Hey everyone. Thanks for joining us for the next fireside chat. Very happy to have CEO Eric Dube and CFO Chris Cline from Travere Therapeutics here for a fireside. I am going to kick things over to Chris to give a quick overview of the company and maybe give a few words around the recently announced CEO transition and his thoughts around the timing and what that means for the company. Chris, or Eric, over to you.
All right. Very good. I am sure Chris can do just as-
Yeah
as good a job. Alex, thanks so much for hosting us. We are really excited to be able to share a bit about Travere. The company has never been in a stronger position with both the commercial performance with FILSPARI, as well as a strong and diversified pipeline that really will help to address some key unmet needs within rare disease. That really has been our mission. I have been with the company for just about eight years now, and earlier this week announced my planned departure from the company. It has been the absolute honor of my life to be able to work with this incredibly talented, passionate team, and also to work with a phenomenal group of investors who have been along the journey with us and patient, and oftentimes impatient at the right points. It has been a decision that I made personally.
I have been dealing with some health issues over the last couple of years that I deprioritized very intentionally to make sure that we focus on delivering the first medicine for the FSGS community, which is exactly why I joined eight years ago. We have done that, and the company is just in an incredible position, and I believe that the best years of Travere are ahead of us. We also announced that Bradley Campbell will be taking over for me on December 1st. I think Bradley is the ideal leader for Travere. He is a known leader within rare disease and has a very strong track record with connections to the HCU community, recently with the FSGS community, and certainly really deep experience in enzyme replacement therapy.
So that, and just being an incredible human being and a great cultural fit for Travere, I am really excited about what the future holds for Bradley. I am sure he will be very eager to speak with you all. But I wanted to just express my sincere gratitude for supporting me and the team for everything that we have achieved to date.
Yeah. Thanks, Eric. Appreciate that, and obviously good luck on all the next steps there.
Thank you.
Obviously pivoting to FILSPARI, your first full quarter in FSGS, obviously off to a very strong start, as you alluded to. You basically doubled start forms from the IgAN run- rate. And on the 2Q call, you alluded to this being driven by obviously the high anticipation for the launch and not necessarily a bolus. I guess, could you talk a little about the distinction between this anticipation versus a bolus and how you are thinking about the trajectory from here?
Yeah. I think most importantly, we see an expected very high demand, and we expect that strong demand to continue. What I think about as a bolus is a very concentrated number of prescriptions that may not be sustainable, and we believe that the demand for FILSPARI moving forward in both indications is sustainable. It's a very unique situation where you have a smaller population and a more severe population as the second indication. That, I think, led to a quick uptake, and we do believe that the uptake in FSGS is going to be different from IgAN. Where IgAN was a rolling launch of accelerated approval, full approval, REMS modification. That's not the case for FSGS. The uptake curve we believe will get to peak sooner.
But it's still only one quarter, so it's difficult for us to be able to talk about what the trends are.
Yeah.
But we are very confident in the strong demand for FSGS and for IgAN.
Yeah. So maybe as it relates to kind of the early dynamics, what do the early adopters look like? Sort of are there particular subsets of both prescribers and patients, and how might this evolve over the next few quarters?
Yeah. What I would say that has been most exciting for us is from a physician standpoint, the uptake has been broad quite quickly. You typically will see a segment of early prescribers, early adopters, and then you start to slowly get to the later adopters. Because we launched in a broad set of IgAN use
we saw pretty broad uptake. We mentioned that 30% of the physicians that prescribed for FSGS never wrote for IgAN.
Yeah.
Peter's talked about a reverse halo effect. That, I think, is really the strong first evidence to support that that's likely to come true over time. And of course, then 70% of the physicians that wrote for FILSPARI were already treating patients with IgAN in their practice. I think the other aspect that's exciting is when we look at the patients, we're seeing very broad use. This is a broad label. Essentially any type of FSGS, as long as they don't have active nephrotic syndrome. And what we're seeing is the broad use across the different subtypes of FSGS, and I think that that signals, again, that strong demand over time.
