Conference Transcript - TVTX 2026-06-03

Maury Raycroft, Analyst — Jefferies

Hi, everyone. My name is Maury Raycroft, and I'm one of the biotech analysts at Jeffrey's. It's a great pleasure that I'd like to welcome Eric Dubé, the CEO of Trevere Therapeutics. Thanks so much for joining us today, Eric.

Eric Dube, CEO

Thank you very much for hosting us.

Maury Raycroft, Analyst — Jefferies

And it's going to be fireside chat format, so maybe to start off, for those who are new to the story, if you can give a one-minute intro to Trevere and key priorities for the year.

Eric Dube, CEO

Sure, absolutely. So Trevere Therapeutics is a commercial and development stage biotech company focused on innovation in rare diseases. You can find more information, including our forward-looking statements, on our website. And we've had some very exciting times at Trevere, really bringing innovation to communities that really have not had any approved therapies. We have Phil Spari, which is the first non-immunosuppressive therapy approved for a rare kidney disease, IG nephropathy. and we continue to see a very strong uptake as more and more patients are treated with Filspari and upgrading from off-label use of RAS inhibitors. We recently received the first approval in FSGS with Filspari and are very pleased with the reception of that approval. We recently reinitiated enrollment in a Phase III program, PEG-debatinase in classical homocystinuria, or HCU, an enzyme replacement therapy that we're very excited to be able to potentially bring to that community. And then yesterday, we announced the acquisition of rights to ciboribrutinib, a BTK inhibitor, that we plan to initiate development in multiple immune-driven rare kidney diseases. So a very exciting and growing portfolio for both near- and long-term growth as we reach communities that really have not had therapies approved for them.

Maury Raycroft, Analyst — Jefferies

Got it. Yeah, it's a great intro. And let's start with the most recent news with Sivirbrutinib. Appears to be a good fit strategically for you. Can you talk to us a bit more about how you see it working alongside Phil Spari and addressing the needs and unmet need in multiple indication?

Eric Dube, CEO

I think, you know, what we're really seeing is a renaissance of innovation within rare renal diseases. Historically, this has been the area of lowest clinical trial investment and activity, and we're hoping to change that. We're certainly doing so with Filspari and FSGS and IgE nephropathy. But there are so many other patients with rare kidney diseases, particularly immune-driven. And so we were very excited about the proof-of-concept data that Everest Medicines generated looking at Ciborbrutinib in primary membranous nephropathy, which was very compelling based on the mechanism of this drug within that disease. But we also see applicability beyond PMN into areas like immune-driven FSGS and minimal change disease, really highlighting areas where Filspari is not currently approved to be able to reach patients, for example, PMN that do not have an approved therapy. So it really is now potentially having two different medicines that are complementary in nature to be able to expand our commitment and reach into rare kidney disease.

Maury Raycroft, Analyst — Jefferies

Got it. And what's unique about this particular BTK inhibitor that sets it apart from some of

Eric Dube, CEO

the others out there? Yeah, I mean, maybe it's important to start with a basis for why BTK inhibition is important within rare kidney disease. I mean, this class of medicines has been around for some time in other therapeutic areas, but now with our better understanding of immune-driven diseases within renal disease, we really are excited about what this brings. And if we think about what would be important for the long-term treatment of patients, for example, with PMN, you want to have something that is easy to take. And oral medicine certainly is providing that. But also having the covalent reversible profile is important for long-term use. Not only do we expect to see and are looking at a rapid onset of action, which is important for patients that, you know, you need to be able to address the damage in the kidney. And for PMN, these patients are very symptomatic and oftentimes are not able to stay in a job or in school because of their symptoms. So onset of action is important, and that's where the covalent nature really is important. But looking at the reversibility and the selectivity of Sivorbrutinib is important because of the long-term use that we would expect, and that is important when we think about the long-term safety, including the immunosuppression profile, becomes very relevant when we look at the treatment within kidney diseases.

Maury Raycroft, Analyst — Jefferies

And maybe talk about just the timing of the agreement and how much effort went into identifying this asset and the diligence.

