All right. Good day, everyone. Welcome to day two of Cantor's Global Healthcare Conference. For the next session, we are very excited to host the team of Travere Therapeutics. Representing Travere, we have Chris Cline, Chief Financial Officer, and Peter Heerma, Chief Commercial Officer. Gentlemen, thank you so much for taking time to attend this conference.
Absolutely.
Happy to be here.
Thank you for having us.
Maybe people are familiar with Travere, but in terms of just provide a quick overview of the key near-term priorities for the company and where are you in terms of the current state of the business?
Sure. Before we jump in, we will be making forward-looking statements, so please reference our full disclosures on Forms 10-K and 10-Q filed with the SEC. At Travere, we're exclusively focused on identifying, developing, and delivering life-changing therapies for people living with rare disease. Our focus is really on four key areas to drive both near and long-term growth. The first two are focused on FILSPARI, which is the first approved product out of our pipeline. There, our efforts are really geared towards getting to the peak potential of more than $3 billion in sales that we have estimated internally. The focal points there are first in IgA nephropathy.
FILSPARI is currently the most approved or most prescribed novel medicine for IgA nephropathy, and Peter's team has done an excellent job of positioning it as foundational care in a space where we expect more and more patients to be identified and treated. The second area for FILSPARI that we're very closely focused on is continuing to have a very strong launch in FSGS. We just got an approval back in April for FSGS. FILSPARI is the only approved product for FSGS, and we reported a very strong first quarter of performance there from the launch that I'm sure we'll go a bit more into. The focus is to continue that momentum. Those are the first two priorities related to FILSPARI.
The other two are really focused on developing and advancing our pipeline, and that's to layer in growth on top of FILSPARI and beyond. The first one out of our pipeline is pegtibatinase. Here, pegtibatinase is an enzyme replacement therapy that is aimed to treat classical homocystinuria or HCU. Here we've got very compelling data from phase I/II study that shows roughly 67% reduction in total homocysteine levels. Our goal is to replicate results similar to that in our phase III that is currently enrolling. There, our goal is to achieve top-line results in the second half of next year, on track for that. That's the main focal point for pegtibatinase at the moment. Lastly, on the pipeline side is civorebrutinib, or civo.
This is the BTK inhibitor that we in-licensed earlier this year, and we look at civo as a potential product or a pipeline in a product. Here, our goal right now is to open an IND, get some of the bridging work done that will help enable the regulatory and development pathway. We expect to be able to move into studies for the indications that we've identified thus far, which are PMN, FSGS, and MCD, and we'll be looking beyond that as we go. Maybe that's a good starting point, and happy to hop into any of those areas.
Yeah. Maybe we can start with FSGS first. No surprises there. You had only two months of launch in the last quarter. Really strong launch, surpassed even the most bullish expectations. I guess, where do you see the initial demand coming from in FSGS, and what has been the feedback?
Yeah. Thanks for that question. We had two and a half months of revenue in the first quarter of launch, second quarter. Overall, to your point, very strong uptake. Not surprisingly, given that this was a highly anticipated launch, the first approval for FSGS. We clearly saw a halo effect based on the experience that physicians already have with FILSPARI in IgA nephropathy. You have to realize this is roughly the same prescriber base as IgA nephropathy. Basically, all physicians that treat IgA also treat FSGS. You build upon a strong platform and brand experience, and that's indeed what we are seeing. That's indeed what we were seeing. About 70% of the prescribers had prior experience with FILSPARI in IgA nephropathy, is what you would expect. At the flip side, what I'm really encouraged by is that you also added 30% new prescribers to the brand.
Given that those prescribers also have IgA nephropathy, it allows you to anchor the position in IgA even further.
Got it. I think one metric you mentioned during the call as well, that most physicians or prescribers have written just one prescription of FILSPARI for FSGS. I mean, what leads to the increase in the depth of prescribing over time?
Yeah, maybe it's good to provide some context of that comment. The question was often like, do you see a bolus, given that this was a highly anticipated launch? Even though you see some pent-up demand, the reason why I don't believe it's a bolus is because there is such a big opportunity. I mean, we see over 30,000 FSGS patients addressable for FILSPARI today. We are really scratching the surface in our initial launch. In that context, I said, like, the majority of the prescribers so far have prescribed to a single patient. It's not like physicians are calling in older FSGS patients, prescribed to older patients, and are kind of like done. There is a lot of depth opportunity, but even more a breadth opportunity to increase the number of prescribers building on the strong momentum you have with IgA nephropathy.
