Civorebrutinib fits naturally with Travere's expertise, infrastructure and long-standing commitment to the rare disease community. It is a rare kidney disease product candidate and the development opportunity where we believe our clinical, regulatory and commercial capabilities can add significant value. Everest is a biopharmaceutical company with a strong track record in the development and commercialization of innovative medicines, and we look forward to collaborating with their team to advance this program globally. With that, I'll turn the call over to Jula to walk through the scientific rationale and clinical data in more detail. Jula?

Thank you, Eric. We are very excited about civorebrutinib because it brings together several attributes we look for in a development candidate, a compelling mechanistic rationale, proof-of-concept evidence in a rare kidney disease with high unmet need and biologic rationale to support the potential for the treatment of several immune-mediated kidney diseases. Patients impacted by primary membranous nephropathy carry a high disease burden, which often includes fatigue, massive swelling with weight gain and brain fog, which not only impacts their quality of life, but also their ability to attend school or work.

Patients with primary membranous nephropathy need therapies that can rapidly reduce both disease activity and proteinuria to minimize ongoing kidney damage and the symptoms and complications of persistent nephrotic syndrome. While current off-label immunosuppressive approaches can be effective in some patients, they are often associated with delayed onset of action, prolonged B-cell depletion and increased risk of hypogammaglobulinemia and infections. There remains a significant unmet need for treatments that provide earlier disease control with less impairment of immune function to reduce the burden of chronic immunosuppression. We believe civorebrutinib has a differentiated potential best-in-class profile.

Let me start with the mechanism. It is an oral covalent reversible inhibitor of Bruton's tyrosine kinase or BTK. Its covalent reversible mechanistic profile is relatively unique within the BTK inhibitor class and is an important part of its differentiated profile. In simple terms, this means civorebrutinib is designed to bind strongly to BTK while also allowing that binding interaction to detach and be reversible. Reversibility is important because it may allow for targeted immune modulation as needed. BTK is a key mediator of B-cell receptor signaling and plays an important role in B cell activation, maturation, proliferation and differentiation into antibody-producing cells.

That biology is highly relevant in immune-mediated kidney diseases where B-cell activation and autoantibody production can contribute directly to kidney injury. In primary membranous nephropathy, for example, the disease is often driven by autoantibodies, most commonly anti-phospholipase A2 receptor or anti-PLA2R antibodies that target the podocyte. This leads to immune complex formation and deposition in the basement membrane and podocyte injury. This disruption in the kidney's filtration barrier results in significant proteinuria and over time, leads to progressive kidney damage. Anti-PLA2R antibody levels are clinically meaningful because they reflect active autoantibody-driven disease and can help guide treatment decisions.

Importantly, reductions in anti-PLA2R antibodies are often an early sign that the underlying immune process is being controlled with reductions in proteinuria that follow as the filtration barrier begins to recover. By targeting BTK, civorebrutinib is designed to modulate B cell signaling upstream of autoantibody production. Importantly, this is distinct from B-cell targeted approaches such as anti-CD20 antibodies, which deplete B cells and APRIL-BAFF inhibitors, which target pathways involved in B cell and plasma cell survival. BTK inhibition is intended to regulate the immune signaling pathways that drive pathogenic B-cell activity without depletion of B cells. Civorebrutinib may also have beneficial targeted immunomodulatory effects compared to B-cell targeted approaches, including effects on myeloid lineage immune cells.

That is important because multiple immune-mediated kidney diseases involve both autoantibody biology and inflammatory immune signaling that can contribute to glomerular injury, proteinuria and progressive kidney damage. The covalent reversible nature of civorebrutinib is also central to why we are excited about this asset and its differentiated profile. It was designed to combine high potency and selectivity with reversible BTK inhibition, supporting a targeted and potentially flexible approach to immune modulation in chronic autoimmune kidney diseases with the goal of limiting side effects traditionally associated with immunosuppression.

The fact that civorebrutinib is a pill is also important. Many immune-modulating therapies used today or in development are IV or subcutaneous biologics. An oral medicine could offer meaningful convenience for patients and physicians, particularly in chronic diseases where treatment burden, adherence, flexibility and the ability to adjust therapy are important considerations. Taken together, the profile of civorebrutinib is compelling. It is orally administered, targeted, designed to provide reversible immune modulation and has the potential to address B-cell and autoantibody-driven disease processes that are relevant across multiple immune-mediated kidney diseases.

Now let me turn briefly to the clinical evidence. Civorebrutinib is being evaluated in an ongoing Phase Ib/IIa study in patients with anti-PLA2R antibody positive PMN. This is an open-label single-arm study with highly encouraging results to date that provide important clinical support for the mechanism. Across the study, civorebrutinib demonstrated rapid and sustained reductions in anti-PLA2R antibodies and proteinuria with stable eGFR. Cohort 1 evaluated 100 milligrams once daily for 4 weeks followed by 100 milligrams twice daily, while Cohort 2 evaluated 200 milligrams twice daily.

At week 12, anti-PLA2R antibody levels declined by approximately 62% in Cohort 1 and 87% in Cohort 2, supporting the rapid immunologic activity observed in this study. There were also meaningful reductions in proteinuria with declines of approximately 77% and 80% in Cohorts 1 and 2 at week 36, respectively. These responses, together with improvements in serum albumin and stable kidney function provide important clinical support for the mechanism. We view the rapid reduction in anti-PLA2R antibodies as particularly meaningful because it is a direct marker of immunologic disease activity in primary membranous nephropathy and believe it also differentiates civorebrutinib from other assets in development for PMN.

From a safety perspective, civorebrutinib was generally well tolerated in the data reported to date. Beyond PMN, we are particularly interested in immune-mediated FSGS and minimal change disease. Everest recently initiated an exploratory Phase II basket study that includes FSGS, MCD and IgA nephropathy, which we believe is consistent with the broader mechanistic rationale for civorebrutinib across immune-mediated kidney diseases. This is another area where civorebrutinib may fit well with Travere's rare kidney disease portfolio. In FSGS, FILSPARI has an established role as a nephroprotective therapy, and civorebrutinib adds a distinct immune-mediated mechanism that may broaden Travere's ability to help patients, including those outside FILSPARI's current indications.

There is clear portfolio fit with continued innovation in FSGS potentially addressing different aspects of the disease biology. Our priority following the close of this transaction will be to work closely with Everest Medicines, FDA and global regulators to align the next stages of global clinical development, including the path forward in PMN and our plans to evaluate civorebrutinib in FSGS minimal change disease and potentially other indications. We are excited by the science, encouraged by the clinical proof of concept in PMN and confident that Travere is the right company to advance this product candidate given our experience in rare kidney disease development and commercialization. With that, I'll turn the call back to Eric. Eric?

Thank you, Jula. We're excited to collaborate with Everest Medicines, whose work has established an important clinical foundation for civorebrutinib. Together, we look forward to advancing the program towards its next stage of development with the shared goal of advancing innovation in areas of significant unmet need for patients living with rare kidney disease. To summarize, we believe this transaction is an excellent strategic fit for Travere for 3 key reasons. First, civorebrutinib is a differentiated oral BTK inhibitor with potential best-in-class attributes, including rapid onset of action, convenient oral administration and a potentially favorable safety profile with proof of concept in PMN.

Second, civorebrutinib will bring pipeline and a product potential across multiple immune-mediated kidney diseases to Travere's rare kidney disease portfolio. Importantly, we believe continued innovation in immune-mediated kidney disease, including FSGS, will involve approaches that address multiple aspects of disease biology. And with civorebrutinib, we will have the potential to add a distinct but complementary profile alongside FILSPARI and its nephroprotective role. And third, we are entering into this transaction from a position of strength, supported by strong performance of FILSPARI in both FSGS and IgA nephropathy. With our established clinical development, regulatory and commercial expertise and infrastructure, we believe civorebrutinib has the potential to become a meaningful long-term growth driver alongside and beyond FILSPARI and pegtibatinase. With that, I'll turn the call back over to Nivi for Q&A. Nivi?

Thank you, Eric. Operator, we can now open up the line for Q&A.

[Operator Instructions] We will now take the first question from the line of Joe Schwartz with Leerink Partners.

Congrats on this deal. I was wondering if you could share civorebrutinib's actual kinome selectivity panel in terms of the fold selectivity over TEC, ITK, EGFR and ERBB2, 4? And also, what is the residence time and occupancy half-life at BTK versus the off targets? And does platelet function recover between doses?

Thanks so much for the question. Starting off with the specific questions for Jula, why don't you take that and you can share what's available to date.

Yes. Thanks, Joe, for the question. So part of the rationale for civorebrutinib is because it has such a high selectivity for BTK. There is some data that Everest has put out with regards to selectivity over EGFR, ITK and TEC. And it has a better profile when you compare it to many of the other BTK inhibitors with regards to selectivity. And that's why we believe that we're going to have a better potential safety profile versus others. What we've seen to date, while I don't have -- I think you asked about the platelet activity in between doses, what I can tell you is the safety data that we've seen to date, and there's been a little over 150 patients and healthy volunteers exposed, and we haven't seen the off-target decreases in platelet count and other adverse effects that have been seen with some of the earlier generation BTK inhibitors.

Your next question comes from the line of Vamil Divan with Guggenheim Securities.

This is Arseniy on for Vamil. Maybe just to follow up on that question and ask more generally. When we compare it to CD20, obviously, it's oral, but what is the main potential advantage? Would it be safety, speed of onset? And then in terms of safety, practically, can you interrupt the treatment if the patient has an infection or is going for surgery? Do you preserve vaccine response when you're taking this inhibitor versus CD20? Just any color on the differentiation would be helpful.

Thanks, Arseniy. Jula?

Yes. Part of the reason we're excited about civorebrutinib is because it's highly selective and it modulates B-cell signaling unlike CD20-targeted therapies that broadly deplete B cells. So we do believe that with functional B-cell modulation rather than B-cell suppression, that can help you potentially reserve some immunoglobulin. So you don't see widespread immunoglobulin, IgG, IgM, IgA depletion rather than targeting intracellular signaling to reduce the formation of those pathogenic autoantibodies. So that's what gives us the confidence that this could potentially be safer over the long term versus B-cell depletion.

And then the other aspect that gets us excited is oftentimes when you're targeting early B-cell line lineage such as CD20, it takes longer to reduce that antibody formation because you're waiting for the B cell survival and you're not targeting the plasma cells that are producing the antibodies. And so the onset of action with this mechanism that we've seen in the Phase I/II data with the reduction in PLA2R occurring very early and then followed by proteinuria reduction also gives us the confidence that this is a solid approach to continue to development.

Your next question comes from the line of Anupam Rama with JPMorgan.

Congrats on the deal here. Can you speak to the -- maybe building off the last question, maybe speak to the off-treatment data that you're seeing here and what that could mean from a formulation and/or dosing frequency considerations in the future?

Thanks, Anupam. Jula?

Yes. We do see continued durability of off-treatment, but it is still very early to be able to discuss that, and we haven't made final decisions around dosing or duration. Once the deal closes, we'll be able to give more details around our strategy and planning for that. Because I think what you're getting at, is this a long-term treatment, Is this induction treatment? The fact that there is some durability off target is promising, but those decisions around duration of treatment haven't been determined yet.

Your next question is from the line of Prakhar Agrawal with Cantor Fitzgerald.

Congrats on the deal. So maybe on the PMN indication first. I think other BTKs like zanubrutinib have some data in PMN as well. So how would you characterize some of the early data that has been generated by Everest in PMN versus some of the other BTKs? And then just as a follow-up, what could the development pathway look like in PMN?

Thanks, Prakhar. Jula?

Yes. So the only other BTK inhibitor that has early data provides proof of concept that the mechanism likely works. However, that's -- and I think you mentioned it's zanubrutinib. However, that is a slightly different mechanism. That is an irreversible covalent BTK inhibitor. And therefore, we do believe that the fact that we are covalent reversible has the potential for a better safety profile overall with regards to why we believe in civorebrutinib as a potential best-in-class for patients with primary membranous nephropathy.

Your next question is from the line of Gavin Clark-Gartner with Evercore.

I guess just to follow up on Prakhar's question a little bit more specifically. Last we saw Everest was planning to start the registrational PMN study this year. Is that still your plan? And on this topic, it seems like 72-week complete renal response is a pretty established registrational endpoint even based on recent conversations. Is that what you're planning to pursue? Or are you discussing a different path with regulators?

Gavin, thanks so much for the questions. With regard to timing, we'll be able to talk a bit more of that after the deal close. But certainly, part of our intent is to make sure that we can move very quickly moving forward. Jula, do you want to comment on regulatory interactions and endpoints?

Yes. So we -- again, when the deal closes, we'll have greater ability to share more with regards to the endpoints, but you're not far off with regards to -- it's known that you can utilize complete remission and select time frames for it, but we'll provide more after the deal closes as far as our strategy and plans for our Phase III design.

Your next question comes from the line of Laura Chico with Wedbush Securities.

I guess I had one more bigger picture strategic question. So obviously, there's a lot of reasons to stay in rare nephrology. But I'm curious what other disease areas or therapeutic verticals were considered when you were seeking out other assets? And would you consider still seeking additional assets in rare nephrology?

Laura, thanks for the question. We certainly have been looking broadly within the rare nephrology space, but not limited there. I think if we think about the work that we're doing in pegtibatinase, there are a number of other areas that we've been interested in. For us, this one was the right asset, not only for the reasons clinically and strategically that we've talked about, but also the timing of development being able to take that over and move through the next phase of development. As we look forward, business development will continue to be a very important part of Travere and the long-term focus on growth. So we'll continue to evaluate other potential assets, and we'll look within and beyond rare nephrology. But we're -- with what we have now, particularly the pipeline-in-a-pill potential, we're very excited about bringing this into our portfolio.

Your next question comes from the line of Mohit Bansal with Wells Fargo.

This is Sadia Rahman on for Mohit. So yes, it looks like very robust data in China. I'm just curious how you expect that data to translate to a Western population? And specifically, can you comment on any differences in background treatment usage in China versus the U.S.

Thanks, Sadia. Jula, I'll turn that one over to you.

Thanks for the question. We do believe that the efficacy data based on what we understand of the underlying disease biology within primary membranous will translate into comparable efficacy as well as safety. Obviously, we still have to do the development plan to demonstrate that, but no reason for us to believe that we won't see similar treatment effects and safety within a different population, including U.S. And again, we will plan to do this globally. So more to come on that.

Your next question comes from the line of Alex Thompson with Stifel.

I was wondering if you could comment on whether we should expect to see more follow-up data from the Phase Ib Phase II study. It looks like the cutoff here was about a year ago. So curious if we should expect more data in the near term.

Thanks, Alex. Jula?

Yes. Actually, Everest is planning on presenting data later this week at ERA. So more to come soon.

Your next question comes from the line of Maury Raycroft with Jefferies.

This is Farzin on for Maury. So a quick question on the safety profile. Like how are you thinking about potential for liver tox signals that have hindered other BTK inhibitors in the systemic autoimmune trials and potential class read-throughs?

Farzin, thanks for the question. Jula, would you like to comment on that?

Yes. So BTK inhibitors are not interchangeable. They can differ quite a bit in binding profile, reversibility, selectivity, potency, dosing as well as the underlying patients that you study the medicine in. I would say that civorebrutinib is differentiated from other BTK inhibitors because it's covalent reversible with high potency and selectivity as well as reversible target engagement. So the data that we've seen today, as I mentioned earlier, in healthy volunteers and PMN patients has shown that civorebrutinib has been generally well tolerated. And with regards to AEs, we haven't seen the AEs that have been associated with some of the earlier irreversible BTK inhibitors such as things like neutropenia or cardiac effects as well as the liver safety concerns. We do know that there is a potential class risk around liver and that, as I mentioned earlier, depends on how you dose and other aspects. But we have not seen safety signals to date to raise concern. Obviously, we will do careful evaluations of safety throughout our development plan as well.

Your next question comes from the line of Jason Zemansky with Bank of America.

Congrats on the deal. I appreciate you can't talk necessarily about time lines yet, but maybe can you outline what are the steps needed to get civorebrutinib into a pivotal study? What needs to happen in order to get that underway? Just give an idea of what needs to happen next.

Jason, thanks so much for the question. So this is something that we'll comment more on once the deal closes, once it is in our hands. But certainly, our intent is to move quickly once we have the asset.

Your next question is from the line of Yigal Nochomovitz with Citi.

This is Caroline on for Yigal. Congrats on the deal. Can you tell us more about your strategy of positioning this asset alongside FILSPARI in overlapping indications? Would you pursue it as a monotherapy or combination or only in patient subsets that fall outside of FILSPARI's current label?

Thanks so much, Caroline, for the question. We are certainly excited about the potential to have another potential medicine for particularly FSGS, and there's a very clear role for both FILSPARI and civorebrutinib. As you might know, FSGS is a heterogeneous disease and some patients really would benefit from medicines that address more than one aspect of their disease. For example, FILSPARI being nephroprotective, whereas something like civorebrutinib would be addressing the immune-mediated disease biology. And what we're particularly excited about is that this would give Travere 2 distinct medicines with complementary profiles that we see the potential to be able to address that over time. With regard to the development and the strategy there, that's something that we are not going to be commenting on today, but certainly look to the future to be able to provide more detail.

Ladies and gentlemen, this concludes the question-and-answer session of today's conference call. I will now hand the call back over to Nivi.

Thank you, everyone, for joining today's call. Have a great rest of your day.

And this concludes today's call. Thank you all for attending. You may now disconnect.

Welcome to this, our second day of our Bank of America Annual Las Vegas Healthcare Conference. On a very toasty day, I am pleased to invite up here on stage with me Travere Therapeutics, Eric Dube, President and CEO; and Peter Heerma, Chief Commercial Officer. Eric, Peter, thank you so much for joining us.

Thanks for hosting us.

Pleasure to be here.

Maybe let's start broadly for investors who may be somewhat new to the story. Eric, can you provide a brief background on Travere and FILSPARI?

Yes, absolutely. And you can go on to our website for a pretty extensive corporate deck with background information as well as forward-looking statements.

Travere Therapeutics is a commercial stage rare disease company. We've been focused on developing innovative therapies for rare kidney diseases that really have been devastating for both IgA nephropathy and FSGS communities.

And we're very pleased to really pave the way for innovation and hope for these communities. We also have a Phase III program in classical homocystinuria with a pegylated enzyme replacement therapy, pegtibatinase that is now currently enrolling Phase III.

And we're really a company that's excited about bringing now the first FDA-approved therapy to the FSGS community. This is a really devastating rare kidney disease. We received FDA approval 30 days ago, and I'm sure we'll be talking about some of the dynamics of that launch.

But this has been really a passion of our company and really one that we've stuck through because we know how important a therapy is for these patients that have just a rapid progression to kidney failure.

So obviously, I think recent attention has understandably been centered on this approval in FSGS. So recognizing the launch is still early, what are you seeing so far in terms of initial demand? And how would you characterize early physician awareness of this monumental approval?

Yes. I would say, overall, there has been overwhelmingly positive feedback from the community. To Eric's earlier point, this is the most progressive glomerular disease, and there were no approved therapies so far.

So this was highly anticipated by physicians. I just came back from the National Kidney Foundation Conference last week with over 3,000 participants and the feedback was highly consistent and overwhelmingly positive.

The FSGS label specifies patients without nephrotic syndrome. I think there was some concern here initially, but why might it not be that big a deal?

Yes. Let me start with saying like it's for a broad patient population. It's treatment of proteinuria in FSGS patients, broadly independent of etiology that are not currently in the nephrotic syndrome state. And nephrotic syndrome is a dynamic state. It's not a static state.

Patient can be in nephrotic syndrome at one point, but with treatment of, for example, diuretics or with steroids, patients stabilize, but having remaining high proteinuria, that patient still remains at high risk, and that's where FILSPARI comes in, which is very consistent to how physicians treat today and also very consistent to the global guidelines KDIGO that was published in 2021.

How challenging do you think it's going to be to educate physicians about sort of managing the system and making sure that patients are in compliance, but still able to receive treatment?

Yes. I think from a physician perspective, I think there's 2 elements, right? There's a patient component, there's a physician component. From the physician component, physicians understand it's a common injury pathway. It's really about podocytopathy independent of etiology that needs to be treated.

Physicians understand as well that this is not competing with a steroid, but it's complementary to, and it's more long-term kidney protection.

From a patient perspective, this is a highly activated patient community. Many are also connected with NephCure, the patient advocacy organization. So far, I'm expecting that we will see high compliance and persistence as what we saw with IgA nephropathy, also given the patient services that we are providing to this patient community.

In terms of early feedback, have physicians given you a sense of where they intend to use FILSPARI relative to ACE, ARBs or the SGLT2 inhibitors?

Yes. Well, first of all, FILSPARI has a component of angiotensin inhibition. So it's per definition, replacing ACE inhibitors or ARBs or for incident patients, they could go to FILSPARI directly.

As I mentioned before, this is the first approved medicine. So I think FILSPARI will be really like an anchor therapy. And to my earlier point, it's about the podocytopathy.

So it's hard to say right now, is there a particular subtype where it's used more than others. I think most importantly is that physicians understand the common injury pathway that needs to be treated, and that's what you do with FILSPARI.

You've guided to faster uptake in FSGS versus IgAN. But what does that mean? And sort of how are you measuring sort of your metrics for a successful launch?

Yes, there's a couple of things to take into account. I mean, if you look at the addressable patient population that we anticipate is more than 30,000 at launch. I'm actually expecting that market to grow quite quickly over time with more biopsies, in particular in secondary FSGS as well.

If you compare it to IgA nephropathy, where we anticipate about 70,000 patients addressable today. So you have, let's say, roughly half the patient population, but then FSGS is regarded as the most progressive glomerular disease with the highest unmet need.

So with IgA nephropathy, we really had to establish the urgency to intervene earlier. That's not needed with FSGS. And on top of that, you build upon 3 years of brand equity. This is basically the same prescriber base.

Physicians are very familiar with the profile of FILSPARI. Many have already experience with IgA nephropathy. So taking those components in consideration, even though it's a small patient population, we do anticipate a faster uptake.

In general, FSGS patients are generally seen once a quarter. So does that impact the cadence of the launch at all in terms of expectations? Or is there just such overall awareness of this drug coming in that it might not matter as much?

Yes. I think it matters within context of -- and often I get a question like do you expect a bolus? Is there like a high amount of patients that will be treated right away? And how I answered that in the past is I don't really anticipate that given the frequency that those patients are being seen by the nephrologist in average, every 3 months, it can be more frequently, in particular when they are in nephrotic state.

I mean sometimes they're in the hospital as well being treated, sometimes with IV steroids as well. But overall, I'm expecting a steady linear uptake.

Yes. I will avoid the word bolus moving forward, gentlemen, for sure. With significant prescriber overlap between the 2 conditions, I guess, how much incremental education is necessary, both around FILSPARI, maybe to navigate the REMS reimbursement program? What's needed there?

Yes. Like I said earlier, like it's a large overlap. It's basically like nephrologists that are focused on glomerular disease are treating both IgA as well as FSGS.

So the profile of FILSPARI is well understood. The nephroprotective nature of the drug, I think, is well understood. The injury in FSGS is slightly different than in IgA. IgA is more about the mesangium disease, while FSGS is more about the podocytopathy. So that's an education.

The indication that we just talked about, broad FSGS, not actively in nephrotic syndrome. That's an educational element as well. And then there's an important dosing component as well. IgA nephropathy, the indicated dose is 2 weeks, 200 milligram and up-titrated to 400 milligram. With FSGS, it's 400 milligram for 2 weeks and then up-titrate to 800 milligrams. So I think those are the 3 elements that you still need to educate nephrologists on.

Got it. You've mentioned that payer feedback has been generally very, very positive. We've talked about the halo effect, and we'll get into that a little bit more when we talk about IgAN.

But is it possible that there's a similar sort of positive payer halo effect there that somehow that facilitates use in IgAN?

Well, let me nuance it first. I mean it's for the launch. So I wouldn't say like all the payers are reimbursing FILSPARI from the get-go. But what we are seeing, and I mentioned it last week in the earnings call is that the initial first pass approval rate for FSGS is higher than what we saw for IgA nephropathy.

So if there is a halo effect, it's really on FILSPARI is already included in most of the formularies and payer plans. And payers review both at the product level as well as an indication level. So when you have the product already in the payer plans, it's easier to build upon that and to extend that with the indication.

And before it's being evaluated by the P&T committees, often what you see is that authorization criteria are applied for the other indication. And that, I think, explains why we see a higher first pass approval rate so far. But it's 4 weeks and launch, I just want to nuance because the payer plans and P&T committees that's really happening in the next few months.

Well, if anyone is going to hold to that, it's Jackie on the team, Jackie?

So looking ahead, there are additional therapies advancing for FSGS. So how important is FILSPARI's first-to-market advantage in establishing share?

Yes. Well, I think, first of all, it is really important. But I think even more importantly is that we have quite a long leeway until the next potential product comes to the market, and they're not competing.

I mean it's complementary to what FILSPARI's mechanism is. I think we're in a very strong position for all the reasons that I just mentioned to create a very strong position in FSGS.

And I think it's great for patients that other mechanistic approaches will be evolving over time. And I think this is encouraging as well new innovation for FSGS patients. This is definitely a patient community that needs new innovation. So I'm actually encouraged by that.

So as these programs mature, should we think about them primarily as potential combination partners, competitive thoughts or more of an opportunity to expand the market?

Yes. I think IgA is a good proxy for that. Are you talking about specifically FSGS or?

Yes, FSGS.

Yes. I mean if you look at IgA nephropathy, I think that's typically a market that needs to be developed. When we launched 3 years ago, as I mentioned earlier, that market really needed to be established because historically, physicians thought that as a relatively benign disease. And they felt like even with high proteinuria, patients relatively stable.

With the investment that we made in more scientific evidence in the RaDaR data set that was then adopted by the global guideline committee, KDIGO led to a much more rigorous and more ambitious treatment target. That's step one, but then you have to create the noise as well in the education and more companies being in the market will help to really develop that market.

And that's exactly what we are seeing in IgA nephropathy. More mechanistic approaches are coming in, more companies bring firepower to educate the nephrology community. And that's actually what you're seeing right now. That market is rapidly growing and we will continue to grow because we're still scratching the surface there.

Yes. I mean I think if I can add, Jackie, one of the most important things that I think we all should be focused on as an industry is reaching these patients sooner. I think what we've seen within kidney disease, particularly if we think about the concept of each kidney has about 1 million nephrons. Once those die, for example, in FSGS, the damage really at the podocyte, the filtering cell, that's it. They're gone.

So that's what leads to the progressive nature of these diseases and particularly FSGS. So the idea of being able to reach these patients earlier in their disease, diagnosing them, biopsying them earlier, that really is going to have the greatest meaningful impact on these patients' outlook.

So for us to be able to do that is one thing. We're certainly going to be doing that as part of our education campaign and reaching these patients sooner.

But that's where as we have more patients -- more therapies coming in, more companies coming in, we hopefully will be able to reach them sooner. We're seeing early signs of that in IgA nephropathy and the data that we've generated in first-line use in IgA nephropathy clearly show that you have a better response the earlier you reach. That really is, I think, what we should be striving for as an industry.

If you think about how you got here, the PARASOL working group is obviously very important in sort of establishing proteinuria as a really good surrogate endpoint for the disease.

And so I'm curious Eric, as you've kind of made the rounds, has that message sort of been taken up amongst the greater community that the idea of the willingness to intervene earlier to maintain this proteinuria prevent it from getting worse?

Yes. I mean I think that, that's certainly going to be the approach. We were very encouraged to see the consistent feedback that FDA gave to another company within this space that proteinuria can be used as an endpoint.

And I think what we would expect to see is being able to reach patients earlier, the awareness is going to be there. I think the incentive for nephrologists to want to biopsy patients earlier because that's not -- that is a risky procedure. It is a painful procedure.

And so I think that's going to help also be able to reach these patients. Hopefully, we'll have more clinical trials within the space. We would expect that now that we have approval of FILSPARI that, that likely will be seen as the foundational therapy in other clinical trials. So I think that, that the space should evolve.

And I mean, just look at what we've seen in the IgA nephropathy space over the last 5 years, it's been tremendous. And let's hope that in the foreseeable future that a patient that's diagnosed with IgAN should never have to see kidney failure.

That, I think with all of the options that we have in innovation coming and how quickly something like FILSPARI has been adopted within clinical practice, there's no reason to believe we can't see that within FSGS, particularly with something like FILSPARI helping to extend these patients to be able to get to, for example, a clinical trial if they do progress.

Maybe this is too philosophical. But as you think about how IgAN has changed with the KDIGO guidelines moving towards a much more aggressive approach. Is that something that's really, I think, resonating with nephrologists and their willingness to intervene in both IgAN and FSGS earlier?

Yes. Peter, do you want to take that?

Yes, I think that's certainly the case. This is a progressive disease. I mentioned earlier like often physicians historically thought about proteinuria, well, my proteinuria is stable, let's say, 1.5 gram per gram.

But the reality that patient is at high risk of progression. That's not a patient that is stable at all. And you need to have the rigor of evidence to show that. And based on the investments we have made, and I think we really spearheaded that early on, the evidence is existing now and you want to build upon that base.

I think one of the easiest ways that we've been able to look at that is what is the median proteinuria level, UPC level at initiation of FILSPARI. We've seen that continue to evolve to earlier levels that still signify patients at risk, but it's encouraging to see that physicians are adopting FILSPARI.

And we would expect to see with other therapies coming, other classes of therapies that address the immune side of the disease that we're going to see an acceleration in the adoption of innovation and hopefully be able to reach these patients sooner with a combination to be able to hopefully ideally prevent them from ever reaching kidney failure.

Maybe let's take that question to -- or that topic to just a deeper level. How much of what you've seen over the past 2 years in terms of IgAN's growth is driven by earlier line use?

How it's hard to quantify that. But I think to Eric's earlier point, what we had commented on earlier is that our -- in the accelerated approval phase, we had a proteinuria target of 1.5. With the full approval, that target was eliminated from the indication.

And from that moment, we started to see that the median proteinuria baseline treatment started going to the left to lower levels, and that's continuing the case. So it's hard to quantify that like how much is driven by the market development, but it's how the market is developing overall to prevent progression earlier on and with lower proteinuria targets, and that's exactly what we are seeing.

Do you think that same sort of bend towards being much more aggressive earlier is going to help open up the market to branded combination approaches earlier?

Well, I think that's exactly right. I think conceptually, the treatment paradigm remains the same. And what I mean with that, it's a two-pronged approach.

Historically, physicians were treating with a nephroprotective treatment being RAS inhibition and then going upstream, impacting the immune mediation with steroids, but now you have superior options. FILSPARI versus ACE and ARBs and FILSPARI is the only treatment that has shown superiority versus a maximally dosed active comparator.

And what you see in the other category is that B cells complement inhibitors are replacing the historical steroids. So you have more efficacious and safe treatments in both categories that would allow you to go to a much lower and more rigorous treatment targets.

And when I'm speaking to like the guideline committee members, they always tell me as well, like we have to take an example, for example, to rheumatology, where you treat much earlier and much more aggressively. And as a nephrology community, we have to go in the same direction, and that's exactly what you're seeing right now.

I guess for both of you, what are your expectations as far as FILSPARI's ability to become foundational in some of the treatments, especially as the newer sort of more immunologically focused assets, the APRIL/BAFFs come into play?

Well, I mean, I think when we look at the guidelines and we look at what thought leaders in the space are saying, it already is foundational. The positioning within the global guidelines is very clear.

And I think reflecting the superior nature of what has historically been foundational ACE inhibitors or ARBs is there. We also have very strong data in combination with SGLT2s, which have demonstrated benefit in IgA nephropathy, and that's what we hear from many physicians saying that really is the ideal combination for foundation.

And the guidelines clearly say that it should be used, patients should have a combination targeting the immune system. But I think perhaps most compellingly is how are physicians changing their behavior now and Peter can talk about our uptake given that we now have innovation within the immune space.

Yes. And one thing to add on that is you have to realize once a patient is being referred to the nephrologist, the vast majority of those patients are already in Stage III.

That means that half of their kidney function has already been lost. Half of their nephrons died. And so the first thing that the nephrologist wants to do a nephrologist to protect those remaining nephrons.

So that's why the nephroprotective treatment is really the foundational component. And then simultaneously, you also want to go upstream to minimize the production of [indiscernible] igA. So I think it's a hand-in-hand approach.

But again, those patients have already lost half of their kidney function to start there. That's why we call FILSPARI foundational.

I think that's a great segue into some comments you made at the last earnings call that the combined opportunity between FSGS and IgAN could be upwards of $3 billion. what goes into those assumptions? And what are the key drivers here?

Yes. So if we look at the number of patients that in the U.S. are eligible for FILSPARI in IgA nephropathy, there are about 70,000 patients. And we believe that, that's going to continue to grow as we've talked about the physicians really helping to identify these patients earlier. There's growing awareness about this.

And I think there's a greater sense of urgency that patients that may be seen as stable or earlier in their disease still are at significant risk over 10 years, and these are patients that oftentimes are in their 20s or 30s. So they've got an extended period of time that we've got to preserve their kidneys.

So we do believe that, that addressable number of patients is going to grow. And with the introduction of other therapies such as B-cell inhibitors, we don't anticipate that, that's going to impede our growth.

When you look at the last 2 quarters, when we do have multiple treatment options available for these patients, we've seen our highest number of number of patients being prescribed FILSPARI.

So that adoption of innovation on both sides of the treatment guidelines is only accelerating, and we anticipate that, that's going to continue. When we look at the other component of growth for FILSPARI over time, it's FSGS.

These patients have been historically been treated with long periods of immunosuppressant and steroids. These patients really have been desperate for something that can be one that is FDA approved, but in many ways, is an option that's better suited for them. And that's really where FILSPARI plays.

There's over 30,000 patients today that are addressable, but we believe that with greater awareness, earlier detection, earlier biopsy that those numbers are going to grow just as we're starting to see early signs of that in FSGS. And it will be a number of years before other therapies are likely to be approved for FSGS.

We are hopeful that these patients have treatment options that could be used with FILSPARI. But at this point, FILSPARI is the option. And as Peter mentioned, the reception from the nephrologist community has been overwhelmingly positive, and we do believe that the uptake is a sustainable one to be able to reach those numbers.

But fundamental to us is a speed of reaching these patients because we know that time matters for these patients and their kidneys.

Maybe just to switch gears a little bit. You obviously have a late-stage development program, as you mentioned earlier, in pegtibatinase.

Could you describe a little bit about the opportunity here? And then as you think about top line data next year, what's sort of the benchmarks we should be looking for?

Sure. Well, so classical homocystinuria, HCU is a genetic metabolic disease. It is part of newborn screening because there is a much older therapy that is approved. It's betaine for these patients. It's not -- not all patients respond to this and don't tolerate it that well, but that's what allowed it to be part of newborn screening.