Eric Dube, CEO

Yeah, so we've been looking at expanding our portfolio for quite some time. And this is one program specifically that we've been looking at and engaging with Everest for a period of time. We felt like this was the right time for us and for the program. I think for us, we wanted to, and we've talked about, doing business development in a position of strength. And we saw that both strength financially were very well capitalized to be able to support this and our overall portfolio. But also, operationally, now with the approval of FSGS, our commercial teams are able to focus on Phil Spari in IG Nephropathy and FSGS, whereas our development teams now can turn their attention to the exciting work that we'll have with C-vorabrutinib. From a program standpoint, we felt like this was the right time for us and our capabilities to take this over. We have established capabilities working with regulators. We have an unparalleled clinical trial footprint in IG nephropathy and FSGS to be able to apply to our work moving forward with this. So it really was the right time for us and for the program.

Maury Raycroft, Analyst — Jefferies

That's helpful. And let's move to the FSGS setup with the recent approval. Can you provide more color on the label and the addressable patient population in the United States?

Eric Dube, CEO

Absolutely. I think we still are absolutely elated to have the first approval for a community that's been waiting for decades. Our indication for FSGS is broad. It's for the treatment, the reduction of proteinuria for patients eight years and older with FSGS that do not have nephrotic syndrome. And so I think there are a couple of components of this. The first is many, many communities in the renal space have been pleading with the industry to study kids. We've been doing that from day one, and we're very proud to now have a medicine that's approved for pediatric patients. The second is that it is agnostic to the type of FSGS, so it expands primary, genetic, and all forms of FSGS, so we're very pleased with that part of our label. The third component, which I think is important to note, is that it's for patients without nephrotic syndrome. That's essentially active nephrotic syndrome. This is a state of the condition that, you know, patients go in and out of, and many patients do present with nephrotic syndrome, which really is three components. It's elevated proteinuria levels above 3.5. It's low serum albumin levels, and it's edema. So these are patients that are in a very active state of disease, But these are, you know, patients that have a very specific treatment strategy to get them out of that state. Once they're out of that state, and what the Cadego guidelines say is that those patients with nephrotic syndrome really should be targeted with immunosuppression. Once they're out, really the goal long-term is to have a nephroprotective therapy. And that's really the role that Filspari plays. And so at some point, nearly all patients will be eligible for Filspari for that long-term nephroprotection of their disease and the reduction of proteinuria long term.

Maury Raycroft, Analyst — Jefferies

And getting them out of that state, it just requires one of those three to be improved. That's right.

Eric Dube, CEO

I mean, often what you'll see is all of those will sort of flow together, but, you know, over a matter of weeks or for some patients based on severity months, patient will no longer be in nephrotic syndrome, and that's when they would be eligible for the treatment with philsparin.

Maury Raycroft, Analyst — Jefferies

And what are you hearing from doctors and payers in the early phase of the launch, particularly around patient identification, the nephrotic syndrome, and access?

Eric Dube, CEO

I think I'll start with the nephrology community. They are overwhelmingly positive about this first approval, and also those elements I discussed that were approved for pediatric patients, and it's a broad indication statement. I think this is really compelling for nephrologists, and I think that's really what led us to believe that we're going to have a rapid uptake with the launch. With regard to payers, that typically takes some time for them to establish their access policies. What I can say is that this has been something we've been working on for a period of time, for a number of years, and we believe that we have a very strong health economic profile. When we look at what payers are actually doing, the early indication that we've been looking at is first pass approvals of patient start forms, and in fact, the rate of first-pass approval is even higher than what we saw with our experience in IG nephropathy in the early days. So I think encouraging thus far, but more work will need to be done to be able to get those payer policies established. Any more specifics on what that rate is? No. What I would say is that we're very pleased so far, and I think it really pretends what should be broad access to provide context for IG nephropathy. About 97 percent of patients have a clear path to approval for IGN for Phil Spari, that's really something that we will aim to do for FSGS patients as well.