Got it. The 30% of new prescribers that have written FILSPARI for the first time, I guess to your point on the halo effect, are you seeing a halo effect on the IgA side as well from that FSGS approval?
Yes. It's a reverse halo effect. It's early days. It's something that you would expect. I would say early anecdotes are confirming that, but it's too early. I think it really takes 3- 6 months to have seen that first experience in FSGS to start also the activation of IgA nephropathy. But the early signs are certainly encouraging.
Got it. The other metric that you said was around the conversion factor that's tracking better than IgAN. I guess, what's driving that?
Well, you build upon a strong history with FILSPARI. FILSPARI, three and a half years approved for IgA nephropathy. Very strong coverage. The broadest coverage across all the novel IgA products. FILSPARI is a known entity for payers. The National Drug Code, the NDC, is already included in payer plans, and that often accelerates also when the Pharmacy and Therapeutics Committees come together for a second indication, in this case, FSGS. You build upon strengths. What we said is, we anticipate a faster conversion compared to IgA nephropathy initially. That's exactly what we are seeing. We're not yet where we are with IgAN today, but we are making rapid progress.
Got it. Regarding the different sub-segments of FSGS and where you're seeing the most uptake, primary, secondary, genetic, is there a way to track that, and what's been the initial feedback on who are these patients who are being put on FILSPARI?
Yeah, I think it's good to point out that we have a broad label for FSGS, independent on the etiology of the FSGS lesion. It includes both primary, secondary, genetic, as well as pediatric patients. To your question, where do you see most of the initial demand? It is in the higher proteinuria levels. That's exactly what you would expect. Physicians often start with the patients that are most worried about, the most severe patients. That indicates that it's probably more primary, but we don't see that patient by patient. There is no ICD-10 code that specifies if it's a primary or a secondary patient. Based on the proteinuria levels, the majority I would expect is primary. But we certainly see utilization in secondary, in genetic, and pediatric patients as well.
Got it. Maybe looking ahead in 3Q and for the rest of the year, what are some of the pushes and pull in terms of FSGS uptake or even broadly for FILSPARI that you are highlighting?
Yeah. I think we are in a strong position. The fundamentals are strong. Having said that, we know in the third quarter, you have a seasonality impact. That's what we have seen in the past. We know that based on claims data, less FSGS and IgA nephropathy patients see their physician during the summer months. That has nothing to do with FILSPARI. That's more like a market dynamic. I think overall, the indicators for FSGS and IgA nephropathy remain strong. The opportunity remains.
Yeah. The seasonality impact, is it similar to the prior years or any changes?
Yeah. We're not commenting on intra-quarter data, but you know historically what we have mentioned and also what other companies in nephropathy have commented on.
Yeah. We talked about this last night as well, but on the addressable population in FSGS, we've talked about 30,000 as the addressable population. Maybe if you can just comment on what does it entail in terms of it excludes active nephrotic syndrome, I believe. There are differences in terms of if you account for secondary FSGS population, for example. If you could just layer in what you think is the top of the funnel there, and how are you getting to 30,000?
Yeah. How did we get to 30,000? First of all, it's patients that have consistent elevated proteinuria levels, confirmed FSGS either by biopsy or by genetics, and patients that have not progressed too far that they're already in kidney failure. 30,000 patients includes primary and genetic FSGS, then you have an additional 10,000 for secondary FSGS. So that's a total of about 40,000. You handicap that for patients that have an acute episode of nephrotic syndrome, and that's why we said over 30,000. It's hard to handicap that for nephrotic syndrome because it's a temporary state of the disease, but that's how we got to the 30,000.
Got it. In terms of gross to net as well, I think Chris, you highlighted some metrics around that. Maybe just talk about why FSGS gross to net could be a little bit different than IgAN, and what's the typical payer mix.
Sure. What we've guided to for the year is gross to nets for FILSPARI as a whole. So both FSGS and IgA together in the mid 20 percentage range, and that's been consistent since the beginning of the year and expectations. The thing that we're looking at for FSGS and really coming into the launch we had expected, was that you would have a little bit more patients falling into Medicaid, Medicare, right? What we've talked about historically is in IgA, it's about a 70/30 split of 70% commercial, 30% that are going to be in CMS. In FSGS, we still expect to be majority commercial, but there is going to be more of a CMS exposure to that.