And unfortunately, as part of newborn screening, half of newborns that have HCU are missed. So the estimates that we have today of about 35,000 patients that are diagnosed, being seen by a specialist and are not controlled, we believe that, that's an underestimate because so many patients may not be diagnosed until later in childhood or early adulthood.

For those patients that are not well controlled, you see a toxic accumulation of homocysteine that leads to dislocation of their lens and eye problems, bone malformation and growth of bones. 25% of these patients have an ischemic event by the time they turn 16 and half of them by the time they turn 30. And unfortunately, for many of these patients, that is fatal.

So there really is a real need beyond how these patients are being treated, which is with a very strict limitation of protein in their diet, a really expensive and terrible tasting protein powder.

And for some patients, about half of the patients, they're responsive to high doses of vitamin B6, which is a cofactor for any remaining enzyme that the patients have to be able to metabolize the amino acids in their diet. And so really where pegtibatinase fits in is to replace that native CBS enzyme. It is a pegylated humanized enzyme replacement therapy.

And what we hear from patients and from their physicians is really the goal is twofold. One, reduce total homocysteine to safer levels and the guidelines currently say that the level should be below 100 micromolar and that leads to your question around what does good look like in a clinical trial.

The second goal is really driven by the experience of patients. They want to be able to have at least moments in their life to be able to eat with their friends, with their family rather than feeling like they have to strictly control all of the protein.

A typical patient will say, I'm able to have 10 grams of protein a day. I'd encourage you with our focus and our culture of high protein, everything, that is a reminder for these patients of how difficult their condition is, and many of them say they never get used to it.

So we really have 2 goals in our Phase III program. The first from a regulatory standpoint and from a clinical standpoint is to see a reduction in their total homocysteine.

In our Phase I/II study at the target dose that we brought into Phase III, we saw a 67% reduction in total homocysteine, 100% of patients in that -- at that dose were able to get below the guideline goal and 50% of them will be able to get even lower at below 50 micromolar. So our goal is to be able to replicate that.

And the trial design and time line and the endpoint is similar in Phase III. So we have every confidence that we'll be able to manage that. And one of the key risks in a study like this is patients eating some of the higher protein.

Part of what we've done in this trial design is to make sure that we stabilize their diet before they're randomized. The second goal in our Phase III program is a sub-study to look at are we able to protocolize an increase in protein intake for those patients that are able to get control of their total homocysteine.

So that less from a regulatory standpoint, but it is incredibly important for this community that's looking for something not just to manage the risk, but also manage day-to-day living.

Maybe we have about a couple of minutes left, but just curious in terms of the overall health of the business. Obviously, FILSPARI is doing extremely well, healthy balance sheet. What's the appetite for further business development, whether it's internal or external?

Yes. Well, I think, first, we're really excited about the 3 opportunities for sustainable growth moving forward in IgA nephropathy, FSGS and HCU.

But we are looking at beyond that. We will be focusing our business development efforts within rare disease, particularly within areas that we really can bring expertise and experience, so rare kidney, rare metabolic disease and then really looking at post proof of concept, so we can leverage the clinical development and regulatory experience that we have as well as the very strong commercial expertise that Peter's team brings. And that's our approach to business development.

Any sort of time lines investors should be sort of thinking about here?

So hard to be able to pinpoint that on business development. What I would say is that our teams are absolutely focused on executing strongly on the launch and in enrolling our HARMONY Study with pegtibatinase, but we do have folks that are actively looking for what's next for us.

Perfect. I think that -- and maybe just squeeze in one more. Look, it's been a fantastic year for you in terms of IgAN patient starts, the approval in FSGS. How do you benchmark success second half of this year?

Well, I think what I would say is that we're going to continue to report on the number of new patients that are prescribed FILSPARI. So that's the most important measure for us is reaching these patients that really need something better for their kidneys.

The other aspect is we are absolutely focused on enrolling our Phase III program. So we have guided to top line data with pegtibatinase in the second half of next year. While we won't be providing enrollment updates, we will certainly remind that, that is a key target for us going into next year.

Wonderful. Eric, Peter, thank you so much for joining us.

Great. Thank you.

Thank you.

Hello, and welcome to Travere Therapeutics First Quarter 2026 Financial Results Conference Call. Today's call is being recorded.

At this time, I would like to turn the conference call over to Nivi Nehra, Vice President, Corporate Communications and Investor Relations. Please go ahead, Nivi.

Thank you, operator. Good afternoon, and welcome to Travere Therapeutics First Quarter 2026 Financial Results and Corporate Update Call. Thank you all for joining. Today's call will be led by Dr. Eric Dube, our President and Chief Executive Officer. Eric will be joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; Peter Heerma, our Chief Commercial Officer; and Chris Cline, our Chief Financial Officer. Dr. Bill Rote, our Chief Research Officer, will join us for the Q&A.

Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement.

Please see the forward-looking statement disclaimer on the company's press release issued earlier today as well as the Risk Factors section in our Forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, May 4, 2026 and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances.

With that, let me now turn the call over to Eric. Eric?

Thank you, Nivi. Good afternoon, and thank you for joining us. This has been a tremendous start to the year for Travere. We've made significant progress across our three strategic priorities. We achieved the first FDA approval in FSGS, we reported a new high in demand for FILSPARI in IgA nephropathy, and we dosed the first new patient in the Phase III HARMONY study of pegtibatinase following restart of enrollment.

April 13 marked a pivotal point for the FSGS community and Travere. Achieving the first full FDA approval for FILSPARI in FSGS established it as the first and only approved medicine for this rare and devastating kidney condition. With the potential to help more than 30,000 people living with FSGS without nephrotic syndrome, this approval is a significant indication expansion for FILSPARI and meaningfully increases the opportunity ahead for us.

The first quarter also marked another period of exceptional commercial performance in IgA nephropathy. We delivered another quarter of record new patient start forms. As we look ahead, we are already building upon our experience gained from the successful launch of FILSPARI in IgA nephropathy and are executing a strong launch in FSGS. Across IgA nephropathy and FSGS, we are now estimating that more than 100,000 patients in the U.S. could be eligible for FILSPARI. Together, we believe this represents a $3 billion potential peak sales opportunity for FILSPARI, reinforcing a compelling long-term growth trajectory for the company.

We are also advancing our pipeline to support further sustainable growth. We recently dosed the first new patient in our pivotal Phase III HARMONY study, evaluating pegtibatinase in classical homocystinuria following the restart of enrollment. Importantly, achieving this milestone puts us on track to deliver top line results in the second half of 2027. Based on the data we've generated to date, we believe this program has the potential to become the first disease-modifying therapy for the HCU community. We expect there are approximately 7,000 to 10,000 people living with HCU globally who would be addressable for pegtibatinase.

I'm incredibly proud of our team's accomplishments and look forward to accelerating Travere's growth as we expand our reach and serve more patients across the rare disease community.

With that, I'll turn it over to Jula for a medical update. Jula?

Thank you, Eric. I'm very excited to have the first ever approved medicine for the FSGS community now available for patients. As a reminder, FILSPARI was approved to reduce proteinuria in adults and children 8 years and older with FSGS without nephrotic syndrome. I would like to take a moment to highlight how nephrotic syndrome is defined in clinical practice and what it means in the context of which patients may be eligible for FILSPARI.

Nephrotic syndrome is a clinical diagnosis and is typically defined by the presence of all three of the following criteria: high levels of proteinuria greater than 3.5 grams per day, low serum albumin levels of less than 3.0 grams per deciliter and the presence of edema. If a patient is missing any one of these criteria, they are not considered to have active nephrotic syndrome. This is different than nephrotic range proteinuria, which is typically greater than 3.5 grams per day. For example, a patient with 4 grams of proteinuria, low serum albumin but no edema will be eligible for FILSPARI.

Importantly, nephrotic syndrome is not a chronic state as a patient with FSGS presents without nephrotic syndrome, which represents the majority of the FSGS population spanning all types of FSGS. They are immediately available for FILSPARI. For those who initially present with nephrotic syndrome, physicians will typically use immunosuppression induction to try to control the patient's proteinuria and stabilize them after which these patients may also become eligible for FILSPARI.

In addition, based on the data from DUPLEX, patients treated with FILSPARI demonstrated sustained reductions in proteinuria over time with proteinuria levels reaching approximately 1.5 grams per gram or less on average at study end. At these proteinuria levels, patients would be expected to have a much lower risk of relapsing to nephrotic syndrome.

Based on our discussions with key opinion leaders following the approval, there is wide enthusiasm for using FILSPARI across the types of FSGS, including among secondary and genetic FSGS. This is supported by our recent publication in [ C JSON ], demonstrating consistent efficacy and safety in patients with genetic FSGS, a population often considered the most difficult to treat. Physicians consistently highlight the need for effective non-immunosuppressive options for long-term disease management.

Now let me talk about IgA nephropathy. We recently published data in [ C JSON ] from the PROTECT study, showing that patients with IgA nephropathy who achieved complete remission of proteinuria to less than 0.3 grams per gram experienced rates of eGFR decline of less than 1 milliliter per minute per year, a rate which is similar to healthy aging. The KDIGO guidelines recommend a treatment approach for IgA nephropathy that addresses both kidney injury and upstream immune drivers and include FILSPARI as a first-line option for patients at risk of progression.

The data published this month reinforce FILSPARI's role as a foundational medicine in IgA nephropathy, demonstrating that FILSPARI helps more patients reach complete remission, which is associated with improved preservation of kidney function over time.

Turning briefly to our pipeline. We are pleased to have reinitiated enrollment in our Phase III HARMONY study of pegtibatinase with the first new patient now dosed. HARMONY is a randomized double-blind study designed to evaluate the efficacy and safety of pegtibatinase compared to placebo with the primary endpoint focused on reduction in plasma total homocysteine, a key driver of disease in classical HCU. The primary endpoint for HARMONY is assessed at 12 weeks, consistent with the primary endpoint timing from our Phase I/II COMPOSE study.

Patients who complete the HARMONY study are eligible to enroll in the ENSEMBLE extension study. This open-label extension will allow us to evaluate long-term outcomes, including sustained homocysteine control as well as meaningful aspects for patients such as the potential for greater dietary flexibility and self-administration. This program is supported by data from our Phase I/II COMPOSE study, where pegtibatinase demonstrated rapid, sustained and dose-dependent reductions in total homocysteine levels.

At the 2.5 milligram per kilogram dose twice a week, pegtibatinase delivered a 67.1% mean relative reduction in total homocysteine from baseline to 12 weeks as well as maintenance of mean total homocysteine below the clinically meaningful threshold of 100 micromoles and was generally well tolerated. pegtibatinase has the potential to become the first disease-modifying therapy for patients living with classical HCU, and as Eric mentioned earlier, we expect top line data from the HARMONY study in the second half of 2027.

Finally, we continue to generate and share new data across IgA nephropathy, FSGS and HCU, and we look forward to upcoming medical meetings, including NKF this week and ERA next month, where we will present additional analyses in both IgAN and FSGS.

I'll now turn it over to Peter for a commercial update. Peter?

Thank you, Jula. I'm pleased to share that we started the year strongly and set new records with our FILSPARI performance. The first quarter marked the highest demand to date as we received 993 new patient [ start forms ], reflecting continued expansion among new prescribers and deepening utilization across established accounts. Importantly, we continue to see an increasing number of practices treating multiple IgA nephropathy patients with FILSPARI with [ VVO ] as a meaningful indicator of physicians' confidence with the medicine's foundational and nephroprotective positioning.

As new treatment options become available for this indication, FILSPARI remains the most commonly prescribed medicine approved for IgA nephropathy in the U.S. This broad utilization supports our confidence in FILSPARI's continued growth potential in IgAN, and we are seeing strong demand in the start of the second quarter.

For the first quarter of 2026, we reported approximately $105 million in FILSPARI revenue despite the typical beginning of the year insurance resets and gross to net dynamics as well as recognizing fewer revenue shipping weeks. The strength of our performance in IgAN and the momentum we have with FILSPARI is directly relevant as we enter the FSGS launch. There is significant overlap in the prescriber base between these two indications, and many nephrologists already have experience with FILSPARI in their IgAN patients.

This will support early adoption in FSGS patients, and we anticipate a faster uptake compared to the initial IgAN launch.

In fact, early feedback from the FSGS community has been overwhelmingly positive.

We received our first patient start forms already on the first day following approval, and we are encouraged by the enthusiasm and engagement we are experiencing. Having spent time in the field over the past 2 weeks, I have seen that enthusiasm firsthand in discussions with nephrologists in their offices, and it reinforces our belief that the FSGS opportunity is expected to be even bigger than IgA nephropathy.

Established payer access in IgAN is helping to position FILSPARI for a supportive access environment in FSGS. In fact, we saw our first FSGS reimbursement approvals already in the first week. Payers often manage access at the product and indication level, and our team is focused on expanding payer plans and formularies to include FILSPARI or FSGS. While education on the FSGS indication will be important, we are starting from a position of strength with an experienced commercial team and an established infrastructure. We believe there are more than 30,000 patients in the U.S. with FSGS who are currently eligible for FILSPARI, and we expect that number to grow.

In summary, the start of 2026 reflects exceptional commercial execution with record demand and revenue growth. With our continuing performance in IgA nephropathy and FILSPARI recent FSGS approval, I am confident in our ability to continue to delivering strong, sustained growth and long-term leadership across these rare kidney disease indications. I am incredibly proud of our team and the impact they continue to have on patients and physicians, and I'm excited for what lies ahead for us in 2026.

I'll now turn the call over to Chris for the financial update. Chris?

Thank you, Peter. As you've heard from the team, we delivered another strong quarter of execution across the business and, recently, we achieved an important milestone with FILSPARI's approval in FSGS that further strengthens our outlook for continued growth.

In the first quarter, we generated $124.5 million in total U.S. net product sales, reflecting strong year-over-year growth. Importantly, U.S. net product sales of FILSPARI grew approximately 88% year-over-year to $105.2 million despite typical beginning of year gross net impact and fewer revenue recognition days. As Peter noted, for FILSPARI, we recognize revenue when product is delivered to our specialty pharmacies. This typically occurs a couple of days after shipment from our logistics partner.

Due to the quarter end timing and typical early week ordering patterns, the first quarter had 1 fewer shipping weeks than usual. As a result, some FILSPARI shipments made in the first quarter will be recognized in the second quarter. Adjusting for this dynamic and supported by record demand during the first quarter, we believe FILSPARI is on a strong trajectory in IgA nephropathy for the balance of the year.

Elsewhere, THIOLA and THIOLA EC contributed $19.3 million in U.S. net product sales during the first quarter, and we recognized $2.7 million in license and collaboration revenue resulting in $127.2 million in total revenue for the first quarter.

Moving to operating expenses. Our research and development expenses for the first quarter of 2026 were $57.1 million compared to $46.9 million for the same period in 2025. On a non-GAAP adjusted basis, R&D expenses were [ $51.5 million ] compared to $42.2 million for the same period in 2025. The increase is primarily driven by the restart of enrollment in the Phase III HARMONY study of pegtibatinase during the quarter.

Selling, general and administrative expenses for the first quarter of 2026 were $80.3 million compared to $60.4 million for the same period in 2025. On a non-GAAP adjusted basis, SG&A expenses were $69.3 million compared to $53.3 million for the same period in 2025. The increase is primarily attributable to investments in preparation for FILSPARI's launch in FSGS, including an expanded field team as well as investments in IgA nephropathy.

Beginning in the first quarter, we revised the presentation of our amortization expense associated with royalty and milestone payments to a separate royalty expense line item in order to provide greater transparency to underlying operating expenses. For the quarter, we recognized $24.8 million in royalty expense compared to $12.4 million for the same period in 2025. The increase is primarily a result of the THIOLA intangible asset reaching the end of its accounting useful life, resulting in amortization of the full amount of the royalty payments accrued this quarter as well as an increase in capitalized FILSPARI royalties.

Under accounting policy, THIOLA royalties will now be expensed to royalty expense in the same quarter as a corresponding net sales. Contractual milestones and royalty payments related to FILSPARI will continue to be capitalized to intangible assets and amortized on a straight-line basis over its useful life with only amortized expense recognized within royalty expense.

Total other income net for the first quarter 2026 was less than $1 million compared to $1.5 million for the same period in 2025. Net loss for the first quarter of 2026 was $37.1 million or $0.40 per basic share compared to a net loss of $41.2 million or $0.47 per basic share for the same period in 2025. On a non-GAAP adjusted basis, net income for the first quarter was $4.1 million or $0.05 per basic share compared to a net loss of $16.9 million or $0.19 per basic share for the same period in 2025.

As of March 31, 2026, we have cash, cash equivalents, marketable securities and receivables of approximately $352 million. Receivables include the $25 million sales-based milestone payment from Mirum Pharmaceuticals that was recognized in the fourth quarter of 2025 and received in April. This is not yet reflected in our cash balance of approximately $264.7 million as of March 31.

Looking ahead, we are well positioned to fund our operations with existing resources. We're investing with discipline across our key priorities, including the commercialization of FILSPARI in IgA nephropathy and FSGS, ongoing evidence generation and advancement of the pivotal HARMONY study of pegtibatinase in HCU, alongside building further pegtibatinase supply. We expect continued strong demand in IgA nephropathy to drive sustained revenue growth, with FSGS further contributing to our top line trajectory.

Overall, we believe our balance sheet, expected top line expansion and disciplined approach to investing in our priorities position us to execute with confidence and deliver durable long-term growth.

I'll now turn the call over to Eric for his closing remarks. Eric?

Thank you, Chris. As we look ahead, our priorities are clear: continue to drive growth by reaching more patients with IgA nephropathy, execute a strong launch in FSGS and enroll our HARMONY study of pegtibatinase. With FILSPARI now approved in IgA nephropathy and FSGS and a pipeline progressing into late-stage development, we believe we are well positioned to deliver meaningful value for patients and shareholders over the near and long term.

With that, I'll turn the call back over to Nivi for Q&A. Nivi?

Thank you, Eric. Operator, we can now open up the line for Q&A.

[Operator Instructions] Your first question comes from the line of Joseph Schwartz with Leerink Partners.

This is Will Soghikian on for Joe. Congrats on all the progress this quarter. The one for us on FSGS, you guys have messaged several times that the launch is expected to progress at a faster rate than IgA nephropathy. Could you please characterize what you're seeing at this early stage and how it compares to the original IgAN rollout a few years ago? It seems like the full approval here could also make a difference, especially since we know nephrologists are sometimes slower to adopt innovative medicines. Is what you're seeing in these early days supportive of a more rapid FSGS launch?

Will, thank you so much for the question. And I am very pleased with the early performance and particularly the execution from our field teams. Peter, with that, why don't you give some color to what you are seeing in the early part of the launch?

Absolutely, Eric. And Will, thank you for that question. And indeed, we are confident in a faster uptake in FSGS relative to the IgAN launch for multiple reasons. First of all, this is a very high unmet need and this is the fastest progressive glomerular disease as well where, for IgAN, we really had to establish the urgency to intervene earlier. In addition to that, we built upon a very strong brand awareness and many of the physicians already have the experience with FILSPARI given this is basically the same core point for IgA nephropathy.

And from a payer perspective, we already are in most of the formularies and payer plans. We have currently over 97% pathway to access for patients. So we built upon a very strong foundation, and that gives me confidence that we will have a more rapid uptake in FSGS as relative to our initial IgAN launch, and we believe it's an even bigger opportunity with FSGS than IgAN.

Your next question comes from the line of Tyler Van Buren with TD Cowen.

This is [ Greg ] on for Tyler. So you noted that the first FSGS PSFs arrives the day after approval and reimbursed treatment started within 1 week. So how many FSGS PSFs have you recorded thus far in the launch? And what proportion of early starts are coming through payer authorizations versus exceptions or appeals? And what are you seeing on initial payer behavior in general?

[ Greg ], thanks so much for the question. While it's too early for us to be able to quantify some of that, Peter certainly can provide some qualitative and directional views on the demand and the payer dynamics. Peter?

Yes. Greg, I would love to answer that question. But this is a Q1 call, so I'm looking forward to share that with you in the second quarter call. But following my answer on the earlier question on the faster uptake in IgA nephropathy, I would say everything we are seeing so far is confirming what I have said with regards to a faster uptake than our initial IgA nephropathy launch. That accounts both for demand as well as for the early approval rates that we are seeing with payers. We're seeing actually a higher first pass approval at the payer level than what we saw initially for IgAN.

Your next question comes from the line of Anupam Rama with JPMorgan.

I was wondering on the FSGS launch if you could build upon some of your prior comments, which was I know you mentioned that there is a need to further educate physicians. I know that it's only 3 weeks post approval. But I was wondering if you could speak to what's resonating with physicians in terms of the label and the product profile. And then within that, where do you think the education is required?

Anupam, thanks so much for the questions. Peter, why don't you take that? And Jula, I know your team has got extensive engagements with thought leaders, so you can add anything that you might want to. Peter?

Yes. Happy to take that question, Anupam. And to my earlier point, overwhelmingly positive responses from the physicians, but you still have to educate them. You still have to [ read ] to them. I was in the field a few days, and many of the community nephrologists in particular, they may not know yet that FILSPARI was approved.

And so that awareness, you have to build. You have to educate physicians also on the label, in particular, with like not being a nephrotic syndrome. That requires some education. Once you explain that, it resonates with physicians because it's very similar to how patients are being treated today. It's actually very consistent also to the guidelines, KDIGO guidelines. But maybe Jula can provide some further context on that.

Yes. Thanks. Our team, as Eric mentioned, has been out at conferences, advisory boards, seminars, and I would say that the approval is getting resoundingly positive feedback from physicians. This patient community has been waiting a long time and they are excited to have a non-immunosuppressive treatment option to control these patients and get their proteinuria down.

You did ask about education. Part of it is a reminder about active nephrotic syndrome is not the same as nephrotic range proteinuria. So we are educating around that. But as Peter mentioned, very positive and excitement to have this option to treat their patients.

Your next question comes from the line of Prakhar Agrawal with Cantor Fitzgerald.

So maybe going back to your comments on faster uptake than IgAN. When I go back to the IgAN launch, in the first few full quarters, you had 400 to 450 patient start forms. Is that how should we think about the uptake for FSGS as well?

And secondly, on access. Do you expect payers to cover the secondary FSGS patients broadly as well despite the segment not being tested in Phase III? Are you hearing any pushback from the payers?

Prakhar, thanks for the questions. With regard to the uptake, we're not going to be providing guidance and we won't be breaking out the PSFs by indication as we move forward. I will reinforce what Peter shared that everything that we're seeing so far in the first 3 weeks of launch have confirmed what we've been saying around a faster uptake around an eagerness to prescribe. And the payer dynamics really, I think, help in getting patients from PSFs on to therapy. With that said, Peter, why don't you take the question around payer access and the different types of FSGS, secondary, et cetera, and any pushback, if any?

Yes. No, absolutely. And maybe good to start with repeating what I just mentioned that I'm mostly encouraged by the early approval rates that we are seeing for FSGS, that it's higher than what we saw initially for IgA nephropathy. Before I specifically answer the question, maybe it's good to provide a little bit of context that payers understand that FSGS is a more rare disease compared to IgA nephropathy with a more progressive nature.

This is what we have been educating payers on over the last 6, 7 months. And in that context, payers are not really focused on like types or subtypes of FSGS. They understand the common injury pathway and how FILSPARI is the first approved medicine for this patient population that is rapidly progressing. So that's what I would say what we are hearing and seeing so far in the context of conversations we have had with payers over the last 6, 7 months.

Your next question comes from the line of Vamil Divan with Guggenheim Securities.

I wanted to just get back the topic around [ the history ] in nephrotic syndrome. I think as we've spoken to some physicians since the approval, there seems to be some confusion about this and if they can prescribe FILSPARI in these patients or not. So I'm just curious maybe you can elaborate there in terms of do you think will payers, physicians focus on you if its history in nephrotic syndrome. And it sounds like maybe you mentioned that maybe educations do need to work on, on that topic. So maybe just elaborate on that in terms of what you're doing to make sure it's clear because it certainly sounds like from your perspective that this should not be a limiting factor.

Thank you, Vamil, for the question. And we firmly believe that this is not going to be a challenge. It's certainly an opportunity to educate. Jula, why don't you talk about the efforts that you're doing and the reaction from nephrologists? Peter, you can talk about how payers may be thinking about this topic.

Yes. This has not been an area of focus from physicians, and we've had a fair bit of engagement and so has Peter's team. So we do not believe that history of nephrotic syndrome should reserve a physician from prescribing FILSPARI. And really, the reason for that is because of our labeled indication. It's for patients without active nephrotic syndrome. And this is very much aligned with KDIGO who recommends patients with active nephrotic syndrome be treated with immunosuppression, while those without it, receive optimized supportive foundational care. And that's where FILSPARI provides the best treatment option for these patients.

And happy to build upon that from a payer perspective. And maybe just to build on what I just mentioned with regards to a more rare disease with a more rapidly progressive disease manifestation. The most important one is to educate payers on that what Jula said. Nephrotic syndrome is a dynamic state. It's not like a chronic state. And payers understand that. These conversations haven't really come up given what I said earlier. This is a rapid progressing disease and payers understand that as well.

Your next question comes from the line of Gavin Clark-Gartner with Evercore.

Actually wanted to pivot over to IgA nephropathy quickly. What are you seeing as a discontinuation rates over time here, let's say, maybe at the 1-year mark and the 2-year mark since patients are in therapy? And how does that actually compare to what you saw in the IgAN Phase III?

All right. Peter, why don't you take that question?

Yes. The compliance and the persistence rate for FILSPARI in IgA nephropathy has been very high. We haven't given specifics on the numbers, but we haven't seen any change or disruption in those rates as well, which gives me high confidence both on the effect it has for patients that they're being helped with it, but also the physicians that they are seeing that this product works for a patient population that historically didn't have a treatment option. Jula, maybe you can provide the context what we are seeing versus what we saw in the PROTECT trial.

Yes. I would say consistent. We saw a fairly high persistence of patients staying on treatment during the 2-year double-blind trial, and I think it's very aligned with what we're seeing commercially. And part of the reason for that is patients have that positive reinforcement. Their proteinuria goes down, they see it, and they feel like they're getting better and with very consistent side effect profile to irbesartan. And so patients tend to stay on therapy, and they understand this should be truly a lifelong -- as long as they keep their kidneys, they should stay on FILSPARI.

Your next question comes from the line of Mohit Bansal with Wells Fargo.

This is Sadia Rahman on for Mohit. So the patient start form number this quarter, again, looks very impressive. Can you provide some color on the conversion rate for these forms to patients ultimately starting treatment? And any reason for any drop-offs along the way?

Thanks, Sadia. Peter, why don't you take that?

Yes. I'm glad that you reflect on the 993 patient start forms as impressive because I'm really impressed with my team that is continuing to show growth in IgA nephropathy in a rapidly [ paced ] environment. With regard to conversion, I would say we continue to convert those patients quite rapidly over time. We continue to make improvements with where we are right now that is not as dramatic as what you saw in the beginning. But we don't see any drop-offs or changes.

And I think with regards to translation, patient start forms into revenue, that may be part of your question, I think Chris was providing some color on that with regards to less ordering shipment weeks in Q1 relative to also having the typical gross to net dynamics that you see usually in Q1. I hope that I answered your question, Sadia.

Your next question comes from the line of Laura Chico with Wedbush Securities.

I apologize if this has been asked already, but one question I had was on IgA nephropathy dynamics for FILSPARI. It's great to see the PSF number continuing to increase, and I'm presuming that's predominantly from IgA nephropathy patients. But we also had a competitive update Novartis indicated the ALIGN confirmatory study for Vanrafia did not reach statistical significance. And while they will pursue an FDA approval, full approval, I'm just wondering how that changes your views on the competitive landscape dynamics for IgA nephropathy with FILSPARI. How are you thinking about pushes and pulls on demand drivers in '26? And then I have a quick follow-up, if that's okay.

Okay. Peter, why don't you take that? And certainly, Jula, add anything further as you see the evolution or consistency of the treatment landscape.

Yes. I'm happy to answer that question. I think most important, that this is a market in development. Most growth in this marketplace is not coming from competitive share but mainly from continuation of growing the market, and that's exactly what we see. That what we were anticipating. I think FILSPARI is very well positioned to continue to grow in this marketplace because it's really replacing RAS. There is no other product that has that ability to do so. Most competition is in the other sector more immune-suppressive agents, where the B cells are now playing together with the component inhibitors and historically steroids. What I would say physicians understand the positioning of FILSPARI as the foundational nephroprotective treatment option and understand also FILSPARI's positioning relative to atrasentan.

And just one thing, Laura, before you get to your next question. You had asked about the PSF increase. That is all based in Q1, so that would be IgA nephropathy before the approval of FSGS. So we do expect to see an acceleration of the demand over time as we look at both indications. But that's a very, very solid number of 993 patient start forms in Q1, reflects our performance in an increasingly landscape of multiple treatment options. So I think it's a really impressive number that Peter's team has been able to deliver. And why don't you go to your next question, Laura?

Yes. Just real quick. So we've got a few weeks in April with the FSGS approval. It does seem like a couple of PSFs are coming through here. Just out of curiosity, are these originating from existing FILSPARI IgAN or versus kind of newly activated FILSPARI prescribers? And I'm just kind of curious, should we be presuming these are already established prescribers in these early days and these early quarters of launch?

L:aura, thanks so much for the question. It is early. Peter, why don't you comment on what you're seeing thus far?

Yes. It's indeed early. We see both, to be honest, and more color to come in the Q2 call. But I think in this context, it's good to talk about the halo effect. I've spoken about the halo effect in the past and halo effect from the experienced prescribers for IgAN that now also adopt FILSPARI for FSGS. But vice versa, we're starting to hear anecdotes as well from physicians that have been on the fence are excited about starting for FSGS and, based on that, now are also excited to start prescribing an IgAN. So I think a halo effect will benefit both indications.

Your next question comes from the line of Maury Raycroft with Jefferies.

Congrats on the quarter. Maybe following up on Laura's question, focusing on PSFs. I'm trying to think about how to estimate that going forward for IgAN. And you talked about atrasentan as a competitor, but Otsuka also had a good quarter for PSFs growth in IgAN. And so I'm wondering if you have any perspective in how Otsuka is launching their drug and how are you factoring that into your estimates, and if there's any more perspective you can offer and just switching to biologics and how you're thinking about that in your total estimate for $3 billion in peak sales.

Okay. Let me take a couple of those. And Peter, why don't you comment on what you're seeing from a competitive standpoint and switching? The first is that the PSFs moving forward will provide an aggregate. So I recognize, Maury, what you're probably trying to figure out is what in IgAN alone. What I would say is there's no reason to believe we can't continue this level of performance because of the number of patients out there and the very unique positioning that non-immunosuppressive kidney-targeted therapies are, which Peter can speak to.

With regard to the peak year sales of $3 billion, that really is based on continued growth in both indications. And we've talked about FSGS being a larger opportunity than IgA nephropathy. So we fully expect there to be growth in both, but a much faster uptake in FSGS is going to allow us to really reach more of those patients over time and contribute more meaningful to growth at peak. What I would say is that we really don't see the dynamics as taking away from our opportunity or performance. But Peter, why don't you talk about that in the context of new patients as well as switches?

Yes. Maury, I think the most important one is that we don't see B-cell as a direct competitor for FILSPARI. I think conceptually, the way patients are being treated for IgA nephropathy is how it was done in the past with RAS inhibition and, on top of that, you use steroids when needed. That concept is now changing well for us in PSFs and FILSPARI as a superior option for those patients. And for those patients that need additional treatment, you have now B-cells as potentially replacing steroids. The growth in this market is not so much competitive growth. It's really like developing the market.

This is a highly underdeveloped market historically. There are still so many patients that are treated with generic RAS inhibitors and generic steroids. You have better options available right now. The KDIGO guideline is reinforcing that. I think you have a more ambitious treatment target nowadays. So that requires often more combination therapy as well. So I think there is space for multiple products to grow. And I think FILSPARI is very well positioned in that nephroprotective foundational treatment category.

Yes. Thank you, Peter. And Maury, maybe if we just take a step back. One of the things that I'd like to reinforce is we talked over the last couple of years around the new entrants coming and really helping to accelerate growth within the IgA nephropathy market. That is not going to take away our performance and our outlook. That's exactly what we're seeing with the entrants that have come to the IgA nephropathy foundation. And I think that the performance that we posted this quarter really reflects the opportunity that we have, but perhaps, more importantly, the opportunity that patients that have been undertreated with off-label therapies have the opportunity to really have innovation moving forward, both with FILSPARI as well as the other therapies. And that's really, I think, going to the foundation for continued performance of FILSPARI.

Your next question comes from the line of Jason Zemansky with Bank of America.

Congrats on the progress, Maybe, Jula, one for you. I was curious as to where you get the sense or are seeing FILSPARI's use sequenced in FSGS. Is it in lieu of the ACE/ARBs? Are these patients usually already on SGLT2s? We've just gotten some mixed feedback regarding if this drug is going to be used first line or whether in those, I guess, uncontrolled well already on an ARB and an SGLT2?

Yes. Thanks for the question. So just like IgA nephropathy, the vast majority of patients are already on some form of a RAS inhibitor, an ACE or an arb, even by the time they get sent to the nephrologist, so predating their diagnosis. It's slightly lower than IgA nephropathy because kids may or may not always be on an ACE inhibitor, but you're still talking at more than 70%, at least 80% of patients are on some form of foundational treatment.

And as far as SGLT2 inhibitor, I would say it is used, just potentially not quite as prevalent, because we don't have as great of data on SGLT2s. But as Peter has mentioned multiple times, these patients are very high risk for rapid progression to kidney failure. So physicians will be pulling at many things as they can in their tool belt to try and stabilize these patients. And now they have FILSPARI, which is better and head-to-head versus a RAS inhibitor. So they are going to take patients off their RAS inhibitor and initiate FILSPARI and ideally at their next clinic visit when they see these patients.

And Jula, maybe I can add something else for Jason's question. Particularly for those patients with primary FSGS and particularly those with active nephrotic syndrome, they are, based on the guidelines, going to be treated with an immunosuppressant. And once they are not in active nephrotic syndrome, they would be eligible and likely placed on FILSPARI. So in terms of them not being first-line use, it's a slight nuance but that's also an opportunity moving forward. But Jula, please clarify if there's anything further you'd like to add.

No, that's accurate.

Your next question comes from the line of Alex Thompson with Stifel.

Just a quick follow-up question on IgAN and then maybe I'd like to ask about pegtibatinase as well. Maybe, Chris, are you able to quantify the shipping week impact at all? That would be helpful for the quarter.

And then for pegtibatinase and the Phase III, congrats on restarting that. Have you met with sort of the FDA review division recently? And how confident are you that total homocysteine is still going to be an approval endpoint here?

All right. Chris, and then we can turn it over to Bill for the pegti question.

Yes. Thanks for the question, Alex. We don't typically break down individual weeks of revenue. So what I would point you to as the best proxy is to take the average for the quarter, we had about 12 weeks of revenue recognition within the quarter, and that will get you to the best proxy there. Bill?