Maury Raycroft, Analyst — Jefferies

Got it. That's helpful. And for the nephrotic syndrome description in the label, what proportion of the addressable patients have this currently? And you've mentioned it's a dynamic process for patients, but is there any risk that payers could overinterpret the definition of nephrotic syndrome and try to exclude patients for having a history of this?

Eric Dube, CEO

So for context, when we look at our duplex study, there was about 20% of patients in that trial that had a history of nephrotic syndrome. When you look at patients that are in active nephrotic syndrome, it is less. It's probably between 10% and 20%. So those are the patients that for that moment in time would not be eligible for Filspari. But as you point out, it's a dynamic state, and really the treatment strategy is immunosuppression to get them out of that state and then look at more chronic treatment with Filspari. And that really is something that payers at this point do understand. We want to make sure that we educate them. We also want to make sure that we're educating nephrologists because some nephrologists equate nephrotic syndrome simply with nephrotic range proteinuria. So there's some education that needs to be done, but nothing that we're concerned with at this point. Our teams are all over it. And with regard to payer access, we've not seen evidence of them saying we're going to look at history. And I think they understand and appreciate that that really is a moment in time. And one of the most important factors that we're using is the Cadego guidelines already separate patients with nephrotic syndrome versus not. And I think it really helps to say for those patients it's immunosuppression first. once they're out of that state, it really is about protecting every nephron possible,

Maury Raycroft, Analyst — Jefferies

and that's really where Filspari plays. Got it. And for those patients who are in active nephrotic syndrome, they get treated with immunosuppression first, how quickly can they become eligible for Filspari after starting induction therapy? Is it weeks or

Eric Dube, CEO

months? Well, it really depends on the severity, but for those patients, and oftentimes it's Patients with immune-driven disease that present for the first time with nephrotic syndrome, that really is an urgent state for the nephrologist to be able to address that active state. And so it depends on the severity. For some patients, it may be weeks. For others, it may be months. But at the end of the day, what we want to make sure is that once the patient is out, that we do everything possible to protect those kidneys. And that's where, you know, Phil Sparrow being the only approved medicine really does come into a clear role.

Maury Raycroft, Analyst — Jefferies

And you've characterized the FSGS launch as it should be faster uptake than IG nephropathy. What gives you confidence in the launch trajectory, and how should investors think about early PSFs versus sustainable demand?

Eric Dube, CEO

Yeah, so there are a number of factors that really gave us confidence that this uptake would be stronger. I think, first, we've been approved in IG nephropathy for three years. And that's given not just a broad awareness of the mechanism and the clinical data for Filspari and IJ nephropathy, a very similar disease, but also for so many nephrologists' personal experience using Filspari in their practice for patients with IGAN. The other aspect is that the REMS has been modified to be simplified. We have full approval in FSGS that gives confidence. We have all of the data from our two-year duplex trial to be able to speak about the longer-term efficacy and safety. So there are a number of components that really have gone into the profile and the awareness of Filspari. But I think fundamentally when we look at the disease, this is a high unmet need. These are patients that are often actively progressing in their disease, highly proteinuric and oftentimes symptomatic. And so there's an urgency to treat patients with FSGS relative to, again, where there was a lot of education to say a patient that may be stable at high proteinuria is not a stable patient. They are at high risk. So we don't need to do that education. There's other parts of the education we need to do with FSGS, but fundamentally there is a real urgency to treat there.

Maury Raycroft, Analyst — Jefferies

And you mentioned the pediatric patient population earlier. What proportion of the total addressable market comes from the pediatric cases?

Eric Dube, CEO

So we've not broken that level of detail for the addressable population. What I can refer to is our duplex trial, which is about 10% of patients there are pediatric, and I think that that's a good estimate. And we've expanded our teams to be able to reach pediatric nephrologists given the unique approval that we have in FSGS.

Maury Raycroft, Analyst — Jefferies

Yeah, and for the sales team in preparation for FSGS, you expanded it. Do you have an optimal size at this point, or do you anticipate having to add more sales reps?

