Hey, everyone. Greg Wiesner and Frances Dovell here, associate biotech analysts at TD under Tyler Van Buren. Thank you very much for joining our 45th Annual Healthcare Conference. For our first session, we have a hybrid presentation and Q&A with Travere Therapeutics, and it is our pleasure to introduce Dr. Eric Dube, President and CEO, and Chris Cline, CFO of Travere. Eric and Chris, it is a pleasure to have you both here. Thank you very much for joining us. I will go ahead and kick it over to you to kick off the presentation when you're ready. Thank you.
Great. All right. Thank you very much to the Cowen team for hosting us. You can look at our website for forward-looking statements. What I'd like to do is first introduce you to Travere. We are a company that is based in San Diego, focused exclusively on rare disease. Our focus really is to transform the treatment standards in those diseases that have historically had little or no approved therapies. You can see here the three areas that we're focused on currently: IgA nephropathy, which really is emerging as a success story within rare disease, where there are now three therapies that are approved to fully, one under accelerated approval. The second disease, FSGS, which is another rare kidney disease, one that is rapidly progressing. I'll talk a little bit more about that. There is nothing approved to date in FSGS.
The third area that we're focused on is a rare metabolic disorder called classical homocystinuria, or HCU. There is one older therapy that is approved, but essentially, the current standard of care is a very restrictive diet. We're looking at our pegtibatinase program as a potential to really transform the treatment outlook for that community. Here's an overview of our pipeline and our portfolio, essentially FILSPARI, or sparsentan, which is commercially available for IgA nephropathy. We have completed a phase III in FSGS, and then we have pegtibatinase in HCU. We also have an older therapy that is currently the standard of care in cystinuria, another rare urologic or kidney disease called THIOLA and cystinuria. For 2025, we have three key priorities. The first is to continue the success that we have in launching FILSPARI in IgA nephropathy, both in the U.S.
as well as with our partners outside of the U.S., in really establishing a stronger foundational therapy that has historically been played by off-label ACE inhibitors and ARBs. We're looking to continue to increase the breadth of use and really, again, replace the traditional role that ACEs and ARBs have played, where 90% of patients are on those therapies, and yet 80% of those ever fail at all to achieve remission of their proteinuria, thereby affecting the potential risk of kidney failure. The other aspect of IgA nephropathy is to modify our REMS for liver monitoring. We have a PDUFA date for that modification at the end of August.
While that has not been a barrier to date, for any patient for whom a nephrologist says, "This isn't for you," whether you have multiple jobs, you have transportation issues, et cetera, we want to make sure that this innovation is made available for them. Our second priority is to submit an SNDA for FSGS. We're on track to do so by the end or around the end of this quarter. We're really excited at the potential for FILSPARI to be approved as the first therapy for FSGS, a community that is eager for anything that is going to be effective for their condition. Finally, our goal is to continue our scale-up with pegtibatinase. We ran into a manufacturing challenge last year in the fall. We've made very good progress with our CDMO partners.
Really, our focus this year is all about manufacturing scale-up so that we can reinitiate enrollment in our phase III in 2026. Across all of that, we continue to look at business development, particularly within the rare kidney disease, where we are seeing a renaissance within RKD, where historically this has been an area of very, very little innovation, and yet is one of the most common causes of kidney failure in this country. If we focus a bit on IgA nephropathy, this is a condition that affects about 150,000 patients in the U.S. The addressable number of patients that we see for FILSPARI is over 70,000. We do expect those numbers to continue to increase with the new draft KDIGO guidelines calling for earlier biopsy. This is a condition that is diagnosed upon biopsy of the kidney.
Symptomatology is typically patients see blood in their urine, protein in their urine upon typical screening, are diagnosed, and then referred to a nephrologist. Historically, these patients are being treated in a two-prong approach. I mentioned that ACE inhibitors and ARBs, based on their ability to reduce proteinuria and are known to be nephroprotective within the broader CKD arena, are used in about 90% of patients. The other aspect historically has been steroids. Systemic steroids have been used to be able to reduce the overactivation of the immune system. We are now seeing innovation to replace the traditional role that systemic steroids have played. When we look at the recently published draft KDIGO guidelines, they continue this framework of a two-pronged approach. Those therapies that are kidney-directed, like FILSPARI, and those that are directed to overactivation of the immune system.