And I will take the pegti question. We've got Breakthrough Therapy Designation for pegti. So that allows us to have a lot of interaction with the FDA. And through that process, we reached alignment on the endpoint for that HARMONY study. And it was noted in the prepared remarks, that mirrors the timing of what we saw in the COMPOSE study. So it was in a collaborative discussion with the agency where we settled on that 12-week endpoint.

Has that happened since the original alignment this year or since you redosed? Or was that originally the alignment?

That's the original discussion. We haven't had reason to discuss the endpoints of the trial once it was agreed and aligned upon.

Ladies and gentlemen, this concludes the question-and-answer session of today's conference call. I'll hand the call back over to Nivi.

Great. Thank you, everyone, for joining today's call. Have a great rest of your day.

Thank you for attending. You may now disconnect.

Good afternoon, and welcome to the Travere Therapeutics Business Update Conference Call. Today's call is being recorded. At this time, I would like to turn the conference call over to Nivi Nehra, Vice President, Corporate Communications and Investor Relations. Please go ahead, Nivi.

Thank you, operator. Good evening, and thank you all for joining us today on such short notice. Earlier today, we announced the FDA has approved FILSPARI in FSGS. A copy of the press release, along with the slides that we'll be referencing on today's call, can be found on our corporate website. Today's call will be led by our President and Chief Executive Officer, Dr. Eric Dube. Eric will be joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; and Peter Heerma, our Chief Commercial Officer. Dr. Bill Rote, our Chief Research Officer; and Chris Cline, our Chief Financial Officer, will join us for the Q&A.

Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance, they involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today as well as the Risk Factors section in our Forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, April 13, 2026, and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances.

With that, let me now turn the call over to Eric. Eric?

Thank you, Nivi. Good evening, and thank you all for joining us. Earlier today, we announced that the FDA has approved FILSPARI to reduce proteinuria in adults and pediatric patients aged 8 years and older with focal segmental glomerulosclerosis or FSGS, without nephrotic syndrome. With this approval, FILSPARI becomes the first and only FDA-approved medicine for FSGS, a milestone that fundamentally changes what it means to be diagnosed with this condition.

For patients and families, this is more than a regulatory event. It is the beginning of a new path forward, where for the first time, there is a medicine specifically approved to reduce their proteinuria, which is central to slowing disease progression. We now have the ability to redefine the treatment landscape. Importantly, the approved population spans across types of FSGS and aligns closely with how the condition is managed in clinical practice, where patients are routinely assessed and treated based on whether they have current nephrotic syndrome. This approval is based on data from our Phase III DUPLEX study and reflects alignment with the FDA on a well-defined population where the evidence demonstrates meaningful clinical benefit, including proteinuria, eGFR and kidney outcomes.

From a commercial perspective, FSGS marks an additional indication for FILSPARI, and we are ready to launch. Together with IgA nephropathy, we believe the addressable patient population for FILSPARI now exceeds 100,000 patients in the U.S. We will be leveraging our experienced rare nephrology teams, established physician relationships and proven success in launching FILSPARI as a foundational care in IgA nephropathy to drive a successful launch in FSGS. This is an extraordinary day for the FSGS community and a defining moment for Travere. It represents both the culmination of years of perseverance and the beginning of a new chapter. Today's approval further strengthens our strategy to accelerate growth in our leadership position in rare kidney disease.

Before I turn the call over to Jula, I want to extend my sincere gratitude to the patients and caregivers who participated in our studies, shared their stories and advocated for new treatment options, the physicians and advocates who've worked alongside us for many years and who, along with regulators, were instrumental in changing the way FSGS is studied today. I would also like to thank the entire Travere team whose dedication and perseverance over the last 10-plus years made today possible.

With that, I'll turn it over to Jula to walk through the approved indication in more detail. Jula?

Thank you, Eric. As a nephrologist who treated patients with FSGS for decades, today's approval represents an incredible advancement for the field and most importantly, for patients who until today had no approved medicine.

FSGS is a rare progressive condition that frequently leads to kidney failure. For many patients, the journey begins with abnormal lab findings, mainly elevated protein in the urine called proteinuria or nonspecific symptoms such as fatigue and in some cases, swelling, eventually leading to a kidney biopsy confirming FSGS. From there, treatment can be complex and iterative with physicians trying different off-label therapies over time, typically starting with steroids and then moving to other immunosuppressive therapies. In the absence of a clearly effective medicine, this often becomes a process of trial and adjustment rather than a defined treatment path.

Proteinuria is a hallmark of podocyte injury, is a key driver of disease progression and is strongly associated with long-term kidney outcomes, making it a critical treatment target. Persistent proteinuria leads to irreversible kidney damage, which over time requires treatment with dialysis or kidney transplant. And even after transplantation, FSGS recurrence remains a real and frightening possibility for many patients and their families with up to 55% recurrence rates post transplant. And in some cases, the disease returns almost immediately.

As Eric highlighted, FILSPARI is now the first medicine ever approved for FSGS and is indicated to reduce proteinuria in adults and pediatric patients 8 years and older without nephrotic syndrome. Importantly, the approved indication for FILSPARI reflects a patient population defined by clinical characteristics. Now many of you will recall that the approval we were originally seeking did not draw this distinction with nephrotic syndrome. Early last month, we met with the FDA to discuss the ongoing review and for the first time, they highlighted this path for patients without nephrotic syndrome based on the strength of the data on proteinuria, eGFR and kidney failure in this patient population.

Nephrotic syndrome is a clinical diagnosis, which commonly refers to meeting all 3 of the following criteria: high levels of proteinuria greater than 3.5 grams per day, low serum albumin of less than 3 grams per deciliter and the presence of edema. Notably, this is distinct from nephrotic range proteinuria on its own. For example, a patient with 4 grams of proteinuria, but without low serum albumin would be eligible for FILSPARI. Also, a patient who has 4 grams of proteinuria, edema and low serum albumin could become eligible after they experience a change in any one of these criteria after treatment with alternative approaches.

In clinical practice, when a patient presents with active nephrotic syndrome, they're typically evaluated promptly, including with a kidney biopsy and started on immunosuppressive therapy such as steroids. This approach is based on the KDIGO clinical practice guidelines, which recommend assessing patients based on nephrotic syndrome status and using immunosuppression for those with nephrotic syndrome versus optimizing foundational care among those without nephrotic syndrome. Importantly, FSGS is a relapsing and remitting condition. And once a patient with nephrotic syndrome has been stabilized with steroids or other immunosuppression, they may become eligible for long-term treatment with FILSPARI.

Patients without nephrotic syndrome represent a population whose disease progression is initiated by podocyte injury and also driven by maladaptive glomerular hemodynamics and pro-inflammatory and profibrotic pathways. All of these mechanisms are directly targeted by FILSPARI's dual endothelin and angiotensin receptor blockade. This is supported by the DUPLEX study, which enrolled a broad population of patients where those without nephrotic syndrome demonstrated even more pronounced treatment effects compared to irbesartan across proteinuria, kidney function and kidney outcomes. The data in patients without nephrotic syndrome included robust, durable and nominally statistically significant reductions in proteinuria with a 48% reduction for FILSPARI-treated patients compared to 27% with irbesartan at week 108.

This subgroup also had a favorable treatment difference of 1.1 mL per minute in mean eGFR from baseline to week 108 compared to maximum dose irbesartan. As noted in our corporate deck, treatment effects on eGFR total and chronic slope both also meaningfully favored FILSPARI over irbesartan and each were nominally statistically significant. And progression to kidney failure over the 2-year measurement period occurred in less than 2% of patients without nephrotic syndrome treated with FILSPARI compared to 8% with irbesartan, which was also nominally significant. FILSPARI was generally well tolerated with a safety profile comparable to irbesartan and consistent across clinical programs as well as across clinical subgroups as noted in our label. FILSPARI will be available through the same REMS program that physicians are familiar with for IgA nephropathy.

From a medical affairs perspective, we look forward to continuing to educate and engage with the nephrology community through peer-to-peer forums and field medical education or engagement to support informed clinical decision-making as physicians integrate FILSPARI into their FSGS treatment plans. This approval represents an incredible advancement for the FSGS community who have waited far too long and we are profoundly grateful to them, their families and the many physicians whose dedication and perseverance made this moment possible. This approval exemplifies a clear commitment to do better for people living with rare disease such as FSGS. I also want to thank our internal teams at Travere, who have worked tirelessly and with urgency to accomplish this outcome for the FSGS community.

I'd now like to pass the baton over to Peter for a commercial update. Peter?

Thank you, Jula. We are incredibly excited about today's approval and the opportunity it creates to bring FILSPARI to the FSGS community. From a commercial perspective, this is a highly actionable opportunity grounded in a patient population that is both clearly defined and actively managed in clinical practice. Nephrologists understand the grave prognosis for most patients with FSGS and are actively seeking to reduce proteinuria in an effort to slow disease progression and preserve kidney function.

Our market research reinforces both the urgency and the opportunity. More than half of the nephrologists believe their patients with FSGS will progress to kidney failure within the next 10 years, underscoring the severity of this disease and the need for earlier intervention. Additionally, more than 80% of the nephrologists view FSGS as an exceptionally high unmet need and one of the most challenging diseases to manage with less than 10% of patients today considered optimally managed. There is a clear need for an effective non-immunosuppressive medicine that can provide long-term proteinuria reduction. The vast majority of surveyed nephrologists indicate that novel non-immunosuppressive therapies are highly desirable in FSGS and recent market research has further shown FILSPARI to be the most familiar and desired product candidate amongst physicians who treat this rare disease.

Based on our current estimates of the -- for the approved indication, we believe there are currently more than 30,000 biopsy and genetically confirmed patients with FSGS, who do not have nephrotic syndrome under the regular care of a nephrologist in the U.S. We expect this number of addressable patients for FILSPARI to grow over time as diagnosis continues to improve and awareness increases. And we are building upon the strength with FSGS as FILSPARI is currently the #1 most prescribed medicine approved for IgA nephropathy in the U.S. And there is a large overlap in the prescriber base for IgA nephropathy and FSGS. So most of the nephrologists are already familiar with FILSPARI and many already have experience in their IgA nephropathy patients.

We also see a meaningful opportunity to expand our prescriber base, including pediatric nephrologists as we extend our reach across the FSGS treatment landscape. Regarding access, also here, we have established a robust foundation. FILSPARI is already included in many formularies and payer plans for IgA nephropathy, and we have been educating payers on the high unmet need of FSGS and the lack of approved medicine. We will now educate payers on the value story of FILSPARI for patients with FSGS without nephrotic syndrome. In the coming months, we expect a supportive access environment to build.

As with any new indication, we recognize that a level of education will be required to support broad adoption. In the early stages of the launch, our commercial and medical teams will be focused on educating physicians, payers and patients on the approved population, the clinical data and how FILSPARI fits into the treatment decision-making process. While education will be necessary to build momentum, we are not starting from scratch. We have already established a commercial team of over 100 field professionals who spent years building relationships in the nephrology community. That team has delivered real results. They have helped drive FILSPARI to become the most commonly prescribed therapy that is approved in IgA nephropathy to date. And now we are able to take that same experience, relationships and executional strength in applying it towards a successful launch in FSGS.

With Travere Total Care, we also have an established patient services model in place for FILSPARI that can be directly applied and customized to FSGS patients, positioning us to immediately execute effectively and support education on this new indication. Just as they do now in IgA nephropathy, eligible patients with FSGS and their caregivers will receive personalized support, including REMS coordination, reimbursement assistance and co-pay support through Travere Total Care.

Overall, we see a clear and meaningful opportunity to drive adoption within the approved population as we work to build momentum through continued education. In addition, we expect there will be cross-indication synergies with IgA nephropathy as physicians gain experience with FILSPARI in FSGS, which we believe will support adoption across both indications.

In closing, we are incredibly excited and ready to launch FILSPARI as the first and only approved medicine for FSGS, and our team is well prepared and ready to serve this patient community. Launching in FSGS, together with our continuing IgAN performance will position us for meaningful and durable FILSPARI growth.

I'll now turn the call back over to Eric for his closing comments. Eric?

Thank you, Peter. Recently, the team at Travere and I had the opportunity to meet Madi. She was diagnosed with FSGS at just 4 years old and spent much of her childhood in and out of hospitals, often unable to participate in everyday childhood moments because of her FSGS. She shared with us and I quote, "I often missed birthday parties, school and recess when I was forced to sit on the bench alone because I couldn't keep up with the other kids. I remember being embarrassed at my kindergarten graduation when my legs gave out on me because I've been standing too long."

What stood out to me was not only her resilience, but the role that she and her family played in advocating for progress in this field. Because of that effort, Madi was able to participate in DUPLEX at the age of 9 years old and ultimately experienced meaningful improvements that allowed her to regain her energy and begin living a more normal active childhood. In her words, "I was finally able to live my life and be free from feeling sick all the time." She's now 15 years old and still thriving.

Stories like Madi's are why we are here today. This approval underscores our commitment to transforming care for patients with rare kidney diseases and importantly, to improving what patients and families can expect after diagnosis. Today marks a defining moment as we now turn our attention to ensuring patients can access FILSPARI as early as possible because we know that time matters in FSGS. It also begins the next chapter of significant growth for our company. And finally, to the FSGS community, thank you for never giving up hope and for inspiring us throughout this journey. We would not be here today without you. Your courage in participating in our studies, your voices and advocacy and your unwavering belief in progress. You are the reason we do this work.

I'll now turn the call over to Nivi for Q&A. Nivi?

Thank you, Eric. Operator, we can now open up the line for Q&A.

[Operator Instructions] We will now take the first question from the line of Joe Schwartz from Leerink Partners.

Congratulations to the whole Travere team on this great win. I guess I'll ask if you guys have a sense of the percentage of patients who initially present with nephrotic syndrome who might ultimately receive a confirmed FSGS diagnosis and might ultimately be label eligible?

Joe, thanks so much for the question. Jula, I will turn that one over to you.

So when a patient presents with nephrotic syndrome, they typically get a biopsy very quickly. And for nephrotic syndrome, you want to find out if they have FSGS, but there are other causes other than FSGS. So it's harder for me to give you an overall prevalence based on nephrotic syndrome or not. But I can tell you, once they get a -- if they've got a diagnosis of FSGS, how many patients might have nephrotic syndrome at a single point in time. And that data comes from the DUPLEX trial.

So in our study, patients who at the time of enrollment who had known FSGS, less than 20% of them had active nephrotic syndrome. And recall, these patients are going to be treated. So they might go in and out of nephrotic syndrome over time. It's not a static condition because this is a relapsing and remitting condition.

Our next question is from Anupam Rama from JPMorgan.

This is Priyanka on for Anupam. Congratulations on the full approval. Just a question on the sales team that's in place. I understand that there will be a proportion that will need to focus on pediatric nephrologists. I was just curious how much larger would you consider growing the broader sales team to help cover that physician population?

Priyanka, thanks for the question. Peter, I'll turn that one over to you.

Absolutely, Priyanka. Great question. And our sales team has already been expanded. We did that at the end of last year. So they're in place. Historically, we have spoken about we have focused on 6,000 nephrologists that cover about 90% of the IgA nephropathy patient population. We're expanding that now also for pediatric nephrologists. So we are now focused on about 7,000 nephrologists in the U.S., and that includes pediatric nephrologists.

And maybe also important to note, and I've spoken about this in the past, there's a high overlap between those physicians that treat IgA nephropathy and FSGS. So we build upon a base that is already familiar with FILSPARI.

Our next question is from Vamil Divan from Guggenheim Partners.

Let me add my congrats also. I know it's been a long process to get to hear. So I guess my question is really around sort of the patient population here because you -- before today, you were already saying 30,000 patients that could be candidates for FILSPARI, but I thought that was more based on primary and genetic FSGS. Now this seems to be a broader approval for secondary, but then you have the exclusion of patients with nephrotic syndrome. But your number is still just saying over 30,000. So I would think the population is maybe much larger than 30,000 now. But does that sort of wash out the sort of broader indication with then removing nephrotic syndrome?

So if you could just sort of walk us through the numbers there a little bit on what the secondary population means or maybe you don't think it would get much uptick there if there's other options or -- and anything around how this broader indication could impact, how you think about it commercially would just be very helpful.

Sure. Vamil, thanks so much for the question. Yes, we do see that today, there are over 30,000 patients that are diagnosed and under the care of a nephrologist that would be eligible based on this approval. What we do -- what we have done is we've added those patients that we believe currently have secondary FSGS and removed the proportion that we believe overall would have current nephrotic syndrome.

Now over time, we do believe that with growing awareness, with the availability of an approved medication that patients may be diagnosed and biopsied earlier, which would allow for that addressable population to grow over time. So we do see this as a very meaningful opportunity. And as we've seen in other rare diseases, we do expect the addressable population to grow.

Your next question is from Laura Chico from Wedbush Securities.

Congratulations. Jula, you mentioned that the nephrotic syndrome discussion with FDA was somewhat new. And I'm wondering if you could expand on that a little bit around the labeling discussions with nephrotic syndrome. What would be necessary to demonstrate, I guess, in a clinical trial setting to expand FILSPARI's label to encompass that? And is that something that you would pursue?

Thanks, Laura. Jula?

Yes. As I mentioned in my prepared remarks, this occurred very recently. In our meeting with the FDA last month, and there were a couple of reasons why they honed in on this patient population. First, the magnitude of the treatment effect against an active comparator on proteinuria was greater in this population versus the overall population and versus those who have active nephrotic syndrome.

The additional aspect is that there was also meaningful and statistically significant effects on eGFR as well as on kidney failure endpoints. And I do want to highlight that even though we don't have as great of treatment effect on proteinuria in the patients with active nephrotic syndrome, it's not that the therapy doesn't work. It's that in this patient population, the treatment effect against an active comparator wasn't as great, and it's a noisier patient population. So the signal to noise, it's messy in this patient population.

And then you additionally asked about what it would take. We do believe that the vast majority of patients with FSGS, whether they're eligible today or will be eligible in the future, can potentially benefit from FILSPARI. And as I mentioned earlier, less than 20% of patients with FSGS have nephrotic syndrome at a single point in time. And it's important to consider that if a patient has 4 or 5 grams of proteinuria and low albumin and edema, if you treat them and change one of those characteristics, and remember, these are sick patients, so you're trying to stabilize them. They can get FILSPARI in the future once they get stabilized. So we are very pleased and believe that this is a broad approval for patients over time.

And next question is from Tyler Van Buren from TD Cowen.

Congratulations on the approval, a tremendous outcome for Travere and for patients. Just wanted to -- obviously, the addressable population for IgAN is significantly larger than FSGS. But I want to get your latest thoughts on what you believe the ultimate penetration of FILSPARI will be in FSGS compared to IgAN over the long term?

Peter, would you like to take that?

Yes, happy to take that question, Tyler. And you're right. I mean we expect that we will see a more rapid uptake in FSGS relative to what we saw in IgA nephropathy for several reasons. One is we don't have to establish the unmet need like every nephrologist you speak with. They are very well convinced that those patients need treatment urgently and that new treatments will be -- are necessary. And as I mentioned earlier, this is largely the same call point as that we have with already experience in a large amount of physicians and FILSPARI is already established well.

Having said that, we also need to educate the stakeholders, both the nephrologists, the patients and the payers, and that may take time. But overall, we see a more rapid uptake in this patient population relative to IgA nephropathy.

Yes. Thanks, Peter. And Tyler, let me add that we see both IgA nephropathy and FSGS as very meaningful opportunities for future growth. And a patient with IgA nephropathy and FSGS deserve equally FILSPARI. As we look out, we see the potential for peak year sales over $3 billion when we look at the combination of these 2 indications. And our job right now, as Peter mentioned, is to make sure that we're out there very quickly because patients deserve it and to be able to educate physicians on this label and the opportunity to do better in FSGS.

The next question is from Prakhar Agrawal from Cantor Fitzgerald.

Congratulations on the approval. Maybe just firstly, you mentioned less than 20% have active nephrotic syndrome. Could you clarify if that's relevant for secondary FSGS as well? And what could be the uptake be in primary versus secondary FSGS given secondary population was not included in DUPLEX, but a much larger segment overall? And maybe just a quick follow-up, if you could confirm the pricing here for the 800-milligram dose. Is it double the price of IgAN? Congrats again.

Thanks, Prakhar. I'll take the last part first on pricing. So the -- yes, the per patient, the dosing is higher for adult patients with FSGS. The per pill is the same. So a patient with FSGS would have a higher cost to payers. And our goal overall is to make sure that every single patient has access to FILSPARI that is eligible.

Jula, I'll turn that first part of the question to you around active nephrotic syndrome and primary versus secondary.

Certainly. So the rationale for having patients with active nephrotic syndrome having a different treatment algorithm, and this is in the Kidney Disease Improving Global Outcomes Guideline is because you're trying to identify patients with clinical characteristics with laboratory findings who are more likely to have primary FSGS and treat -- be needed to be treated with an immunosuppressive therapy. So that's why that characteristic and classification is even there because patients who do not have primary FSGS typically don't have nephrotic syndrome.

So your question was at the heart of it, how many patients with secondary FSGS or even undetermined cause or genetic have active nephrotic syndrome, it's a low proportion. When we took an all-comers population, primary genetic, we did try to rule out secondary, but we've got patients with undetermined cause. We do see that at that single point in time when patients got into DUPLEX, as I mentioned earlier, less than 20% had nephrotic syndrome. But it's not a typical presentation for patients with secondary FSGS.

And with regard to uptake, I think it's too early for us to comment on that. I think we see that there is a high unmet need and an urgency to really intervene with better therapies like FILSPARI. So our goal is to make sure that we're reaching all of these patients. And I'm not sure that we've heard much in terms of physicians saying that they're not excited across the board. We really are going to be trying to reach every one of these patients.

Our next question is from Mohit Bansal from Wells Fargo.

This is Sadia on for Mohit. Congrats on the approval. I'm just wondering on the question of nephrotic syndrome. In clinical practice, when doctors think about nephrotic syndrome, is the focus on that proteinuria level that patients have? Or are they also focused on edema and the albumin criteria that you outlined?

Thanks, Sadia. Jula, I'll turn that one over to you.

They're focused on all of them. So in order for a patient to have a definition -- a clinical definition of nephrotic syndrome, they need really elevated proteinuria, low serum albumin. So that's also part of it and edema. So it really is the triage of all 3 of those in order for someone to have active nephrotic syndrome. And as I said earlier, the reason you want to classify someone according to that clinical criteria is because you treat them differently. You're going to give steroids to a patient who has active nephrotic syndrome or other immunosuppression, and you're going to support them with supportive therapies if they don't have that clinical presentation. So it is an important characteristic, something that we look for to try and figure out how we should appropriately treat that patient initially.

The next question is from Gavin Clark-Gartner from Evercore.

You have [ Ivy ] on for Gavin. Congratulations on the approval. Could you provide some color on if you'll be providing FSGS-specific PSFs moving forward? Or any metrics to break out FSGS versus IgAN contribution and whether your gross to net will now change as you launch FSGS2? And the second part of my question is if you could comment on the current discontinuation rates seen in IgAN and how FSGS could compare to that?

Okay. Chris, I'll turn the first part over to you. And Peter, you can talk about discontinuation rates.

Perfect. Thanks for the question, [ Ivy ]. First on the PSFs and the planned reporting for metrics, no change at this point. We'll, of course, continue to evaluate as we move forward. But the plan for now is to provide aggregate PSFs and revenue. And then on the gross to net front, no change there. The expectation remains the same for this year. We're anticipating gross to net in the mid-20s for the full year.

So Peter, I'll turn the one over to you.

Yes. With regards to the discontinuation, what we have seen is very high compliance and persistence for FILSPARI in IgA nephropathy, and I'm expecting similar rates for FSGS because this is an even more -- even higher motivated patient population that has been waiting for the approval of FILSPARI. So I'm expecting a high compliance and persistence rate there.

Yes. And Peter, if I can, I'm just going to complement your team with Travere Total Care. They do an outstanding job of supporting these patients throughout their journey. I think that, that is something that we will continue, as Peter mentioned, for the FSGS patients as well.

Next question is from Maury Raycroft from Jefferies.

I'll add my congrats on the approval. As it relates to PSF, do you have perspective into numbers of eligible patients waiting for therapy at launch? And could there be a bolus effect? And I also wanted to check on whether there are any new post-marketing requirements from FDA?

All right. Peter, why don't you take the question on eligible patients, and Bill will give you your first question on post-marketing.

Excellent. Well, Maury, thanks for that question. Your question was about warehousing. We do not expect a significant bolus of patients as FSGS patients are seen on a regular base by their nephrologists. Typically, they see the nephrologists every 3 months. And so I would think that is a natural cadence for future uptake, especially if you realize how busy, especially community nephrologists are. So not a significant bolus, but a steady uptake I'm anticipating.

And with respect to post-marketing requirements, we had no new requirements added with the approval of FILSPARI for FSGS.

The next question is from Yigal Nochomovitz from Citigroup.

Yes, congratulations as well on the approval. I was just curious, given that you mentioned that this topic of nephrotic versus non-nephrotic syndrome came up very recently last month. I'm curious if you could elaborate now on what was asked at the end of December in 2025 when you got those late data requests from the FDA. Were there clues there that they were looking down this path regarding nephrotic or non-nephrotic? Or was that something entirely different?

Bill, I'll hand that over to you.

Yes. No, it's a good question. This was a recent development. As you've heard on the call, we learned about the agency's preference for this subgroup early in March. As we stated before, the IRs that we received right at the holidays, those were related to the overall clinical meaningfulness of FILSPARI. And there, they were looking at the overall population in DUPLEX, and it wasn't split based on any subgroups at that point.

Okay. And then if I could just follow up, the definition of the nephrotic syndrome, is that a single point in time? Or does it have to be measured at multiple points to qualify?

Jula?

It's one single point in time is typically how you use it to define a patient who does or does not have active nephrotic syndrome. And again, this is a relapsing and remitting condition. So a patient can get treated with an immunosuppressant therapy today as well as other supportive care if they've got active nephrotic syndrome with the goal of changing their condition. So it certainly can change over time. So a patient who may not qualify at one point in time could qualify if there's a change to any one of those parameters. Maybe their proteinuria goes down or their albumin goes up in their blood or their edema goes away, treat them with the diuretic and the edema goes away, they would no longer be considered to have active nephrotic syndrome.

Our next question is from Jason Zemansky from Bank of America.

Congrats on the approval. Peter, maybe to connect the dots on some of your comments regarding commercial dynamics, but what are the key levers you're focused on in terms of driving adoption here? I mean I know you've mentioned education and having the large bolus of patients. But what are the, I guess, primary hurdles in getting a patient on treatment?

Yes. I don't think I set a large bolus of patients. Just to clarify on that one. I think for FSGS, I mean, this is highly anticipated. And as I mentioned before, we do anticipate a faster uptake relative to our IgA nephropathy launch because like FILSPARI is a known entity for many of these nephrologists with an overlap of over 80%. But still, you need to educate them. I mean they need to be educated that FILSPARI is now approved, what the patient population is. The same you do that to nephrologists as well as the payers and the patients. So this is the regular uptake, educating the prescriber base, the patients and the payers. But we're building on strength. I mean that's what I mentioned earlier. FILSPARI is already included in many of the formularies, the payer plans. So we build upon that access approval as well. So I think we're in a very strong position but we still need to educate the individuals, and that's our core focus in the next few months.

Our next question is from Alex Thompson from Stifel.

Congrats on the approval. Maybe one on IP. You've talked about in the past like working on expanding IP for FILSPARI and potentially extending exclusivity beyond 2033. Could you talk a little bit about the progress there and if we should expect any developments in the near future?

Alex, thanks for the question. So our current planning assumption, as you state, is 2033, and we do have several applications, some of them ongoing review. And there's no specific updates at this time, but I can say that they are actively being reviewed and we're actively working on them. And certainly, having today's approval, we believe, gives us continued support of the LOE, including our expected orphan drug exclusivity.

Ladies and gentlemen, this concludes the question-and-answer session. I'll hand the call back over to Nivi.

Great. Thank you, everyone, for joining us this evening. We're very excited about our path forward, and we'll continue to share more updates along the way. Have a great rest of your evening.

Ladies and gentlemen, this concludes the conference call. Thank you for your participation, and have a nice day.

Good afternoon, and welcome to the Travere Therapeutics Fourth Quarter and Full Year 2025 Financial Results Conference Call. Today's call is being recorded.

At this time, I would like to turn the conference call over to Nivi Nehra, Vice President, Corporate Communications and Investor Relations. Please go ahead, Nivi.

Thank you, operator. Good afternoon, and welcome to Travere Therapeutics Fourth Quarter and Full Year 2025 Financial Results and Corporate Update Call. Thank you all for joining. Today's call will be led by Dr. Eric Dube, our President and Chief Executive Officer. Eric will be joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; Peter Heerma, our Chief Commercial Officer; and Chris Cline, our Chief Financial Officer. Dr. Bill Rote, our Chief Research Officer, will join us for the Q&A.

Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today as well as the Risk Factors section in our Forms 10-Q and 10-K filed with the SEC.

In addition, any forward-looking statements represent our views only as of the date such statements are made, February 19, 2026. and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances.

With that, let me now turn the call over to Eric.

Thank you, Nivi. Good afternoon, and thank you all for joining us today. 2025 was an incredible year for Travere, one that was defined by achieving a new high in the number of patients we were able to reach with our approved medicines and clear advancement of our pipeline. This success was driven by focused execution against our strategy, strong commercial performance and an unwavering commitment to bring new medicines to communities that have been waiting far too long.

In IgA nephropathy, we saw record demand and strong revenue growth in the fourth quarter, even as additional therapies entered the market. Physician confidence in FILSPARI continues to build as real-world experience reinforces our long-term clinical data and its role as a foundational nonimmunosuppressive therapy that can be used chronically and in combination. These results reflect growing use of FILSPARI in clinical practice, supported by strong execution across access, fulfillment and patient support. We remain confident in our ability to deliver continued growth in IgA nephropathy and reach more patients in 2026 and in the years ahead.

We also continue to advance the next phase of growth for Travere. In FSGS, patients face a rapidly progressive disease with no FDA-approved medication today. The acceptance of our sNDA and for an FSGS indication for FILSPARI last year marked an important step towards our goal of delivering the first approved medicine for this community. In January, we received notification of a major amendment to our sNDA following additional information requests received before the holidays. As a result, our new FDA PDUFA target action date is April 13, 2026. While the date for an action by the FDA has shifted, our conviction in the clinical profile of FILSPARI as a potential FSGS therapy and the benefit it could provide to the FSGS community remains unchanged. We will continue to work with the agency as they advance their review. And with our expanded commercial team fully established are ready to execute with excellence, if approved.

Beyond FILSPARI, we are also advancing pegtibatinase for classical homocystinuria, or HCU, which we believe has the potential to become an important contributor to growth beyond FILSPARI. Pegtibatinase has the potential to be the first disease-modifying medicine to address the underlying cause of the disease. Notably, we have recently resumed site activation for our pivotal Phase III HARMONY study to enable enrollment globally. As we look ahead, our priorities are clear: solidified FILSPARI's foundational role in IGAM, successfully delivered the first approved medicine for FSGS, if approved; advanced enrollment in our Phase III HARMONY study; and continue to build a durable, growing rare disease company grounded in execution and scientific rigor. We entered 2026 with focus, discipline and confidence in our path forward. and most importantly, with a continued commitment to delivering meaningful progress for patients.

With that, I'll now turn the call over to Jula to talk more about the advancement of our programs. Jula?

Thank you, Eric. We are pleased with the consistent nephrologist feedback about the critical role of dual antagonism of endothelin and angiotensin as part of the foundational treatment paradigm to preserve kidney function in patients with IgA nephropathy.

As we continue to generate FILSPARI barring data across a broad spectrum of patients with IgA nephropathy from early after diagnosis to recurrent post transplant as well as in combination with other therapies, we are hearing consistent feedback from nephrologists that they are aligned with KDIGO and that FILSPARI has the potential to replace the historic role of RAS inhibitors and provide long-term nephro protection for patients with IgA nephropathy. This support is rooted in data such as our recently published secondary analysis of PROTECT, which demonstrated that achievement of complete remission of proteinuria to less than 0.3 grams per day, of which 80% were treated with FILSPARI was associated with an annual eGFR decline as recommended by KDIGO of less than 1 ml per minute per year. reflecting meaningful preservation of kidney function.

Importantly, we believe the convergence of physician conviction and robust clinical evidence positions FILSPARI as foundational care in IgA nephropathy as we look ahead.

Turning to FSGS. We continue working towards our new PDUFA date of April 13 and look forward to working with the agency as the review advances. We remain confident in FILSPARI's clinical profile and its potential, if approved, to meaningfully advance treatment for patients with FSGS by protecting [indiscernible] site health. This confidence is based on the strength and consistency of the data generated across our Phase II DUET and Phase III DUPLEX studies, which together represent 2 of the largest interventional clinical trials ever conducted in FSGS.

Across these studies, FILSPARI consistently reduced proteinuria, a well-established driver of long-term kidney outcomes in this disease. Importantly, the trial data demonstrate consistent proteinuria reduction across a heterogenous patient population, including both primary and genetic forms of FSGS as well as in pediatric patients. And the magnitude of treatment effect on proteinuria observed with FILSPARI versus active comparator irbesartan translated into a clinically meaningful reduction in kidney failure events, both within the DUPLEX trial and when extrapolated based on external data such as radar.

In our ongoing engagements with the nephrology community, we continue to hear strong alignment around the clinical relevance of the DUPLEX data, which is even more compelling given the absence of any FDA-approved medication indicated for FSGS today and the urgent need for earlier, more effective interventions relative to historical standard of care.

Many clinicians emphasize the importance of proteinuria reduction as the primary treatment goal and recognize the consistency of FILSPARI's antiproteineric effect across patient subgroups. Taken together, the totality of the data and the feedback we continue to hear from the FSGS community reinforce our belief in FILSPARI's potential to meaningfully change the treatment paradigm for patients living with FSGS and we look forward to the FDA's upcoming review decision.

Let me now turn to Pegtibatinase and classical homocystinuria. Classical HCU is a serious genetic metabolic disorder with limited treatment options. These patients are born with a deficiency in their CBS enzyme that would normally help to metabolize certain proteins in their diet. This deficiency results in a toxic buildup of homocystine, which can lead to serious and life-threatening thrombotic events such as stroke and pulmonary embolism or deep vein thrombosis in addition to vision and skeletal abnormalities and developmental delays. To put this into context, if untreated, approximately 25% of these patients have an ischemic event before they become a teenager and 50% experience an ischemic events before they turn 30.

Pegtibatinase is an investigational inbound replacement therapy designed to address the underlying CBS enzyme deficiency that drives toxic homocystine accumulation rather than managing downstream consequences alone. The Phase I/II composed data demonstrated clinically meaningful reductions in total homocystine, including normalization for 1 patient, a clear dose response and a favorable tolerability profile, supporting advancement into Phase III development. In 2025, we achieved key manufacturing process optimizations, an important milestone that positions the program for late-stage development and future potential commercialization. We have now resumed activating clinical trial sites for the Phase III HARMONY study and the long-term extension study on Sabal, which are designed to evaluate sustained total homocystine control and explore outcomes that matter to patients, including the potential for greater dietary flexibility.