Eric Dube, CEO

We did this expansion late last year in anticipation of an approval on FSGS. There was a high overlap in physicians that treat IG nephropathy and patients with FSGS. So really, it was about a modest expansion to incrementally reach more nephrologists, including the segment of pediatric nephrologists. So we believe that we're optimized in the size right now. and I've been incredibly impressed with their execution and the early signs of the FSGS launch thus far.

Maury Raycroft, Analyst — Jefferies

Let's shift gears to IGAN. Phil Spari continues to show strong demand there. You had a record 993 PSFs in first quarter this year, despite emerging competitors. What's driving the continued uptake, and where do you see the biggest remaining opportunities for penetration?

Eric Dube, CEO

Yeah, well, I think let's put into context what the performance is. in two regards. First, I've been in the commercial side of our industry for nearly 30 years, and what I can say is that this is one of the few examples where you continue to see inflections upward two to three years after approval, and I think it reflects several factors. One is we have a phenomenal field-based team that has deep experience within rare disease, renal disease and have great relationships. I think the second factor is the profile of this medicine. The mechanism is unique in a single molecule, once a day pill, addressing two core defects of nephra protection in the kidney that is reflected in superior data in our phase three and has very strong support in the guidelines. And so I think that evidence to be able to support this is key. The other factor I think that's important to put into context of our performance thus far is if you look at the aggregate number of patient start forms, we've really only reached about 10% of addressable patients. So there are so many more patients out there that are lingering with high proteinuria that are only on off-label ACE inhibitor or ARB. These are patients that are at risk that do not have optimized nephra protection. And so we do believe that as physicians continue to upgrade those patients from RAS inhibition to Phil Spari, where you get dual inhibition, which is, again, recommended by the guidelines, that gives us confidence that even with other immune-targeted therapies coming to the patient communities, there's a lot more opportunity for us to grow. And nephrologists recognize that, and that recognition continues to strengthen that with B-cell therapies that are coming through FDA, they play a very different and a very important role, but a complementary one to Filspari. And that, I think, is that Cadego guideline recommendation of combination therapy addressing those two pillars. We don't see that changing in the foreseeable future, and that's where we believe that patients are going to be optimized on a better foundational therapy and a better immune-targeted therapy once those therapies are available.

Maury Raycroft, Analyst — Jefferies

And for the proportion of first quarter 26 PSFs, what proportion were treatment-naive newly diagnosed patients versus the upgrading from generic RAS inhibitors versus switching from other therapies like Tarpeo or Ben Raffi?

Eric Dube, CEO

Yeah, great question. So if we look at the source of business, There is a small proportion of patients that are addressable that are treatment-naive, and we are seeing some use there. And I think that that's driven by, one, an early recognition of needing to do better for these patients, starting innovation earlier, based on particularly the data that we've generated. So the data that we have from our SPARTAN trial, which is the only treatment-naive study ever done in IG nephropathy, shows a compelling level of proteinuria reduction and EGFR stabilization. But also we have the head-to-head data from our PROTECT trial showing superiority. So physicians are starting some patients with Filspari, but that's a small proportion of the addressable. The majority of patients that we see addressable are already on ACE or ARB, and that's where the majority of our use is. I think, you know, with regard to switches, we're seeing very little evidence of switches, either switches, you know, away from Filspari or switches of other approved therapies to Filspari. I think fundamentally most of the switch is from ACE A or B to Filspari, and that's what we would expect moving forward. You know, the other component of the dynamic market is combination therapy. We do expect that there is going to be more combination therapy moving forward, essentially a combination of SGLT2, Filspari, plus an immune-targeted therapy. That really is the optimal treatment of the future, and that's what the Cadego guidelines recommend.

Maury Raycroft, Analyst — Jefferies

Got it. That's helpful. And you've talked about more uptake in community settings versus academic. Can you talk more about the split there and whether it's evolving and why there's a difference?

