Good day, everyone. Welcome to day one of Cantor Fitzgerald Global Healthcare Conference. For our next session, we are very excited to host Travere Therapeutics, and representing Travere, we have Chris Klein, CFO, and Peter Heerma, CCO. Gentlemen, thank you for joining us.
Pleasure.
Thank you for having us.
Maybe before we start, if you can provide a brief intro about Travere and where the company is at right now.
Sure. So just before we jump in, I do wanna highlight that we'll be making forward-looking statements, so please see all of our disclosures on our Forms 10-Q and 10-K for additional information. But you know, specifically with Travere, we are exclusively focused on identifying, developing, and delivering life-changing therapies for people living with rare disease. And really, at the core of our focus is our pipeline, which is focused on rare kidney and rare metabolic disorders. And it's actually a very exciting time for us 'cause we just got full approval of our lead product, sparsentan, which is now Filspari. That was converted from accelerated approval to full approval just a few weeks ago.
And we're also advancing the same molecule, sparsentan, for additional rare kidney disorder called FSGS, and we're looking forward to some regulatory and community updates here in the near future for that program as well. And lastly, we have another program, pegtibatinase, in phase III development for a rare metabolic disorder called homocystinuria. So a lot going on and exciting time.
Great. And maybe since it's a very recent update, what were the key highlights from the full approval for Filspari and IgAN?
Sure. So, you know, on September fifth, as I mentioned, we received full approval, so this was a conversion from accelerated approval that we had last year to full approval. And I would say that the first thing that was, you know, a very welcomed response was a broader indication. And so specifically, this is pointed at proteinuria, which under accelerated approval had been specifically for patients that were at greater risk of progression in IgA nephropathy, and that's really how FDA has sort of approached doing all accelerated approvals in the IgA space. And what we saw was that greater progression, or that the patients that were at greater risk of progression, that was removed. So now our label indicates that Filspari should be used for all patients at risk of progression, at all.
That's the first step of the label that's very encouraging. The second aspect of it is the two-year eGFR data that's now included, and with that, we have in our label now an analysis that shows superiority over irbesartan, which has been the historical standard of care in IgA nephropathy, and really the only medicine that's shown an accrual of benefit over that time. Having that in the label, and specifically being able to talk to that accrual benefit over two years is gonna be very helpful for Peter and his team.
Then, lastly, just on the safety aspect of things, we now have a label that reflects two years' worth of safety data, which is very encouraging, given that we continue to have Filspari look comparable to Irbesartan and no new safety signals and no signs of any kind of liver toxicity or injury or anything like that. Overall, it was a very great outcome for Filspari and for patients in the IgA community.
Got it, and during the call, you talked about some of the kidney guidelines update as well, maybe some of the key takeaways from that.
Yeah, maybe to, to take that one. Like, I would say timing could not have been better. I mean, to, to have the new, draft guidelines of KDIGO, it's a global guideline committee, within one week from our full approval, is absolutely perfect, and both speak about a broadening of the market. Chris was talking about it a little bit, broadening of the label. In the, accelerated approval, we had like a guidance of generally patients with proteinuria levels higher than 1.5. There's no longer a threshold in the label. That means that, the addressable patient population that we had anticipated at the, accelerated launch a year and a half ago of about 30-50 thousand has now increased to over 70 thousand patients.
So a much broader patient population that we can tap into and that can benefit from, from the benefits of Filspari. I think that's one. But especially now that you also have the guidelines that basically moved from one gram per day now to point five gram, or preferably point three. So basically what the guideline says: every patient that is not in complete remission should be diagnosed and should be treated, and should be treated with, like, a kidney-targeted, product. I think that is very revealing in the KDIGO guidelines. It's an immune-mediated disease, so what KDIGO says is, like, you have to target the immune system, but simultaneously, you also need to target the kidney, because most of those patients that are being referred to the nephrologist have already substantial nephron loss.
The vast majority of the patients is already in phase III or further advanced. That means that at least 50% of those nephrons have been lost, and as a nephrologist, the first thing you wanna do is protect the nephrons, the remaining nephrons, and that's exactly what Filspari does in the most beneficial way, and Chris was talking about it. But let me further amplify the importance of that. I think our label really is very competitive. It's not only talking about beneficial effect on the kidney; it also talks about the accrual of benefit over time. That means year-over-year, that separation versus irbesartan is getting bigger. The first year, it was almost two ml per minute; in the second year, almost four.
So those are substantial differences, and I think we can really make an impact by being the most efficacious product that is being registered that is targeting the kidney and really can be used as foundational therapy for IgA nephropathy.