Harmony is a randomized double-blind study of Pegtibatinase versus placebo. The double-blind period will follow patients for 24 weeks, which includes the primary end point measuring change from baseline in plasma total homocystine averaged over weeks 6 through 12, with durability of treatment measured as a secondary endpoint to week 24. There's also a 4-week screening period, and following initial screening, there is a pretreatment diet stabilization period of up to 6 weeks to help minimize protein intake variability. The total study duration can range up to 38 weeks prior to entering into the Ensemble extension study.

We believe Pegtibatinase has the potential to become the first disease-modifying therapy for classical HCU, and importantly, to meaningfully improve the day-to-day lived experience for patients and families. Our focus is now on building momentum as the trial resumes, and we expect to reinitiate dosing of new patients in the near future.

Across our programs, we're looking forward to presenting new data at medical congresses this year. In IGAM, these efforts are intended to further support FILSPARI's role as foundational therapy, while in FSGS, they're focused on deepening the understanding of FILSPARI's clinical profile and its potential role in addressing the high unmet need in these patients.

With that, I'll now turn it over to Peter for a commercial update. Peter?

Thank you, Jula. I am pleased to share that the fourth quarter of 2025 marked a strong finish to the year for FILSPARI with continued momentum driven by growing physician adoption, robust demand and increasing confidence in FILSPARI's role as a foundational therapy in IgA nephropathy.

During the fourth quarter, we saw a record demand of 908 new patient platform for FILSPARI. Notably, we are seeing a strong level of demand continue into the first quarter. The demand in the fourth quarter was driven by both new prescribers and increasing use among established prescribers. Importantly, we continue to see an increasing number of practices treating multiple patients with FILSPARI, which we view as a meaningful indicator of physicians' confidence and experience in the therapy's effectiveness, tolerability and long-term utility.

The strong demand translated into robust growth to the end of the year. In the fourth quarter, FILSPARI generated approximately $103 million in net product sales and approximately $322 million for the full year of 2025, representing a 144% year-over-year growth. We believe these results underscore the momentum and a significant growth opportunity for FILSPARI and its ability to continue to perform strongly as the IgA nephropathy treatment landscape evolves with new entrants.

We believe FILSPARI's continued success in the fourth quarter was driven by a differentiated profile, simplification of the ramps monitoring requirements and the publication of the KDIGO guidelines. As a once-daily nonimmunosuppressive oral therapy, FILSPARI provides a proven and convenient option for chronic use in a disease that requires long-term nephroprotective treatment. In addition, FILSPARI's ability to be used in combination with other therapies provides flexibility for nephrologist as they tailor treatment strategies to individual patients.

We are also seeing broad utilization of FILSPARI across the full spectrum of adult patients with IgA nephropathy, with increasing adoption in patients with elevated popery levels, but below 1.5 gram per gram. This trend is consistent with the direction of the KDIGO guidelines, as they emphasize a lower treatment target and earlier intervention. It is important as well FILSPARI continues to be used in patients with higher levels of proteinuria, we are seeing accelerating adoption in those below 1.5 grams per gram, which represent approximately 2/3 of the addressable IgA nephropathy population.

From the patient perspective, feedback indicates that satisfaction with FILSPARI and our patient support services remain high with strong patient compliance and sustained persistence observed over time. Patients frequently cite the convenience of a once-daily oral medicine in the nonmunisuppressive and nephroprotective profile with long-term kit depreservation as important factors in their treatment experience. In parallel, we have continued to build commercial readiness in anticipation of a potential approval in FSGS. Given the rapidly progressive nature of FSGS and the lack of approved therapies today, we believe our existing relationships, experience in IgA nephropathy and commercial infrastructure position us well to support patients and physicians in this setting.

Based on the feedback from the FSGS community, we believe this indication is approved could be an even larger opportunity with a more rapid uptake compared to IgA nephropathy, and we stand ready to deliver for this patient community.

In summary, the fourth quarter of 2025 demonstrated exceptional commercial execution and performance, evidenced by record demand and revenue. Building on our established commercial foundation and the strong performance amidst additional treatment options becoming available, I am confident in FILSPARI's ability to deliver sustainable growth and long-term leadership in rare kidney disease care. I couldn't be proud of our commercial team and the impact they make on patients' lives on a daily basis. And I'm excited about how they will continue to support patients and physicians in 2026.

Let me now turn the call over to Chris for the financial update. Chris?

Thank you, Peter, and good afternoon all. We ended the year in a strong financial position. This was bolstered by continued net product sales growth, focused investment in key priorities to support our current performance and sustainable growth potential and strategic partner milestones that added to our balance sheet strength.

Beginning with revenue. For the fourth quarter, we reported U.S. net product sales of $126.6 million and for the full year 2025, total net product sales were $410.5 million. This marks significant year-over-year growth in our revenue base. FILSPARI generated $103.3 million in U.S. net product sales for the fourth quarter, resulting in $322 million in net product sales for the full year 2025.

Thiola and Thiola EC contributed $23.3 million in U.S. net product sales during the fourth quarter and $88.5 million for the full year 2025. For the fourth quarter and full year 2025, we also recognized $3.1 million and $80.3 million, respectively, in license and collaboration revenue.

Moving to operating expenses. Our research and development expenses for the fourth quarter of 2025 were $57.9 million compared to $62.1 million for the same period in 2024. On a non-GAAP adjusted basis, R&D expenses were $54 million compared to $58.6 million for the same period in 2024.

Selling, general and administrative expenses for the fourth quarter were $101.7 million compared to $69.5 million for the same period in 2024. And on a non-GAAP and adjusted basis, SG&A expenses were $76 million for the fourth quarter compared to $51.6 million in the same period in 2024. The increase in SG&A is primarily attributable to investments in preparations for a potential launch in FSGS, including the first full quarter with an expanded sales force, increased amortization expense related to FILSPARI royalties as FILSPARI continues to grow significantly as well as increased investments to support commercial efforts for FILSPARI and IgA nephropathy.

Total other income net for the fourth quarter of 2025 was $11.4 million compared to less than $1 million for the same period 2024. The difference is largely attributable to approximately $10 million in proceeds received as a result of the Reais acquisition by Chugai that was completed in the fourth quarter.

During the fourth quarter, we also recognized approximately $25 million of income from discontinued operations. This resulted from Veran Pharmaceuticals achieving a sales-based milestone of $25 million that is expected to be paid to Travere in the first half of this year.

Net income for the fourth quarter of 2025 was $2.7 million or $0.03 per basic share compared to a net loss of $6.3 million or $0.73 per basic share for the same period in 2024. On a non-GAAP adjusted basis, net income for the fourth quarter of 2025 was $33.3 million or $0.37 per basic share compared to a net loss of $39 million or $0.47 per basic share for the same period in 2024.

As of December 31, 2025, we had cash, cash equivalents and marketable securities totaling approximately $322.8 million. This balance reflects the proceeds of the $40 million milestone payment received from CSL during the quarter as well as approximately $10 million from the renals acquisition by Chugai.

Looking ahead in 2026, we expect meaningful net product sales growth from FILSPARI and Iga nephropathy to continue strengthening our financial position. While we anticipate modestly higher gross to net discounts compared to last year, as Peter mentioned, underlying demand remains strong, and we expect FILSPARI to deliver robust growth of foundational therapy. If approved by FSGS, we believe this represents a meaningful opportunity to build on our momentum from IgA nephropathy and further support potential top line growth. And from an operating expense perspective, we will continue to invest thoughtfully to advance both our current performance and long-term growth potential.

We expect moderate operating expense growth versus 2025, primarily driven by the restart and execution of the global Phase III HARMONY study as well as supply for Pegtibatinase, continued evidence generation for FILSPARI and commercial investment to support a potential FSGS launch. Importantly, we do not anticipate a near-term need for additional capital to support our current priorities. Our strong balance sheet, coupled with expected revenue growth and a focused investment approach position us to drive near and long-term value.

I'll now turn it over to Eric for his closing comments. Eric?

Thank you, Chris. In closing, Travere is well positioned as we enter the next phase of growth with strong commercial momentum in IgA nephropathy, a meaningful potential opportunity in FSGS as FILSPARI advances through the regulatory review process and a pipeline advancing with purpose. Our strategy is focused. Our teams are executing with discipline, and our balance sheet provides the flexibility to deliver on our priorities.

Most importantly, we remain driven by the urgency felt by the patients and families we serve and by our responsibility to deliver meaningful progress on their behalf. Now let me turn the call over to Nivi for Q&A. Nivi?

Thank you, Eric. Operator, we can now open up the line for Q&A.

[Operator Instructions] We will now take the first question from the line of Vamil Divan from Guggenheim Securities.

Great. So just want to dig a little deeper into the IAN performance, obviously, strong inpatient start forms. I'm wondering now that you've been in the market for a little bit, we also have some new competition, obviously, in the market over the last year or so. If you can give a little more detail in terms of how and where are the products being prescribed in IDM more of a breakdown between community-based nephrologists and those that maybe more academic centers and then also in terms of the treatment paradigm. So where is it being added on? And sir, in combination, are you seeing any issues with providers trying to use 2 branded products at the same time, as the payers push back and mean providers to prioritize one over the other?

Vamil, thanks for the question. Peter, I will turn that over to you, and I'll make sure that we capture all the kind of questions that Vamil asked there. Go ahead, Peter.

Yes. Thank you, Eric, and thank you, Vamil, for that question. And I did get your several components, so let me try to unpack that. And Vamil, let me know if I answered your question to your satisfaction. But first of all, to your point on like what was driving the demand in Q4? And to your point, like a very strong demand quarter with 908 new patient platforms, which was mainly driven by the modification of our REMS requirements as well as the publication of the KDIGO. And the education of the broader community really allows for a growth opportunity on the market, FILSPARI in particular.

We can like built into your second part of your question, like where do you see most of the utilization community relative to academic prescribers. And as we mentioned in the past, I mean, the vast majority of those patients reside in the community and our utilization is reflective of that. So we have more use in the community, consistent to where the patient community resides.

I think the last component of your question was regarding a changing treatment landscape, what is the payer situation. Well, as we have discussed in the past, we have a very strong position in payer formularies. We -- our objective was always to have broad utilization, and we have accomplished that with like over 96% of the patient population have a pathway to reimbursement for FILSPARI. And that remains unchanged in this evolving landscape with new competition going in. I think I did answer all 3 of your questions, but Vamil, please add if you - if I didn't.

No, that's helpful color. I'll jump back in the queue...

Vamil, one thing that maybe I can just add is that we see a robust level of growth that's coming not just from the dynamics that Peter talked about, but also from new and repeat prescribers. When I think about sustainable growth in terms of the longer-term potential, this is exactly what we would hope to see that we're seeing new physicians start to prescribe as driven by the modification of REMS, KDIGO and the comfort that they're hearing from their peers, but we're also seeing physicians find new patients as repeat prescribers. That is very encouraging and particularly as new treatment options come to these patients, we're very encouraged and I want to emphasize one thing that Peter mentioned in his prepared remarks, which is these trends for strong demand continued in the first part of this year to start out this year very strongly. So we're very excited about the future potential growth for FILSPARI and IgA nephropathy.

Our next question comes from the line of Tyler Van Buren from TD Cowen.

Great to see the progress during the quarter. Can you tell us if you've had more significant data requests from the FDA following the last disclosure in the new year? And if so, what the nature of them were? And maybe just as a kicker here, given the ALIGN IGAM study data with 2.5 years of follow-up that Novartis reported for Benrafia last week, can you help us put that into context and compare it to what you've all reported for FILSPARI?

Tyler, thanks for the questions. I'll take the first one on FDA, and then I'll ask Jula to comment on the IgA nephropathy data. So we are continuing to have FDA engage and review our file. Our practice is not to comment on ongoing reviews. We did provide comments on the information request that we got at the end of last year just based on the unusual timing of those. But at this point, I'd say we provided FDA what they've asked for and we're on track for the April 13 PDUFA date. Jula?

Yes. And with regards to the ALIGN trial data, we can't really make cross-trial comparisons given there's different trial designs and different time points for the end points. But I want to reiterate FILSPARI was studied for 2 years against a max dose active comparator, which we know also preserve kidney function versus atrasentan was setting against a placebo with an endpoint in about 2.5 years. But let me reiterate what we demonstrated in PROTECT with FILSPARI. First, there was a 3.7 milliliter greater absolute preservation in eGFR at 2 years versus an active control. And this effect was nominally statistically significant.

Importantly, we saw an accrual of benefit on kidney function over time, such that at 1 year, there was a 1.8 milliliter greater preservation in eGFR. And as I mentioned, at 2 years, this grew to 3.7 milliliter difference.

Lastly, our primary endpoint of total eGFR slope in the preferred FDA analysis, which we have in our label, that was statistically significant with a treatment effect of 1.2 milliliters per minute per year versus active comparator. So in totality, we're confident in the data to support FILSPARI provide superior long-term nephroprotection versus a max dose irbesartan in PROTECT and that's what provides support for its first-line placement in the KDIGO guidelines.

Our next question comes from the line of Laura Chico from Wedbush Securities.

For the FILSPARI sNDA, I'm sorry if I missed this in the earlier response, wondering if you could further elaborate on some of the specific aspects of clinical benefit characterization the agency is focused on. I guess I'm just trying to understand whether this signals any change in the agency's receptivity to proteinuria as an endpoint for FSGS? And then just a separate follow-up for Peter. What proportion of the new 4K PSF came from patients with proteinuria less than 1.5 gram per gram? It sounds like it's an increasing proportion. I'm just wondering if you could kind of contextualize that versus the earlier days of launch.

Laura, thanks for the questions. I will take the first one on the sNDA and then I'll hand over to Peter on the PS. We've not provided the level of detail on the types of information request that FDA provides us. Our practice is not to comment on that level of detail. What we have said is that all of the information requests we received late last year were focused on clinical benefit. And what I would say is that from what we've seen throughout our engagements with the FDA as well as what other sponsors have commented on in their discussions around Premier is an endpoint, we believe that this is the endpoint that could be used as a validated surrogate endpoint for full approval. So we're on track for the PDUFA date. And there's nothing that we've seen that would suggest that they're questioning or walking away from proteinuria as an end point.

And with that, I'll turn it over to Peter.

Perfect. Thank you, Eric, and thanks, Laura, for that question. To clarify your question, we still see demand also with patients with proteinuria levels of 1.5 and higher. But if you look at the totality of patient start forms that we are receiving, you see more and more patient platform with proteinuria level below 1.5. And if I look at the median, it continues to go down. it's well below 1.5, but we haven't split it out like in percentage-wise. So I can't comment on that.

Our next question comes from the line of Anupam Rama from JPMorgan.

This is Priyanka on for Anupam. Can you remind us of the sales infrastructure for IgAN and how this will need to be expanded for an FSGS approval?

Priyanka, thanks for the question, and I will hand that one over to Peter.

Yes. Thanks, Priyanka. So first of all, I think it's good to realize that the prescriber base for FSDS is very similar compared to IgA nephropathy. I mean in the past, I've called out there is like an over 80% overlap between IgA nephropathy and FSGS. The only real different prescriber base would be pediatric nephrologist, but to the point that you're making, we want to make sure that we continue to deliver for IgA nephropathy patients while also really optimizing the opportunity for FSGS. And so we have expanded our field team for that, and that is fully operational already.

That's right. And we previously commented that we had about 80 field-based personnel and we have expanded that to more than 100 in the field. We've not broken down that, but I think that certainly provides us with a very strong infrastructure to be able to realize strong growth in reaching patients with IgA nephropathy and FSGS, if approved.

Our next question comes from the line of Joe Schwartz from Leerink Partners.

I was wondering if you could elaborate on your commentary earlier regarding gross to net and give us some insight into how we should expect that to evolve over the balance of the year.

Joe, thanks for the question. I will hand that one over to Chris.

Sure. Thanks for the question, Joe. So just in terms of the mechanics for gross to nets, we anticipate the flow of them to be similar to what we've seen in previous years. That being that we would expect that in the first quarter, you're going to see the highest differential in growth in that -- or the largest discount, and then you'll see that lessen in the second and third quarters. So a very similar dynamic.

I think the thing that is a little bit different this year is that our gross and net are expected to increase modestly. So this year, we're expecting to be in the mid-20s -- mid-20 percentage for the full year for FILSPARI and that's up a little bit from last year where we ended the year right around 20%.

Our next question comes from the line of Prakhar Agrawal from Cantor.

Congrats on the strong quarter. So I had 2. Maybe firstly, on FSGS. Given that externally, we have limited information on the nature of these information requests from the FDA. What is your confidence level in getting FILSPARI approval for FSGS based on FDA's level of questioning and what is driving that conviction? And secondly, on IgAN with the Otsuka's launch of their April blocker seems like they have got 500 patient start forms since launch. Where are beginning new patient starts versus FILSPARI? And how much impact from orcas drug and future bacipril drugs? Are you incorporating in 2026?

Prakhar, thanks so much for the questions. I will take the first question on FSGS, and I'll hand it over to Peter for the discussion on the evolving treatment landscape. So with regard to FSGS, again, we've provided information on the nature of the questions, but not specifically. What I can say is that our confidence has only increased in the profile of FILSPARI as a potential treatment in FSGS because not only do we see the data that we've presented and published as part of the New England Journal of Medicine, but all the work that we've done to be able to contextualize in the context of the parasol analysis showing how proteinuria has an independent predictive value of longer-term kidney -- risk of kidney failure further strengthen through our review and through our further analyses, some of which was presented at ASN in the fall.

So again, our confidence remains very high in the profile. And as Jula mentioned, 2 of the largest studies ever done in PROTECT -- in FSGS, now reflective of some of the conclusions that we saw coming out of Parasol.

Jula, is there anything else that you'd want to add on the data?

No. Just we continue to feel quite confident in the data that we presented, as you mentioned as well as what we submitted in our file and presented at ASN. FILSPARI clearly reduces proteinuria, as I mentioned in my prepared remarks across a broad spectrum of patients with FSGS and we have strong conviction that it should be available for treatment for the high-risk patient population that really has very little other treatment options.

And Peter, why don't you take the question about the Azuca launch?

Yes, happy to do so. I think the 500 basis platforms that you were referring to from Otsuka is really indicative of the overall IGAN market growing and the urgency to intervene earlier is reflecting that. And I think KDIGO is really outlining that this is a two-prong approach. You need to have kidney targeted therapies that historically was done with Agin ARPS and now with FILSPARI as novel superior alternative. It had historically generic steroids, and now you have B-cell therapy that could replace that. And what we are hearing so far is that physicians act accordingly. They really see this as replacing steroids in the higher proteinuria patient population.

And maybe good to articulate to my earlier comment in the prepared remarks, we see a very nice continuation of demand -- strong demand in the first part of the year, which indicates that we are not seeing any signs of switching, and we're not seeing any signs of sequencing B-cells before FILSPARI. So I'm very encouraged by what we are seeing right now, and it's very consistent to how we were anticipating the marketplace and very consistent also to the KDIGO guidelines.

Yes. Thank you, Peter. The way that I like to think this -- about this as we take a step back is, this is going to be a marketplace that is going to have a real acceleration of growth as there are new treatment options for these patients. And certainly, the KDIGO guidelines outline why that's going to take place. We expect to see therapies that are immune targeted like the Asuka compound grow in parallel to the growth that we expect to see as we look to replace the traditional role of RAS inhibitors just as they will be replacing the traditional role that steroids play. So there's going to be evolution of innovation that really is going to fuel growth for both sides of the treatment algorithm.

Our next question comes from the line of Mohit Bansal from Wells Fargo.

This is Sadia Rahman on for Mohit. So you've been seeing really good traction in the market recently and it sounds like you expect robust growth this year. So just wondering if you can comment on how penetrated the U.S. market is today and how you view FILSPARI's potential, how much further you think this can grow? I think The Street's expectations currently imply that penetration could double over time from current levels, which still seem low. So just wondering if you think that's appropriate given the new competition that's coming? Or do you think FILSPARI's expansion potential might be underappreciated?

Thanks, Sadia. Very insightful and great questions. Let me first start before I hand it over to Peter in saying we're not -- I don't want to provide any type of guidance. But I think what we can talk about is some of the potential and some of the dynamics. And I think, Peter, if you can start with what are we seeing with the estimated penetration, I think then we can reflect on what is the real potential for further growth in our segment of this market.

Yes. I think that's a good way to start. I think overall, you have to realize this was a market that historically was treated with generic medicine. And if you look at proxies in other disease areas, you see there is a substantial opportunity for branded superior treatment options. And with our data, I think we have a very strong opportunity. I mean if you look at our cumulative amount of patient start forms, we don't even hit that 10% of the addressable patient population. So I think that allows a very strong growth opportunity ahead of us.

I mean if I think about the amount of bases are still treated with ACE inhibitors or ARBs for IgA nephropathy, while there is a superior treatment available that's the opportunity we have. And to provide a finer point on that, I think there are 3 categories, how I would classify continued growth. I think the first one to my earlier point, innovation matters. We have the opportunity with the superior product to replace generic RAS inhibition with FILSPARI.

The second point is as we mentioned earlier in the prepared remarks, and Eric was mentioning in answering the earlier question as well, with KDIGO and with a recognition to treat those patients earlier and more aggressively. We have an opportunity to further build that market and expand the patient population that are yet untreated. And I think the guidelines really allow us to move into that segment as well.

And then the third category, building on what Eric said earlier on the Otsuka question, we are expecting that you will see increased combination therapies, in particular with like in a more ambitious treatment target. One treatment category may not bring you there, and that's why we are anticipating that you will see a continuation of use of novel foundational therapies like FILSPARI as well as immunosuppressive -- novel immunosuppressive treatment agents like, for example, the B cells or the complement inhibitors. All in all, I feel that this market is going to grow. I think with FILSPARI, we are very well positioned in that foundational treatment category. And I think this -- you will see that this market will continue to grow.

Yes. Thank you, Peter. And just to round out, Sadia, the other aspect is that we have shared that at peak. We believe that IGA nephropathy alone, FILSPARI will be well above $1 billion potential. So real opportunity for further growth in the years to come.

Our next question comes from the line of Gavin Clark-Gartner from Evercore.

I was just wondering what your plans are for communicating with the investor community more broadly as we approach the FSGS PDUFA over the next 2 months or so.

Gavin, thanks for the question. I will hand that one over to Chris.

Thanks, Gavin. We're going to approach this very similar to how we did the last time around, and we're going to enter into a quiet period here at the end of the month. And then once we have a material communication from the FDA on their decision for the PDUFA action, we'll provide an update and make sure everybody is on the same page. But it will be done very similar to before we'll go into quieter and you shouldn't expect to hear much from us on an incremental basis between now and then.

Next question comes from the line of Maurice Raycroft from Jefferies.

You've commented a few times on the demand going into your first quarter can you set expectations for first quarter as it relates to new patient starts and how insurance resets or other variables could influence your sales number relative to fourth quarter 2025? And then for FSGS, have you had any discussions with FDA on the label yet? And what are your latest expectations on what the label could look like?

Maury, thanks for the question. Peter, I will have you talk about demand in Q1. And then Bill, if you can take the question on the FSGS label.

Very good. Well, thanks, Maury, for the question. And yes, indeed, we are very happy with the very strong demand exceeding $900 million. I think it's too early to say if that would be our new baseline, but I'm in course is what we are seeing so far in the beginning of the year. Having said that, I also want to make sure that we realize this is a rare disease and that you may see variability quarter-over-quarter. But most importantly, I'm confident to deliver sustainable growth and long-term leadership in IgA nephropathy with FILSPARI.

And I'll tackle the label question. We're about 7 weeks out from our action date, which is a little bit early for us to be getting the initiation of label negotiation. We expect that to begin as we get a little bit closer. As to what the label should look like, we believe that FILSPARI has broad applicability in FSGS and should be used across all forms. We've submitted a label that matches that intent. And we have seen across all patients used very broad efficacy with a consistent safety profile. So that's the expectation that we have around the indication of the...

And Maury, maybe just to add 1 thing on the revenue side on 1Q to answer your question fully. I mentioned earlier on the call that we expect higher growth than us for the year. But in the first quarter, you see the biggest effect of that. So 4Q going to 1Q, you will see an increase in that discount. So I want to make sure that everybody is thinking that into account for the model. Again, same as what we've seen in previous years, but we will see a higher discount in 1Q relative to the other quarters.

Next question comes from the line of Jason Zemansky from Bank of America.

Congrats on the progress in. Peter, one for you, if I may. Can you speak to the potential of a halo effect if FILSPARI receives approval in FSGS for IgAN? I know you said the prescriber base overlaps about 80%. But I guess, any opportunities for increased awareness or I don't know, potentially a lowering of some of the friction points that might cause an IgAN prescriber, some pause or, I don't know, underlying inertia.

Thanks, Jason. Peter?

Yes, I think, Jason, for that question. And I think it's a very good point that you bring up. Is there a halo effect once you get an FSGS approval and wouldn't have a good reflection on our IGN property as well.

Well, to your point, I mean, given that this is largely the same prescriber base, I think you're absolutely right. There will be a halo effect and there will be some cross talk between the 2 indications. And yes, I think even more reason to be very excited about the FSGS opportunity, not only for serving this patient community that has been without an approved treatment for far too long, but also how that could reflect them on further confidence in the profile of FILSPARI for IgA nephropathy patients.

Got it. Any idea of kind of magnitude or...

Tough to say. I think directionally, we absolutely expect there to be a synergistic effect between the 2. And certainly, as you point out, simplifying the process for these offices that are incredibly busy, particularly community nephrology offices. But I'd say it's too early for us to be able to quantify. But directionally, absolutely, we would expect there to be a synergistic effect.

Next question comes from the line of Alex Thompson from Stifel.

Maybe again on FDA interactions over the last few months related to filing. Could you comment on the consistency of interactions among members of the cardio real division? Has it been the same group throughout this process? And does it continue to be the same group?

Thanks, Alex. Bill, I'll turn that one over to you.

Sure. Recently, we've been made aware of some changes within the review team, but I think it's important to note that we also see continuity through the team, especially in those folks that were involved in the PARASOL project, looking at proteinuria as an endpoint for FSGS.

Importantly, our recent interactions have also included the division level of leadership, and that leadership has remained consistent and engaged throughout the process.

Our next question comes from the line of Yigal Nochomovitz from Citi Group.

I had one on FILSPARI and then one on Pegtibatinase. So I was just curious, looking at the quarter-on-quarter trends from 3Q to 4Q, you were up 13% and on revenue, and you were up just almost twice that on start forms. So I wonder if you could expand a bit in terms of the lag between the strong growth in the start forms of 25 -- 24%, 25% and the quarter-on-quarter revenue growth?

And then secondarily, on Pegtibatinase, with regard to the study that you're conducting, can you just describe what the -- what you would need to see in terms of reduction in homocystine levels to be stats on the primary endpoint? And also, are you looking at some responder analyses, for example, percent of patients that get below, say, 12 micromolar or even lower, say, below 10 micromolar or those part of the analysis?

Yigal, thanks for the questions. Peter, why don't you take the one on demand versus revenue? And then, Jula, if you can take the question on our endpoints.

Absolutely. Thank you all. Yes. The last few quarters, we actually had the opposite. We had strong revenue growth relative to patient start forms. I think the most important point is to the point that you made. There's always a time lag between patients start from generation and revenue recognition. And we saw the same phenomenon after our full approval in September 2024. Too specific to call out here on December was our strongest month. So they will carry over into Q1 revenue recognition. And the second part is something that we highlighted in the Q3 earnings call is that our gross to net will be higher in Q4.

And then I'll talk about the HARMONY study. We haven't stated externally what treatment effect we need to reach statistical significance, but I'll point back to our COMPOSE study where we had about between 5 and 6 patients per cohort. And we saw a 67% reduction in total homocystine, which was highly statistically significant with the small number of patients. We're obviously going to a larger sample size. We have about 70 patients that we're planning to enroll for this and are well powered to achieve statistical significance if we even reach something comparable to what we saw or less.

And I'll reiterate that we have already looked at long-term durability of treatment effect. Our primary endpoint is 6 to 12 weeks, which is where we saw that 67% reduction in total homocystine in our Phase I/II study, but we've also seen a durability when we follow these patients from Compose out to even 1 year where they still maintain a greater than 50% reduction in total homocystine 1 year. So we feel very confident in our study design to be able to achieve our primary end point.

In addition, you've asked about some secondary endpoints or other things. We certainly will look at clinically meaningful thresholds I would say you asked about -- a little bit about a responder, importantly, but we've seen to date with Pegtibatinase as everyone has a reduction in total homocystine based on the mechanism of action and in our study. So we feel comfortable with our study design and that we'll be able to show both a clinically meaningful treatment effect and then different thresholds that we will look at.

Ladies and gentlemen, this concludes the question-and-answer session of today's conference call. I'll hand the call over back to Nivi.

Thank you, everyone, for joining today's call. Have a great rest of your day.

This concludes today's conference call. Thank you for participating. You may now disconnect.

Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I am one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Priyanka Grover, [ Joy Shao and Rati Pinhe ]. Our next presenting company is Travere. And presenting on behalf of the company, we have CEO, Eric Dube.

Good afternoon, everyone, and thank you to JPMorgan, Anupam and team. My name is Eric Dube. I'm the President and CEO of Travere Therapeutics. It's my pleasure to be here, and I appreciate your time learning a bit more about the work that we're doing at Travere.

You can see here our forward-looking statements, which you can find this and other details on our website. For us at Travere, being in rare disease is a deep commitment and for so many of us is personal. There are so many of my colleagues who joined Travere because they themselves have a personal connection to rare disease, whether they themselves are a patient, a mother or a father or a friend to someone in rare disease or like me, a rare cancer survivor. So for us, it is personal, and we bring a patient-inspired approach to everything that we do.

Earlier this afternoon, we provided an announcement around our 2025 performance as well as some other updates on our 3 priorities. And we have some very exciting updates for each of our priorities that I'd like to go through.

The first is that we reached an all-time high in the number of patients that we reached with FILSPARI in IgA nephropathy. We reached 908 new patient start forms in quarter 4, and I'll go into a bit more detail of those dynamics and that performance. We also have achieved 143% growth in our revenue for 2025 compared to 2024. So another outstanding year of execution in being able to reach more patients, and it's another year of outstanding results.

We also announced that the FDA is continuing to review our sNDA for FSGS, which I will touch on momentarily. We also announced that our pegtibatinase Phase III program, the HARMONY Study, will be reinitiating this quarter, and that's for the treatment of homocystinuria or HCU.

And we also ended the year with a very strong financial foundation. We achieved $410 million in net revenue. That broke down between $323 million for FILSPARI and about $88 million for our THIOLA portfolio in cystinuria. We ended the year with $323 million in cash, which we have sufficient funding to be able to support all 3 of our priorities into the future.

Now with that said, I do want to provide an update on the regulatory engagement for our FSGS sNDA. I can imagine that's on the minds of all of you.

What I can share with you is that Travere is charting new territory within rare disease, and there's no better example than in FSGS, where our understanding of the disease and the understanding of the endpoints used in clinical development are evolving with the evidence. And we're in a very unique position. Tomorrow is our PDUFA date, and this is what I can share with you as of today.

Just before the holidays in December, right as we were awaiting a draft label from FDA, we started to receive a series of additional information requests from the FDA that are focused on further characterizing the clinical benefits of FILSPARI. Importantly, none of those requests were related to safety or to manufacturing. And as of Friday, just 3 days ago, we provided the FDA and submitted responses to those questions that we believe should address the questions that they've posed to us. And those responses are currently under review by the agency.

Now I'm sure it's no surprise to any of you that there are -- the regulatory delays have become more commonplace over the last year. And while I can't say that that's the case here, what I can say is that the agency has engaged at a high level with us throughout this, and we have engagement with them, including the highest levels of leadership within the cardiorenal division. So unfortunately, I won't be able to share a lot of detail with you today as this is -- our PDUFA date is tomorrow.

What I just shared with you is in as much as we can, and I recognize you may have questions. What I will share with you and the expectation is that when we receive notification from the FDA, we will certainly share more.

So with that, what hasn't changed are the 3 priorities that we have at Travere. And I'd like to go into a little bit more detail with you for each of those. Our goal of making FILSPARI the foundational therapy within IgA nephropathy continues with success. We've seen our strongest quarter to date last quarter and the strongest month since launch last month. Our teams are exceedingly executing very well in reaching patients even in the face of additional treatment options that have become available.

I'll cover further updates on the opportunity and the strength of our data in FSGS. And I'll also cover the opportunity that we have in our Phase III program within homocystinuria or HCU.

So with that, let's turn our attention to IgA nephropathy. IgA nephropathy is a rare kidney disease that often affects patients in the prime of their life. The typical age of someone being diagnosed is in their 20s and 30s and the median time to kidney failure is about 11 years. And over the last couple of years, largely due to ours and others' work, we now understand that this is not a slowly progressing disease. These patients, once diagnosed and if they have proteinuria, are at significant risk. And that's now reflected in the recently published KDIGO guidelines. The KDIGO guidelines are the global kidney guidelines for treatments, including for IgA nephropathy, which was updated a few months ago. Currently, there are about 70,000 patients who we believe are addressable, and that reflects those patients that are diagnosed based on biopsy that are under the care of a nephrologist and have proteinuria levels that are -- place them above 0.3. So they're essentially not in complete remission of their disease.

And so there is a tremendous number of patients that we believe could benefit from innovation, including with FILSPARI. And this is a tremendous opportunity for us as well as for others that are entering this space.

I'd like to share with you why we believe that FILSPARI is uniquely positioned to be the new foundational therapy within IgA nephropathy. This is a once-a-day pill and the clinical data that we have generated with FILSPARI demonstrates a very clear differentiated profile.

Our PROTECT Phase III program is the only head-to-head study conducted within this space, and we are able to demonstrate not just a profound reduction in proteinuria compared to the current standard of care RAS inhibition, but we also see and has been very well received by the nephrology community, an accumulation of benefit in kidney function measured by eGFR over 2 years. And it was with the availability of our 2-year data from our Phase III that really helped to build further confidence and further use of FILSPARI in the real world.

FILSPARI is non-immunosuppressive and based on the profile, really gives flexibility for nephrologists to use this in combination, which we continue to see in the real world.

And as we look at our performance last quarter, I couldn't be prouder of the execution and the results that my team have delivered. We have seen the highest level of new patients achieved in the fourth quarter.

And again, just as we're seeing new treatment options be available for patients with IgA nephropathy. 908 new patient start forms in quarter 4. And that growth is based on both existing nephrologists who have had a good experience with FILSPARI and are looking for other patients to benefit from moving from RAS inhibition to FILSPARI. But we also see some of the greatest growth coming also from new prescribers finally deciding to adopt innovation for their patients with IgA nephropathy starting to use FILSPARI in their practice.