Eric Dube, CEO

Yeah, so I think not surprisingly, a lot of the early uptake was in academic centers where you would expect to see greater awareness and perhaps oftentimes more severe patients that need earlier intervention. When we take a step back and look at where are these patients being treated, the majority of patients with IG nephropathy and FSGS are actually treated in the community setting. And so we do expect there to be continued uptake there. But we also are seeing very strong performance in the academic setting.

Maury Raycroft, Analyst — Jefferies

And maybe just going back to the Tarpeo or Van Raffia, is there a way you can capture patients from either of those competitors? and just thinking about Tarpeo patients, if they don't stay on that drug for a long period of time, where do they go after that drug?

Eric Dube, CEO

Yeah, I mean, I think, you know, first and foremost, there's a role for each of these medicines. What we see is the real opportunity is for us to upgrade patients that are on RAS inhibition. Whether they were on Tarpeo or not, you know, those patients need and deserve full nephral protection, which is really about dual inhibition of angiotensin and endothelin. So our focus is any patient that is on ACE-ARB and still has proteinuria, they should be on Filspari. That's the most important thing. And, you know, if we take a step back, Filspari is the number one prescribed medicine that's approved for IG nephropathy, and we've continued to see very strong performance there. So while, you know, the other medicines that are approved have a key role, we've not seen them really erode the strong performance in the market share that we've

Maury Raycroft, Analyst — Jefferies

been able to have over the number of years. Got it. Okay. And last week, you received a notice of allowance from the USPTO for a method of use patent. Our understanding is that this allowed claims that guide on step-up dosing for IG nephropathy. Could you clarify what other claims are included and what the implications are for the duration and strength of market exclusivity?

Eric Dube, CEO

Absolutely. We were very pleased with this positive update on our patent, and we would expect that patent to be granted in the near future, and we'll look to immediately list that in the orange book, which could give us a stated date for this particular use of sparsenta in IGAN out to October of 2037. And that is very specific methods of use. We do have other applications, including a very similar one in FSGS that we will, you know, provide an update at the right time once the patent office has decided. But essentially the one that was recently provided the notice of allowance really is about, you know, strengthening the unique profile that we have in the methods of use in IGAN.

Maury Raycroft, Analyst — Jefferies

Okay. Okay. And you've mentioned potential for $3 billion and peak sales for Filspari. What are the underlying assumptions for FSGS and IGAN and the trajectory ramp to get to this $3 billion? And how long did your guidance contemplate when you gave the $3 billion peak opportunity?

Eric Dube, CEO

Sure. So that guidance of peak year sales was before this recent notice of allowance for the patent update. And the assumptions that we have around the 3 billion is the addressable population that we see across IG nephropathy and FSGS of over 100,000 patients in the U.S., and a continued use of Phil Spari as the foundational therapy in IG nephropathy. We do expect that the addressable population will continue to grow with earlier identification and biopsying of these patients, but also we would expect to see continued strong compliance and adherence. We've been very pleased with that thus far, and we would expect that to continue. And even as other therapies come to these patient communities, we expect a strong demand for Filspari given the unique clinical data, the unique mechanism of action, and the very strong positive clinical experience that patients in nephrolisis have had to date.

Maury Raycroft, Analyst — Jefferies

And you sort of answered this question with your responses, but for the $3 billion assumption, how do you project competition in IGAN, including Venrafia and the B cells entering the market?

Eric Dube, CEO

Yeah, I mean, again, they all have a very important role to play. And I mean, I have to say, as a rare cancer survivor, to actually have treatment options for a rare disease, I don't take for granted. So I am very pleased that these patients will have not just treatment options, but the ability to combine innovation that is superior to the off-label therapies that patients have had to endure for a number of years. I think what our hope is for this community and is really fundamental to our outlook of our business is that patients are going to be using innovation earlier. We're seeing that with Filspari, with patients with IGAN being treated earlier in the disease, but also earlier use of combination. That's what the guidelines say. That's what we believe is best for patients. And ultimately, we hope to see a day where no patient with either of these diseases will ever need to be in a dialysis chair because they're using more effective therapies early. That's really what we hope to do. And again, what we've seen thus far in IG nephropathy is as new therapies come, the market expands because patients are treated better. And that's not eroding the role or the use of Phil Spari.

