Everyone, thank you for joining us. My name is Edward Nash, Senior Biotech Analyst here at Canaccord Genuity and Equity Research. I'm joined today by Travere Therapeutics. Joining us from the company is Chris Cline, Chief Financial Officer. We cover the company currently with a buy rating. Appreciate you joining us, Chris.
Oh, it's great to be here, Ed. Thanks for having us.
Sure, absolutely. So maybe just to kick things off, if you could just maybe give us a general overview of Travere, and just kind of what the company's mission is, and what the drugs you currently have approved, just from a 10,000-ft view, and then we can dig in.
Sure, happy to do that. Before I hop in, just a quick reminder that I will be making forward-looking statements, so please review our full disclosures on our 10-Q and 10-K filed with the SEC. With that, at Travere, we are exclusively focused on identifying, developing, and delivering life-changing therapies for people living with rare disease. At the core of our focus is really the rare kidney space, and here there's been a lot of excitement, which I'm sure we'll talk about, with a lot of innovation in the last few years, and we're proud to be one of the leaders in the space there, and also in rare metabolic disease.
And so, you know, at the core of our focus is, we have two therapies that we believe can become the standards of care in three different indications. And so the first of that is FILSPARI, and FILSPARI is a dual mechanism angiotensin receptor blocker and an endothelin antagonist, that is in development for IgA nephropathy, which is a rare kidney disease, and also FSGS, another rare kidney disease. And we got our first approval, FILSPARI is our first approval from the pipeline, which was granted accelerated approval for IgA nephropathy in February of last year.
So we've been in the market with FILSPARI and been having a very strong launch since February of last year, and now we're, we're very excited to be coming up upon our full approval PDUFA date on September 5th, so very soon here with that. With FSGS, that's another, as I mentioned, another rare kidney disorder where we've generated strong Phase III data that has shown a statistically significant difference in proteinuria reduction and clinically meaningful outcomes on kidney function. And we're working with the regulators to see if we can establish a pathway there following those results and some additional work that the community's doing. And the other program is pegtibatinase. So pegtibatinase is in the rare metabolic space.
This is an enzyme replacement therapy that is in development for something called classical homocystinuria or HCU, and within HCU, there's really no effective treatment option that is, you know, addressing the actual underlying cause of the disease, which is a defect in the CBS enzyme. And so pegtibatinase has the potential to be the first one approved for that condition. That's actually addressing the underlying cause of the disease, and we've got very promising phase I and II results that are supporting our move now, into a phase III study that kicked off at the end of last year. So a lot of exciting things coming. We've had a big first half of the year. We've got a lot to come in the second half.
That's great. Maybe we could talk a little bit, just on FILSPARI now that the drug's been out for about a year and a half on the market. Can you talk a bit about how that launch has gone, just how it has gone actually, and then based upon what your internal expectations were for the drug?
Sure. So the launch has gone very well. And if I take a step back, and I look back to the vision that we put out for people when we got to accelerated approval in February of last year, we expected then, and we expect now, for FILSPARI to become the foundational care for IgA nephropathy. And what we tried to outline for everybody then was, you know, we're going to get to foundational care, but it wasn't gonna happen overnight. So the first year, that being last year, was gonna look similar to some of the benchmark products that we're often compared against. And really, what's driving or what drove that was going through the reimbursement process, going through all of the processes to get drug to patients, educating nephrologists, and driving the awareness.
But we really expected that beginning in year two, that being this year and beyond, that we would outperform all of those benchmark products, and that's what we're seeing. So now in, you know, coming into year two, we ended last year very strong, Q4 great results, Q1 and Q2 very strong continued demand that's being driven by increasing breadth and depth of prescribers, seeing a nice increase in revenue, and we've had a strong start to the third quarter. So all in all, what we laid out back in the accelerated approval of last year, it's coming to fruition, and we're on our path to get to foundational care for IgA nephropathy.
New patient forms are obviously something we're watching very closely with the drug. How long does it normally take for a new patient form to be submitted and patient actually get drug in hand?