What we're also seeing is a continued decrease in the median UPC level when they start to prescribe, meaning that the physicians are starting to prescribe for earlier and earlier patients. And that's important for 2 reasons. One, that's what the guidelines are now recommending that patients are not safe if they have proteinuria at any level above 0.3. And second, this is where the majority of patients are, those addressable patients, the majority of them are in those lower UPC. So we're really seeing growth where the majority of patients are.

And the other aspect of our performance last quarter is that we have finally achieved over $100 million in revenue for the quarter, $103 million, which represents 108% growth versus the same quarter prior year. And that's really benefited by not just the growth that we've seen in demand, but also the consistently high compliance and persistence rate. Once patients are on FILSPARI, they see the benefit and they continue on with therapy.

And as we take a step back and look at the uptake of our revenue over the last 3 years, I think it really reflects a differentiated profile. When we launched 3 years ago, we guided that the first year of the FILSPARI uptake will look very similar to other rare renal launches, which is exactly what you see here. But there are 2 very important inflection points. The first is upon full approval and the availability of our 2-year efficacy and safety data, including the 2-year eGFR data showing accumulation of benefit versus an active comparator over time. And the second inflection is more recent with the update of our REMS, simplification of our REMS as well as the final publication of the KDIGO guidelines that strongly position earlier use of innovation therapies, combination use for patients with proteinuria and a very strong positioning and support for FILSPARI being used given the head-to-head nature and the superior profile versus RAS inhibition.

And when we look at the -- a similar type of chart looking at patient start forms or demand, you can see very clearly those inflections in demand once we had full approval in 2-year data and then more recently, when we had the support from KDIGO and from REMS. And if we look in aggregate of the patients that we've been able to reach over the last 3 years, we still have not even reached 10% of the addressable population.

What that means is that the overwhelming majority of patients are still able to benefit from FILSPARI. They still are on RAS inhibitors and are not at goal. And so there's a tremendous opportunity for growth for us moving into the future as well as for the other treatment options that will become available for this community.

And I'm confident in our ability to grow even with the additional treatment options that are coming because of our understanding of this disease and in the way that it's described by the KDIGO guidelines. Historically, patients have been treated with RAS inhibition and steroids. And that's because nephrologists recognize that every single patient without exception, with IgA nephropathy really has 2 diseases. They have an overactivation of their immune system. And that's really what's driven the need to use steroids, but now with more innovative therapies that are developed for IgA nephropathy, we expect an increase in the use of those other therapies, but not at the expense of FILSPARI. FILSPARI is targeting the second component of this disease, the disease that occurs within the kidney because every single patient has a kidney disease as well.

By the time a patient is diagnosed with IgA nephropathy, the average patient with IgAN has lost half of their nephrons, and those are not coming back. And so a nephrologist's goal is to protect it as much as they possibly can. And that really is where FILSPARI or a foundational therapy comes in. With our head-to-head data showing superiority over the historical standard of care RAS inhibition and the data that we've generated showing an additive benefit when FILSPARI is used with SGLT2s, we believe that the best approach for protecting those nephrons is with FILSPARI. And the guidelines recommend that patient should be used in -- these patients should be used in combination.

So there's a tremendous opportunity for better treatment and as part of that growth with FILSPARI. And it's with this success and our very strong execution in IgA nephropathy that we are equally committed and excited to be able to provide FILSPARI to the FSGS community.

And I'd like to go into a little bit more about what drives our commitment and our confidence within FSGS. FSGS is a cruel disease. It is rapidly progressing. These patients oftentimes lose most of their kidney function and for some patients within a year, go from diagnosis to the dialysis clinic. And perhaps most cruelly, those patients that are fortunate enough to receive a kidney transplant, 55% of those transplants fail because the disease comes back.

Every single year in the U.S., thousands of patients lose their kidney because of FSGS and thousands more lose their life. This is a dire need for innovative therapies. And there's been a tremendous amount of attention and work on how best to do that in recent years. The PARASOL group was formed a couple of years ago really with this urgency in mind. The PARASOL group is comprised of the global leaders within FSGS, the patient community, leading statisticians within this space as well as leaders from EMA and FDA. And their goal was very simple. How do we best identify the endpoints that would be most effective for the development of medicines in FSGS because with the emerging evidence, we've learned that the hypothesis of how proteinuria and eGFR work was not right. It was very different in FSGS than it was in IgA nephropathy.

And so by capturing as much of the real-world databases that the PARASOL group could, they had enough data to be able to assess what was going on with kidney function in FSGS. And these are the conclusions that the PARASOL group came to. The first is very clearly the evidence shows these patients are at significant risk of kidney failure. They disproportionately represent patients in dialysis clinics, and there is an urgent need for innovation. The second is that when you look at what's going on with the disease in the kidney, it is a disease of the podocyte. That is the cell that filters the blood and the urine. And over time, you have more of these podocytes that die off. And as a result, you have increased proteinuria, but there's also a vicious cycle that occurs when you have proteinuria that damages any healthy podocytes, which is why you get such a rapid progression of this disease.

And so proteinuria became the primary candidate for understanding whether it could be an endpoint. Part of their conclusion was that eGFR is not going to work in a clinical trial setting because it's far too variable and you would need to have such large sample sizes that it becomes unfeasible for a rare disease to be able to be studied in this way.

And so the work focused on proteinuria and their analysis, which I think is summed up perfectly by the lead statisticians quote here, Abigail Smith, is really that if you can reduce proteinuria within 2 years for these patients, it is strongly associated with a significant reduction in the patient's risk of kidney failure over time.

And so with that in mind, I'd like to turn your attention to the proteinuria reductions from our Phase III DUPLEX Study. This is the only study that's been conducted in this space as a pivotal study, the only head-to-head study as well. And what you see, let's first look at the gray line with an active control maximum dosed RAS inhibition, irbesartan. And irbesartan reduced proteinuria from baseline by 32%.

When you look at the very limited literature of clinical trials in this space, ACE inhibitors and ARBs reduced proteinuria and FSGS by about 30%. When you look at the addition of endothelin, which is what sparsentan does, you see a rapid, sustained and superior reduction in proteinuria. By the end of this trial, 50% of proteinuria was reduced on average.

Now PARASOL also looked at certain thresholds of response of proteinuria. How much control of proteinuria do you need to have in order to reduce the patient's risk of kidney failure over time. These are the prespecified analyses from our Phase III DUPLEX Study looking at those levels of response comparing sparsentan to irbesartan. And in every single one of these thresholds, you see that sparsentan helped more patients achieve proteinuria control compared to active control maximum dosed irbesartan.

And importantly, PARASOL showed us that if you're able to achieve these levels of control, a patient's risk of kidney failure over 8 years is reduced by 80% to 90%. So these responses are incredibly powerful in the context of what PARASOL has showed us. And when you look at the most rigorous level of proteinuria control, complete remission, which here is represented as 0.3 grams of protein or less, patients on sparsentan were 2.5 more times likely than active control irbesartan to achieve complete remission, conferring a substantial potential reduction in kidney failure over time.

Now there was an additional threshold that PARASOL introduced, which is 0.7 grams of protein. Here, you can see a similar analysis. This was not prespecified because it historically was not a threshold that was considered. PARASOL wanted a threshold that not only conferred reduced risk over time, 0.7, if you achieve 0.7 grams of protein or less, a patient's risk of kidney failure is reduced by 85%, but they also wanted one that was able to be clinically meaningfully reduced from baseline. And typically, you would expect to have a patient at baseline have a proteinuria level of 1.5. So to go from 1.5 to 0.7 is a meaningful reduction.

In our 2-year trial, you can see that those patients that were able to achieve this level of response, this level of control had a substantially lower risk of kidney failure in 2 years. So not projected, but actual hard events in our trial. That's represented by the blue bar of 3.6% of patients versus those that were not able to gain control, 11.2% of patients hit kidney failure.

And when we look at the overall rates of kidney failure in our DUPLEX trial, 6.5% of patients on sparsentan reached kidney failure compared to 11% of patients on irbesartan. When you look at some of those large databases, the real-world databases in FSGS, the 2-year kidney failure event is 11% to 14%. And so very comparable to what we saw in our control arm. So it suggests that with the better proteinuria reductions that you get with sparsentan, it may confer a reduced risk of kidney failure over time.

And we did an additional analyses that was recently presented at the ASN this fall. What we looked at was the reductions in proteinuria over the 2-year period. You can see here the 50% and the 32%. And we said, what would that confer looking at a matched sample from these large long-term real-world evidence databases. And that difference of 50% versus 32% confers an additional 26% reduction in the risk of kidney failure based on the treatment effect of sparsentan. So certainly a meaningful one in the context. And as we've done all of these analyses, it further strengthens our confidence in both the consistency of benefit, the consistency in the relationship between proteinuria and actual hard endpoints and also the consistency with the findings from the PARASOL group.

So with that in mind, we are -- we remain very confident that sparsentan should be approved in FSGS. And whether it is approved on time or whether it is approved on a delayed time line, our teams are ready. We will take all of the relationships, all of the momentum and all of the learnings that we've had in the success of launching in IgA nephropathy and take that to FSGS for what we believe should be an even more rapid and stronger uptake. And that's for the following reasons.

The first is that patients with FSGS have an urgent need. There is no arguing with any nephrologist that this is an urgent need to treat. The second is that there is a growing awareness, but more importantly, growing clinical use of FILSPARI in nephrology practices. That success that we've seen in the uptake of IgA nephropathy, these are the same physicians that are treating FSGS patients. So the awareness and the overlap is there. We also expect that because these patients are being seen so frequently by their nephrologists that there will be a very rapid uptake if approved.

So with that, I will turn our attention to our third program with pegtibatinase for classical homocystinuria or HCU. We announced that we are reinitiating our Phase III HARMONY Study this quarter. HCU is a genetic metabolic disease. These are patients that are born with a defect in their CBS enzyme. And the CBS enzyme is responsible for metabolizing certain proteins in our diet. And because of the defect that these patients have, they get a toxic accumulation over time of homocysteine. And that accumulation of homocysteine leads to a whole constellation of symptoms.

It leads to vision problems often occurring in childhood. There are cognitive and psychiatric symptoms that occur. There's bone malformation. And most alarmingly to many patients, 25% of these patients have an ischemic event before they are a teenager and 50% of them have an ischemic event before they turn the age of 30.

And sadly, even though HCU is part of the newborn screening panel in the U.S., 50% of these babies are missed on newborn screening. And so they are diagnosed only after these symptoms or these events start to emerge. And so there is a tremendous opportunity that we have to be able to help this community.

The current way of treating these patients is a very, very strict protein-limited diet as well as the use of betaine and vitamin B6, unfortunately, most patients are not responsive. And so there's a real urgent need for a therapy that is disease-modifying like pegtibatinase, an enzyme replacement therapy. There are about 7,000 to 10,000 patients in the U.S. About half of those, we believe, are addressable today. But with greater awareness, greater education, we believe that those rates will certainly grow.

You can see here a profile of pegtibatinase from our Phase I/II study. There is a very clear dose response relationship. And at the dose selected to go into Phase III, patients achieved a mean reduction in their total homocysteine levels of about 67%. Perhaps to put that into context, 100% of the patients on pegtibatinase were able to achieve levels of homocysteine that got them below the current treatment guidelines. And we have one patient, one young man who normalized their homocysteine levels so that they were able to actually eat a more normal diet. And so we're looking to replicate this in our Phase III program. Importantly, it was generally well tolerated in our Phase II as well.

Let's turn our attention to the Phase III HARMONY Study. We're looking to essentially have a similar primary endpoint, which is the average change from baseline in total homocysteine level, a biomarker between week 6 and 12. We'll continue to follow those patients beyond week 12 out to week 24, but the primary endpoint is the reduction between 6 and 12.

Perhaps most exciting to this community is our Phase IIIb study. There are 2 really important components that are different from our Phase II study. One is that we'll be testing self-administration to make sure that these patients are able to give themselves pegtibatinase at home. And the second is to be able to go beyond clinical control of this disease, which is really important to regulators and important to the treating physicians. But when we listen to patients and their families, the #1 thing they want is to be able to have a meal with friends and with family, to not have to feel isolated, to not have to just only eat a handful of vegetables and to really worry about everything in their diet.

And so in a very innovative trial design, we are looking at those patients that are able to achieve control of their homocysteine level in the double-blind period and look at a protein tolerance to see how much protein they can increase in their diet and still maintain control of their homocysteine levels. So we're very excited to be able to reinitiate this trial this quarter. We've been working in parallel with the manufacturing scale-up as well as activating and identifying sites globally. And we've been working very closely with the HCU community to ensure their readiness and willingness to enrol in this clinical trial. So we want to move quickly in this space.

As I take a step back and look at our financials, you can see a snapshot here. Again, I won't go through the revenues as I did before, but we're in a very strong position. We do not have a need for additional capital to be able to support our 3 portfolios. We have what we need to continue the strong launch in IgA nephropathy, a very rapid launch in FSGS and the continued progress of developing pegtibatinase. And we've done a very strong job last year of further strengthening our financial foundation.

What I'd like to do is close by introducing you to Jennifer. Jennifer is a woman that I met last year who at the age of 22, just graduating college, starting her career and starting a new relationship, was diagnosed with FSGS. Within 6 months, she was in a dialysis chair in kidney failure. She describes her journey with this disease as devastating, not just because of the disease, but she describes in great detail the effects that she's had of having chronic steroid use, the weight gain, the isolation, the depression, all of those elements of what is unfortunately the standard of care for so many patients. Her story is so similar to many that I've met in the 8 years that I've been at Travere.

What really struck me with Jennifer is 2 things. One, she's had 4 kidney transplants. Three of those have failed because the disease came back. And the second is she is the greatest optimist that I've ever met. In fact, she is the author of a book called the Incurable Optimist that describes her journey living with FSGS. And she is a beacon of hope and optimism for the FSGS community. And her story, while may be very similar to many in the FSGS community is unique in her ability to bring hope. And I can tell you that every single one of us at Travere takes her example, and we will offer a beacon of hope and a complete commitment to making sure that we have a better future for those patients that are affected by FSGS.

Anupam, with that, thank you all, take questions.

Thank you, Eric. I wanted to just start with just thinking about tomorrow in FSGS. So I see 4 outcomes and 3 of them are pretty binary, right? Approval, CRL, extension and then you just don't hear, right, which has happened. Is that a fair assessment? And how would you communicate in that last scenario to us what's happening?

Yes. Well, tomorrow is our PDUFA date. And we do want to make sure that we provide a meaningful update. So we have been planning for a communication tomorrow. We're assuming that we will have a notification from FDA, and we will be sure to communicate once we have something meaningful. We want to make sure that, that is something that is based on what we hear from the FDA.

And then just as a confirmation, when you heard before the holidays from the FDA, that communication, was it a deficiency letter or just needing more information on what you've already filed?

So it was not a deficiency letter. Let me go back to what I shared at the beginning for those of you that may have joined after. It was a series of information requests that the FDA had about the characterization of clinical benefit for FILSPARI.

And then those characterizations, where -- what -- was it related to proteinuria? Was it related to eGFR? And as a clarification, did you present the FDA with some of that 0.7-gram data in the filing that was critical in the PARASOL assessment?

So I'm not going to be able to go into details on the information requests. I want to make sure that I maintain the consistency of not going into detail when it's an ongoing engagement.

What I would say is that our original file included all of our data in the prespecified endpoints. So that 0.7 was not prespecified in our trial because it came out of the PARASOL work, not in our SAP originally with the file -- or with the trial, sorry.

Okay. Let me see if there are any questions from the audience.

You characterized that you submitted the data Friday. Was this an ongoing? Did you submit several other iterations of the data along the way and Friday was the last submission of a piece of the data that you were able to gather?

And have you responded to all of the requests in your opinion now by last Friday? Were there several different submissions and Friday was the last one? Or did you put a package together that they all -- that they saw on Friday?

So what I would say is we received a series of information requests. So a number of different questions. I'm not going to get into the time line of when we did it. But what I would say is that as of Friday, we believe that FDA has everything that they need.

Was there one submission on Friday -- what I'm asking is one package on Friday that you took all the submissions, put them in one package? Or have you been sort of an ongoing dialogue with the FDA along the way?

Yes. So I won't go into the specifics of what was submitted and when. What I would say is that we've had ongoing dialogue and strong engagement with the FDA. And again, I think the important aspect is we believe that as of Friday, the FDA should have everything that they need to answer the questions that they've submitted to us.

Could you characterize if it was new data that they didn't have or reanalysis of data that was in the file?

So what I would say is that it's information that we had. Most of that is in the file. Typically, what you get for information request is analysis, sensitivity analysis, reanalyses of information that are there, but I don't want to go into detail of what specifically was requested or what we submitted.

Could you comment if Eliza Thompson was part of this information request? She was the internal champion, we had assumed.

Yes. When I said we've got engagement with the highest levels of leadership in cardiorenal, it certainly would include Dr. Thompson.

Then is all of the PARASOL data now with FDA to review that was included with FILSPARI?

So PARASOL was a separate initiative and that we do not have the data from PARASOL. So what I would say, to make sure I understand your question, they would have access to PARASOL independent. If there were any additional analyses that came out of PARASOL, for example, the analysis of 0.7, that certainly could be part of our overall package if they want to analyze the data at that cutoff.

Okay. Questions from the audience?

All right. Trying to slice the apple a different way. PARASOL and KDIGO, like you have the FDA with those in there. Were they potentially asking for different cuts of your data in order to kind of align them with pre you submitting your NDA or your sNDA? Were they potentially looking just to say, okay, did these align with the current guidelines? Because guidelines have changed since you folks have talked with the FDA the first time around. Is that probably a fair characterization of it?

So the KDIGO guidelines that were recently updated were for IgA nephropathy. So we've not seen updates for FSGS for a number of years.

But they're likely going to use that kind of as cheche.

I can't speak for the FDA and what they're looking at. I want to make sure that I don't go into detail on the specific analyses that they may have requested. What again, I'd say is they should have everything they need to approve FILSPARI.

Okay. Can I ask a follow-up on pegti?

Sure. Go ahead.

Pegtibatinase?

Yes.

Okay.

HARMONY, why 6 to 12 weeks for the primary when you've got to go out to 24 anyway?

Yes. So we saw a very rapid reduction and very consistent response in our Phase I/II, where the majority of the benefit we saw early in the trial. So 6 to 12 weeks should give us sufficient time to be able to see that. We want to be able to follow up longer for safety and for durability.

The other aspect is a large part of our design of this program was to minimize variability that patients could have to fate if they have a cheap diet. The longer you go, the more likely you're introducing that risk that patients are not compliant with their diet.

Back on FSGS, just quickly, had you at any point, entered into labeling negotiations for the product in FSGS?

So we received those information requests at the time we were expecting our draft label. So what I would assume is typically, you would get a draft label once those information requests are -- and those -- the review of those are complete. In other words...

Then you would have entered into a label negotiation once you've got your draft.?

That's right. That's right. Okay. That's right.

Final question in the back. Okay. Thank you, Eric.

Okay. Thank you. Let me leave you with our commitment to the rare disease community. We are ready for an approval, and we believe that FILSPARI should be approved in FSGS, and we are committed to redefining the standard of care in IgAN, FSGS and HCU. Thanks so much for your attention today.

Thank you.

Good afternoon, and welcome to the Travere Therapeutics' Third Quarter 2025 Financial Results Conference Call. Today's call is being recorded.

At this time, I would like to turn the conference call over to Nivi Nehra, Vice President, Corporate Communications and Investor Relations. Please go ahead, Nivi.

Thank you, operator. Good afternoon, and welcome to Travere Therapeutics' Third Quarter 2025 Financial Results and Corporate Update Call. Thank you, all, for joining.

Today's call will be led by Dr. Eric Dube, our President and Chief Executive Officer. Eric joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; Peter Heerma, our Chief Commercial Officer; and Chris Cline, our Chief Financial Officer. Dr. Bill Rote, our Chief Research Officer, will join us for the Q&A.

Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the Risk Factors section in our Forms 10-Q and 10-K, filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, October 30, 2025, and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances.

With that, let me now turn the call over to Eric.

Thank you, Nivi, and good afternoon, everyone. The third quarter marked exceptional progress across our three key priorities: delivering strong commercial execution in IgA nephropathy, preparing for a potential FDA approval in FSGS, and successfully advancing the manufacturing scale-up of pegtibatinase to support restarting enrollment in the pivotal HARMONY study in 2026.

The core driver of our performance is FILSPARI's continued growth in IgA nephropathy, where we delivered sustained commercial excellence in the third quarter. Physicians continue to confidently adopt FILSPARI as a foundational nephroprotective therapy for their patients. This confidence reflects consistent real-world outcomes, robust long-term data reinforcing FILSPARI's differentiated profile and its recent inclusion in the KDIGO guidelines for earlier first-line use to optimize nephroprotection in IgAN. Additionally, in August, the FDA approved a modification to the FILSPARI REMS program, removing the embryo-fetal toxicity REMS and reducing the liver monitoring frequency to quarterly, which aligns with routine clinical practice and our clinical trial experience. This change not only simplifies care for physicians and patients, but also reinforces FILSPARI's long-term safety profile.

Our U.S. performance continues to be complemented by strong progress from our partners globally. In Europe and the U.K., CSL Vifor is expanding access, following full regulatory approvals and the progress has been culminated in the recent achievement of a meaningful market access milestone.

In Japan, Renalys completed enrollment in its registrational trial in IgAN and remains on track to deliver top line data in quarter 4. The company also reached an agreement with the PMDA of Japan to initiate 2 Phase III trials for sparsentan in FSGS and Alport syndrome and recently announced its planned acquisition by Chugai, a leading innovator in renal and rare disease research in Japan. Together, these milestones underscore FILSPARI's expanding global footprint and the growing excitement around its long-term potential to transform care for renal rare kidney diseases.

Beyond our progress in IgAN, addressing the urgent need for an approved medication in FSGS is both central to our mission and represents the next pillar of growth for Travere. Today, there are no FDA-approved medicines for this disease. Patients often experience rapid disease progression with many reaching kidney failure within just a few years of diagnosis, often requiring a transplant. Even then, the disease recurs in approximately half of transplant recipients. The consequences are devastating for patients and their families. Earlier and more effective treatment is desperately needed, which is why the opportunity to bring FILSPARI forward in FSGS is so meaningful for this community who have waited far too long.

In September, the FDA communicated that an advisory committee is no longer needed for our sNDA in FSGS. We have been pleased with the progress of our review and our ongoing engagement with the agency to date. Pending approval, FILSPARI will become the first and only approved medication for FSGS, representing a landmark moment for this community, and given the urgent need for an effective approved medication, a transformational opportunity for Travere. Our teams are fully prepared to execute a rapid launch upon approval, building upon the commercial foundation we've established in IgA nephropathy.

Beyond FILSPARI, we have successfully manufactured the first commercial scale batches of pegtibatinase and are looking forward to an expected restart of the pivotal HARMONY study of pegtibatinase in classical HCU next year. PEG-t remains a promising potentially disease-modifying investigational therapy that could address a substantial gap for patients living with this rare metabolic disorder.

I'll now turn the call over to Jula for a clinical update. Jula?

Thank you, Eric. One of the most significant milestones this quarter was the inclusion of dual endothelin angiotensin receptor antagonism in the updated KDIGO guidelines for IgA nephropathy, a strong external validation of FILSPARI's role as foundational treatment. KDIGO includes FILSPARI as a first-line option for patients who are at risk of IgA nephropathy progression, recognizing it as the only therapy with proven efficacy versus optimized RAS inhibition.

The guidelines also recommend simultaneous treatment of the 2 drivers of IgA nephropathy progression, targeting both the upstream immune activation that causes pathogenic IgA deposition and the downstream glomerular injury that leads to nephron loss.

This holistic framing of disease management aligns with FILSPARI's mechanism of action as the only fully approved non-immunosuppressive nephroprotective treatment, which can be combined with immune-targeted medications to optimize long-term outcomes for patients living with IgA nephropathy.

Across our KOL engagements following the publication of the guidelines, nephrologists have described the new KDIGO framework as a true paradigm shift that validates early and comprehensive intervention. We believe this recognition cements FILSPARI's position as foundational care in IgA nephropathy, guiding a new era of evidence-based treatment sequencing.

A further testament to our leadership in rare kidney disease is our focus on data generation and dissemination, as exemplified by numerous scientific presentations and engagements at recent congresses, including our 11 upcoming presentations at ASN Kidney Week. A few highlights of this data include the Phase II SPARTAN trial in RAS inhibitor naive patients with IgA nephropathy, demonstrating that irrespective of baseline proteinuria levels. FILSPARI consistently reduced proteinuria and led to significant reductions in urinary biomarkers of disease activity, including reductions in immune system and complement activation markers, indicating potential disease-modifying qualities of FILSPARI.

We also have two new presentations from the Phase III PROTECT trial in IgA nephropathy. One, evaluating efficacy across historical histopathology from kidney biopsies and another assessing outcomes based on time from IgA nephropathy diagnosis. Both presentations reinforce the SPARTAN findings and align with the KDIGO recommendations, showing that earlier treatment of patients with FILSPARI can lead to greater nephroprotection.

We also continue to generate and present real-world and long-term data across a broad spectrum of IgA nephropathy disease severity, demonstrating FILSPARI's consistent benefit in reducing proteinuria and preserving kidney function.

In FSGS, as Eric highlighted in his opening remarks, we are pleased with the progress of our review. The agency remains engaged on our submission. And from our perspective, the process continues to be similar to our experience during the IgAN NDA review.

Ahead of a potential approval in January 2026, our Medical Affairs teams are deeply engaged, expanding disease education, strengthening nephrologist awareness around the importance of proteinuria in FSGS disease progression and responding to queries regarding how the DUPLEX data could translate into real-world benefit for this underserved patient population.

At ASN, we are presenting several new analyses from the DUPLEX study, including a late-breaking analysis that demonstrates that patients treated with FILSPARI achieved proteinuria levels of less than 0.7 grams per gram more frequently versus maximum labeled dose irbesartan. And patients who achieved this threshold had a lower risk of kidney failure, irrespective of treatment arm. This analysis demonstrates further alignment and supports the conclusions of the PARASOL working group that lower levels of proteinuria translate into meaningful improvements in kidney outcomes.

We also have data that extrapolates the antiproteinuric treatment effect of FILSPARI versus irbesartan seen in the 2-year DUPLEX trial into longer term kidney failure outcomes from the U.K. Rare Disease Renal Registry or RaDaR. And we also have subgroup analyses of pediatric patients and patients with collagen 4 genetic mutations, demonstrating a consistent antiproteinuric treatment effect with FILSPARI versus irbesartan in these 2 high-risk difficult-to-treat patient populations.

With no approved medicine for patients with FSGS today, the opportunity to bring FILSPARI forward is both urgent and transformative. The supportive data from DUPLEX and our regulatory momentum give us confidence in the path ahead.

With our goal to provide FILSPARI as a foundational treatment for patients with IgA nephropathy and ultimately those with FSGS, we are pleased that the FDA approved modifications to our REMS program, removing the embryo fetal REMS and reducing the frequency of liver monitoring to quarterly.

The feedback we have heard from nephrologists is that these changes are welcomed. The monitoring frequency aligns with how they care for their patients in clinical practice. And these changes can help increase access for the subset of patients for whom monthly testing was an impediment.

Turning to our pegtibatinase development program for the treatment of classical HCU. We recently presented long-term data at the ICIEM Congress from Cohort 6 in our Phase I/II COMPOSE open-label extension. At the 2.5 milligrams per kilogram twice weekly target dose, patients treated with pegtibatinase achieved sustained and clinically meaningful reductions in total homocysteine and methionine over an additional year of follow-up, remarkable results in the context of an open-label study. Importantly, we have successfully manufactured the first commercial scale batches of pegtibatinase and have generated data to support FDA interactions. This progress positions us for an expected restart of enrollment in the pivotal Phase III HARMONY study next year, reinforcing our commitment to advancing the only investigational therapy with disease-modifying potential for patients with classical HCU.

I will now turn the call over to Peter for a commercial update. Peter?

Thank you, Jula. I am very pleased to share that the third quarter marked another period of strong commercial performance and continued momentum for FILSPARI in IgA nephropathy, reinforcing its position as a foundational therapy.

FILSPARI net product sales reached approximately $91 million in the third quarter, representing another quarter of strong growth, driven by consistent demand and deepening engagement among new and experienced prescribers.

Demand for FILSPARI remains robust with 731 new patient start forms received during the quarter despite experiencing summer seasonality as is typical in the summer months. In fact, in September, we recorded our highest daily patient start form rate since launch and we are seeing that trend continue into October.

Throughout the quarter, we saw durable utilization among existing nephrologists and a continuation of new prescribers. Importantly, we are seeing a steady increase in the number of practices treating multiple patients with FILSPARI, which highlights growing confidence in the therapy's profile and real-world performance.

As the IgA nephropathy treatment landscape evolves, we continue to hear consistent feedback from the nephrology community, reinforcing that physicians view FILSPARI as the preferred novel therapy, not only because of its proteinuria efficacy. But because it delivers a meaningful long-term improvement in kidney outcomes while allowing patients to maintain a normal lifestyle through a once-daily oral regimen. And we are encouraged by the response of the nephrology community to the modification of our REMS program. This simplification makes FILSPARI treatment even more convenient, particularly for newly diagnosed or lower-risk patients as quarterly monitoring is consistent to nephrology clinical practice.

We are pleased to see continued uptake of FILSPARI among patients with lower proteinuria levels, reflecting growing recognition that patients above 0.5 gram per gram remain at risk of progression in alignment with our broader label and the KDIGO guidelines. Patient satisfaction is strong as evidenced by consistently high compliance and persistence.

As we continue to expand FILSPARI's reach, our patient services and fulfillment programs remain an important contributor. We have maintained broad payer coverage with easing of prior authorization requirements to reflect FILSPARI's broader label, long-term evidence and positioning in the guidelines.

Turning to FSGS. If approved, FILSPARI will become the first approved medicine for FSGS, a leading cause of kidney failure. Given the high degree of overlap between the FSGS and the IgA nephropathy prescriber base, we will be able to build upon strong brand awareness and familiarity of FILSPARI with many physicians that have already had experience with the product.

Given the high unmet need for an approved medication and the progressive nature of FSGS, we believe this could be an even bigger opportunity with a more rapid uptake versus our launch in IgA nephropathy. We know the FSGS community is eagerly awaiting an effective medicine. And we will be ready to launch in January, if approved.

In summary, the third quarter represents another quarter of exquisite execution and continued growth for FILSPARI in IgA nephropathy. The combination of clinical product differentiation, early intervention, strong prescriber confidence and a consistent patient experience continues to drive momentum and position FILSPARI as a foundational and nephroprotective choice among IgA nephropathy therapies.

With our strong commercial foundation and expanding real-world experience, we remain confident in FILSPARI's ability to deliver sustainable growth and long-term leadership in rare kidney disease care. I am sincerely proud of the continued performance of our commercial teams and the dedication they bring every day to support patients and physicians. Their success in establishing FILSPARI in IgA nephropathy gives us great confidence in our ability to execute effectively in FSGS, and we will be ready if approved.

Let me now turn the call over to Chris for the financial update. Chris?

Thank you, Peter, and good afternoon. This quarter, we delivered another strong set of financial results with continued significant revenue growth and disciplined financial investments. As Peter mentioned, our top line expansion reflects the strength of our underlying FILSPARI business and the consistent execution across our key commercial initiatives, momentum that we believe sets us up for durable growth ahead.

We also further strengthened our financial foundation by repaying our remaining 2025 convertible notes and significant value was generated from our partnerships, including the recently achieved $40 million market access milestone from CSL Vifor and the announced acquisition of Renalys by Chugai, both great examples of how our collaborations continue to create value and validate the potential of FILSPARI globally.

Starting with revenue. In the third quarter, we generated U.S. net product sales of $113.2 million. FILSPARI continued to grow significantly in the third quarter, generating $90.9 million in U.S. net product sales, which represents an increase of more than 155% year-over-year. From a gross to net perspective, FILSPARI had a onetime benefit of less than $2 million during the quarter. And we continue to anticipate higher discounts in the fourth quarter.

Elsewhere, DILI contributed $22.3 million in U.S. net product sales. And we also recognized $51.7 million of license and collaboration revenue, which results in total revenue of $164.9 million for the quarter. Included in the license and collaboration revenue line this quarter is a $40 million market access milestone that was achieved by CSL Vifor. We recently received payment, which will be reflected in our cash balance in the fourth quarter. Also included in the license and collaboration this quarter is $9.3 million in noncash revenue that resulted from the relinquishment of our option to acquire Renalys in anticipation of their agreement to be acquired by Chugai.

Moving to operating expenses. Our research and development expenses for the third quarter of 2025 were $51.9 million compared to $51.7 million for the same period in 2024. On a non-GAAP adjusted basis, R&D expenses were $47.8 million compared to $48.4 million for the same period in 2024. Selling, general and administrative expenses for the third quarter were $86.5 million compared to $65.6 million for the same period in 2024. On a non-GAAP adjusted basis, SG&A expenses were $63.5 million for the third quarter compared to $49.7 million for the same period in 2024. The increase in SG&A is primarily attributable to investments in preparations for a potential launch in FSGS in January, increased amortization expense related to FILSPARI royalties as well as an increased investment in supporting commercial efforts for FILSPARI in IgA nephropathy following full approval.

Total other income net for the third quarter of 2025 was less than $1 million compared to $1.3 million for the same period in 2024. Net income for the third quarter of 2025 was $25.7 million or $0.29 per basic share compared to a net loss of $54.8 million or $0.70 per basic share for the same period in 2024. On a non-GAAP adjusted basis, net income for the third quarter of 2025 was $52.8 million or $0.59 per basic share compared to a net loss of $35.6 million or $0.46 per basic share for the same period 2024.

As of September 30, 2025, we had cash, cash equivalents and marketable securities totaling approximately $254.5 million. This balance reflects our repayment of the remaining $69 million in 2025 convertible notes. And as I highlighted earlier, it does not yet reflect the proceeds of the $40 million milestone payment from Vifor and it also does not yet include any proceeds from the recently announced acquisition of Renalys by Chugai.

As we move forward, we are well positioned to sustain our momentum in IgA nephropathy, execute a successful launch in FSGS if approved and advance the reinitiation of enrollment in our pegtibatinase Phase III study next year. Importantly, we're doing all of this from a position of financial strength with no near-term need for additional capital to execute on our core objectives. This foundation gives us confidence in our ability to execute on our key priorities and continue advancing our mission for patients.

I'll now turn it over to Eric for his closing comments. Eric?

Thank you, Chris. In Q3, we made tremendous strides across all of our programs. And I am proud of how every employee shows up with passion and focus to advance our mission. One great example is our pegtibatinase team, who has diligently solved scale-up challenges so that we are positioned to restart the HARMONY trial next year.