In fact, any patient that is biopsied, diagnosed with IgA nephropathy, and has proteinuria above 0.5 grams, the KDIGO guidelines call for simultaneous combination therapy to attack both of these approaches. We talk about FILSPARI as a new foundational therapy. What we mean by foundational therapy are those therapies that target the kidney, where the damage is, that are nephroprotective, and that they provide long-term prevention or protection of eGFR, which is essentially the predictor of how long you have until kidney failure, and that can be used in a broad range of patients chronically. That places FILSPARI quite nicely in that foundational therapy, and it is non-immunosuppressive, which is really important for many patients. That also can be used in combination with any of these other therapies, like targeted steroids or any of the potential immunosuppressants, B-cell complement, that are eventually approved for this condition.
Combination therapy with a kidney-targeted and immune-system-targeted therapy really is the way of the future. Even with all of the potential therapies that are coming, this framework will continue to be the one that drives the treatment paradigm. When we look at the profile of FILSPARI, we are very well positioned to become the new foundational therapy. It is a once-a-day therapy that targets two aspects of overactivation within the kidney that are common injury pathways within this disease: angiotensin and endothelin, both of them very well characterized in their mechanism within kidney damage. The second is it's the greatest magnitude of proteinuria that has been seen in a phase III program. We have two-year data on safety, two-year data on the accumulation of preservation of kidney function with eGFR, as well as a sustained benefit on proteinuria out to two years. It is non-immunosuppressive.
Again, based on that mechanism, we believe it can be used in combination with many of the therapies that are currently in development. When we look at our fourth quarter performance, this is the first quarter since full approval, as well as the publication of the draft KDIGO guidelines, we saw a very meaningful inflection in demand, with nearly 700 new patients being prescribed FILSPARI, as well as an inflection of nearly 40% growth quarter over quarter. With very broad and improving payer access, we continue to expect these dynamics to fuel growth into the future. In fact, these are the key drivers of growth as we look to the future and being able to reach many of those 70,000 patients.
It's the broad label, the new broad indication statement under full approval, the support from the KDIGO guidelines, as well as the call for earlier diagnosis, earlier biopsy, and more aggressive and more combination therapy. We believe this is critically important. The other aspect that is called out in the KDIGO guidelines is that FILSPARI is the only therapy that went head-to-head in a phase III program. We have superiority data over the historic foundational therapy of RAS inhibition that is clearly called out in the KDIGO guidelines. We also see that we can continue to increase the number of nephrologists that are shifting from the use of ACE inhibitors and ARBs to FILSPARI as a key growth driver.
All in all, it's a really exciting time in IgA nephropathy and one that I believe will be representative of not just the opportunity of growth for FILSPARI, but also for much of the innovation that's coming to this community. We have two partners outside of the U.S., CSL Vifor, that has begun to launch FILSPARI within Europe, as well as Renalis, that is looking at Japan and parts of East and Southeast Asia. We're very pleased with these collaborations and the progress that they have made. Turning our attention to FSGS. This is another rare glomerular disease that affects about half the number of patients as IgA nephropathy. Oftentimes, however, these patients are diagnosed earlier, many times in childhood, and the rate of progression to kidney failure is twice as fast as that in IgA nephropathy.
There is a real sense of urgency for treating these patients with FSGS. The other aspect of this disease that is unique, it is not a linear progression from diagnosis to kidney failure. It is a relapsing and remitting disease, which causes variability in kidney function over time, which has made it a challenge in clinical development. The other aspect is that we have a completed phase III program, the only phase III program that's been completed in this disease. It also was a head-to-head study looking at superiority versus max tolerated ARB. What we saw in that phase III program is a rapid and sustained reduction in proteinuria.