Sure. So for a new patient form, there's a number of steps that go into place. So the physician will have a conversation with the patient, the prescription will be written, that will be submitted. You then go through the reimbursement process and having the validation of that, and then it would go to the specialty pharmacy, where they then work with the patient to make sure that all of the requirements are taken care of, that being anything related further from reimbursement side or from anything required from a monitoring aspect. You know, that process, if you look at benchmark products, you know, what we see is a range of 20-60 days.
What we have said is that we started last year when we launched closer to the higher end of that range because of those elements that I highlighted earlier for the first part of launch. You're still going through and getting reimbursement, you're still working through the efficiencies in your process overall, and so you're at the longest end of that range. Where we've gotten to today is closer to the shorter end, the 20-day range of that. And the commercial team is continuing to build in further efficiencies and make greater progress there, and so we've really gotten to a pretty good stable state.
And can you talk a little bit about the sales force size, and then how many touches is it normally taking per prescriber before you see them writing a script? And then maybe touch on abandonment of scripts?
Sure. So on the sales force size, we've got about 80 field reps that are out there, and they're able to reach, you know, about 6,000 or the target of 6,000 nephrologists. And that's gonna get to about 85% of the overall population in which we're trying to achieve, and so we've got a very good sort of reach there. You asked the question on how many touch points do you have to have. You know, I would say on average, it takes a few touch points, right? You're not-- You're gonna have some prescribers that are right out of the gate, they're writing scripts.
But then typically, especially with nephrologists, they tend to be a little bit more conservative in terms of how they're addressing treatment, because there haven't really been many developments for new treatments in the last few decades. And so they take a few more call points to get educated on the medicine, learn what to expect. And then one of the interesting things that we're actually seeing is that as physicians have an experience with FILSPARI, what you would expect to have with a good experience, they're writing to more of their patients, and they're also sharing that experience with more physicians. So it's driving additional uptake, which is exactly what you would wanna see. You asked about abandonment. So what I would say is, for abandonment, we've seen... What we see is in line with benchmarks.
We had in the first part of the launch, during the period in which we had accelerated approval, and you, you have very limited, marketing tools that you can use. You can really only use the package insert, so there's not much patient-friendly material that you can use to educate on, on the various aspects of the, the drug. We saw that there were some patients that had more questions about how to think about the, the REMS monitoring or some of the other aspects, where, there, it was taking a little bit longer for patients to actually come on to therapy in the early stage.
But our teams made a very nice adjustment to be able to add support services on the onboarding part of the process, and also, once we got past day 180, we could use real materials that were able to educate on a way that people can understand very well and put everything into perspective. And so we've seen all of that sort of go back to where you would expect it to be in the normal course of your benchmark products.
Yeah. I know it's still early, just being out just over a year and a half, but just with regards to... Can you talk to me historically, what the prevalence of IgA has been, and do we see those numbers going up a bit, just because now that we have new therapies out there, maybe more patients are being identified or identified sooner, and that's adjusting the prevalence numbers?
Sure. So I would say that you're certainly seeing more awareness of IgA, more education, right? Even if I think back to, you know, 5-7 years ago, there were no approved treatment options, so physicians were using off-label therapies as their standards of care. There was little investment in understanding more about the disease, and there was little in the way of investment or education materials for patients and physicians. And so we've seen that all evolve significantly over the last number of years. So now we have 3 approved medicines. FILSPARI is, you know, the only one that is a non-immunosuppressive agent and the only one that has the actual potential to replace the historical standard of care of ACEIs and ARBs.
And with that, you're seeing more patients and more physicians looking to use treatments and to, you know, being identified and treated. And so, you know, when I think about the overall picture of the estimates and sort of where we would look to the addressable market, what we had said and have said since accelerated approval was, we thought there'd be about 30,000-50,000 patients that would be addressable for FILSPARI. And when we think ahead to what we expect to happen at full approval, which is the broadening of the label, and then with the potential changes with some of the guidelines, we anticipate that that can actually grow from 30,000-50,000 to up to 70,000 patient addressable. Seventy thousand addressable patients.
So meaningful growth within what we think is addressable and certainly more awareness and more identification to come.
When is the next opportunity for FILSPARI to be included in the guidelines?