October is HCU awareness month. And it is a fitting reminder of how much work is still needed to allow families affected by HCU to live with a little less worry and a bit more hope. We've entered the final months of 2025 confident in our ability to sustain FILSPARI's growth in IgAN to successfully execute on a potential approval and launch in FSGS and to advance our pipeline with focus. We have the right people, a strong financial foundation and the momentum to bring incredible innovation to the rare disease communities that have been waiting far too long.

I'll now turn the call over to Nivi for Q&A. Nivi?

Thank you, Eric. Operator, we can now open up the line for Q&A.

[Operator Instructions] We will now take the first question from the line of Joe Schwartz from Leerink Partners.

Congrats on another strong quarter of execution. With the new label approved in August, can you quantify either qualitatively or quantitatively the early impact of the REMS adjustment? Are you seeing new prescribers or a new patient base that might have been more reluctant previously. It seems like with such a strong beat this quarter, you might not be seeing any competitive impacts? Or are you seeing any at all and it was just offset by the updated label? Any color you could provide would be great.

Thanks, Joe. Peter, why don't you take that question?

Yes. Thanks, Joe. It's a good question. I think you're asking two questions. One is what is the impact of the REMS modification so far? And two, are you seeing any impact of competitive dynamics? I think overall, I would say we see very consistent demand since we had our full approval last year. And that consistency have not been impacted by launches of new products that came into the marketplace. So I think very robust continuation of growth.

I think to your first question with regards to the REMS modification, I think that is certainly a tailwind that we are having and that has been very positively received by the nephrology community. What we are seeing is that we have a continuation of new prescribers, while we also continue to expand within experienced prescribers. And I think especially the REMS modification from a monthly base to a quarterly base in the first year really helps for those patients that are not as sick at the higher proteinuria levels, but still are at significant risk of progression of disease. Those patients may not see the physician on a monthly base or may not do traditional testing on a monthly base, but certainly do it at a quarterly base. So I think the timing of the REMS modification fits very nicely in the expansion of the patient population that we are seeing.

Any insight into any competitive pressures at all? Or have you not detected any?

Yes. As I mentioned, we have seen very consistent demand. I would say Q3, we saw less of an impact of seasonality than we saw last year and that in a more competitive landscape. So I would say that gives you a color of our execution and performance in Q3.

Yes. That's great, Peter. And the only thing that I would offer in addition, Joe, is that not only did we see the modification of REMS, as you alluded to, which makes it just that much easier for physicians and patients. But we also saw the publication of the KDIGO guidelines that further reinforce the positioning of FILSPARI. And I think both of those in combination, of course, with the phenomenal execution of Peter's team continues to reinforce our strong position within this market.

Laura Chico from Wedbush.

Just two quick ones for me. First, with respect to FILSPARI at this point, do you have a sense as to what the typical baseline proteinuria level is at start of prescribing? I think Peter made a comment about perhaps some patients coming in now with a lower level. Second, are you detecting any off-label use in the FSGS setting at this point?

Thanks, Laura, for those questions. I'll take the second one regarding FSGS. We do see some limited prescribing and use in FSGS. We, of course, do nothing to promote that. But we are seeing some physicians make that choice.

I will turn it over to Peter to ask your question or answer your question about baseline UPC.

Yes. Thanks, Laura. So what we have seen since we had a full approval last year in September is that we have seen consistently the baseline proteinuria levels are well below 1.5 gram per gram. And it's what you would expect. I mean, the larger patient population, about 65% of the patient population have proteinuria levels below 1.5. And we're making good inroads in penetrating that market segment. And what you would expect is that you will see a continuation of lower proteinuria levels at initiation.

Anupam Rama from JPMorgan.

Congrats on the quarter. Just in the context of the beat that you guys had here with FILSPARI, how do we think about sort of the quarter-over-quarter declines in patient start forms? I know you mentioned some summer seasonality, but there were those tailwinds from guidelines and REMS. What are the considerations there? Anything to note on gross to net or inventory?

Yes. Maybe I can frame this and then have Peter and Chris offer anything further. I think the strong performance in demand in Q3 really reflects that underlying expectation. And I'll have Peter talk about some of the trends within the quarter that we saw. But it really is about the seasonality. While we didn't see as much impact this year as we did last year, we certainly did see some of that in terms of the slower months.

Peter, maybe you can allude to that. And Chris, you can talk about the gross to net impact in Q3.

Yes. Happy to comment on that, Anupam, and thanks for that question. I'm actually really pleased with the performance and the demand we saw in Q3. In particular, what I outlined during the call, September, we had the strongest daily patient start form generation and that trend has continued in October. So I think very strong demand. And as I mentioned earlier, we have seen less of an impact of seasonality in a more competitive environment. So I think the performance is really strong. And yes, I couldn't be more proud of the team to continue to execute in the way they do.

Anupam, on the gross to net factor for this quarter, we did highlight that there was less than $2 million benefit. And really, that's just working through the first year here in Part D and having the true-ups as we go throughout the year.

Looking ahead, we've guided to throughout the year that the back half may have higher gross to net. That remains the same for the fourth quarter. But we're still right around that guidance of around 20% for the year. And the fundamentals, as Eric and Peter highlighted, very strong. So we're looking forward to the end of the year here.

Tyler Van Buren from TD Cowen.

This is Francis on for Tyler. What can we expect in terms of communication leading up to the FSGS PDUFA date in January? Is it possible that you'll disclose if and when you're in labeling discussions?

Francis, thanks for the question. It's been our practice not to comment on ongoing FDA interactions. And like we did during our IgAN review, we'll be entering a quiet period as we approach the PDUFA date. So you wouldn't expect any updates from us during that time. But we will provide and look forward to providing updates on January 13.

Yigal Nochomovitz from Citigroup.

So I wanted to ask about REMS and KDIGO. I'm just curious, when you're in the field now with the new message around the reduced REMS and the better KDIGO guidelines, how many of the practitioners are sort of aware of these changes or were informed outside of the channels through Travere? Or is it really that the information is coming from Travere in terms of learning about the better REMS and the KDIGO? Just how is that information flowing? It would be interesting to understand a little better.

Yes, Peter, do you want to take that? And then, Jula, do you have anything further from your engagement with KOLs? Peter?

Happy to take that one. I mean it was a year ago that KDIGO disclosed the draft guidelines. And I think familiar, the key opinion leaders and the thought leaders, they were well familiar with the KDIGO guidelines. But what we are seeing now is the full publication that it really trickles down to the community nephrologists as well. And so that publication really helps there. And our team is certainly -- it fits nicely in our educational efforts with physicians.

With regards to the REMS modification, that is really up to us to communicate to physicians. And like I said in the prepared remarks, I'm really pleased with the reaction and the response we got from physicians of that modification in the first year and how this fits very nicely with their clinical practice, not having to have that monthly monitoring, but doing it at a quarterly base from the get-go. And like I said -- I mean, this is something that they are doing on a quarterly basis anyway. So there is no additional burden for the physician, neither for the patient.

Then on pegtibatinase, just very quickly, is the scale-up basically a completed project now? Or is there any more work to do to make sure you have enough supply for the whole HCU market?

Thanks, Yigal. Bill, why don't you take that one?

Certainly. Well, we're very pleased to have completed our first commercial batches. This enables us to engage with the FDA as was planned, which enables the restart of the study in the next year. We will continue additional manufacturing campaigns in parallel with the study running to do the further characterization work that's required for the BLA and to build stock for launch. But the key milestone is getting to this scale of manufacture, so that we can restart enrollment in the Phase III study.

Gavin Clark-Gartner from Evercore.

I'm sorry to go back to kind of the net price discussion. But even if I take a couple of million out there for the onetime net price boost, I think the revenue was still a little bit higher than some investors were anticipating based on the PSS trajectory. I'm just curious like is this volume of PSS trajectory that you got, like this quarter and last quarter, which is fairly consistent. Is the revenue growth you're seeing based on that something we should be extrapolating going forward? And like how much is the Q4 gross to net impact?

Thanks, Gavin. Chris, why don't you take that?

Sure. So I think one of the things that Peter has mentioned along the way is that we've continued to refine our pull-through process and we've really made good progress there. So I think that's part of what's driving the revenue growth that has been able to outpace the PSS growth over time. We've also seen very strong compliance and persistence. I think, again, that's another testament to the overall profile for FILSPARI.

On the gross to net front, we haven't broken it down specifically by quarter. But the third quarter was similar to the second quarter, slightly lower. We would expect that to increase in the fourth quarter. And overall for the year, we're expecting to come out right around the 20% mark. So that's about as much of the guidance as we can provide at this point. But hopefully, that gives you a better sense for how to model that out, Gavin.

Mohit Bansal from Wells Fargo.

Congrats on the progress. So in FSGS, I think we might see some data from Novartis soon with atrasentan from their basket trial. Can you talk about advantages you see with a dual ERA mechanism in this indication compared with an agent like atrasentan, which doesn't have the RAS inhibitor component, especially this being an indication where there is not as high background use of RAS inhibitors compared with IgAN?

Thanks for the question. Jula, why don't we have you answer that?

Certainly, it is quite important in FSGS, which is a true podocytopathy that's at the heart of the disease to target it with both endothelin and angiotensin II together to have the greatest nephroprotective potential. And we also see that with the magnitude of proteinuria reduction we see in this patient population of FILSPARI being used. We see about a 50% reduction in proteinuria that's durable out to 2 years. And that's where we have the confidence that this is the right way to target these patients to provide them long-term kidney protection. I understand there might be some use of single agents. I won't comment on the lack of data that we have regarding atrasentan. We really haven't seen anything to date.

So I can't comment on what that gap might leave behind when you don't target both mechanisms. We know when we target both mechanisms, we have -- we get more patients into complete remission as well as greater reductions in proteinuria and FSGS, and that's what really matters.

Prakhar Agrawal from Cantor.

So Novartis during their earnings said that they have 20% NBRx share, 10% of that is coming from Venrefa and the rest is from Fibralta. So maybe if you can expand on where you are seeing Venrefa and Fibralta as gaining share? And then another follow-up on IgAN. You said September was the strongest month, and October you're also seeing good consistent demand. So should we expect the new patient start forms to increase sequentially in 4Q?

Thank you for the questions. Peter, why don't you take those?

Yes, I'm happy to take that question. I mean what we have seen -- and I mentioned that before, is that we see very consistent and steadily growing demand since we had our full approval in September last year. And the launch of atrasentan or iptacopan has not really changed that. I mean, iptacopan was launched basically at the same time as we have full approval. Atrasentan was launched like 6 months ago. But it hasn't really changed our trajectory and our continuation of the momentum. So I couldn't be more pleased with the execution and what we are seeing. And I think now with the REMS modification as well as the KDIGO guidelines, I think those are additional momentum builders for us. And so I remain very confident in a more competitive landscape.

Yes. And just to add with regard to whether you can expect sequential increase we've not provided guidance. What Peter shared in the past is, I think, two really important components of that. One is we expect that demand to be above 700 in terms of that quarterly demand. We certainly have seen that as he talked about. But also we think about the large opportunity to be able to have these patients move from RAS inhibition to dual inhibition with something like FILSPARI or the addition of ERA.

Most of these patients still are on only RAS. So there is a tremendous opportunity for growth. We're clearly making that progress. We're seeing those occur. And I don't want to speak about other companies' performance. They're clearly helping to be able to increase the shift from RAS inhibition. But as you can see, we've not really seen an impact from their launches.

Maurice Raycroft from Jefferies.

Congrats on the quarter. You mentioned that your increased SG&A for the third quarter includes additional investment in preparation for a potential FSGS launch. Can you talk more about how you're prepping for the launch and how we should think about SG&A expectations going forward?

Sure. Peter, why don't you take the question with regard to how your team is preparing for the approval? And Chris, you can talk about SG&A.

Yes, Maurice, first of all, I think it's good to realize that this is basically the same prescriber base in FSGS as what we have seen for IgA nephropathy. Basically, the only nephrology segment that we haven't called upon is the pediatric nephrologists. But overall, there's a high level of overlap. So we build upon strength and high brand familiarity. We will have an incremental increase in our commercial footprint to really continue that momentum in IgA nephropathy while also enabling the early uptake that we are envisioning for FILSPARI. So we are building upon strength. And like I said, we have that incremental increase of our commercial footprint.

Maurice, as you can take from Peter's comments, with bringing on some additional sales team members and some other support services here, we do expect to see an incremental increase in SG&A. We started to onboard a number of those people this quarter. But really, you'll see more of that effect in 4Q and going forward. And then around the time of launch, you would also anticipate that we'll have an increase in investment level as we're really making sure that we're providing the right resources to have a very strong start out of the gate early next year. So incremental increases as we go, but we are building from a very strong base. And we're going to be able to leverage a lot of synergies from Peter's team that's performing quite well right now.

Jason Zemansky from Bank of America.

Congrats on the great progress. I wanted to revisit the efforts to now completely remove the REMS. I guess, first, given the acceleration in patient starts here and therefore, overall exposure to FILSPARI, have your time lines changed at all? And then I guess, any other updates on this front now that the original REMS modification has occurred?

Thanks, Jason. Bill, why don't you take that question?

Sure. And we're excited about the REMS modification that was granted in August. And I think we've seen the tailwinds that that provides and the positive feedback from physicians and patients. Our strategy has always been for ultimate removal of the REMS. And with our prior interactions with the agency, we've approached it with a 2-step process with seeing the frequency change first and then removal second.

As we've noted in the past, the FDA has been anchored on our PMR study, which requires exposure across about 3,000 patients for 2 years. So our process really hasn't changed. Consistent with our approach, we'll continue to engage with the agency and align with them on our next steps.

Alex Thompson from Stifel.

Maybe a follow-up on the commentary on some off-label FSGS use. I wonder if you could comment as to whether those patients are coming in at about 2x the IgAN dose or if they're still early in their treatment course and maybe not titrate up fully yet.

Alex, thanks for the question. So we do have limited insight into some of that information. And I would not want to generalize around the dosing at this point. I think what's important is that upon an approval, we would make sure that physicians are appropriately educated on the label, on the target dose. And of course, as we have with IgAN, we've got strong patient services support for the patients and their offices to ensure that they're at the appropriate dose.

Joe Pantginis from H.C. Wainwright.

So first, I want to talk more about the expenses that you mentioned earlier, but to the totality of the expenses going forward. I won't ask you to project profitability timing. But I guess, can you directionally speak to especially R&D going forward as you're going to bringing PEG back into the clinic and how we should sort of view that offset by FILSPARI revenues?

Secondly, I'm just curious with regard to Renalys and Chugai, any change in time lines for development of sparsentan in Japan, South Korea and Taiwan?

Joe, thanks for the questions. I'll quickly address the last one and then turn it over to Chris to answer the questions on expenses. No change in time lines. We've been incredibly impressed with the speed and quality of work from Renalys and we have a high regard for Chugai Pharmaceuticals. We would expect that they would be just as focused when they initiate the FSGS and Alport syndrome programs. We can't speak for them. But what I can say is what we've seen thus far has been very impressive. Chris?

Joe, on the R&D front for operating expenses, we're in the midst of the budgeting process now. So I'll be able to come back with a little bit more clarity on that post 4Q. But you are right that we do expect to have additional investments for pegtibatinase as that clinical operation really ramps up once we restart. And we're looking at investments there to have that be the fastest enrollment and time line to top line data while maintaining quality that we can.

For sparsentan, there are -- as you might imagine, with DUPLEX and PROTECT, we do see a ramp down in activity in that. But there are also other evidence generation efforts that could potentially be helpful both in IgA nephropathy, but then also in FSGS pending approval here where we believe we can help generate even more value.

The last thing I'll highlight with FILSPARI that's still going to be an investment is going to be the transplant studies that recently kicked off and are in the recruiting phase now. So there are still investments that we need to make on the R&D front. But to your point or question around the context of the revenue, we expect revenue to continue to grow very nicely and be able to support our efforts here.

Ladies and gentlemen, this concludes the question-and-answer session of today's conference call. I'll hand the call back over to Nivi.

Thank you, everyone, for joining today's call. Have a great rest of your day.

This concludes today's conference call. Thank you for participating. You may now disconnect.

All right. Hello, everyone. My name is Prakhar Agrawal. I'm a biotech analyst at Cantor. Welcome to day 2 of the Cantor's Global Healthcare Conference. For the next session, we are very excited to host the team of Travere Therapeutics. Representing Travere, we have Eric Dube, President and CEO; and Peter Heerma, Chief Commercial Officer. Gentlemen, thank you for coming.

Thanks for hosting us.

My pleasure.

So obviously, a lot going on at Travere right now. We'll go into the specifics. But maybe just to level set expectations, why don't you start with an overview of the key priorities right now for the company?

Sure. So this is indeed an exciting year for Travere and the role that we look to play within the rare kidney and broader rare disease space. Our #1 priority for this year is to continue the success of the launch of FILSPARI in IgA nephropathy. And we've been very pleased with the performance for the first half of the year. And we've got some very exciting updates to continue that success in the back half of this year, including the recent modification of the liver monitoring REMS and the removal of the pregnancy testing REMS, which makes it that much simpler for patients to access.

The second priority is the ongoing work with FDA for the potential approval in FSGS. This would be a transformational approval for that community that's been waiting far too long and has nothing approved for them. In the background, we have continued the work on our pegtibatinase program in classical homocystinuria or HCU. That progress has gone according to plan, and we're on track to reinitiate enrollment in our Phase III next year.

And yesterday, we presented at the Inborn Errors of Metabolism Conference in Japan, the data at 1 year from our Phase I/II that shows a long duration of effect for those results for patients in the open-label extension. So giving further excitement to that community for something that really addresses the direct cause of the disease.

Okay. Maybe let's start with the FSGS side of things for FILSPARI. Just start with a brief overview of the PARASOL initiative and the FDA's involvement throughout the process?

Sure. For background, PARASOL was formed in the fall of 2023. It's a public-private partnership from thought leaders within the FSGS space, the patient advocacy organizations as well as global regulators, including the FDA.

We have been able to observe some of the workshops that were done, but we are not directly involved within that PARASOL work. It was formed really in the intent much like the kidney health initiative to use evidence in that disease to best identify and define endpoints for clinical trial development within that space.

And whereas there was a limited literature that helped us to define both the potential for partial remission and eGFR for approval. Certainly, with the readout of our Phase III DUPLEX trial, we showed that we were able to show a profound reduction in proteinuria that did not translate into a statistically significant effect in eGFR. So PARASOL really started with that premise and said, what is it about this disease that we need to better understand to identify endpoints.

And they really came away with 3 conclusions. Those conclusions were based on an analysis of 26 different real-world registries of patients with FSGS with long-term follow-up. The first conclusion was that eGFR, of course, is important to any kidney disease, but it's not a feasible endpoint in a trial design for FSGS because it is highly variable.

And it's highly variable for 2 reasons. The first is that FSGS is a heterogeneous disease. The second is that patients' individual eGFR can vary significantly over time, contributing to a lot of variability within a 2-year clinical trial. And so you would need to have nearly 1,000 patients per treatment arm in order to show a statistically significant difference for the magnitude of treatment effect that sparsentan showed over an active comparator.

So the conclusion was eGFR important, but not feasible. The second conclusion was we need to look at what is the biologic plausibility of another endpoint. And when you look across the different types of FSGS, there's one commonality, and that is the podocyte. This is the filtering cell within the nephrons. This is really what helps to keep protein within the blood. And unfortunately, with patients with FSGS, those podocytes begin to slough off that leads to proteinuria. That proteinuria actually directly causes further injury to healthy podocytes, which leads to this vicious cycle of proteinuria increase over time.

So that really led to the third conclusion, which is can proteinuria independent of eGFR predict the patient's risk of kidney failure. And that's what they found that if you can reduce proteinuria at 1 to 2 years, you're able to substantially reduce the patient's risk of kidney failure at 7 years. And so it sets us up to then have a discussion with our Phase III data of what does this mean for the potential of sparsentan in FSGS.

Got it. So you have the upcoming AdCom for the FSGS indication. What's the latest thinking on the topics for the AdCom?

Sure. Well, we don't yet have insight from FDA about the specific questions. We assume that that's going to come much closer to them announcing the date of an advisory committee on the -- publicly and on the public register. We do have some insight into how they would be thinking about our file. So after PARASOL reported out, we had a Type C meeting with the FDA to ask whether they would be open to us filing this sNDA. And they agreed and they said that this review is largely going to focus on understanding your clinical data in the context of PARASOL.

So we've obviously been very focused on making sure that we can articulate what is the clinical benefit of this proteinuria reduction and the superior proteinuria benefit that we see over a nephroprotective medicine, irbesartan, and then see whether there is a consistent pattern of results with what PARASOL saw in these registries.

Okay. And if we had to nitpick the PARASOL analysis, the database included a lot of observational data. So has the robustness of the PARASOL data or the sample size really come into the conversations with the FDA?

So we've not had discussions with FDA about PARASOL or their robustness. What I can say is this is not just typical of rare disease. This is actually a fantastic example in rare disease where oftentimes you have academic physicians that are reluctant to donate their data. This is a proprietary data set for them.

We were amazed to see how eager these nephrologists were to donate their data. 26 different registries across the globe gave sufficient power to really look at longitudinal data that is robust. And we would love to be able to have clinical trial data to aggregate and do a meta-analysis or pooled analysis, much like was done in IgA nephropathy years ago. Unfortunately, those trials just don't exist. Our DUET and DUPLEX trials are really the only trials, interventional trials that were done in FSGS.

Okay. And those trials were not part of the PARASOL foundation, but is that something that could be part of the data updates that we see in the foreseeable future?

Yes, it's a great question. And we were very intentional not to contribute our data for that initial analysis in PARASOL. We wanted to maintain the independence. And so that any type of endpoint recommendation that comes out of PARASOL is not dependent on what we see with sparsentan. So we don't bias those results.

We think that, that maintains a high level of integrity with the PARASOL recommendations. Certainly, we'd be open to contributing that later if there is a strong rationale, but we think that where we stand going into a review shows that our clinical trial evidence actually is consistent with what PARASOL showed in a real-world setting.

Right. And do you have a sense of endpoints that the FDA could focus on regarding approval? I know you mentioned about proteinuria-based endpoints, but any specific threshold, time frame, anything that you can add?

What I would say is reflecting what was discussed at the PARASOL workshop when the committee, including FDA was asked, and that is that those recommendations are going to be based -- they're going to be up to the sponsor to the company to recommend. And there was an important reason why.

And that is because what threshold or what endpoint or measure of proteinuria may be dependent upon the types of patients that you enroll. Pediatric patients are different. If more advanced patients have more scarring and so you may only be able to show certain types of reductions in proteinuria compared to earlier patients.

So I think it was wise that the PARASOL panel said they're going to leave it up to the company. What we -- what's important within our data set is every single threshold that we prespecified shows a meaningful difference in superiority over active control irbesartan.

I want to be cautious that most of those at 2 years are nominally significant. All of them are nominally significant. We do have alpha protection showing statistical significance at 9 months with our partial remission endpoint because that was the primary endpoint in our trial.

Okay. And so we still get some lingering questions on the level of eGFR data that could be required here. Like will there be a focus on eGFR on the FSGS regulatory side?

It's hard to know at this point what level of detail will be the focus at an advisory committee. What I would say is in that type meeting that we had with the FDA, there was no discussion of eGFR. It was really understanding our data in the context of PARASOL.

Of course, we will be absolutely prepared to talk about the eGFR data, which was all about the slope of eGFR. We saw that there was a numeric benefit of sparsentan on the slope of eGFR over time compared to irbesartan and that there was no evidence of harm on eGFR or on kidney function. But I don't believe if you assume and accept the results of PARASOL, then the role of eGFR becomes less important in assessing the benefit is what I would assume.

Right. And it's been a few months since the recent FDA changes. Anything you can comment on based on your interactions with the regulatory agency on -- specifically in the cardiorenal division?

Sure. We've been very pleased with the level of engagement. We see the same types of changes within FDA broadly, but the cardiorenal team has been consistent. The only change that I would say of note is that the long-standing Director of Cardiorenal, Norm Stockbridge, retired earlier this year.

And so Aliza Thompson, who was the lead nephrology reviewer and the Deputy Director is now the Director of Cardiorenal. She's been actively involved in rare kidney disease endpoints through the Kidney Health Initiative and PARASOL. So we've been not only pleased with the stability of staffing there, the level of engagement. And keep in mind that we've had another sNDA on our REMS modification with the FDA, and they approved that not just on time, but a day early. So we've been very pleased with the level of engagement.

And because this is an sNDA, will Aliza Thompson be the ultimate sign-off on the up?

That's our understanding for an sNDA, the Division Director is responsible.

Okay. And any latest thinking on the timing of the AdCom?

So the typical advisory committees are held 4 to 8 weeks before the PDUFA date. That would put us in the November, December time frame. And they're typically announced in the public register for anywhere from 2 weeks to 6 weeks before. So I think we can expect to hear in the next month or so.

Okay. I did want to touch on the commercial side for FSGS as well. I guess once FILSPARI gets approved, just talk about the strategy there in terms of the launch, the addressable market that you...

Yes. Yes, great question. Maybe it's good to talk first on like how we see the opportunity for FSGS. We think FSGS is an even bigger opportunity for FILSPARI than IgA nephropathy. I think both have the potential to be blockbuster indications.

The reason why I'm so confident about FSGS is the unmet need is very well established. Every nephrologist has FSGS patients top of mind as this is the most rapidly progressive glomerular disease and patients are often symptomatic. With IgA nephropathy, we really had to establish the urgency to intervene earlier. That's not the case for FSGS.

On top of that, this is basically the same prescriber base. So physicians have a strong brand awareness for FILSPARI. Many of them have already experience. And from a payer perspective, we are already in formularies and payer plans. So all the heavy uplift that you do normally in the first 12 to 18 months prior to launch is already established. So I'm expecting an even bigger opportunity for FSGS, but also a more rapid uptake.

Okay. And so how much is the overlap with the current IgAN prescriber base?

Yes, it's over 80%. Basically, every physician that is treating IgA nephropathy is also treating FSGS patients. The only target physician that we haven't targeted so far is the pediatric nephrologist. We anticipate that we will get an indication, including pediatric. And so that's a new call point, but overall, very consistent and similar to IgA nephropathy.

Right. And for the FSGS launch, how much of an incremental sales force expansion would you need?

Yes. So we will be expanding our field force to the point that I just made, given the high overlap, it's not like a full new field team that you have to add. But it's still incremental sizing that we are doing because we want to make sure that we remain competitive in IgA nephropathy and really take the opportunity, and we are on a very strong trajectory that we can continue that trajectory, but that we also have the uptake that I was just talking about in FSGS.

Okay. And you mentioned about access that's already there for the IgAN market. So does that help ramp up the coverage of FSGS? Or like do you have to sort of renegotiate the contracts and the policies with them?

Yes. So you still have to add like the indication. So we have the value proposition in place and our account team is already actively having conversations with payers for them to understand that indication. But to your point, I mean, once you are in the formulary as a product, it's much easier to do an add-on for an additional indication.

Got it. And what's the latest thinking on pricing for the FSGS indication?

So it's linear pricing. So it's the same price. But for FSGS, it's -- since it's a sicker patient population, spilling more protein, it's double the dose for the adult patient population.

So you expect linear pricing?

That's right.

Yes. Yes. And I think importantly, if we take a step back from the dosing, our strategy for pricing across both IgAN and FSGS is really based on the position that we think it will play in the treatment algorithm, which is broad foundational therapy longer term. And so we've done a lot of work over the years to understand for both indications, what is that price that's going to be delivering the right value proposition and that really is established for this chronic condition of foundational therapy.

And we're very pleased that we're able to provide strong access so far in IgAN. We would expect that we would see that same broad access with this pricing in FSGS. I mean this is a therapy that patients should be able to get access to.

Okay. So how many diagnosed FSGS patients could be out there? And like how does it compare versus IgAN?

Yes. So we have done quite some research on it over the past. We anticipate that it's about 30,000 addressable patients FSGS at launch. That could increase over time when you see more biopsies and earlier biopsies. But to Eric's earlier point, I mean, there is no approved therapies for FSGS, and we don't anticipate there is anything else in the foreseeable future.

Okay. And so longer term, do you see FSGS as a bigger opportunity than IgAN?

We see IgAN as a blockbuster opportunity, but we see FSGS as an even greater opportunity.

Got it. It's a good segue to IgAN. 2Q, great quarter. And we're doing some analysis where it seems that within the IgAN market, a lot of the products have started to see some sort of hockey stick growth, including FILSPARI in 2Q. So what's -- just talk about the market dynamics that you're seeing.

Yes, there's definitely a lot of dynamic in a rare disease market, very uncommon in rare disease. But to your point, I think we are on a very strong trajectory. When I think about the launch so far, it's basically 2 phases.

The first phase was within accelerated approval. We were at about 400, 500 new patient start forms per quarter. After we had full approval last year in September, we grew that basically was 40%, and we have been stable around 700 new patient start forms per quarter Q4, Q1 and Q2. And that's on top of a very strong compliance and persistence for patients that are already on the drug.

Right. And you had some recent updates to the label with the removal of REMS for pregnancy and reduction in liver monitoring frequency. So is there a way to quantify the impact there in terms of new patient starts?

Yes. The opportunity that I really see for the REMS modification is twofold. One, it's broadening the patient population because physicians often have a certain patient profile in mind that would be compliant to monthly monitoring. Quarterly monitoring will broaden the patient base.

The second part is the competitiveness. You spoke earlier about the dynamic. You have more entrants coming to this market, and we want to make sure that FILSPARI remains competitive. This is an angle that the competition was focusing on. I think that this takes part of the wind out of their sales.

And so what will be the next step for the REMS removal completely?

Yes. So we've had over the years a strategy of 2 steps to be able to first modify the REMS, and we're very pleased to be able to now achieve that. Second step would be removal of the REMS, and that would take additional exposure data and again, assuming that we continue to see no cases of Hy's law, so -- which we've not.

And we'll continue to work with FDA on the level of exposure that they would want to see. They have -- we have a post-marketing requirement for 3,000 patients for 2 years. We'll continue to see whether the amount of information we have is sufficient given that they've recently approved another therapy in the class without a liver monitoring REMS.

Right. And so with that therapy's approval, do you think there might be more flexibility in terms of the safety exposure database that's required?

It's hard to say. Certainly, that's a question we'd like to explore with the agency, but I wouldn't be able to speak for them at this point on that.

Okay. And maybe if you can comment on the competitive dynamics here. Novartis is -- WINREVAIR was recently launched. So what are you seeing in the market in terms of the impact?

Yes, it's still early days. They were approved about 5 months ago, so early in April. So the second quarter was the first full quarter that we were competing against them. It was our strongest quarter. So the initial signal is positive. I think it's also good to realize that the biggest challenge that we had in the launch was really to establish the urgency to intervene earlier. I was talking about it earlier. When you have more competition coming into the market, they kind of like reinforce that message.

The second part is with Novartis now also having an endothelin inhibitor is also reinforcing the importance of endothelin inhibition as part of foundational therapy. So in that respect, it will help us to establish the class. Within the class, then you're competing. We have the long-term data, the broad label.

We are well established in the mindset of the physicians and the payers. So I think we have a strong position. Also given the differentiated profile, FILSPARI is a dual mode of action, so it provides a consistent nephroprotection with the long-term superior data versus a maximal tolerated RAS inhibitor. So I think we are in a very strong position there.

And so are you -- in terms of the impact, any impact in terms of the new patient starts? Or is it like the market is just growing?

It's hard to say because Novartis is not disclosing their patient start forms. The first quarter that they were in the market was a strong quarter for us in a new patient start form perspective.

Okay. And so some physicians have highlighted the ease of new patients that can get on WINREVAIR because you don't have to discontinue any medication. So just speak to how are you managing that dynamic in the market?

Yes. It's an interesting one. I've occasionally heard that. I often hear the opposite side that physicians actually are pleased that they can stop a medication for IgA nephropathy. In particular, when you think about this is a patient population that in average takes about 5 different medications. And historically, there were no approved medications for IgA nephropathy. What we are hearing from physicians is that patients are saying, for the first time, we feel we are winning.

For the first time we hear from the nephrologists, you are doing well, you're hitting the target levels and you can actually stop a medication. So it's the way you look at this. I think in this dynamic market where you will have different mode of action and different modalities, it will be adding and adding and adding. FILSPARI is taking away a treatment. I think that's a positive rather than a negative.

Yes. We've not heard one patient say, "Oh, I'd rather add another medication rather than stop and get to a medication that was actually designed for them.

Okay. And maybe on the other competitor that's upcoming, Otsuka's anti-APRIL drug will be launched in 4Q, and there will be a lot of B-cell modulating agents launching in the next 1 to 2 years. So just talk about the dynamics there.

Yes. We actually don't see that class of medicines as competition. We see the B-cell therapies as complementary and another treatment option. And I think if we take a step back to how this disease historically has been treated and how it's characterized in the global KDIGO guidelines, I think it gives a very clear sense that there is an important role that both FILSPARI plays as well as immune-targeted therapies like B cells.

Patients with IgA nephropathy have essentially an overactive immune system that damages the kidney. But by the time every patient is diagnosed, they already have kidney damage. They have kidney disease that is demonstrated based on their biopsy. And so the guidelines really are recommending that you have every patient with proteinuria with IgAN is on combination therapy.

A nephroprotective foundational regimen, we believe that the best option is FILSPARI plus SGLT2s, and we now have really exciting data to demonstrate the additive benefit of FILSPARI plus SGLT2 and then addressing the overactivation of the immune system. Historically, that's been steroids. There's been a shift away from steroids in this space because of the safety tolerability aspects.

And we believe that the B-cell therapies when they come, like Otsuka's launch potentially soon will help to be able to shift for more patients to be on that regimen. But those are all being studied on top of foundational nephroprotective therapies. And so I think the evolution is going to be increased combination and patients are essentially going to be treated better. I really hope that in the years to come, we have a future where no patient with IgAN will ever have to see kidney failure, whereas 5 years ago, every single patient with IgAN was modeled to have kidney failure within a 10- to 12-year period. So I am really optimistic that we're going to see that combination in that future that's best for these patients.

And is that data something that you guys can generate in terms of the combination or...

We're certainly eager to. Yes, we're eager to, we're open to. I would suspect that those types of studies would only happen once those therapies are approved. I think that's what makes most sense for development. But as we've done with the 2 studies we've completed with SGLT2 combination, we'd be very open to looking at combinations with B-cell inhibitors.

And maybe on the market, I think one thing that is interesting is the duration of therapy for these drugs. I think we've been trying to do some work around that. Are you able to put numbers on what you are seeing as the average duration of therapy given the drug has been launched for a couple of years now, more than a year, a couple of years?

Yes. So to Eric's earlier point, I mean, FILSPARI is really focused on protecting the remaining nephrons, and you want to do it in a chronic way. So FILSPARI is used chronically. What we have seen so far is that both the compliance as well as the persistence has been incredibly high, much higher than I was anticipating beforehand based on historical data on chronic often nonsymptomatic disease.

So I think the high compliance and persistence speaks to, one, the efficacy of the drug, but also the patient services support that we are giving that is well appreciated and allows for long-term protection of the nephron that Eric was talking about.