When you look at whether it's the change in proteinuria over time or the proportion of patients that were able to get to thresholds of proteinuria control, including complete remission, you see a superior profile of FILSPARI compared to max dosed irbesartan. At the end of two years, however, we were not able to show a statistically significant difference in eGFR, despite a clinically meaningful benefit in that endpoint. This surprised many, not just us, but the nephrology community. This galvanized the community of patients and nephrologists, the experts in FSGS, to come together to work on a better understanding of this disease and what endpoints may be feasible so that there can be innovation in FSGS like we're now seeing in IgA nephropathy. This group is called the PARASOL Group. It is comprised of the patient community, global experts in FSGS, as well as regulators, including FDA.
What they first concluded is looking at many different registries of FSGS. This is the largest analysis of FSGS patients that have been done to date that was reported out in the fall. The first conclusion was eGFR is not a feasible endpoint. It is important clinically, yes. Is it feasible in a clinical trial of two years? No. That is because it is highly variable. That relapsing and remitting nature of this disease makes it very challenging to reduce variability in a clinical trial. Also, when you look at the heterogeneity of this disease, you have patients that have primary FSGS that may be immune-mediated. There may be patients that have genetic FSGS or of unknown cause. All of that contributes to variability.
In order to power a study within a two-year period to show a benefit on eGFR, you would need to have nearly 1,000 patients per arm. Clearly not possible to be done. The second aspect was to look at this disease and say, what are the other endpoints that could be meaningful? You have to first look at what is going on in the disease process. What they concluded was that proteinuria, and particularly proteinuria caused by issues with the podocyte, which is the filtering cell within the glomeruli, is a common injury pathway within FSGS, regardless of the etiology. It is all about the podocyte, which causes proteinuria, but also proteinuria in and of itself is injurious to the podocyte. It really was a narrowing focus on proteinuria.
The next task of the PARASOL Group was to look at whether proteinuria can be an independent predictor of kidney failure independent of eGFR. Historically, proteinuria has a relationship with eGFR. eGFR is a surrogate endpoint, validated surrogate endpoint for kidney failure. How do we skip eGFR knowing that that's infeasible? The PARASOL Group, through 20 different databases and thousands of patients, clearly showed that if you can get patients' proteinuria below certain thresholds, you can have a profound reduction in their risk of kidney failure over eight years. Those data were presented at ASN in the fall, and that really has opened up the opportunity for us to go back to regulators, back to the FDA, and say, are we able to submit on our phase III DUPLEX data?
We had a type C meeting with FDA where we do now have a pathway, and this is the basis and the context in which we will be looking to submit for an SNDA for this indication around the end of this quarter. These are the data that were published in the New England Journal of Medicine about a year and a half ago from our phase III program. When you look at all of the pre-specified thresholds of proteinuria all the way down to complete remission of less than 0.3, you can see an increasing treatment effect of sparsentan compared to max dose irbesartan. A very profound and meaningful in one of the most proteinuric of the kidney diseases. Turning our attention finally to classical HCU. This is a genetic disorder that is oftentimes caught at newborn screening, but not always.
About half of patients, despite being born with classical HCU, are missed at newborn screening. This leads to, through eating protein in your normal diet, a toxic accumulation over time of homocysteine, which leads to issues of vision, mental acuity, bone formation, and perhaps most concerning to patients, half of them have an ischemic event by the time they're 30. The number one need of patients is not just in controlling their homocysteine levels. It's being able to eat a diet because the standard of care today is to severely limit your protein and really to have protein intake through a terribly tasting medical protein. This is an area of significant unmet need, and we're excited with pegylated enzyme replacement therapy that has shown promise in our Phase I/II COMPOSER study. Here you can see across different doses.