Yep. Then one of the other early dynamics here, particularly on price, that Chris, I think we've talked about, is that obviously there's a titration element here, and then there's going to be differences around gross- to- net relative to IgAN. Can you walk through, at least in the early part of the launch, how we should think about titration, net price, and then ultimately gross- to- net?
Sure. On the titration side of things, in IgAN, you have a titration from 200 mg to 400 mg, and that is over the first two weeks. 200 mg, 400 mg are the same price. That dynamic has been relatively linear over time, and well understood. In FSGS, it is slightly different, where we are going from 400 mg as a starting dose to 800 mg. The 800 mg is two 400 mg pills. That first two weeks is going to look more like an IgAN price rather than an FSGS price, and then it will titrate up over time. On the gross- to- net side, what we have seen, and this is consistent with our prior guidance and what we expect for the balance of the year, is to be in the mid 20% range.
Typically what we see is in the first quarter, you have the largest discount with the beginning of the year resets on the plans, et cetera, and 2Q tends to be slightly better than 1Q. Then we are expecting for 3Q, 4Q for it to be slightly higher than we saw on 2Q.
That is mainly driven by, to your question, in FSGS, we do anticipate having more patients that are going to have CMS exposure. IgAN is about 70/30 split commercial to CMS. FSGS is still expected to be majority commercial, but it is going to be more CMS exposure than what we see in IgAN. Still early days, so we will give some more color on that as we go through the balance of the year. Things are so far shaping up to expectations.
Obviously, Eric, you talked about IgAN still growing, still strong growth trajectory there. How have you seen the BAFF -APRIL launches at all impacting this space? Can you talk about the importance of the KDIGO guidelines here and sort of that differentiation among those classes of drugs?
Yeah. Well, we've done a lot of work over the last three years to understand how this field is likely to evolve and work with the top thought leaders. Everything that we've seen thus far is very aligned with our assumptions and expectations. We're excited that these patients have multiple treatment options, and treatment options that can be used in combination.
Yeah.
That's exactly what the KDIGO guidelines recommend, and I think what we've expected as B-cell therapies are approved is there's going to be an acceleration in the size of the IgAN market. That's driven by patients being treated earlier. That's a great thing. It's patients being treated earlier, not just with off-label RAS inhibitors and steroids, but being used approved therapies. We're now seeing that. In FILSPARI, a lot of our growth is coming from earlier initiation. Then, of course, we're expecting alignment with the guidelines around the use of combination. Patients should be on a kidney-directed and immune-targeted therapy. We're seeing early signs of that as well. Encouragingly, we're not seeing a lot of payer barriers around that. I think that they're watching to see how this all unfolds.
From our view, there's nothing that is a surprise and nothing that I would say is going to impede the role that FILSPARI plays as the best kidney-directed therapy that's approved.
Yeah, I think some of our payer work suggests that, yeah, there really haven't been barriers yet to combination utilization. But I think they're starting to ask the question around data generation. I guess, how can you help generate that combo data and sort of maintain your positioning as this sort of other foundational therapy moving forward?
Yeah, it's a great question. We're eager to be able to collaborate with other companies around combination. I think there's, rightly so, hesitation to do so before you have full approval.
Yeah.
Let's see how companies operate as they move forward. What we would imagine is that there are going to be physicians that have case studies of patients that are on combination to be able to share that. I think a great example of how we've seen that evolve, one of the key questions that we got early on was, well, what happens for patients that have recurrent IgAN or FSGS post-transplant? We saw some physicians that use that publish their own case studies, and then we actually have initiated two trials to be able to look exactly at that population that has a high unmet need. We've done combination studies with SGLT2s, and we'd be happy to do so with B-cell therapies at the right time.
Yep, makes sense. Maybe pulling it all together, you again talked about incremental demand growth in IgAN last quarter. You're now at this sort of 2,000 start form run- rate, it seems like. Is that a good trajectory to think about moving forward for the balance of the year? What are some puts and takes around how the quarters could look moving forward?