Okay. And as we look forward to second half of 2025, what are some of the headwinds and tailwinds that Street should be focusing on?

Yes. I think the -- if I think the remainder of '25 and then moving into '26, some of the things that we talked about already, one is the modification of the REMS. Second component that we didn't talk about is the KDIGO, the global guideline final publication. The draft publication was disclosed a year ago.

We do anticipate the full publication this year. That helps us 3 points. One is that the treatment target will be more aggressive. Historically, that was 1 gram per day. What the draft guideline indicated was 0.5 or preferably 0.3. So a much more aggressive treatment target, number one.

Second one is what Eric was just talking about. This is basically 2 diseases. So you want to protect the kidney, but you also want to impact the immune oversuppression. So FILSPARI is positioned in a certain way. And then the third one is FILSPARI in the draft was called out as the only drug that has shown superiority versus a maximally tolerated RAS inhibitor.

So I think that will further help us as well. So that's the second part. The third one is really in preparation for FSGS. We will be expanding our field force. And I think once you have the FSGS approval, I think there will be a halo effect from FSGS on IgA and vice versa.

Okay. Yes, if you can talk about that, like once FSGS is approved because it's the same prescriber base, how does it help you competitively? How does the FSGS approval help you in terms of the competitive dynamics in IgAN?

Yes, because the physician will see a broader utility for this medicine that other products don't have. And rather than to have different products in different indications, it further reinforces the utilization for FILSPARI.

Right. And given the KDIGO guidelines, the draft guidelines have been there for about a year. Are you seeing more physicians treating earlier in the disease like in terms of the proteinuria baseline that you're seeing?

Yes, we certainly see that. I think it also is indicative a little bit to the hockey stick that you were talking about earlier on. I see it more in the thought leader community and the academic hospitals. I think there's an opportunity to really educate the broader community nephrologist, and that's where the majority of the patients reside.

So I think that's where really I see the opportunity. And take in mind, we see this IgA nephropathy as an addressable market of about 70,000 patients. In my opinion, we only scratched the surface so far.

Got it. And maybe just longer term because Street is probably not there at blockbuster sales. So what's the long-term sort of opportunity for FILSPARI in just IgAN indication?

Yes. I mean I would say it starts with what is the role in the treatment algorithm. 90% of the patients with IgA nephropathy are on an ACE inhibitor or an ARB. If we look at the new treatment guidelines of ideally getting these patients into complete remission, only 10% of patients on a RAS inhibitor are in complete remission.

So they're essentially nonresponders to that degree and really can do better with FILSPARI. So this is a very broad opportunity for us to be able to reach. And as we're seeing in the data, in the guidelines and in the KOL opinions, combination of RAS inhibitor, ERA, SGLT2 and immune targeted is the way of the future. And so we're going to play a very important role for continued growth that will help us to be able to reach that status.

And maybe just last question, and we don't have to bring Chris on the stage for that. But on the cash runway, like what does it cover, especially in the context of you preparing for the launch of FILSPARI in FSGS?

Yes. What we've said is that we've got cash into '28 potentially beyond, and that's based on the growing revenues and the net income of milestone payments. And that really covers the continued support of the IgA nephropathy launch, preparation for the FSGS launch and really fully supporting that opportunity and all of the ongoing work that we have with pegtibatinase going into Phase III next year. So we're very well positioned from a capital standpoint to really invest in these 3 very important community opportunities.

Right. That's all the time we have today, but thank you to the Travere team for joining us, and thank you to the audience for listening in.

Thank you.

Thank you.

Great. Thank you very much for joining us today. My name is Mohit Bansal, and this is the post-lunch session. So we have an exciting company there with us. And I'm also joined by my colleague, Sadia Rahman, as well on the stage. And we have Travere Therapeutic's Eric Dube, President and CEO of the company; and Peter Heerma, the Chief Commercial Officer of the company. Thank you, Eric and Peter, for joining us.

Thank you for hosting us.

Awesome. So I have Sadia for all the tough questions here as well. So I'll kick off. So Eric, if you remember, I mean I always ask this question every time, like what would make you feel good about next year. And now we are a year after that conversation. So if you look back at the year, what do you think your key accomplishments were? And what is the investment case going forward?

Yes, I have to say I'm incredibly proud of my team for the accomplishments year-to-date. Since we had this conversation last year, we, of course, launched for full approval in IgA nephropathy with an incredibly strong uptake that continues, but we had our strongest quarter to date last quarter. And just as that space becomes filled with many other treatment options, physicians continue to build a strong perception and use of FILSPARI. And I think that, that takes a tremendous amount of effort and great data. So I'm very proud of my team with that.

We've made very good progress on continuing to build a strong profile of FILSPARI in IgA nephropathy. Last week's FDA approval for REMS modification, removing the REMS for pregnancy testing for embryo-fetal toxicity and simplifying the REMS for liver monitoring from monthly in the first year to quarterly, makes it just that much easier for patients and aligns their treatment or their monitoring schedule to how they often see their nephrologist. So that took a tremendous amount of effort to make sure that we're doing that and continuing to build easy access for patients with IgA nephropathy.

And of course, we now have an accepted sNDA for FSGS. This is a community that we have worked very closely with over the last 10 years. We know many of their stories, and we know that this is a community that's really desperate for a therapy that's going to work for them and that is approved for their condition. So we are excited about the work that we're doing there, and we're engaging with FDA along their review in anticipation of an approval on our PDUFA date of January 13 next year. So hopefully, next year's conversation becomes even more exciting with that potential approval. And I think those were the main areas of focus that I mentioned for last year.

Awesome. So yes, quite a lot to discuss here. So like -- I think starting with IgA nephropathy launch and I mean, uptick so far, it's like every quarter, we think that this is probably the highest new patient starts you'll see, and then you have been out doing those. So can you talk a little bit about, I mean, how you -- where you are finding these patients? And in what inning you are in terms of finding those patients?

Yes. Thanks, Mohit. Well, first of all, to Eric's point, very pleased with the continued performance. Second quarter, that we disclosed a few weeks ago, was the strongest quarter we had so far. But basically, I would say I see the launch of FILSPARI in 2 phases. The first phase was the accelerated approval. And then since September since we had the full approval, we saw a meaningful growth of about 40% in our demand uptake. And we have -- we've been quite consistent in generating new patient start forms of around 700 since Q4 last year, which was the first quarter after full approval.

With regards to the dynamics, what you're asking for, like where are the patients coming from, we see a nice continuation of new prescriber coming into the mix, but we also see a good amount of repeat prescriptions of experienced prescribers. I think that's exactly where you want to be in about 2.5 years into the launch because it speaks to the positive experience that physicians have, but also that the patients have. The compliance and persistence of FILSPARI is really high. And we start to see that also, physicians are feeling comfortable to prescribe to patients with increased proteinuria levels, but maybe not as high as 1.5 or higher. So we believe that, that's where the majority of the patient population is. About 70% of the patient population has increased proteinuria. But below 1.5, this is exactly the segment we are moving into. I think the REMS modification that you mentioned earlier will help us to further occupy the particular space.

Can you elaborate on the drivers of the recent jump in PSF and why PSF growth recently outpaced revenue growth in past quarters? And can we expect more momentum in revenue growth going forward?

Yes. It's a great question. You saw indeed a bit stronger revenue growth in Q2 relative to patient start forms. It also speaks to what I mentioned earlier since September, we had the full approval. So you start to have prescriptions of patient start forms coming in that was maybe below the initial label. The initial label with an accelerated approval, kind of like the first phase that I was describing. Our label was basically for patients with proteinuria levels of 1.5 or greater. After full approval, there's no threshold for proteinuria. So basically, all patients at risk of progression in IgA nephropathy qualified for prescription, but that always lags a little bit from a payer perspective because the payer may not have updated their authorization criteria. And so that lag is what you kind of like saw in the second quarter that you had like that uplift that we saw in Q4 is now kind of like translated into revenue in Q2.

The only other thing that I would add is just on a gross-to-net standpoint. In quarter 1, you often will see insurance resets, and that's often the quarter with the highest gross to net of the year, but that starts to moderate starting in Q2. And so I think that also contributed to what seemed to be a very strong quarter.

And I'll cover in terms of the outlook. Well, we've not provided guidance just yet. And it's still a bit early when we look at companies in terms of when they start to provide guidance in their launch. We do expect continued growth in our revenues moving forward for the reasons Peter mentioned. We have a very strong compliance persistence with the patients that we reach based on the great clinical profile, but also the support services that we provide. And with the continued reach of patients with patient start forms, that just allows us to continue to grow those revenues.

And if you look at the cumulative number of patients that we've been able to reach, we're not even at 10% of the full addressable population. So we really do see that there are so many other patients that could benefit from upgrading from off-label RAS inhibitors to something that is superior like FILSPARI.

I guess on the point about payers removing restrictions, have most payers removed those 1.5 threshold restrictions? And are you seeing differences in how payers are covering atrasentan at this point with their accelerated approval?

Yes. I'm very pleased with the continuation of updates of payers with regards to our full approval. And to the point that you're making, there's a new kid in town since 4 or 5 months now, atrasentan that was introduced in the market, there's still an accelerated approval, a more limited label, 1.5 and greater, plus FILSPARI has the long-term benefit.

And I think from a payer perspective, what is the payer looking for, well one, the highest rigor of evidence. FILSPARI has that with a head-to-head trial versus a maximally dosed active comparator, plus the long-term data, and we have priced for broad access. So that allows for a very strong inclusion in formularies and payer plans. And atrasentan is early in the state. So I think we have a very strong position in payer plans for FILSPARI.

And then on compliance and persistence, you've highlighted strong compliance and persistence compared with other rare disease launches. Can you elaborate on that? And any shift you expect now with reduced monitoring?

Yes. I would say, first, other rare disease ones. But I would say, in general, the compliance and persistence for nonsymptomatic chronic disease, what we have seen so far is as high as it gets. I think we are really exceeding any expectations that I had initially.

And I think to Eric's earlier point, it speaks to, one, the efficacy of the product and the safety profile, but also patients feel encouraged to take it because they see it works. And for the first time, they feel they are winning against their disease and actually can stop another medication, the RAS inhibitor. So the compliance and persistence remains very high. I think it's part of the efficacy of the product, but it's also the support services that we are providing to those patients.

Can you talk a little bit about the REMS. So now that REMS has -- so like when I look at FILSPARI versus atrasentan, I mean they are -- like one -- you have 2 mechanisms. They have one mechanism. You have an advantage of first mover, but the only benefit they have is probably at this point, the REMS benefit. How you are seeing that in the marketplace and now with the newly updated label? How -- like where do you see competitive positioning?

Yes. I think the REMS modification, I see 2 main opportunities. One is what I mentioned earlier with the change of the label in September and full approval with no proteinuria threshold. You see that we are moving the median proteinuria level is actually below 1.5 and continues to move to the left, meaning lower proteinuria. So you get to a patient population that may not be monitored on a monthly base. But all those patients basically are seen by the nephrologists every quarter. As part of the routine, the physician is always asking for [ lab ] values before the visit. So this fits very nicely within the routine of nephrologists by doing lab values every quarter. So I think it allows to occupy that broader patient population without additional obligations of monitoring.

The second aspect, to your point, is the competitiveness because I think you're right, atrasentan has been really focused on their REMS as their core differentiator. I think with the quarterly REMS consistent to what is the general routine for those patients. Like the REMS obligation is really like a quarterly attestation of the patient that have done the laboratory. So there's nothing more to that for the physician perspective.

Got it. And I think we discussed yesterday, I mean you talked about potential to remove these REMS. So can you talk a little bit about how do you see -- like what is the -- what could the path look like and time lines here?

Yes. So we've had those discussions with the FDA over the last 2 years since we received accelerated approval and their decision to label us with a REMS. And they said that with additional data, they would reconsider the need for a REMS. Obviously, we now have seen that with the modification for liver monitoring and the removal of the pregnancy testing REMS for embryo-fetal toxicity.

We've always had a 2-step process. The first was to modify it to be better aligned to the frequency of visits for patients. And the second step would be full removal. That full removal really requires additional exposure data. Our post-marketing requirement is 3,000 patients exposed for 2 years. We've made good progress on that, and we'll continue to have discussions with FDA about when the right time for us to be able to submit an sNDA for full removal. But we do see that, that is a potential for the future.

Got it. So it's the time line -- can you talk about time lines? I mean, do you have...

So roughly. We've not provided specific time lines on that, but what we have said is that we would be looking to submit that after our PDUFA date for FSGS. We would not want to submit an sNDA that could potentially slow or delay our PDUFA date for FSGS, but this is something that we would look to engage with FDA to have the conversation about submission perhaps next year.

Got it. Very handful.

Yes, just on the IgAN launch, the -- can you talk about the prescriber base for FILSPARI currently and how that's been evolving as the launch progresses? Are you reaching a lot of community physicians? And what's your strategy to compete effectively with Novartis?

Yes. So let me answer it in 2 ways. First, on the prescriber base. The vast majority of the patients are actually being seen by the community nephrologists. So over 70% of the patients are being managed by community nephrologists. I feel that we have a strong position there. We have had a strong position. And I think we are certainly competitors there.

With regards to your second question about how do you compete against the new kid in town. I think atrasentan is the only direct competitor in the positioning of FILSPARI. But I feel very confident in the profile that we have for FILSPARI given that it's a different motivation. It's a dual inhibitor that inhibits both bad actors in the kidney that are [ accelerating ] damage in the kidney, being angiotensin as well as endothelin. You want to have the consistency of inhibition of both to really have consistent nephroprotection.

The second part is the superior data that we have for a submaximal tolerated dose active comparator with the long-term kidney preservation data as well. It's something that atrasentan doesn't have. And then the third one is the ease of access, the strong position we have in payer plans. And that proposition resonates very well with physicians. So consistency of nephroprotection, long-term benefit and ease of access with strong payer access.

And then the KDIGO guidelines. I mean I think we are expecting them to be finalized later this year. So how do you -- like do you think -- like there was a draft guideline but now with the final guidelines, do you see a further inflection in 2 patients who are lower than one?

Yes, I think I was really excited about the draft KDIGO guidelines. That was basically disclosed the week before we got the full approval. I think KDIGO, the global guideline committee recognized that this is a disease that requires much earlier intervention and much more aggressive intervention. And they basically lowered the treatment target from 1 gram per day to 0.5 or preferably 0.3 grams per day, meaning like complete remission. So basically, what they're saying, every patient on IgA nephropathy that is not in complete remission should be a target for FILSPARI. So that's number one.

Number two, I think they also articulate very clearly that there is 2 treatment categories for this disease. And when I spoke with Jürgen Floege, who is the Chair of the KDIGO guidelines, what he was mentioning is like, if I talk to my patients, I often tell them like you have 2 diseases. You have a kidney disease and you have an immune mediated disease, and we need to target both. That's exactly how the KDIGO guideline is being written as well. You need a treatment that is targeting the kidney to protect the remaining nephrons, so nephroprotective treatment, and you need a treatment that is immunosuppressive. And so that positioning, I think, is really important. So that's number two.

The third one is the way FILSPARI is being articulated in the guidelines as the only medicine that has shown superiority. There's a maximal tolerated RAS inhibitor and active control comparator. I think those 3 concepts will remain in the final guidelines as well. We have to see that -- how that materializes. We anticipate that in the fall, it will be published. The opportunity for us is to educate like the broader community on that. I think the thought leaders are quite familiar with KDIGO. But I think in the community, there's still an opportunity to educate nephrologists on those 3 aspects that I just highlighted.

Got it. So like since you talked about nephroprotection as well as then immune portion of the kidney disease, that could probably bode well for B-cell therapies, right, because like your drug is nephroprotective plus [ B-cells ]. So do you see a combination approach there over time, especially with the KDIGO guidelines asking for lower is better.

Well, that's essentially right. I mean to the last point that you make, if you have more rigorous treatment targets and if you go from 1 to preferably 0.3, that means that you go 3x as low. The probability that you get there with one mechanism of action may be less likely. So you will see more -- more combination therapies. It's why FILSPARI, we position it as foundational. Start by protecting the remaining nephrons, see where you get. We have actually the strongest data with regards to complete remission. I think it's very well appreciated by nephrologists. But if you may not get there, you could add other mechanisms on top of FILSPARI.

Got it. I mean, so at this point, you do not think [ B-cells ] will become the first-line therapy for now? Or at least you're -- in front of conversation with the doctors?

Yes, to the point that I'm making, I think you need to act on both parts of the disease, right? Nephroprotection, especially -- take in mind, when a patient is being referred to the nephrologist, 75% -- over 75% of the patients have already lost half of their kidney function. Kidney loss is irreversible. So a nephrologist, the main thing they want to do is protect the remaining nephrons. And so that's why FILSPARI, we position it as foundational. Immune suppression is important as well, but you have to do both at the same time.

Got it. And the guidelines, the draft guidelines, well, let's see where the final ones come out this year recommend that any patient that is diagnosed with IgAN that has proteinuria really needs to be on a combination for both of those categories. I think that gives the patient the best opportunity to stave off or slow the progression to kidney failure because the data is clear, every patient in their lifetime with IgAN will face kidney failure if they have proteinuria. So we have the opportunity now with this innovation across these classes to be able to prevent that.

I think there's a very strong rationale for combining these classes. But how do you think payers will implement or look at combinations given these will be high-priced drugs?

You want to take that?

Yes, absolutely. Well, I think to my earlier point, I think there are 3 aspects that the payers are looking at. What is the price level. And we anticipate FILSPARI to be foundational treatment, but there would be more competition as well in potential combination therapy. So we price FILSPARI for broad access. I think that's one component.

The second one is the rigor of evidence. The payer is very keen on the highest rigor of evidence, and the highest rigor is head-to-head trial versus some maximally dosed comparator. We have that data.

And then the third component is the long-term evidence. Is the drug providing the long-term protection to the kidney? That's what we have shown as well.

New medicine coming to the market, and you were referring to the APRIL compounds, initially, they will be under accelerated approval, the more limited data, no long-term data in their Phase III trial and no head-to-head data. So I think that's a very important aspect from a payer in how they are evaluating the different treatments. And I think we have a very strong position based on those 3 aspects.

I think it's also important to keep in mind that all of those trials are being done on top of foundational therapy, nephroprotection. So mostly RAS inhibitors, some including endothelin receptor antagonists like FILSPARI. So payers will be looking at the trial design and the inclusion criteria, and those medicines are being used on top of those therapies.

Do you have any plans to generate additional data, like more robust data set with combinations with FILSPARI with newer agents? Or do you think physicians will be comfortable prescribing these in combination?

I think -- the first answer is, yes, we are eager. We believe that we are leaders in the space, and leaders really invest in generating evidence that answers the question of physicians, not just of regulators. And if you look at the data sets that we have generated, we're really, I think, paving the way for how you understand not just FILSPARI, but also this disease.

So we have the only trial that's been conducted head-to-head, as Peter talked about, to demonstrate why a physician should use FILSPARI over RAS inhibitors. We have the only trial that's done in treatment-naive patients, where we're looking at what is the benefit of starting with a more robust therapy to start. And then we repeat biopsy to understand not just what's going on with their EGFR and their proteinuria, but what's going on in the kidney. We've also done 2 studies in combination with SGLT2s. We have data on top of steroids in our Phase III program. And we've also just recently initiated program looking at recurrent disease in post transplant, which is one of the highest areas of unmet need within the rare kidney space.

So we're really proud of the work that we're doing to answer the questions that nephrologists have, and we welcome the opportunity to collaborate with those companies that have B-cell therapies to be able to address some of those questions. We anticipate that, that would occur after these medicines are approved, where they demonstrate their safety profile and have FDA approval. But we do know that this is one of the key questions that physicians will have. May not stop. Physicians will likely use these in combination because the mechanisms are well understood. But I think there still is value in generating the evidence around safety and benefit. I think we really have answered quite a bit with our SGLT2 combination showing very clearly an additive benefit when you use FILSPARI on top of SGLT2, which is fantastic for patients.

So let's just move to FSGS. So of course, you are in the discussions with the agency under the review. So can you talk a little bit about how your conversations with the agency ongoing right now? And what are the outstanding questions at this point that agency wants an answer?

Sure. I'll characterize the engagement since we've submitted the sNDA as very consistent with the engagement that we had with FDA during our review of the sNDA for full approval in IgA nephropathy. The types of questions, the frequency of questions, the timing of that, very consistent with our experience, which has been quite reassuring.

The questions that we get, I would frame in the context of the discussion that we had with the FDA during our Type C meeting before we submitted for this indication. That's the meeting in which we asked FDA whether they would be open to a submission using proteinuria. And in that discussion, they said that this review is going to very much focus on understanding the benefit of sparsentan in FSGS in the context of PARASOL. PARASOL being this independent public private initiative to better understand what the endpoints should be for clinical development in FSGS.

Got it. So is that fair to say like FDA buys into PARASOL. FDA understands PARASOL, like the data that they have generated? And basically, they are trying to understand how your drug and their data fits into the PARASOL paradigm?

Yes, I certainly don't want to speak for FDA. We do know that FDA has been part of PARASOL They were core members of this, including their reviewers as well as their statisticians. So I believe that they understand the implications of PARASOL and the procedures and the findings of PARASOL.

How much that means in terms of their review of FILSPARI, I think is separate. So PARASOL was very much around understanding endpoints in this disease. And the conclusions from PARASOL were very clear, which is EGFR is very important to kidney disease. It's a measure of kidney function. It's just not a feasible endpoint in FSGS because it's a highly heterogeneous population. There's high variability even within an individual patient over time when you measure EGFR.

And when you look at the biology of FSGS regardless of the subtype, there's a common podocytopathy. There is a continual damage of the podocyte in the kidney, which is the main filtering cell, that leads to progressive proteinuria, which led the committee to assess proteinuria as a validated surrogate endpoint in this disease. And what we saw from PARASOL is that when you can lower a patient with FSGS' proteinuria below certain thresholds, you're able to reduce their risk of kidney failure over 7 years by over 85% to 90%, which does help to validate that independent of EGFR, proteinuria levels can predict a patient's risk of kidney failure. We're seeing a very similar pattern in our clinical trial.

What's important to keep in mind is that we did not donate any of our clinical trial data on sparsentan to PARASOL to maintain the independence of that as they develop an endpoint. So FDA may certainly understand and appreciate the end point. Their job now with this review is to assess the robustness and consistency and the clinical benefit of our data. And what we believe and what we've heard from many of the top experts in the field is that we certainly do see a consistent and robust benefit on proteinuria, particularly compared to maximum dose irbesartan, which we know is a nephroprotective agent.

Helpful. One question. I mean, given that the administration is new, so implications on the FDA, that question we get a lot. So you have had discussions with the agency before this new administration and then lead the overall administration and then after that administration is changed as well, have you seen any difference in the tone or questions about the filing at this point?

So our experience with the agency throughout this entire development, including recently with the new administration, has not changed. They've been consistent. And one of the things that we found reassuring is the feedback that they gave to another company in this space with a Phase III program in FSGS was very consistent with regard to the use of proteinuria as an endpoint for approval. So we do believe that there's consistency. And our job is to make sure that we're answering their questions and providing the right data to ultimately get this approved in January.

Got it. One last question on FSGS. I mean, is there an overlap between IgAN and FSGS in terms of prescriber base? Or like would you have to actually expand beyond just IgAN?

Yes. It's a very similar prescriber base. Over 80%, 90% overlap. The only prescriber that we haven't called upon is the pediatric nephrologist. It's about 1,000 in the U.S. But further on, basically, the prescriber for IgA nephropathy is the same prescribers for FSGS, which I think gives me confidence as well that we will see like a rapid uptake in FSGS much faster than what I was -- first anticipated in IgA nephropathy is given that you have the same prescriber base, the high unmet need, but also the product is well established in this prescriber base, high brand awareness and many of the nephrologists already have the experience with FILSPARI.

Got it. I want to touch up on pegtibatinase as well. I mean this is a program which doesn't get a lot of attention. But I think you presented some data, I think something came out this morning as well. So can you talk a little bit about your excitement around this program and the manufacturing part of it, which kind of pushed you back a little bit, but again, now you're going for commercial manufacturing. Just talk a little bit about that and why investors should be excited about it?

Sure. Well, we're really excited about the opportunity to serve the HCU community. This is classical homocystinuria, which is a genetic metabolic disease that affects about 7,000 to 10,000 patients in the U.S. and similar numbers of patients in Europe as well as in other parts of the world. This is a disease that for half of the patients, they are diagnosed at birth during newborn screening. And unfortunately, half of the patients are not diagnosed and go on to eat a normal protein-rich diet that then leads to a toxic accumulation of homocystine. These patients then start to develop a constellation of symptoms, including cognitive deficits, bone malformation, lens dislocation in their eyes. And by the time they're a teenager, 1/4 of them will have an ischemic event. Before a patient reaches the age of 30, over half of them will have an ischemic event, if they are left undiagnosed and untreated.

The primary way of treating this disease is in a very restrictive diet, basically minimizing any of the protein you have in your diet, and to have a supplement of protein -- medicalized protein, which tastes horrible and is costly for these families. And patients will be on betaine or vitamin B6, which can help some patients, but not all. You contrast that with pegtibatinase, which in our Phase I/II program, we had 100% of the patients respond and get below the clinical threshold, 50% of them below a threshold that would allow their physicians to really consider liberalizing their diets. So we're really excited about the opportunity.

And the data we presented this morning was from our open-label extension of the Cohort 6 dose, which is the dose we're bringing into Phase III, that shows that, that maintenance of effect in that reduction in methionine as well as homocystine with no new safety signals emerging. So really exciting profile that really meets the needs of not just physicians and maintaining the level of homocystine, but also the needs of patients in maintaining that and allowing them to consider additional protein in their diet.

So we did initiate our Phase III last year. We paused enrollment because we saw some challenges when we went from commercial manufacturing scale -- or from clinical to commercial. We paused that. We are well underway to resolving that, and are on track to reinitiate enrollment of our Phase III next year. And so stay tuned for additional information and update on that. But we're really excited about the potential to be the first disease-modifying therapy for the HCU community.

Got it. Very helpful. So maybe coming to the last question, again, same question every year. Hope we are sitting here next year, you and me both, and then if I ask you the question, like what would you make -- what would make you look back at the year and say it was a great year for us?

Yes, I want to focus on one word that you said, and that's hope. There are tens of thousands of families that hope that there will be something for them, that hope that they will have a therapy for their child with FSGS or that there would be a clinical trial or a therapy for their child with HCU. I've spoken to mothers that have multiple children in their family with HCU. I've had fathers cry in my arms, leading with me to do everything we can to get sparsentan approved for FSGS.

If we sit here next year, I think we will be in a world that offers a lot more hope to those families, not just in the promise of FILSPARI, but in actually having access to the first medicine for FSGS and certainly, the first Phase III program in HCU. And I think next year can be a really, really powerful year for the rare disease community.

The best. Thank you very much.

Thank you. Thank you.

So thanks, everyone, for joining for the next session with Travere Therapeutics. I'm Yigal Nochomovitz, a biotech analyst here at Citi. For those in the room, please ask questions, just raise your hand and we can take the questions and also welcoming those listening on the webcast.

So it's my pleasure to have with me the CEO of Travere, Eric Dube; and the CCO, Peter Heerma. Thank you both very much for coming out and joining our conference.

So just in the last couple of days or 3 or 4 days, you've had some very good positive news. So I'll let you share that and explain the significance of that positive FDA decision for your sparsentan.

Yes, Yigal, thanks so much for hosting us. So the FDA recently approved a modification to our REMS. I'll explain what it is, and Peter can talk a bit about what that could mean for us moving forward. When we were approved under accelerated approval about 2.5 years ago, based on the variable liver safety profile of other endothelin receptor antagonists, we were asked to have a REMS where patients for the first year of their treatment would need to be measuring their liver function every month and then thereafter every quarter.

Also as part of the endothelin class, we had a REMS for embryo fetal toxicity. Last week, FDA approved the removal of the embryo-fetal toxicity and pregnancy testing REMS and changed the liver functioning testing to every 3 months, which aligns with how most patients with IgA nephropathy, one, see their nephrologists and two, are tested for their kidney function. So very much more aligned with how these patients are being seen under standard of care.

So Peter, maybe you can speak about what this...

Yes. The significance commercially for the modification of the REMS is that patients are now monitored like every 3 months, which is, to Eric's point, for most of the patients that are being seen by the nephrologist. So there's no additional homologation for patients. I think in particular, 2.5 years into the launch, this is really relevant because last year, in September, we had a full approval. Within the accelerated approval, we had a label that read of for patients that rapidly progress generally with a proteinuria level of 1.5 and greater.

Since September, with the full approval, there is no proteinuria cutoff. And so we see a shift to the left to patients that start FILSPARI with proteinuria levels lower than 1.5. Many of those patients are not seen monthly but quarterly. And so I think this is the right time to have this modification. Physicians often are preselective in their mindset like what patient will be compliant on monthly monitoring. I think that will open up right now for a broader patient population, in particular, what I mentioned with lower proteinuria levels.

And we believe that that's where the majority of the patients are. We believe that 70% of the addressable patient population resides with a proteinuria level of lower than 1.5. This is where we start to penetrate. And I think we have a very strong proposition and the modification of the REMS helps us with quarterly monitoring, which is consistent to other medicine in this market and consistent to how often patients are being seen by nephrologists.

So since it's very new news, just explain how you communicated it to the practitioner base. I mean you immediately sent out a message yes, that now you can shift and they're implementing that immediately.

We had, indeed, the next day at 8:00 in the morning, we had a call with our full field force to inform them. But it's also important to realize it's not only about the REMS. I mean FILSPARI, we believe, is a better product because of the consistent nephrop protection it provides by inhibiting dual bad actors in the kidney being angiotensin as well as endothelin. That's the reason the physician prescribes and the ease of access is the contributing factor with the REMS modification.

So I think there is no reason why a physician shouldn't prescribe it. It's a better product and the modification of the REMS now allows for monitoring that is consistent to other products as well.

And we've talked in the past about the REMS and going from the monthly to the quarterly has exactly happened. And then is there a further plan to go to less frequent or nothing, for example, every twice a year or nothing? Is that in the cards? Or is that even needed to do -- to move things further?

Yes. So our plan has been -- well, first, let me take a step back. When we spoke with FDA at the accelerated approval 2.5 years ago, they said, look, we recognize that your data safety package and your benefit has not yet been fully established because it's under accelerated approval. We didn't have the full safety data package. But they said they are open to revisiting the need for REMS.

What we have decided is that a 2-step strategy would be the most expeditious for helping patients access. The first is -- step one is what we just achieved, which is to get to quarterly, which is, again, similar to how patients are being seen in the real world. It's also how patients were being studied in our clinical trial in terms of study frequency.

The second step would be full removal. And we still have not seen any cases of Hy's law in both the clinical trial exposure as well as real-world exposure. Assuming that, that continues and we have exposure, FDA is looking as part of a post-marketing requirement, 3,000 patients follow-up for 2 years. We're well underway to be able to do that. And so we do have opportunities to go back to the FDA. We'll take every opportunity we can to be able to share the additional exposure data and request full removal.

We think that certainly is going to be helpful in ensuring that no patient is left behind to say, I don't think that this patient can be on FILSPARI because they won't comply with liver testing. So it is our goal. While we don't see that the REMS currently is a barrier, we don't want it to be able to be perceived as a barrier or a perceived safety liability with the medicine.

And have you communicated that level of exposure you described, when might you have that in place to make that argument to FDA?

Yes. We've not specified specifically when because a lot of that is based on the exposure in the real world, right? We've been very successful with the launch, but it's very difficult to predict with that level of accuracy, but we are well underway to be able to do that. We also want to make sure that we're taking every opportunity to go back to FDA, particularly given that they've approved another medicine within this class without a REMS. So we do want to make sure that we're taking every opportunity to go back to them and request the full removal now that we have the modification.

Right. And Peter, you mentioned the proteinuria levels that are moving now below the cutoff, the old cutoff. Do you -- is that possible to track that in the real world, like what that average tends toward and how it progresses over time?

Yes, we have multiple tools to monitor that to see what the general proteinuria levels is when you get patients on board, patient chart audit data, market research data, et cetera.

But you haven't commented specifically on what the numbers are, how it's moving below the 1.5 or.

Yes. We haven't mentioned a specific number. What we have mentioned is that the median proteinuria level moves to the left and is now below 1.5 and continues to move in the direction that we would like to see, which you would expect with more repeat prescribers because often like what the first patient a nephrologist is prescribing FILSPARI for is the patient that the physician is most worried about. when the experience is good, both from an efficacy and a safety perspective as well as from a patient experience.

And I think the high compliance and persistent levels speak to that as well, then a physician is more eager to start prescribing also for other patients often with lower proteinuria levels.

Okay. So of course, the REMS is important, but that's only one piece of the puzzle. And then there's another piece of the puzzle or at least one other piece of puzzle, which is the KDIGO guidelines, which we've talked about a lot. So can you walk us through what to expect there for the update? And how you see that driving FILSPARI's launch relative to REMS and how they work together?

Yes, it's a great question. Last year, I mentioned earlier that in September, we had our full approval and basically no longer have a proteinuria cutoff in our label. In the same week of our full approval, there was also the draft global guideline called KDIGO that actually went for a much lower treatment target for proteinuria. Historically, that was 1 gram per day. It was moved to 0.5 or preferably 0.3, meaning complete remission in their draft guidelines. Very soon, we anticipate that the full guideline will be published.

And I think that will further reinforce, one, that every patient should be treated towards full remission, but also that there is 2 categories of treatment options, one that is really focused on protection of the nephron kidney targeted. That's the space that FILSPARI plays in. The other space is more upstream to go on the immunosuppressive side of the equation. That's the treatment category where you have the steroids, the complement inhibitors, potentially the APRIL compounds, the B cells that are coming to -- they may come to the market. So I think that reinforces the positioning for FILSPARI as well.

The third one is the way FILSPARI is being called out in the draft guidelines as the only medicine that has been showed superiority versus a maximally tolerated active RAS inhibitor. So I'm very pleased with the language that was being used. FILSPARI is also approved in the U.S. and in Europe. And so I think that will help us to have a strong positioning in the guidelines.

And is there a sort of a specific date when they're getting published? Or is it more of just a general statement like if -- somehow I think it's in October, but that might not be right.

It sometimes it's fall. It did not change a specific date, but sometime very imminently.

Okay. And then you obviously had the second quarter numbers, which look good and you got over this sort of 700 start form plateau. Can you just talk more generally about the momentum in the -- on the commercial side? And of course, these 2 drivers. But how do you see the trajectory moving now?

Yes. Maybe I'll make a comment generally, and then, Peter, you can provide a more meaningful response. So we've not yet provided guidance for our revenue outlook, but we remain very confident in continued growth of revenue throughout the year and certainly throughout next year based on the very strong demand and based on the opportunity that we have. If we think about the addressable population of our full approval in IgAN alone, there are about 70,000 patients in the U.S. that we believe can benefit from FILSPARI that would be addressable today. When we look at the cumulative patient start forms that we've received since accelerated approval, we're not even penetrating 10% of that addressable population.