At the target dose that we've taken into phase III, you see a 67% reduction in homocysteine levels. 100% of these patients were able to get below the guideline target of 100 micromolar. Our phase III program, which was aligned with the FDA, really is innovative in one particular area. Not only are we looking to replicate the findings in our Phase I/II with a very similar placebo-controlledq trial, but also what we're looking at, and was one of the first times ever, is to protocolize the intake of protein in your diet to be able to address the number one need that these patients tell us. Our focus is this year to increase manufacturing scale for commercial scale, but then be able to reinitiate enrollment next year very quickly. These patients are waiting.
We're excited to be able to bring potentially the first therapy that really targets the core defect of HCU. With that, I'll end with a financial snapshot of Travere. We are very well financed to be able to support those three priorities. We continue to see growing revenues, and we're excited to be able to bring hope to these three communities that have been waiting far too long. Thank you.
For those in the audience, please feel free to chime in and raise your hand if you have a question. Maybe to start, can you give us a little bit of insight into what we can expect for FILSPARI's performance throughout 2025? And do you anticipate a similar quarter-over-quarter growth trajectory to what was observed in 2024?
Certainly. When we look at the drivers of growth within the IgA nephropathy arena, we do expect that most of these patients still are not in remission. There is a tremendous opportunity for newer therapies like FILSPARI to be able to reach these patients. Again, most of these patients are still not at remission and are on ineffective ACE or ARB. This is the key area that our team is focused on, to replace that and upgrade that foundational therapy. We do expect there to be a similar level of demand like we saw in the fourth quarter. In terms of quarter-over-quarter growth, know that I do not expect to see a 40% growth every quarter. We do expect to see that level of demand like we saw with the 693.
With that said, we've been incredibly pleased with the level of compliance and persistence with these patients because of the benefit they're seeing. We do expect that any additional demand that we see will fuel very strong revenue growth into the future.
Great. With the supplementary NDA acceptance in hand, what is the likelihood that the FILSPARI REMS modification will be updated? Furthermore, what steps remain towards the goal for full removal of the REMS?
Certainly. We have had discussions with FDA along the way, including when we first learned that we would be getting a REMS for liver monitoring. When we met with them about the opportunity to modify the REMS, we understood what they needed to see from us, including all of the exposure data. To date, we have still not seen cases of drug-induced liver injury, and our request was to shift from monthly monitoring for the first year to quarterly monitoring, which better aligns with how the majority of these patients see their nephrologist. With regard to full removal, we have a requirement, a post-marketing requirement to study these patients, 3,000 patients for two years of exposure. We are well on our way to be able to do that, and that is the point at which we would go back to them.
Again, assuming a consistent safety profile we've seen to date, we would go back and request full removal.
Okay, great. The IgA nephropathy landscape is evolving with several similar or mechanistically differentiated therapies nearing approval or in late-stage trials. How do you anticipate FILSPARI will be positioned as these new options emerge?
Sure. Look, it's a really exciting time for IgA nephropathy. If you think about going back to the illustration, you've got therapies that are targeting the kidney, like ACEs and ARBs, FILSPARI. You have those therapies that target the immune system, which causes the kidney damage. Historically, steroids, systemic steroids, and now a whole different number of classes. That combination therapy will continue. Our focus is to replace the role that ACEs and ARBs play because most of those patients are ACE/ARB failures. There is plenty of room, particularly with the guidelines now calling for simultaneous combination therapy across those two approaches. There is a lot of opportunity for growth, and I think the opportunity for many companies to educate nephrologists about the innovation that's there and the need to be more aggressive with the therapy.
For context, nephrologists were historically trained that IgA nephropathy was a slowly progressing disease. That is clearly not the case when you look at the rates of kidney failure. You typically will see someone diagnosed in their 30s, and they're told they have 10 years. That's something that we definitely need to change.
Maybe considering the potential H1 regulatory decision around atrosentan, do you think that atrosentan will or will not get a similar REMS?
It remains to be seen. I think if we look at what FDA told us and the rationale for a REMS for liver monitoring, this is a therapy that is in the broad ERA class. ERA class under primary pulmonary arterial hypertension does have a history of liver damage. Out of an abundance of caution, particularly under accelerated approval where your safety package and your efficacy package are not yet fully characterized, that was the rationale. We are prepared either way, but what happens with their approval? Again, the profile that we have with the FILSPARI is very clear.