The next opportunity would be the next update of the guidelines. So you're speaking specifically of KDIGO.
Yeah.
and, you know, they are expected to come out imminently. You know, I kind of joke that we look each morning to see if they're out, because we've been told that they'll be coming any day now. And, you know, I think that that will be a good opportunity for a couple of things. One, it'll be the first time that we see FILSPARI included in the treatment guidelines, which is very important. And I think that we'll see how KDIGO decides to characterize the different paradigms, but everything we keep hearing is that combination therapy is the way of the future for IgA nephropathy, and we feel very good about how FILSPARI will be positioned as the only medicine that can replace ACEIs and ARBs and address the specific activation that happens in the kidney.
So I think that the KDIGO guidelines will help in sort of unifying that idea and also, putting us in the treatment paradigm for the first time. The other aspect goes to what I mentioned earlier, where, you know, the increasing addressable population. We expect the KDIGO guidelines are likely to lower the preliminary treatment threshold. So historically, it's been, a 0.8 g, and what we've learned over time is that that's not enough. Those patients that are getting to this historical level that physicians thought were okay or was okay, it's not. They're still progressing to kidney failure. And so that's been something that has really resonated within the IgA community. This has come out of the registry, the RaDaR registry database over the last couple of years.
What we expect to see happen is that treatment threshold to go down to something like 0.5 or 0.3. If that happens, then you're going to see physicians look to diagnose earlier, treat earlier, and to be more upfront with their treatment to try and get patients as low as they possibly can with proteinuria, which is great for all medicines in IgA nephropathy, nephropathy, especially for FILSPARI as foundational care.
So when those, when that guideline drops, is that more related to the fact or is there some part of it that's coming into play that they know now that there is a drug out there that patients can use that's safe and effective, whereas if they were to use the standard off-label standard of care that was off-label drugs, where there are some issues associated with it, that puts the patient more at risk. So is that what partially allows them to drop that down?
I think it is. I think it is. I mean, we're not directly involved in the KDIGO guidelines.
Yeah.
But you know, from everything that we hear from the community, that's certainly it. I mean, it goes back to what I was mentioning earlier, where we're going from having off-label treatments to, all of a sudden, you have three medicines that have really been directly trialed in IgA nephropathy, approved specifically for IgA nephropathy. And what you're hearing from the community is a vast excitement that's being driven by the fact that physicians feel like they have the tools to be able to treat the disease, and patients actually feel like they're winning. We're hearing that anecdotally back from the patients that are taking FILSPARI, that they feel like they're winning.
And so when you look at it that way, and you know that you have these, these treatments that are now developing 2 years plus worth of data, it adds added confidence to be able to shoot for those kind of goals.
So getting added to the guidelines clearly makes sense, that that would help in seeing greater usage of FILSPARI. Maybe you can talk a little bit about the actual going from accelerated approval to getting full approval. Exactly what happens mechanistically with the label, et cetera, that would potentially allow for expanded use there?
Sure. So the accelerated approval process, the whole point of it is to allow medicines to be approved on a surrogate endpoint, with the goal of enabling access for patients while you're still generating additional data that that's confirmatory. And so when we got approved with FILSPARI and IgA nephropathy in February of last year, that was based off of our interim data, which was very strong. So we had a 50% reduction in proteinuria and, you know, a very strong safety profile. And what the agency or the FDA has decided to do with accelerated approval, specifically for... And this is consistent now across the three approvals that have come in for IgA. They make a treatment threshold of generally 1.5 g.
So they're saying: We want physicians to think about the patients that are most progressive first, while you're under this accelerated approval timeline. Then, once they have the confirmatory data, the idea is then that you open it up to more patients because you've confirmed the benefit of the drug and understand more about the safety. So what we expect for full approval that's that we're planning for here on September fifth is a broadening of the label, and we're basing that off of not only our own data from the phase III studies but also from precedent. So that's really the only indicator that we have to give insight to where FDA is until we're done with the actual sNDA review process.