So there are many patients out there that are diagnosed that are treated with off-label RAS inhibitors. The overwhelming majority of them are failures of RAS inhibition alone and are not at goal. With the KDIGO guidelines, that's only going to accelerate the uptake and the need for something better than these unproven therapies. And that's really where FILSPARI comes in. So we do believe that there is a strong opportunity for us to continue to grow.

There's been a lot of focus on, well, what's going to happen when you have these B-cell therapies come to be available for these patients. But as Peter talked about, this is really about the future of combination therapy. Patients -- we have no evidence to show that patients would benefit from an immune suppressant like a steroid or immune targeted therapy like a B-cell alone. All of those are being studied on top of nephroprotection like RAS inhibition and some of them on top of FILSPARI. So the future really is that combination.

Our focus is to really upgrade these patients foundational therapy from being a RAS failure to lowering their proteinuria further by switching to FILSPARI, regardless of whether they're on a combination with an immune-targeted therapy and regardless of which one that is. And so that's really what gives us great confidence in the outlook for growth. At some point, we'll look to provide guidance. At this point, we have a lot of dynamics and catalysts in the near term to be able to work through before we do that.

But Peter, maybe you can talk a bit more about what you're saying.

Yes. No, absolutely. Based on the last point that you made, it's a very dynamic market, especially for rare disease. I've not encountered so much new treatment options in rare disease, which I think is a good thing. First of all, it's a good thing for patients. But second, I think it's good for us as well to have more modalities and more companies coming to the market because the biggest challenge we were initially facing was really to reinforce the urgency to intervene earlier in this disease.

Historically, IgA nephropathy was seen as a relatively benign disease by nephrologists. And it was really until we like really invested in like registry data, and we had 2,500 patients from the U.K. in the RADR study, longitudinal followed that actually indicated that every patient in that registry did face kidney failure in their lifetime. But the average time towards dialysis was 10 to 12 years. And that was really an eye-opening for a lot of nephrologists, and that's also what is now being reflected in the guidelines and why the treatment target is much more aggressive moving from 1 gram per day to 0.5 or preferably 0.3.

I think all the new [ products ] are coming to the market are reinforcing that same message. And to Eric's earlier point, we believe that the addressable market is about 70,000 patients. The majority, 70% of the patients remain with proteinuria levels below 1.5. So I think that's -- those patients are still at risk, but we were underestimated what the real risk was. And I think that will help us to further penetrate.

So the pie will be getting bigger. It's up to us to take a big piece of the pie. But I believe we have a very strong proposition with the full approval, with the data, the head-to-head long-term data that FILSPARI has and a very strong position also in formularies and payer plans.

And do you have a view on which of these REMS versus KDIGO sort of more of the bigger driver of further uptake? Are they going to kind of work in synergy?

I think it's going to work in synergy. I think it's really difficult to parse out both the very strong profile clinically of FILSPARI, having both superiority data versus an active comparator and having 2-year data showing the only drug over 2 years to be able to have a cumulative benefit on kidney function. And we're one of the only companies in this space to have actually disclosed complete remission data. These are really important to nephrologists as they think about why they would choose to select one medication over another.

But the other aspect, the KDIGO guidelines, as Peter talked about, is going to drive that sense of urgency. I think the REMS is going to be important for a segment of patients that may have been reluctant. I certainly don't like to get my blood tests, et cetera, to do it every month versus every 3 months. I know what I would choose. So it's certainly going to help. But I think the broader opportunity is to be able to expand beyond these patients being undertreated by ACE inhibitors and generic steroids for decades.

So most -- I mean, most, if not all, of the patients that are starting on FILSPARI have had some other intervention for IgAN. Is that right? Or do you get anyone that's newly diagnosed or that's unlikely?

Yes. We have seen some, but the overwhelming majority of patients that we see as addressable will have been on an ACE or an ARB plus an SGLT2. Most of the patients that we see in terms of their journey, they will have been diagnosed or at least treated for proteinuria by their primary care physician before being referred. What I think is important about your question is one -- is twofold. One, the majority of patients are already on ACE inhibitors or ARBs and are not at goal. 90% of the patients with IgAN are on an ACE or an ARB and 90% of those patients are not at goal. So we have about 80% of the addressable population that can be better served by FILSPARI.

But the second aspect that would answer your question is we've done -- we're the company that's conducted the only treatment-naive trial in the space. So we have a trial called the SPARTAN trial, where we looked at patients that were completely treatment naive. They were just diagnosed based on biopsy for their IgA nephropathy. And we -- these patients were not on ARV. They were not on an SGLT2, -- they were not on a steroid. Their first therapy for their kidney disease was sparsentan. And what we saw was compelling. We saw that there was about a 70% reduction in their proteinuria out to 24 weeks. Nearly 2/3 of them were able to get into complete remission of their proteinuria and their eGFR was stable for that 6-month period.

At the end of 6 months, we did a repeat biopsy. So a very intensive clinical protocol, but one that is going to inform us not just on the function, but the structure of the kidney when you're treated with FILSPARI. So we are seeing a very compelling profile when you initiate FILSPARI early, and it makes sense because when you think about a nephroprotective therapy, you want to intervene earlier.

On average, the patient with IgA nephropathy is diagnosed, they've already lost about 50% of those nephrons. Those nephrons are never coming back. And so what you want to do is everything you can to protect the remaining nephrons you have. So to be able to start with a superior therapy like FILSPARI early at diagnosis is going to give the patient the best opportunity to be able to retain those nephrons. And then we've got other treatment options if this patient does need more, for example, the potential for B-cell complement, et cetera.

And that data is sort of -- is that sort of within the scope of the current label? I mean a physician could find a new patient and employ FILSPARI from right out of the gates, right? Or is that -- would there be more work that needs to be done in terms of the label language to kind of carve that out in a more structured way?

Yes. So the SPARTAN data, the treatment-naive data is not within our label. We've not submitted that to FDA. The indication statement, however, is broad for the treatment of IgA nephropathy. So a physician for their own decision can decide whether they want to start with FILSPARI or whether they want to start with an ACE or an ARB and then wait for that patient to fail. That's really up to the physician and for the payer to be able to decide.

Peter can certainly speak to what we're seeing in terms of physician prescribing behavior.

Yes. Maybe one point to -- like anecdotally, what I've heard several times now is that based on CADIGO and based on the RADR data set that I was referring to earlier, that actually biopsies are being done early on. And I heard examples like patients with proteinuria levels like 0.4 that wouldn't be biopsied historically, but are being biopsied right now. Physicians saw sclerosis, identified IgA nephropathy and actually started FILSPARI right away. This patient was not on RAS inhibitors. We don't promote that specifically, but I hear anecdotally feedback and it is consistent with the label we have right now.

You mentioned, of course, being a foundational therapy and the intersection with the B cell modulators. What about some of the other recent launches like this drug called Vanrafia? How do you see that playing out?

Yes. To Eric's earlier point, you have basically 2 treatment categories. One is really focused on protecting the remaining nephrons. The other is more upstream on the immune suppression and immune modulation. [ Vanrafia ] and FILSPARI are the only 2 novel medicine in that foundational category. FILSPARI, I think, is differentiated because it is a different mode of action. FILSPARI is inhibiting both bad actors in the kidney that are actually causing damage being endothelin as well as angiotensin. And you want to suppress both simultaneously.

Atrasentan is the other product that you are referring to. It's a single endothelin inhibitor, but it's kind of like dependent on RAS inhibition. We know that generic RAS inhibition in clinical practice is often suboptimal. And you basically see that in all long-term compliance and adherence trials. And we often hear that from the community as well. My hypothesis, and it's my personal hypothesis that may be the reason after 9 months, you saw less of an absolute reduction in proteinuria with atrasentan relative to FILSPARI. And then FILSPARI has the long-term benefit that we have shown published and is being reflected in our label as well.

So I do believe based on the consistent nephroprotection that you have by inhibiting 2 bad actors in the kidney, together with the long-term data and the superior effect versus a maximally dosed RAS inhibitor, that we have a very strong position versus atrasentan. The only aspect that they could say like, well, we are better in that is the REMS that you asked earlier about. But I think the modification to now 3 monthly monitoring is consistent to what they actually have in their label as well, even though it's without REMS.

Okay. We could keep going on IgAN, but we want to talk about the other indication, which is an important one, potentially the first approval, if it happens, which is a PDUFA coming up in January 13. Of course, this is -- I'm referring to FSGS. So tell us about the work there, about the Phase III work as well as the work with this Parasol working group and the plans for which is an expected AdCom later in the year.

Yes. So this is a story that I think we've seen previously within rare diseases where oftentimes you need to design a trial, select an endpoint and power a trial without having a rich literature to base it on. In FSGS, when we designed our DUPLEX trial, the only data that we had was from our Phase II DUET study, which showed a superior profile in proteinuria over maximum dose irbesartan. And like many other kidney diseases, we were basing our view on reducing proteinuria in a trial can improve the eGFR over time or can stabilize eGFR over time.

What we learned when we completed our DUPLEX study was that we showed a profound reduction in proteinuria that was superior to irbesartan, and we showed a clinically meaningful difference in the chronic slope of eGFR of about 0.9 milliliters per minute per year, but that was not statistically significant. The eGFR difference was not statistically significant. And so we were not able to file an sNDA for this indication.

FDA told us at the time, don't file based on eGFR data, continue to do work with the FSGS community for us to better understand these results. That's really where PARASOL was born. PARASOL was born out of a public-private partnership with FSGS KOLs globally, the patient community as well as global regulators, including FDA. We were not involved in PARASOL. But the real objective of PARASOL was to identify what the right endpoints were for this disease because I think our results really shocked everyone that you were able to get a 50% reduction in proteinuria that did not translate into a benefit in kidney function within 2 years.

And what PARASOL did was they asked KOLs around the world with FSGS data to donate their registry data. 26 registries were donated to be able to pool and look at these patients over time to see what we were missing in studying this disease. And the first conclusion that came out of their analysis was eGFR is, of course, important. It's a measure of kidney function. It's just not feasible in an FSGS clinical trial. And that's because the variability is too high.

And the variability in FSGS is high for 2 reasons. The first is it's a heterogeneous disease. Unlike IgA nephropathy, where the etiology of the disease is very well defined and it's singular, in FSGS, you can have FSGS that is immune-mediated. It could be genetic. And within genetic, you can have different genotypes or it can be an unknown cause or it could be secondary to another disease. In addition, you can have variability within a single patient where over time, this is a relapsing and remitting disease, and so the eGFR can be highly variable. That contributed in our trials to variability in our FSGS trial that was more than double the variability that we saw in our IgAN trial. So PARASOL really basically explained what we saw in our programs.

The second conclusion from PARASOL was to say, if it's not eGFR, what possibly could the endpoint be, and they looked at what is biologically plausible with this disease. Regardless of what type of FSGS you have, if you have FSGS, you have a disease of the podocyte. You have a podocytopathy where over time, the podocytes, which are the filtering cells within the nephrons, begin to die, they begin to swap off, and that is what contributes to progressive proteinuria which led them to their third conclusion, which is, can proteinuria be independently predictive of a patient's risk of kidney failure over time. And what they saw is that for patients that are able to lower their proteinuria to certain thresholds, you're able to reduce a patient's risk of kidney failure at 8 years to 85% to 90%, which is what led PARASOL to say proteinuria really should be the endpoint for FSGS trials.

With that in mind, when that -- those conclusions were reported out, we went back to the FDA and said, are we able to then submit an sNDA evaluating the benefit of sparsentan in our Phase II and Phase III, showing a robust and consistent reduction in proteinuria. The FDA said they are open to that submission, and they now are reviewing the program. They said that they're planning to have an advisory committee to review our results. And we've not yet seen that in the public register. So we'll see what comes with it, but the engagement with the FDA has been consistent with our experience with our IgAN review.

And what do you -- how do you expect the discussion to go, assuming there will be an AdCom. You're going to make essentially the same points that -- the same conclusions that PARASOL came away with. You're going to reiterate those at the AdCom? Or will there be additional analyses as well? How will that work?

Yes. So we don't yet know what FDA would focus on for the advisory committee, assuming they have one. What we can go on is based on what they shared with us at our Type C meeting, which they said our review of this file is essentially going to be understanding the benefit of FILSPARI in the context of PARASOL. So we do believe that PARASOL is going to be a very important aspect to educate the panelists on why does eGFR not work? Why did we miss our endpoint in a trial that was well designed, well conducted and clearly showed this benefit on proteinuria. So I think that's going to be an important context setting.

What's important also is to remind everyone we did not contribute or donate our data to PARASOL. We wanted to retain the independence of our data set so that FDA can independently review our data in the context of what was recommended as an endpoint for PARASOL. So what we believe is going to be important is to show that what PARASOL would predict, you actually see in the first clinical trial, the first Phase III interventional trial done in this disease, which is if you can lower proteinuria, you actually have a benefit on hard endpoints. And we had an analysis that was presented at the European Renal Association meeting this year from our Phase III study.

When you look at patients in our Phase III study, they were able to achieve either partial or complete remission, their risk of hard endpoints, so kidney failure, renal replacement, their eGFR is less than 15, so essentially kidney failure. The risk is reduced within a 2-year time frame by 67% to 77%. That is incredibly meaningful when you think about the progressive nature of this disease. And so it does replicate for the first time in a clinical trial setting, what we're seeing in PARASOL.

So that's really what we're preparing. Of course, we'll look to learn more from the agency on what they want to ask at an advisory panel, but that's the focus of ours given what they shared with us at the Type C meeting.

And for that analysis, you just described it, it was sort of like you picked a point below which you saw that much improved risk profile.

So what we looked at was the way that PARASOL analyzed the data is they looked at patients between week or month 12 and 24. So if patients were able to achieve certain thresholds of proteinuria control within that 12-month period, they then looked at what happens at 7 to 8 years. So the hypothesis is if you can get proteinuria below a certain point, that's going to have some kind of effect longer term.

What we looked at is within our 12 -- our 24-month trial for patients that were able to achieve those, what happens within that same 24-month period because we didn't yet follow them longer than that. But even within a 2-year period, we were able to show that very meaningful reduction in the risk of hard endpoints. We have other measures that were prespecified like our partial remission endpoint showing that there's a very consistent treatment effect, whether that's measured at 9 months or 2 years or at any point in that 2-year trial, showing a consistent 1.5 greater proportion of patients that achieved partial remission.

So there are a number of different ways that we can look at proteinuria. When you take a step back, what's important is it doesn't matter. Every single way that we look at proteinuria, you see a superior treatment effect compared to maximum dose irbesartan.

So I guess what I was getting at is -- I mean, there was a specific proteinuria -- there was a number that you went above and below that showed this risk stratification. Did you do that in kind of like as a latter, like as you progressively lower the proteinuria, you continue to see even better long-term risk? That's what I'm getting at.

Sorry. Yes. So for context, PARASOL showed that the lower you get, the better. It's incremental. You basically -- once you get below 1, you're getting most of the risk reduction from that trial. When you look at the data from DUPLEX, -- when we look at partial remission, which is less than 1.5 grams of protein and a reduction of greater than 40% of proteinuria from baseline, you see a 67% risk in hard endpoints. When you get further down to complete remission, which is less than 0.3 grams of protein, that risk reduction further improves to 77%. So you do see that step...

Right. So you're getting 2 points on the line. So I mean that should be quite a strong argument, right? I mean...

We think so. We think so. And we're certainly working with many of the experts to make sure that we are able to provide a very cogent and robust description of our data, again, particularly in the context of the PARASOL findings.

Okay. Okay. We have 3 minutes. So one more -- a somewhat unrelated program, pegtibatinase. Can you talk about that one, please quickly? And how that ended up being part of Travere and what the origins of that were? And then also, what are the plans given now you're restarting the manufacturing?

Yes. So we're very excited about our program with pegtibatinase, which is for classical homocystinuria or HCU. This is a program that came out of the University of Colorado. HCU is a genetic metabolic disease. It is a disease that for half of the patients is diagnosed upon newborn screening. The other half of the patients are missed, but continue to have a toxic accumulation of homocysteine that manifests then symptomatically within oftentimes their childhood and teenage years.

By the time patients are a teenager, about 25% of them will have an ischemic event. Before their 30th birthday, half of them have an ischemic event. So it's a very significant disease that current standard of care is really inadequate nutraceuticals and a very, very strict protein-restricted diet that is the worst part of the disease for many of these patients. This is a humanized pegylated enzyme replacement therapy and would be the first disease-modifying therapy that really addresses the enzymatic defect for these patients.

We showed in our Phase II a profound improvement of 67% reduction in homocysteine levels and 100% of these patients were able to get below the guideline target of 100 micromoles of homocysteine. 50% of them were able to get below 50, and some of them have been able to normalize their homocysteine levels. The key of our Phase III, which we are in is to be able to replicate those, but also as part of a substudy, demonstrate what patients want most, which is keep control of the disease, but allow me to eat a little bit more protein, allow me to normalize part of my diet.

So that's where we are. We ran into a manufacturing challenge when we moved from clinical scale to commercial scale. We paused enrollment to make sure we were able to resolve those. We have made very good progress in resolving those manufacturing scale-up challenges. And our target has been to reinitiate enrollment of our Phase III next year. We're well on track to be able to do that, and we'll look to provide further updates as soon as we can. And we want to make sure that we're able to move very quickly in Phase III because these patients have been waiting very patiently for what could be the first therapy approved in decades for their condition.

And now why it fits with us? We're a rare disease company. We've had other therapies. Some of them we've out-licensed or divested to Mirum that really is very similar to the capabilities within HCU, but also core to what we've been doing with sparsentan is identifying these patients, working with regulators and thought leaders to identify the right endpoints, particularly where there have not been a regulatory pathway and to be able to enroll these trials have been very challenging.

So Peter's team has done an amazing job with the launch of FILSPARI. We continue to have a cystinuria treatment, Thiola that is the gold standard for that condition, and we'll take a lot of those learnings to get to the commercialization of pegtibatinase.

So that one, you'll take that one to commercialization yourself.

That's our plan. That's our plan. It's a very meaningful opportunity for the company and certainly for this community.

And you have the global rights from University of Colorado.

That's right. That's right.

Okay. So that could launch sometime, I guess, when what are we talking about?

Well, we've not provided the timing. We want to make sure the gating factor is really to resolve the manufacturing scale up. Once we get through to Phase II, that's typically we'll have better line of sight to that time line.

Okay. Excellent. All right. Well, thank you so much. I appreciate it, and we'll be chatting again soon.

Thank you, Yigal. Thank you.

Alright, welcome.

Good afternoon, and welcome to the Travere Therapeutics Second Quarter 2025 Financial Results Conference Call. Today's call is being recorded.

At this time, I would like to turn the conference over to Nivi Nehra, Vice President, Corporate Communications and Investor Relations.

Thank you, operator. Good afternoon, and welcome to Travere Therapeutics' Second Quarter 2025 Financial Results and Corporate Update Call. Thank you all for joining.

Today's call will be led by Dr. Eric Dube, our President and Chief Executive Officer. Eric will be joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; Peter Heerma, our Chief Commercial Officer; and Chris Cline, our Chief Financial Officer. Dr. Bill Rote, our Chief Research Officer, will join us for the Q&A.

Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by the statement.

Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the Risk Factors section in our Forms 10-Q and 10-K filed with the SEC.

In addition, any forward-looking statements represent our views only as of the date such statements are made, August 6, 2025, and Travere specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances.

With that, let me now turn the call over to Eric.

Thank you, Nivi. Good afternoon, and thank you all for joining us. The second quarter of 2025 was a standout for Travere, a reflection of strong strategic execution and continued momentum in delivering against our mission.

At the heart of this progress is FILSPARI, where we are advancing our leadership in rare kidney disease by deepening our impact in IgA nephropathy and laying the foundation for potential expansion into FSGS.

In IgAN, we delivered our strongest commercial quarter to date with continued demand driven by both new and repeat prescribers. As the IgAN treatment landscape evolves, physicians are increasingly adopting FILSPARI as foundational care, recognizing the meaningful and consistent outcomes it delivers and doing so earlier in the disease process.

This growing confidence reflects our ongoing strategy to establish FILSPARI as the new foundational therapy for IgA nephropathy. There are several pillars to this strategy that we expect to be further solidified through year-end.

First, the continued generation of robust clinical evidence to support the use of FILSPARI across a broad range of patients and in combination with other classes of medicines.

Second, broad access aligned with the full approval indication statement, payer coverage, and an expected modification of the liver monitoring REMS and removal of the pregnancy testing REMS.

And finally, the continued real-world clinical experience and growing recommendation by nephrologists and treatment guidelines that recognize FILSPARI's ability to reduce proteinuria and reinforce the benefits of getting patients to complete remission.

I am pleased with the tremendous progress that our team has made to date, which sets us up for sustained growth in an expanding IgAN market.

Our performance in Q2 reflects the strength of this positioning and the growing use of FILSPARI as a foundational nephroprotective treatment in IgAN, even as new treatments enter the market.

While it's still early days in the evolving IgAN treatment landscape, FILSPARI's performance is directly aligned with the expectations that we have set over the last few years and validation of its path to foundational use.

Jula and Peter will review the progress of our strategy in greater detail. We've also seen strong progress outside of the U.S. by our partners, CSL Vifor and Renalis, as they look to expand access to FILSPARI internationally.

We've entered the second half of the year from a position of strength, and we're ready to build on this momentum.

The sNDA review process for a potential second indication for FILSPARI in FSGS is advancing as expected. We're preparing for what could be an extraordinary milestone for Travere and the FSGS community.

If approved, FILSPARI would become the first ever treatment approved for this underserved patient community, a breakthrough for patients and a near- and long-term growth opportunity for our company, given that there are no other FSGS therapies likely to be available in the near future.

Beyond FILSPARI, we continue to advance our pipeline with a drive to transform paradigms in rare diseases like classical homocystinuria, and we remain on track to reinitiate enrollment in the HARMONY study for pegtibatinase next year.

With a robust and growing foundation in IgAN, the potential to be the first approved medicine in FSGS, and a pipeline built for continued innovation, we remain confident in the road ahead.

I will now hand the call over to Jula for an update on our clinical programs. Jula?

Thank you, Eric. As a nephrologist, it's incredibly rewarding to witness the continued innovation in IgA nephropathy, a disease where, not long ago, patients had very few options.

We are expanding the body of evidence that supports the foundational role of FILSPARI across a broad spectrum of IgA nephropathy patients at risk of disease progression, ranging from those who are newly diagnosed to those with recurrent disease post-transplant.

FILSPARI's unique ability to target 2 pathways causing kidney injury, endothelin 1 and angiotensin 2, provides patients with IgAN nephropathy a non-immunosuppressive treatment option to help preserve kidney function.

We were pleased to engage with the medical and patient community at several recent congresses where we presented important new data that continue to reinforce the nephroprotective effects, strong safety profile, and emerging disease-modifying potential of FILSPARI.

Select data from these congresses included in the Phase II SPARTAN trial, when used first line in treatment-naive IgAN nephropathy patients, FILSPARI-treated patients achieved an approximately 70% proteinuria reduction, with nearly 60% of the patients in the study reaching complete proteinuria remission and stable eGFR through 24 weeks.

Also in the SPARTAN study, an analysis of patient samples showed that FILSPARI-treated patients with IgA nephropathy demonstrated rapid and sustained reductions in urinary B-cell activating factor or BAF, and complement factor C5b through 9, as well as reductions in pro-inflammatory and pro-fibrotic biomarkers.

When taken in combination with our preclinical data showing FILSPARI protects from mesangial deposition of IgA, these data suggest a potential role of optimal dual inhibition of endothelin-1 and angiotensin 2 in modifying the underlying disease.

In the Phase III PROTECT open-label extension that is ongoing, patients transitioning from maximally titrated irbesartan to FILSPARI after the double-blind period also achieved approximately 50% reductions in proteinuria and a relatively stable eGFR out to 1 year.

Together with the kidney function preservation FILSPARI provides, these new data further reinforce FILSPARI's disease-modifying potential in IgA nephropathy without immunosuppression.

As the IgAN treatment paradigm evolves, we expect combination therapy to become the new standard to help more patients reach complete proteinuria remission, which is recognized as a treatment goal in the draft update to the KDIGO guidelines.

FILSPARI remains uniquely positioned as the only medicine to replace RAS inhibitors as a more effective foundational therapy in IgA nephropathy with a profile that is complementary to the emerging therapeutic classes.

We are also approaching the August 28 PDUFA date for the removal of the embryo-fetal toxicity REMS and the potential modification of the liver monitoring REMS to quarterly. With no cases of Hy's law to date, we remain confident in the safety profile of FILSPARI to support this change.

Turning to FSGS. Our sNDA seeking full approval of FILSPARI in FSGS was accepted by the FDA with a PDUFA date of January 13, 2026.

As a reminder, the work by the independent PARASOL group established proteinuria as a valid surrogate endpoint for kidney failure in FSGS and helped pave the way for regulatory consideration of proteinuria reduction for full approval.

The sNDA review process is advancing as expected, and we're preparing for an advisory committee to discuss FILSPARI as the first potential approved medicine for FSGS.

Our team is actively preparing to present the strong data from DUPLEX and DUET in the context of the independent PARASOL findings. For example, earlier this quarter, we presented new analysis from the DUPLEX study that confirmed the PARASOL findings.

In DUPLEX, significantly more FILSPARI-treated patients achieved either partial or complete remission compared to irbesartan. Importantly, those patients who achieved partial or complete proteinuria remission in the study, irrespective of treatment arm, had a 67% to 77% lower risk of kidney failure, respectively.

These data represent the first trial-level evidence in support of the independent PARASOL analysis of proteinuria as a validated surrogate endpoint in FSGS.

Lastly, on our HCU program, we continue to be excited about the potential of our investigational enzyme replacement therapy, pegtibatinase.

We have made strong progress on our manufacturing scale-up to support our Phase III trial and a future commercial launch, and are on track towards restarting patient enrollment in the Phase III HARMONY study next year.

I'll now turn the call over to Peter for a commercial update. Peter?

Thank you, Jula. I'm pleased to report that our commercial team executed exceptionally well in Q2, as demonstrated by our strong performance metrics.

FILSPARI net product sales reached approximately $72 million in the U.S. in the second quarter, representing significant year-over-year growth.

This performance was driven by strong demand, expansion, and deepening of the prescriber base, as well as further efficiencies in our fulfillment process and solid therapy compliance and persistence.

As the only fully approved non-immunosuppressive kidney-targeted therapy for IgA nephropathy, FILSPARI remains uniquely positioned to replace the historical standard of care in this evolving treatment landscape.

The growing recognition of FILSPARI's nephroprotective profile, not just from returning prescribers, but also from nephrologists who are newer to the brand, resulted in 745 new patient start forms this quarter, approximately a 43% increase compared to the same period last year.

At a time when new treatment options are emerging for IgA nephropathy, feedback from our field teams and recent market research emphasize physician confidence in FILSPARI's established position in clinical practice.

Nephrologists regularly cite FILSPARI's consistent, rapid, and sustained proteinuria efficacy with long-term kidney preservation benefits, a safety profile that allows for chronic use, and a patient-friendly, once-daily oral administration that optimally inhibits 2 critical kidney-damaging pathways as key reasons for making FILSPARI their foundational therapeutic option.

Importantly, many physicians are choosing FILSPARI earlier in the treatment journey. This reflects a growing emphasis on earlier intervention and a shift away from legacy approaches, such as the off-label use of RAS inhibitors or steroids.

Based on our research, about 70% of the addressable patients with IgA nephropathy have elevated proteinuria levels but below 1.5 grams per gram.

With the proteinuria threshold being removed in the FILSPARI label at full approval, FILSPARI is particularly well-positioned in this large patient segment, allowing for sustainable demand potential.

As we look to the remainder of the year, as with any rare disease product, seasonality could drive some variability quarter-over-quarter, but we expect that we will continue to identify new prescribers and that the use of FILSPARI will further deepen as foundational care amongst current prescribers.

We believe this will be driven by continued positive experience consistent with FILSPARI's superior clinical profile relative to the historical standard of care, and also driven by the anticipated final KDIGO guideline publication and the potential REMS modifications, which may further simplify access for patients.

Turning to FSGS. If approved, FILSPARI would become the first approved therapy for FSGS, a progressive and often debilitating rare kidney disease with a significant unmet need.

Given the feedback from nephrologists and the broader FSGS community, we believe FSGS could be an even bigger opportunity with a more rapid uptake versus what we have experienced with our launch in IgA nephropathy.

We are actively expanding and preparing our commercial organization to be ready to serve this patient community, beginning with potential approval early next year.

In summary, Q2 was another quarter of strong execution and meaningful growth for FILSPARI amidst the evolving IgA nephropathy treatment landscape.

We remain confident in our strategy and are encouraged by the feedback from the medical community and the continued momentum in U.S. adoption.

With a growing body of clinical and real-world evidence, expanding prescriber engagement, and the potential to serve more rare kidney disease patients through future label expansions, FILSPARI is well-positioned to continue its leadership as a foundational treatment.

Let me now turn the call over to Chris for the financial update. Chris?

Thank you, Peter, and good afternoon, all. Our financial foundation continues to strengthen.

In the second quarter, net product sales grew approximately 82% over the same period last year, and we continue to make disciplined investments in areas of high growth, such as in building further momentum for FILSPARI in IgA nephropathy, preparing our organization for a potential launch of FILSPARI in FSGS and advancing manufacturing to restart enrollment in the pivotal pegtibatinase study.

Beginning with revenue. In the second quarter, we generated U.S. net product sales of $94.8 million. As Peter highlighted, FILSPARI continued to grow significantly in the second quarter, generating $71.9 million in U.S. net product sales.

THIOLA and THIOLA EC contributed $23 million in net product sales for the second quarter, and these medicines continue to be a meaningful option for patients living with cystinuria. But as we've highlighted previously, we anticipate more generic competition in the coming quarters.

During the second quarter, we also recognized $19.6 million of license and collaboration revenue, resulting in total revenue of $114.4 million.

Included in the license and collaboration revenue line this quarter is the previously announced one-time $17.5 million milestone payment from CSL Vifor, which resulted from the conversion of conditional approval of FILSPARI to full approval in Europe earlier this year.

Turning to operating expenses. Our research and development expenses for the second quarter of 2025 were $49.4 million compared to $54.3 million for the same period in 2024.

The decrease in R&D is largely attributable to reduced clinical activity in the Phase III HARMONY study while we optimize our manufacturing efforts.

On a non-GAAP adjusted basis, R&D expenses were $45.4 million compared to $50.6 million for the same period in 2024.

Selling, general, and administrative expenses for the second quarter were $76.2 million compared to $64.8 million for the same period in 2024.

The increase in SG&A is largely attributable to increased amortization expense related to FILSPARI royalties, as well as increased investment to support the ongoing launch of FILSPARI in IgA nephropathy following full approval and preparing for a potential FSGS launch in January.

On a non-GAAP adjusted basis, SG&A expenses were $55.5 million for the second quarter compared to $48.3 million for the same period in 2024.

Total other expense net for the second quarter of 2025 was immaterial compared to the net expense of $1.9 million in the same period in 2024.

Net loss for the second quarter of 2025 was $12.8 million or $0.14 per basic share compared to $70.4 million or $0.91 per basic share for the same period in 2024.

On a non-GAAP adjusted basis, net income for the second quarter of 2025 was $11.9 million or $0.13 per basic share compared to a net loss of $50.1 million or $0.65 per basic share for the same period in 2024.

As of June 30, 2025, we had cash, cash equivalents, and marketable securities totaling approximately $319.5 million.

As I highlighted earlier, this cash balance reflects the net proceeds of the $17.5 million payment we received from CSL Vifor during the quarter, and we remain on track to potentially achieve additional milestone payments tied to key market access achievements later this year and sales-based achievements in the future, which should further enhance our financial flexibility.

Looking ahead, we expect continued revenue growth driven by robust underlying demand for FILSPARI and IgA nephropathy, with a strong balance sheet and potential additional incoming milestone payments as well as a disciplined approach to investing in our key growth drivers, we are well positioned to execute on our strategy and deliver sustainable value over both the near and the long term.

I'll now turn the call back over to Eric for his closing comments. Eric?

Thank you, Chris. As you've heard, our team has delivered strong performance across our priorities for the first half of 2025.

We are well-positioned and eager to continue this momentum. My team and I are deeply motivated to support the rare disease communities we serve.

Recently, I had the honor of attending the annual Spark Patient Meeting of the IgA Nephropathy Foundation. At the meeting, I heard many stories of resilience and of hope. This community has been advanced advocating and hoping for a future with therapies developed for them that can save off kidney failure.

We are proud to be part of this journey, and we are committed to the same goal for the FSGS and HCU communities.

Now let me turn the call over to Nivi for Q&A. Nivi?

Thank you, Eric. Operator, we can now open up the line for Q&A.

[Operator Instructions]

We will now take the first question from the line of Joseph Schwartz from Leerink Partners.

This is Will on for Joe. Congrats on the strong progress this quarter. So one for FSGS. As you prepare for the ADCOM, what do you anticipate the major topics could be? And how do you plan to respond to the FDA's inquiries here? Do you have a sense for who might be on the panel itself?

And given this group of experts will likely include nephrologists and cardiologists, how do you plan to effectively message your case to these 2 different groups of physicians?

Well, thanks so much for the questions. Jula, I will turn those over to you.

Thanks for the question. So good point. Anytime a rare disease goes before an advisory committee, there's certainly an educational component that we need to do about the disease and the pathophysiology.

Importantly, there are both nephrologists and cardiologists part of the panel, and they all know that proteinuria is harmful, and they know the importance of blocking both the RAS system and endothelin-1 to reduce cardiovascular and renal outcomes.

So, we certainly are prepared to educate the mix of panelists, I think importantly about the biologic plausibility supporting proteinuria as a validated endpoint, why eGFR is challenging in FSGS, and then followed by the strong clinical data showing sparsentan meaningfully and significantly reduced proteinuria compared to an active comparator.

Our next question comes from the line of Anupam Rama from JPMorgan.

Just wondering if you could comment a little bit on the cadence and level of engagement you've had with the agency heading into the REMS update for FILSPARI, just given the evolving landscape and what we've seen from a regulatory perspective in other cases in the sector.

Thanks for the question, Anupam. And certainly, we've been monitoring the overall landscape with regard to the FDA. Bill, why don't you comment on what we've seen with our programs?

Yes, certainly. What we've seen is basically through the lens of 2 sNDAs, both with the sNDA for the modification of the REMS frequency and the removal of the embryo-fetal toxicity REMS, as well as the sNDA for FSGS.

Our interactions have been progressing as we'd expect. And the back and forth have been very similar to what we experienced just last year with the NDA for full approval in IgA nephropathy.

The frequency of interaction, the types of questions, it feels just the same. So we certainly see, on our part, a very engaged and active review team.

Our next question comes from the line of Laura Chico from Wedbush.