We'll see how that evolves over the balance of the year and then can give a little bit more insight as to what that looks like for next year. But you've still got the majority commercial, so it will be somewhat similar to IgA.
Got it. Okay. Maybe moving on to IgAN. I think a lot of people have been surprised by how resilient the growth of FILSPARI has been in IgAN despite more competition. Maybe just your broad overview on the market right now as you see with different drugs and different modalities being launched as well.
Yeah, I think physicians understand overall the positioning of FILSPARI relative to immune-mediated treatment options, and I think that's reinforced by the KDIGO guidelines last year. KDIGO is the global guideline for nephrology. Last year, they updated their guidelines, and they clearly outlined that you have to treat with two different modalities, two different treatment categories. Kidney-targeted, more nephroprotective treatments. This is where FILSPARI plays, really replacing the traditional RAAS inhibition. RAAS inhibition for the last 40 years has been well-characterized as nephroprotective. We know that FILSPARI is superior based on our head-to-head data versus a maximal tolerated active comparator. Then you have the second category, the immune-mediated therapies, historically steroids, and that's where complement inhibitors and APRIL compounds play as well.
I think physicians understand it's a two-prong approach in how FILSPARI is not directly competing with APRIL compounds, but more complementary to, and that's the feedback we are hearing from the marketplace as well. For those patients that are not controlled to the target treatment levels yet, APRIL compounds could be a good addition to FILSPARI.
Got it. I guess, what are the patient segments that are driving FILSPARI growth right now? Because I think you've said that the proteinuria levels are moving downwards in terms of the patients who are being put on the drug.
Yeah.
What's the growth right now?
Well, we see broad utilization of FILSPARI across the different segments. If you look from the last three and a half years to where we are today, you see that you move from higher proteinuria to relatively lower proteinuria levels, but still elevated. To put it in perspective, historically, the treatment target was 1 gram per gram for proteinuria. Last year, that was reduced by the guidelines to 0.5 or preferably 0.3. That often requires more treatment combination as well, but it also shows that you go to lower proteinuria levels because physicians now have an increased awareness that even below one may not be good enough.
Patients at, let's say, a 0.8, 0.9, still are at significant risk, and that's reflected in the FILSPARI use as well, going to a lower level of proteinuria.
Okay.
It may be good to point out as well, the majority of the patients resides in that below 1.5 category. 70% of the patients have a proteinuria level of below 1.5.
Okay. How's the diagnosis and treatment rate changed with more players in the market? Do you have any metrics around that?
Yeah, I think more players in the market is a good thing in that respect for market development. You have to realize IgA nephropathy was a relatively underdeveloped market. Till three, four years ago, physicians often thought about IgA nephropathy as a relatively benign disease. Physicians felt quite comfortable with proteinuria levels above 1.5, and felt that patients were relatively stable. With the RaDaR data set that we helped to develop, it actually showed that patients, even with proteinuria levels of 0.7, 0.8, have still double the risk of progression to kidney failure compared to full remission of proteinuria being 0.3. So that guideline was established last year and more companies coming into the market that reinforce that message further elevates the urgency to intervene earlier.
Got it. The other drug that was launched, atrasentan from Novartis, VANRAFIA. What's been the feedback from physicians on why do they still prefer FILSPARI over VANRAFIA, and how are you driving some of the messaging from your side to that?
Yeah. VANRAFIA was launched a year and a half ago, marketed by Novartis. I was talking about the two treatment categories before.
Yeah.
FILSPARI replacing RAAS inhibition. In that category, atrasentan or VANRAFIA is positioned as well. Other than FILSPARI, VANRAFIA is a single endothelin inhibitor, while FILSPARI blocks both angiotensin as well as endothelin. In particular, the profile of the drug is preferred by physicians because it's one pill rather than two, and you have a better efficacy profile.
Okay. Got it. As we look forward to 2027 and beyond, is there a reason to believe that FILSPARI would slow down anytime soon in IgAN because there's obviously a lingering debate as more competition comes, especially with the you talked about the B cell-modulated drugs as well, that at certain point, the market will saturate. What are you sort of discussing internally and your planning assumptions?
Yeah. We see 70,000 patients as addressable for FILSPARI today, 70,000 IgA nephropathy patients. To be honest, I think we're still scratching the surface. There's still so many patients that are on generic RAAS inhibition that remains at elevated proteinuria, and all those patients are candidates for FILSPARI. I think the story is well established. The positioning is well recognized. FILSPARI doesn't compete versus immune-mediated therapies, but really is positioned to protect the kidney, to protect the remaining nephrons, and I think we still have a strong opportunity moving forward.