Maury Raycroft, Analyst — Jefferies

So let's shift gears to your HCU program. which is back on track. What's the latest on the program? And can you talk about the market opportunity? How many addressable patients in the US versus ex-US?

Eric Dube, CEO

Absolutely. So we're really excited about the innovation that's coming to the HCU community. There are therapies that are older that are being used, essentially vitamins and nutraceuticals and very strict diet. This is a genetic metabolic disease. Patients basically are not able to metabolize certain proteins in their diet, which leads to a toxic accumulation of homocysteine in their body, which leads to a whole host of outcomes and negative symptoms, such as eyesight problems, thrombotic events, et cetera. So to be able to replace native enzyme with a humanized pegylated enzyme, pegtabatinase, we believe that we'll be able to offer a more effective therapy long-term for these patients. And there are about 7,000 to 10,000 addressable patients today worldwide, about 3,500 to 4,000 patients in the U.S. And we would expect that, you know, with greater awareness and earlier testing, that those numbers will grow.

Maury Raycroft, Analyst — Jefferies

Got it. And maybe talk about the phase three study, timelines there, and when could we expect to see top-line data from the phase three, and what should we expect in that?

Eric Dube, CEO

Sure. So the phase three program is enrolling now. We can expect to see top line data from that in the second half of next year. And we've designed the trial in a similar way to how we've studied pegdabatinase in our phase one, two. So this will be dosed at two and a half milligrams per kilogram for patients twice a week. And we'll be looking at the reduction in total homocysteine out to week 12 for a primary endpoint following these patients out to 24 weeks to look at longer term safety and durability. And in our phase one, two, at that dose, we saw about a 67% mean reduction. So very compelling. And we were able to maintain those patients below the target total homocysteine of 100 micromoles. So we would expect to see, you know, something similar in that timeframe in our phase three, which would give us a very strong package to go

Maury Raycroft, Analyst — Jefferies

back to FDA. Got it. That's helpful. And just kind of backing into the second half, 27 updates, you'd probably want to complete enrollment in first quarter of next year. We've not provided

Eric Dube, CEO

guidance on enrollment trends and timelines, but if our timelines change in any way for data next year, we'll certainly let you know. But right now we are on track to meet that. Okay. And looking

Maury Raycroft, Analyst — Jefferies

ahead. So you've got the recent BD deal they just announced yesterday. Can you talk more on

Eric Dube, CEO

pipeline expansion and BD opportunities this year? Yeah, we're very excited about the portfolio that we now have to be able to deliver innovation and growth, both short-term as well as long-term. I think with Ciboribrutinib and Pegdibatinase, we're going to be adding revenues on top of what we expect of Filspari, but also beyond Filspari. And business development and innovation in rare rare diseases is really at the heart of what we do at Trevere, to be able to develop, work with regulators, and to commercialize. So our work there is not done. We'll continue to look at areas of unmet need through business development, but we're going to continue to be disciplined, and we believe that our balance sheet allows us to support all of our priorities now, but also to be able to do so looking at future sources of growth. Got it. So it's been a great conversation.

Maury Raycroft, Analyst — Jefferies

Maybe in closing, if you want to just highlight your cash runway assumptions, expected timeline of profitability, and key catalysts ahead.

Eric Dube, CEO

So we do not have any near-term needs for capital. We have what we need, and the growing revenues from Phil Spari, we believe, will help to be able to support our priorities. And with regard to catalysts, so continued performance commercially with Phil Spari and IG Nephropathy FSGS, the top line data from PEG to batonase in the second half of next year and then once the the deal closes with ciborbrutinib we'll be able to provide updates on that development program the first step for us is to meet with regulators to be able to align on those programs and we'll provide updates at that right time got it thanks so much for joining us Eric thanks Maury