Got it. And so how does the addressable market change with both of these updates, the label as well as the kidney guidelines, which I realize it's draft, but how will that change?
Yeah, like I said, it's. I think it's really a call to action for nephrologists, and I've spoken with several people of the committee, and they said, like: "Well, as a nephrology community, we have to be, we have been too conservative in this particular patient population." And bear in mind, historically, IgA nephropathy was regarded as a relatively benign disease, as a slowly progressive disease, often early diagnosed in the early twenties or thirties. With the investments we made early on in the biggest rare kidney disease registry in the world, is the RaDaR dataset in the UK. We found two and a half thousand patients that were longitudinally followed, and what that revealed is that basically every patient was facing kidney failure in their lifetime.
In fact, even patients that were being managed to 0.5 gram, one out of five or one out of four even, was progressing to kidney failure within 10 years. This is a younger patient population, so that call to action I think, is really important, and I think that came through in the KDOQI guidelines, and I think that, that allows us to be more upfront in our conversation with nephrologists and treat those patients earlier and more aggressively.
Got it. And I realize it's only been a couple of weeks since you got the label update, but any even qualitative feedback from the physicians?
It is very early because we got Thursday, two weeks ago, we got the full approval. Monday we brought the full field force together to train them on the new KDOQI guidelines, on the new label. Our field force is ready and eager and hungry to get out there. Yesterday was really the first full field day that we had with the updated messaging, campaigns, materials, et cetera. The anecdotal feedback I've received myself directly after approval is that this is a great win for patients and that we should be very proud of the label and the full approval of Filspari.
Got it. And on the draft guideline update to diagnose and treat these patients earlier and maybe more aggressively, when you talk to physicians, what are you hearing on how this could impact their prescribing behavior?
Yeah, like I mentioned, it's really the call to action to prescribe earlier and more aggressively. I think historically, and that's what we saw initially as well when we launched Filspari a year and a half ago, is that automatically you get your first prescription at higher proteinuria levels. That's when physicians start to make a treatment change. I think now is the call to action. I'm expecting that patients will be treated with lower proteinuria levels and higher eGFR. The physicians are not waiting till a patient has progressed to a point that it's kind of like too late to really make an impact. I was talking about the impact of two mL per year and four mL per year.
If you think about that, if you do that early on, what the separation could be over time, and based on the extrapolation data that we have shown, it means that a patient could be off dialysis for four and a half years. Think about it, four and a half years of moments in your life that you are off dialysis. That's meaningful.
Got it. Could there be any differences in how community and academy incorporate these updates?
Yeah, it's a good question. Like, in general, the guidelines are written by academicians, so academia is closer involved, and it's now important to get the guidelines out as quickly as we can. We have been speaking about the RaDaR dataset that I was just referring to for the last year and a half, and now I think with the KDOQI guidelines, you have a further validation of this call to action. We do work together with KDOQI. We have an opportunity to educate the broader community physicians as well, because, like, the majority of those patients are actually under the care of community nephrology.
So it's a very important element to make sure that they are being trained and educated on the new guidelines and see the value of Filspari very soon as well.
Got it. And maybe on the discussion with the FDA on REMS modification and what additional data might be needed to support this?
Sure. So on the REMS, I think the most important thing is we're making progress with that. And what we have pointed to is that the NDA review process was really the first natural juncture to go back to FDA and talk with them about the REMS for the first time post-accelerated approval. And through those discussions, it was very clear that that is... well, that's the right time to engage. It also runs on an independent parallel track because it involves multiple parts of the division.
And what we learned through that is that, you know, they're certainly open to revisiting the REMS, and what we're working towards right now is aligning on what is it that we can go back with, what data do we have today that we might be able to go back with and be able to submit an sNDA to have a modification of the REMS. So we're working on that alignment now, and assuming we can get there, then we would look to submit that quickly and more to come on the data at that point.
Got it. Are there any drug analogs that you look at where the REMS was removed, and what data was needed to support that?
There are some analogues out there, but there aren't any that are specific to rare disease or-
Okay
... in this case, IgA nephropathy, that I would point you to. But there are other endothelin, for example, that have had the REMS removed over time with additional data. I think the most important thing for us is that based off of the data that we have compiled to date, and that's inclusive of our PROTECT phase 3 study, our DUPLEX study, our DUET study, and then also the real world experience, you know, we have gotten to a point where we feel like we are likely to have a path, but now it's about aligning on that.
Got it. And so how much of a barrier has been REMS commercially, now that you have some time in the market with the drug? And how impactful could the REMS modification actually be?