But what we've seen so far is that with the other medicine that came before us, they went from the 1.5 g per gram threshold and proteinuria target to having no threshold there. So it just says, "For at risk of progression, for patients at risk of progression of disease." And so you open the, you know, the indication statement up to more patients just with that. So that's an important aspect of full approval. The other piece of it will be, we have two-year data that's very compelling. So, you know, we've seen a sustained benefit on proteinuria, we've seen kidney function preservation out to two years, and we have two-year safety data that puts all of the risk-benefit in a profile that is very favorable for FILSPARI.
And so we haven't been able to talk to any of that with physicians. You know, you can educate in medical forums and the congresses, but our sales team hasn't been able to educate on any of those data. And so the full approval will give us the, a real opportunity to go out and do all of that. It's almost like a relaunch with all of this new information and drive even greater excitement for FILSPARI, and I think that that's gonna drive even greater conviction and utilization.
And then, as you talk about with IgAN in general, where do we stand with Europe at this point, or European approval?
Sure. So with Europe, we have a great partner, CSL Vifor, who, you know, they are the leaders in rare nephrology in Europe, and they are leading the process over there. The two of us recently gained conditional marketing authorization in Europe earlier this year, and so the CSL Vifor team is working on a launch imminently. So you should expect to hear more from them in the near future, and we would anticipate seeing the typical European approach, where you're going to go sort of country by country and make FILSPARI available. The one thing I would add, just on the European side of things, is that from a label perspective, we ended up with the best label yet for IgA under the conditional marketing authorization.
That being at the treatment for 1 g or more, and that's similar to what we studied in our trial, and that's a little bit different than the drug that came before us, where they had a higher threshold. So I think that just speaks to the depth of the data that we have and the strength of it, and we're excited to see what CSL Vifor will do.
What does the TAM look like for Europe as compared to the U.S.?
It's similar numbers.
Okay.
You know, we haven't broken down the specific breakdown that we do because... Sorry, the breakdown that we do because we, you know, we've done a lot of work to just get to the addressable pieces in the U.S., and that's CSL Vifor's work-CSL Vifor's work over there. So more to come from them, but it's a similar overall profile.
Okay. And you talked earlier about the ability that IgAN is really all about combination therapy or treating is. Can you talk a little bit about the competitive landscape? There are quite a few late-stage drugs going after IgAN. Do you see all of them being kind of complementary in usage, mechanistically with FILSPARI?
Sure, nearly all of them, yes.
Okay.
So the way we look at the evolution of the market space is, you have two aspects of the disease. You have the overactivation in the immune system, and you have the overactivation in the kidney. You have to address both. And the interesting thing for some of the other compounds that are coming, they're all being trialed on top of ACEIs and ARBs, and so they have that - they have something there that's addressing the activity that's happening in the kidney, and FILSPARI is gonna be replacing that. So the future is FILSPARI taking on ACEIs and ARBs there. There is no medicine in development or available now that can get all patients to complete remission. So that's inevitably the goal, is you wanna get all patients away from kidney failure.
And so combination use will absolutely be where the future goes, and it's gonna be a question of, well, what do you use to treat the activation in the kidney? There we've seen that FILSPARI is by far and away the best option for patients. And then you'll have your choice of what is best to use from an immune perspective, and that's where we're seeing a lot more activity. You have TARPEYO that's approved now, you have Fabhalta that was recently approved, you have the APRIL/BLyS compounds, and that's exciting because patients are gonna have more options. But it's also exciting for FILSPARI because you know that they have to have that control of the kidney aspect of the disease in conjunction with those.
You know, that's really driven by proteinuria, where all patients, or nearly all patients, show up with proteinuria, and that's the hallmark of the damage in the kidney that you have to treat. When we think about the future, we see that we're gonna have a great positioning from a combinations standpoint, with those other medicines. With the other medicine that is similar in mechanism to ours, it has the endothelin component, it doesn't have the angiotensin component, we believe we have a very strong competitive profile, where at 36 weeks, we show a 50% reduction in proteinuria, and their medicine shows a 38% reduction, and that's on top of another pill, so they have to take an ACE or an ARB with it. Just from a profile perspective, we think we're in very good shape.
So you seem like you're really a backbone therapy at this point for the renal indication for it. Then, can you give us an update on FSGS? Everyone, that's obviously an indication that was moving full force, and now you've gone back to the agency to kind of get feedback from them on what they're looking for.