Got it. I did want to touch on the pipeline as well. We have made certain investments there as well. Maybe on FILSPARI IP, talk about the work being done there on the IP, what are you guiding to LOE at this stage?
Sure. Maybe starting with IgA nephropathy, we recently had a patent that was granted for methods of use in IgA last month, that goes out to 2037. That's an addition to the IP estate. We also have a very similar patent that we're working on for FSGS, that's currently with the PTO. If that were to be granted, that would also be a patent specific to FSGS that would go out to 2037. Beyond that, we have additional patents that we're working on and have filed relative to the recent approval in FSGS. We'll continue to make sure that we're doing everything we can to have ongoing strength in that section.
Okay, got it. In terms of the pipeline, civorebrutinib is a pretty interesting asset. We think the data looks really good on PMN from your Chinese partner. Maybe just taking a step back, what was so attractive for this asset when you were scouring the landscape?
Yeah, I think that specific to civo, there we see a pipeline and a product potential. There's a very clear unmet need in PMN, in FSGS, and MCD, some of the immune-mediated kidney diseases that we've spent time in both in IgA and FSGS, understanding and building a clear infrastructure and expertise in the rare nephrology space. When we look at civo, it layers in very nicely, both with our internal expertise and the ability to layer that into the clinical development expertise that we've developed over time, but then also navigating the regulatory pathway and ultimately into Peter's team in the commercial landscape. For us, it layers in very nicely and complementary to FILSPARI. Even if you think about for FSGS, for example, FILSPARI, we expect to become foundational therapy there.
But as Peter highlighted, you have a proportion of patients that have very active immune-driven FSGS, and civorebrutinib would be an excellent candidate for them to start with and potentially complementary to FILSPARI. There is a very nice synergistic approach with civo that we are looking forward to progressing, both in the areas that we currently know. But then there are additional indications where we think it may also have utility. That is part of what the team is working through now in terms of getting the IND open, doing some of the PK bridging work that we want to make sure we have in hand before we open up development in PMN, FSGS, MCD, and then we are going to look beyond that as well.
Right. And maybe on the PMN market, if you just provide some overview of how big is that market. Is that really addressable by your current commercial infrastructure as well? I know it is longer- term, but the data is pretty clear. As you do your planning, how much is the overlap with the current sales force as well?
PMN is about 90,000 patients that we see as potentially addressable. It is early stages, but we have a strong nephrology infrastructure that Chris was commenting on, and there will be a significant overlap as well for the prescribing physician. I think we build upon strengths. To Chris's earlier point, there is a strong strategic synergy between where we are today with FSGS and IgAN, and how we further expand upon that with civorebrutinib.
Right. The drug looks really active, looks safe. You are doing the PK bridging, but when do we hear more about the sort of the development path, and what is stopping you from being very aggressive on making sure that you maximize the value of this asset across different indications?
Yeah. More to come on the specifics in terms of a timeline. What we want to make sure we are doing is getting it in-house, getting the IND open, doing the bridging work, and then engaging with regulators. We want to make sure we have alignment there before we are going out with any plans. To your point, there is every reason to believe that we can be ambitious with our development plans. You have very strong proof of concept data in PMN. There you see a very rapid response on anti-PLA2R and then also on proteinuria. Those data go out to 52 weeks and are very consistent. I think that there is every reason there to be ambitious, and that is our plan. More to come once we get through some of this early work here.
Okay. For HCU, we have the phase III readout next year, second half of 2027, I think is your guidance. Maybe this indication or asset in general has been flowing on the radar given investors have been focused on FILSPARI, FSGS, and IgAN. Maybe just talk about what is driving some of the conviction in terms of phase III success as well as longer- term, how do you think the commercial impact is going to be?
Sure. Maybe I can start on the outlook, and then Peter, you can jump in on the commercial side of things. We are very excited about pegtibatinase. When you think about the opportunity, you have classical homocystinuria where you have 7,000- 10,000 patients that we think will be addressable. Unfortunately, today, the only treatment options are vitamin B6 and betaine that are generally not effective. For the vast majority of patients, they are facing clinical outcomes like an ischemic event, stroke, cognitive impairment, ocular lens dislocation, and osteoporosis, potentially in your 20s and 30s. There is a very clear unmet need in classical homocystinuria, and pegtibatinase is the only asset that is currently in clinical development. We have the potential to be the first and only disease-modifying therapy if approved.