I think there's a couple of components I would like to point you to. Like, one is the certification process for physicians, and that's a very easy process that is like less than two minutes. It's really like an attestation of having read the prescriber guide and the PI. The second component is the patient certification in the beginning, in the first, especially in the first one hundred and twenty days, and take in mind, Filspari was initially approved under accelerated approval. That means in the first one hundred and twenty days, you have limited promotion and educational opportunities, really focused basically only on PI.
At that time, we had a pocket of patients that required further education and hand-holding by their physician because they couldn't conceptualize what it meant to have a box warning and a REMS certification. After those one hundred and twenty days, we had more opportunity to educate patients directly with more patient-friendly materials. We have seen that we have made a material impact, and that the pull-through improved substantially after that as well. I would say from a REMS, like, what is the impact commercially? I think in particular, physicians often have a certain idea of what patients will comply to the monthly monitoring. So I think there is a pre-select them in the mindset of the physicians.
Maybe that explains also the very high compliance rates that we have seen, as well as adherence, so patients that are on Filspari, they see the benefit, they see the effect, and they stay on drug, and I'm very pleased with that, and I think the REMS actually is a positive contributing factor to that as well, so not only negative, there are positive elements to a REMS program as well.
Got it. And do you have a sense of what percentage of physicians are waiting for the drug to get full approval before prescribing it, being an active prescriber?
Yeah, and I wanna be careful how to prescribe it. But I think in general, since there has been so little innovation in nephrology over the last thirty, forty years. I mean, think about it. For IgA nephropathy, there was basically no approved product till two years ago. But that also means that the adaptation is relatively slow in nephrology. It's a relatively conservative audience. And so I hear from physicians that say, like: "Well, the data looks great.
Proteinuria effect is really impressive, but I wanna make sure that it's doing on the kidney what I'm expecting it to do, that it really has a long-term beneficial effect on the kidney, but also that I can use it safely to those patients." With the two-year data, and Chris was talking about the open-label safety data as well as the kidney preservation data, I'm sure there is a group of physicians that will be starting prescribing Filspari quite soon. And in fact, we had already identified a group of over a thousand nephrologists that had a positive attitude towards Filspari. Many are already REMS certified, and many of those already have patients in mind that they wanna prescribe for Filspari, but were waiting for the validation of full approval.
Got it. And just looking at the revenue trajectory for the drug, you've seen a steady add of new patient adds throughout the year. And now that since you have received the full approval, there is a draft kidney guideline, do you see some sort of an inflection with the full approval, or it's more about a steady add?
Yeah, I have to be careful because we are mid-September, so we're getting close to the end of the quarter. What I would say for this quarter, we continue to see very steady fundamentals. That's what we had outlined as well when we launched the product a year and a half ago. I think the inflection that you're talking about, like the full approval, having two weeks left in Q3, I think the real acceleration I'm expecting in Q4.
Q4? Got it. Any color on how is the persistence and adherence tracking for the drug, and what does it mean for the duration of therapy?
Yeah. Well, Filspari is a chronic therapy, different than some of the other products that are approved for IgA nephropathy, which is more intermittent. It's a chronic therapy, and so compliance and adherence is really important for this drug, in particular, for the accrual of benefit on kidney preservation over time. And so compliance is of critical importance for these patients. And what we have seen, and I was just talking to it, the compliance rates have been really, really high, especially in current disease. I'm really pleased with what we're seeing so far.
Got it. Maybe if I know you won't quantify, but any analogues in terms of what does high mean in terms of a compliance on a chronic therapy? Like the diabetes therapies, you look at an analogue, or are there other therapies like B-cell modulators in multiple sclerosis?
Yeah, it's, it's-
A big range.
If you refer to diabetes, hypertension, cardiovascular products, I would say it's at the high end what you would expect.
Okay, got it, and last quarter, you had a great quarter. The conversion from patient starts forms to patients getting on therapy was also improving and ultimately showing up on revenues. Anything specific on that quarter, or is that something that's sustainable?
No, I would certainly think it's sustainable. Like early in the launch, you have to educate the payers, making sure that you get into the formularies, that the ease of getting access to drug is smooth and goes quickly. That takes time, and I think now, a year and a half into the launch, I think we are in a very good shape. I was also earlier referring to the amount of patients, so like a pocket of patients that needed additional hand-holding. I think now we have the materials, the organization in place to have a continuation of the fulfillment and conversion rates.
So I think it's certainly sustainable, and I think we are learning as we go, and I think certainly the full approval will help us further to educate patients and physicians in the process as well.
Got it. And thinking about next year, any qualitative commentary on the uptick trajectory?
Next year?