Sure.
Do you have any idea of when we expect to get that feedback?
Yeah. So with FSGS, you know, I mentioned at the beginning, we've generated some very strong data, and it's actually the DUPLEX study is the largest study that's ever been conducted on FSGS, the largest controlled study. What we saw there was a statistically significant response on proteinuria, and that translated to a clinically meaningful difference on eGFR, but it wasn't statistically significant. The main driver there was variability. FSGS presents differently than IgA nephropathy. FSGS, there's a waxing and waning aspect of the disease, and it's very difficult to measure in a linear way, measurements like eGFR. So what has happened since our data came out is there's been a movement towards trying to identify other endpoints.
And so there's a consortium called the PARASOL Group, and this is a group that's made up of U.S. FDA, the EMA, patient advocacy organization, and all the thought leaders in the glomerular disease specific with FSGS. And they've really been working on going through all the available datasets to potentially identify other endpoints for FSGS. And that work is expected to be completed and come out in the October timeframe. So they've guided publicly that they expect to have some sort of presentation or publication around the ASN meeting in October. And if the target there ends up being proteinuria based, we believe we have a very strong dataset, right? So every way that we look at proteinuria in the DUPLEX study is very favorable for FILSPARI. So what we anticipate doing is once those...
That sort of consensus paper or publication is available, and we understand where this group is headed in terms of the recommendation. We'll engage with the FDA with what we have, and put our best foot forward and see where the FDA is. If they're amenable to us moving forward, we would look to file an sNDA and potentially have another indication for FILSPARI as early as next year. We need to see where PARASOL ends up in FDA's view, but we feel we've never been more optimistic since our data came out.
How do the KOLs feel about proteinuria as its importance with regards to FSGS, as an endpoint?
Yeah, it's very important. Similar to IgA nephropathy, it's the thing that nephrologists look to as the indicator of disease progression and the thing that they can measure most frequently. When you look at FSGS, it's actually a much more proteinuria disease. You see higher levels of proteinuria, and they're, you know, nephrologists are really looking for anything that they can get their hands on to help patients get that lower, because they know that the higher it is, the longer it stays that way, the faster they're gonna progress to kidney failure.
Yeah. Well, it seemed to work with IgAN because that was what allowed them, the agency to finally go with accelerated approval looking at proteinuria. So it seems likely that they would kind of follow that, but I guess we won't know until we know.
Yeah.
Yeah. Yeah. So the time we have remaining, I'd definitely wanna make sure we get pegtibatinase in here for HCU. Maybe you could just give us an update there. It and everyone's always focused on FILSPARI and how that launch is going. So, but you do have that program, so maybe you could talk a bit about it, because it is important.
We do, we do, and we're excited about pegtibatinase. So pegtibatinase is, as I mentioned in the beginning, you know, it's an enzyme replacement therapy, and it really does have the potential to be the first disease-modifying therapy for patients that really, you know, right now, they, they have, you know, the clinical outcomes of, of, heart attack and stroke, ocular lens dislocation, and cognitive decline, and there's nothing that is really effective for most patients. So, a very high unmet need there, and we have very compelling results from our, our phase I and II study. So in that study, we demonstrated that with pegtibatinase, you can reduce, on average, total homocysteine levels, which is the key biomarker for HCU.
We can reduce it by 67%, and we've actually seen that we've been able to get a patient into normalization of homocysteine levels, which is something we hadn't seen before. And so that gives us a lot of optimism for pegtibatinase in terms of it being an effective medicine, and you know, it's enrolling in our phase III now. So we started that at the end of last year, and you know, we've guided to top-line data in 2026. And in parallel, we're working on the enrollment and working on CMC scale-up, because we went from phase I/II to phase III, we're scaling up our CMC both for the full phase III program and commercial. And you know, we're looking forward to working towards that goal of 2026 data.
Fantastic. Well, we definitely look forward to getting the full approval on FILSPARI and getting feedback from the agency on FSGS. Really appreciate you taking the time to be with us today.
Very good.
Thank you.
Thanks for having us, Edward.