Based on our phase I/II data from COMPOSE, where we saw a 67% reduction in total homocysteine levels, there is every reason to be very excited about what we may be able to show in the phase III study. Specific to HARMONY, our phase III study, we have tried to bring as much of the phase I/II design over to that as we can. One of the things that we did include into the phase III was a diet stabilization period in the beginning. Really the goal there is to make sure that the patients that are enrolling in the study are working with a nutritionist to align on a diet that they are going to stay on for the whole 24-week period.
That, I think, will actually help in reducing any kind of variability in total homocysteine levels and potentially give us an even clearer picture on efficacy there. We're very excited about that program. As you mentioned, on track for data in the second half of next year. Maybe I'll turn it to Peter to talk a little bit about just the commercial opportunity.
Yeah. Well, to Chris's point, clearly a lot of excitement. First disease-modifying potential for classical homocystinuria patient population with a high unmet need. It's more typical rare disease if you compare it to FSGS or IgA nephropathy, which is almost specialty.
Right.
Every nephrologist that we're targeting has at least a handful of IgA nephropathy or FSGS patients. In classical homocystinuria, it's much more about patient finding, so it requires a different commercial infrastructure. We build upon strengths because we have a patient services model that can really be utilized as well for this patient population. The sales model will be slightly different and more likely smaller because there's more concentration of care in classical homocystinuria.
Got it. In terms of the commercial model, I guess the level of investments that are required here for a launch in HCU, I guess, are you able to leverage some of the backend work as a company in terms of finding these patients and increasing awareness? How much of the investment required would be on the, I guess, sales force side?
Yeah. Some of the patient finding we are investing in already. That's also something that you're doing for your recruitment of your trial. It's something that we're doing also for FSGS and IgAN clearly. To my earlier point, you have a patient services model that you can utilize. That's an established infrastructure that you can utilize for a different patient population. If you talk about sales specifically, it's a different call point. It's a different profile of the sales rep as well. It's a smaller field force.
Right
It's more concentrated care. So that would be an additional investment.
Got it.
And maybe one other thing just to highlight, Prakhar, is with HCU, many patients are missed early in diagnosis. It's largely driven by the fact that newborn screening is not reliable. For a host of different reasons, patients, roughly 50% of them, don't end up being caught until later on in life. So I think that there's some investment that we've already started and will continue to do to try and improve some of that early screening and help find, identify patients and get them on treatment earlier as well.
Got it.
Yeah.
Got it.
Well, building on Chris's point, there is also a significant amount of patients that is lost to follow- up.
Okay.
Patients often travel quite far to go to more specialized metabolic clinics. There are basically no treatment options today. To make that effort without changing any of your treatment options, I think that is a patient population that we could reactivate once you have the approval for pegtibatinase.
Right. In terms of manufacturing and scale up as you get ready for commercialization as well, where are you in terms of that?
Yeah. Late last year, we had completed our optimization process for the manufacturing, and really that was going from clinical scale to what can support commercial supply. Last year, we ran the first successful batches that enabled us to restart enrollment activities earlier this year. Now we're in the process of scaling up. Running the batches, and we are on track to be in good shape for supporting a commercial launch.
Okay. Maybe on the balance sheet and cash, given the strong uptake of FILSPARI in IgAN as well as FSGS, how are you thinking about profitability and the cash flow generation? You have this cash coming in, but you also have investments that you're making into the pipeline.
Sure. We haven't yet given guidance specific to timing of profitability or magnitude or otherwise. I think with FILSPARI's growth, we've obviously got a very clear path to financial strength. We do have investments that we're still making, right? When we think about FILSPARI, we still have work ongoing to support post-transplant in FSGS and IgA. That's an area where we think that we can generate some additional data and potentially help even more patients. We talked about pegtibatinase where we're enrolling a global phase III and doing CMC scale up. Those are meaningful investments. Then for civo, there we're looking at potentially multiple late-stage programs, right? There is still investment to be made, but with FILSPARI's growth, we've got a very strong outlook. We reported about $489 million in cash at the end of last quarter.
We believe that that can support all of our current operations. We do not have a near-term need for capital to support any of what we have here. I think we are in a very good position as we are going forward here to operate on all those priorities.
Okay. I think that is all the time we have today, but thank you so much to the Travere team for joining us. I am looking forward to the next set of updates.
Thank you.
Thank you.