Sure, I'll take that. Yeah, I would say for next year, you know, going back to what Peter had mentioned earlier in terms of the accelerated approval, we had guided everybody to say, "Look, year one is going to be it's gonna look similar to other products that we're oftentimes compared to, but year two, that being this year and beyond, we expect to see outperformance, right?" We're on track right now to do that this year, and we would expect to see significant growth continue next year. We're not in a position where we've given any kind of specific guidance at this point, but we do expect to see meaningful growth for all the reasons that, you know, Peter has mentioned, not only from a label perspective, but also the KDOQI guidelines.
I do think that we're going to see a sea change, if you will, of how physicians are really looking to identify and treat earlier and really get to those lower proteinuria targets. So all of that, I think, comes into concert here as we're going through this year and into next. Yeah.
Maybe building on that, I mean, this is really a great time for IgA nephropathy patients, with all the evolution that's happening. The guidelines, new products, new modalities that are in development, and I think Filspari is really well-positioned. In particular, if I think about the KDIGO guidelines, I mean, it's really talking about, like, a two-prong approach, that you really have to target two systems simultaneously. You have to target the kidney, making sure the nephron loss, the remaining nephrons are being protected, as well as addressing the overactivation of the immune system. Within the kidney-targeted medicine, I think Filspari is really well set up. It's the only study that has direct head-to-head, maximal dose, label dose, comparison, and shows superiority.
If you look at the proteinuria benefit after two years, it is a factor twenty times as effective as the active comparator, fully dosed, and like, a factor twenty, it's not like 20% better, it's, it's a factor twenty better, 40% remaining proteinuria after two years, compared to 2% in the active control arm. I think the data is really strong. Within the kidney-targeted medicine, I think there is relatively little competition compared to the immune system, where you see much more competition with steroids, with complement inhibitors, and with B-cell therapy, so I think the future looks bright for patients with IgA nephropathy, but the future looks bright for Filspari as well.
Right. What about access for next year? Should we expect any updates on access next year related to this year?
The access situation, I think, is really strong. We have 96% of the patients have actually a pathway to reimbursement. I think the next step for us and our teams is to make sure that the full approval label is now reflected in the authorization criteria, in the formularies, and in the plans of payers, as well as the KDIGO guidelines. And payers often refer both to the label, but they also refer to guidelines. And so to educate payers on those two aspects and get it reflected in the label, so we make sure that we allow for that broad access to patients, I think that is the next step for us.
You probably get this question a lot, but how does the potential approval of B-cell modulators impact the long-term opportunity for the drug?
Yeah, I don't think it really impacts the long-term opportunity because, first of all, I mean, the data looks promising, but we haven't seen any approvals in this category. But most importantly, as I just mentioned, like what clearly is outlined in the KDIGO guideline, it's a two-prong approach. You have to target the kidney patients. The majority of those patients have already half of their kidney is being lost. You wanna make sure that the remaining nephrons are being spared and protected, and that's why you need a nephroprotective drug like Filspari. Simultaneously, you wanna make sure that you also address the overactivation of the immune system, and I think that's where the B-cell therapies play as a place.
Got it. So it could be used in combination or-
Very much so, yeah.
Got it. And I think you have some presentations at ASN on SGLT2 combinations. Maybe talk about that and any other presentations of note.
Sure. So we're excited about ASN this year. It's in San Diego, so we'll have a big home presence there. And you know, obviously, Peter and his team have an opportunity to engage with nephrologists. And I would say from a data perspective, we have two different elements that we're really focusing on in order to build further evidence for use of Filspari, and really, it's broadening the use of it. The first is, as you mentioned, with SGLT2. So we know that a substantial number of patients today with IgA are being treated with SGLT2s. And what we wanted to do, and we set this in motion years ago, was look at what would the combination of Filspari plus an SGLT2 do for patients.
And what we've seen so far in the data is that combination, when you add Filspari to a patient with an SGLT2, you see a further reduction in proteinuria and a safe combination. And so we'll look to elucidate further data on that and build that story further. Because, again, as Peter just highlighted, simultaneous treatment is gonna be key, and SGLT2 will be one of the key components of that as well. The other element that we're gonna have some more data on is earlier use of Filspari, and so this will generally be coming from our SPARTAN study, which is a very interesting study where patients who are treatment naive, the first time ever getting anything after diagnosis for IgA nephropathy, are starting on Filspari, and they're actually going through a repeat biopsy.
This, the data that have come from this so far have shown that if you start Filspari first, that you could end up with a proteinuria reduction in the ballpark of 80% and a stabilization of eGFR. So further building this evidence and more data from that specific study will come, and I think it's gonna really round out the picture very nicely for physicians to reach for Filspari as foundational treatment.