Are there any plans to assess FILSPARI with add-on ARBs or B-cell modulators? Or do you think that they will largely play in different segments of the market potentially?
I think we are very eager with FILSPARI as a new foundational therapy to be able to demonstrate the benefit with other classes. We've done so with SGLT2s. We've studied also within our trials what the combination with steroids looks like. It's very difficult to do those combination studies before you have full approval, but we certainly are open and eager to be able to do that. With that said, when we look at those therapies that are coming behind us in the very near term, all of those are likely to be approved under accelerated approval. What that means is that they're likely to be limited in their indication statement to the most severe patients, those above 1.5 grams of protein and above. Also, those companies will not be able to discuss their eGFR data until full approval.
When we look at that segment of patients that are 1.5 grams and above, that's about 30% of the addressable population. There is going to be, I'd say, much more dynamism within that segment, which will be decreasing because when you look at the therapies that are available now under full approval, FILSPARI, Tarpeyo, you're able to address that and reduce their proteinuria so that is a segment that is going to be decreasing. The broader number of patients that have IgAN are likely to grow, those less than 1.5. Yes, they will come with, there will be combination therapy, but where they compete will be very different from those that have full approval.
Sure, absolutely. Great. For the next part of the Q&A, I'll kick it over to my colleague Frances to ask some questions about FSGS.
Yeah, so moving on to FSGS, what do you believe to be the probability of success that the FDA will accept the SNDA for FILSPARI and FSGS?
Certainly. I can't speak, and we don't typically speak about our regulatory interactions. What I can say is that we had a type C meeting after the PARASOL group reported out, and we believe that we've aligned on a path forward for submission. What we understand is that we have all of the data that are needed for that, and the FDA wanted to be able to have us provide that package of data in the broader context of PARASOL to be able to understand the potential benefit. That's really where we are, and we're eager to be able to get that file into the FDA within the next month.
Wonderful. What do you believe to be the peak sales opportunity for FILSPARI in FSGS, and how does that compare to the opportunity in IgAN?
Both opportunities are very meaningful. Most importantly for us is that FILSPARI in itself for these patients is incredibly meaningful and an improvement over what they've been offered to date. When we look at the size of the opportunity in FSGS, we believe that financially it could be even greater than IgA nephropathy for several reasons. The first is nephrologists know that this is a devastating and rapidly progressing disease. There is a high sense of urgency, and we think that the uptake will be fast. We already have established quite a bit of clinical experience. There is a broad awareness of FILSPARI based on IgA nephropathy, and payers also have experience with FILSPARI. We also have a target dose that is double that of IgA nephropathy.
While we're not in a position just yet to talk about pricing, you can assume that the pricing per patient will be higher in FSGS, all leading to estimates that we believe will be higher. The other aspect is we do hope that our potential approval accelerates other companies wanting to go into FSGS because this is also one that we believe will be needing combination. There is nothing on the competitive landscape for many years behind us.
To wrap up, what do you believe are some of the most underappreciated upsides of Travere?
Certainly. Certainly FSGS is one that we are absolutely laser-focused. This is a community that is really watching what we can do for them. There's nothing else for them. I think there's certainly been a growing recognition about the possibility of being approved in FSGS, but I think the other aspect is in IgA nephropathy. I think there's been a lot of focus on the potential for new immune-mediated therapies to come, but I think that there has got to be a recognition that nephrologists see the future of IgAN as combination. This is not one therapy that is going to solve it for patients. We are absolutely focused on making sure that FILSPARI becomes a core part of that combination therapy, and I think that that's underappreciated when you think about how rapidly and how broadly the IgAN market is going to grow in the future.
Great. With that, Eric and Chris, we thank you both for your time, and thank you to the audience for attending our conference. Everyone have a great rest of the day.