Got it. Moving on to FSGS, what's the latest on the regulatory side there?
Sure. So just with FSGS, it's worth taking a minute to just talk about the DUPLEX data, which is our phase III study, which was the largest study ever done in FSGS. And what we saw with that was sparsentan versus irbesartan, again, as an active control. We had a statistically significant outcome on the interim assessment. That's a proteinuria-based endpoint. We saw a continued reduction in proteinuria out to two weeks to the magnitude of 50%. But on eGFR, we saw a beneficial response for sparsentan relative to irbesartan, but it wasn't statistically significant. And the reason it wasn't statistically significant is there is high variability in eGFR, specifically in FSGS, far greater than IgA nephropathy.
And so it really begged the question, if you have a molecule like sparsentan that can reduce proteinuria to the degree that it did, and in the largest study and longest one that had been run, but it can't show an eGFR outcome, what can, right? And so it provoked a conversation and really an action from the PARASOL Group, and this is a consortium of patient advocate leaders, all the thought leaders in the FSGS and glomerular disease communities, as well as FDA and EMA, to come together and do analyses on all the available datasets in FSGS, with the goal of identifying other endpoints that might be used for an approval of a product for FSGS.
You know, we know that complete remission is one thing that has been pointed to in the past in eGFR, and we now know that those are very difficult to do in an FSGS setting. So the goal here really will be to come somewhere in between those, and you know, so far, there's been a lot of discussion about proteinuria. We'll see where that lands. We'll know here in at least some direction next month. So they've got a public workshop that's occurring in early October, and then they'll have a presentation at ASN at the end of the month, and that'll give us a sense for where this group is lining up in terms of potential endpoints.
Following that, what we would do is look to engage with FDA, with what we have in our own dataset and you know, putting the full picture together for them to understand if there's a pathway forward. Certainly, if there's a path to an sNDA based off the data we have, we would look to submit very quickly and hopefully getting Filspari to the patients with FSGS.
Right. And so after this PARASOL update at ASN, what could the timelines and the process look like? Any details there?
More to come. So what we wanna do is see what the outcome of the PARASOL group is, and then engage with FDA. You know, FDA has certain schedules that you'll have to request the meeting and, you know, it's dependent upon their availability. But, we know we're certainly looking to do that quickly because we know the unmet need is very high in FSGS, and we wanna be able to move quickly for patients.
Based on your discussions, are the regulators more receptive to proteinuria reduction or any other endpoints, and realize that if eGFR could be such a challenging endpoint in this indication?
It's a good question, and I think the PARASOL outcome will tell us a lot about where the regulators-
Mm-hmm
... you know, are sort of viewing things, 'cause they are directly involved. I would say that it's been very abundant in our conversations with FDA over time, that they recognize the significant unmet need in FSGS, and so I think they are very much so coming in with a patient focus to the discussions, and I think it speaks a lot to the fact that they are involved directly in the PARASOL work. And so we're looking forward to seeing where things come out and you know, certainly there could be an evolution there.
Got it. What's the IP on Filspari?
Sure. So our expectations for IP would be into 2033.
Okay. And in the last couple of minutes, if you can remind us of the cash runway and the key milestones ahead for the company?
Sure. So at the end of last quarter, we had $325 million in the balance sheet, and our guidance is that that should support operations into 2028. When we think about the milestones that are coming up, we'll obviously learn more about FSGS here in the near term, and so that's an exciting opportunity for us. You know, especially when you take a step back and look at the FSGS market, you're talking about an addressable population of roughly 15-30 thousand patients, and there's nothing really out there close in development, and there's a really great opportunity for us to help patients there. So excited to learn more about that. We'll have more commercial performance from Peter and his team, and so we're excited to get to those updates along the way.
Also, our partner, CSL Vifor, they're in the midst of launching in Europe, and so we're excited to see what they will be able to do with Filspari over there, and more to come.
Got it. And on the Europe launch, if you can lay out the timelines and any milestones that you will be getting?
Sure. So as I mentioned, they're launching imminently, so you should expect to hear more from them in the coming months. And I think that they're taking the traditional approach of, you know, launching in the key regions that-
Mm
... that are the best sequentially to do that. And what we've guided to so far for milestones is that we are expecting to be paid a $17.5 million milestone from CSL Vifor as a result of the conditional marketing authorization that we currently have in Europe, transitioning over to full approval. And then we would also anticipate another milestone payment that hasn't yet been disclosed to come next year, and that's really based off of achievement of market access-based milestones that they will go and achieve as they go through country by country process.
Got it. That's all the time we have today. Thank you for joining us.
All right. Thank you much. Thank you, everybody.