Yeah. So, 2,012 patient start forms last quarter. We were really excited to see the strong uptake in both indications. As we look forward, it's, I'd say, really difficult for us to project out after only one quarter of launch. We're obviously eager to share Q3 results at the right time, but we also have to acknowledge that we got one quarter behind us.
Yeah.
We have seen in prior years some summer seasonality, so we have to take that into account. That's a short-term dynamic.
Yeah.
But I think the most important thing, Alex, is as we look at the long-term opportunity to reach more patients, we see incredible opportunity in both IgAN and in FSGS.
Yep.
We're seeing retention of these patients over time with the good profile, the good response, and our patient services that we fully expect that we're going to continue to grow over time.
Yesterday, you put out a press release around a new NOA for an FSGS method of use patent out to 2037. This follows an IgAN announcement earlier this year. I guess, could you talk about the strength of this IP and your confidence that you can actually protect FILSPARI out to 2037 at this point?
Yeah. Let me share three updates that have occurred very recently. The first is we now have that IgAN method of use patent in the Orange Book that has
Yeah
a stated date of October 2037. As we announced yesterday, a very similar method of use notice of allowance for FSGS that also we expect to have Orange Book listing out to October 2037. We also recently heard around the patent term extension that we expect to have as well. All of this, we believe, further supports the protection over time. I don't believe that it's one individual patent
Yeah
but it's overall the approach to protect the incredible and innovative evidence that we generated. We're continuing to look at other opportunities. There are other applications with the PTO that are being reviewed. We'll provide those updates at the right time. But I think overall, it allows us to continue to invest to reach these patients and to generate data that nephrologists have been very eager for the industry to do.
Great. So maybe I want to pivot to siborotinib because I think this is a super interesting molecule. Just maybe ask at a high level, what got you confident about the profile here, especially the safety, given sort of the questions around the broader BTK class and some uncertainty there over time?
Yeah, I think the really interesting aspect is that this builds on a strong foundation within rare kidney disease.
Within Travere, the strong relationships, the clinical footprint that we have. As we look at siborotinib or sibo specifically, we see this as a really exciting addition because it could be a potential pipeline in a pill.
Yeah.
Obviously, we're very interested in a couple of lead indications. Primary membranous nephropathy being one of them. The other aspect is that this is an oral, very selective, reversible BTK that is unique in many ways. It's early in terms of the data, but it supported our view on proof of concept and the potential that it could be used longer term in a way that may confer some safety tolerability differentiation.
Yeah. Maybe can you talk about some of the data generated to date, and what that looks like in pMN?
Yeah, I think the most important aspect in terms of the data so far is that we see a very clear link between reductions in PLA2R, which is the key autoantibody that is suspected in pMN. You see a very rapid and profound reduction there that is followed pretty quickly by a similar reduction in proteinuria. There is a lot of work within PARASOL and within the community to really understand
Yeah
that link, and can we actually accelerate some of the development for medicines in pMN through some of the work that we are seeing.
Yeah, that is a good transition. PARASOL is meeting right now as we speak, to talk about primary membranous nephropathy. What are you looking for out of that meeting? I guess as it stands right now, the path to approval in pMN is a two-year trial.
Do you see analogies to FSGS here in this context to sort of maybe run a shorter pivotal study, and what would that look like?
Yeah, I think that optimistically is what we would hope is that we could see a faster path to development. I think that there's alignment in that expectation. The evidence has to support it.
Yeah.
Let's see what PARASOL does. But I think what PARASOL has done for FSGS and what they're looking to do for others like pMN really gives me hope that with the alignment across the different stakeholders and a broad set of evidence, that we potentially could. Our hypothesis from the work that we've seen with sibo suggests that there is a relationship between the antibody and proteinuria reduction. I think we've got to see what they come up with.
This is still pretty early in the PARASOL stage for MN, is that correct?
Yes.
I guess as you think about pivotal development here, which is sort of the next step for you, is that discussion part of how you're thinking about pivotal development? Do you expect to run a two-year study, I guess? Or is it possible that based on the PARASOL discussions and discussions with FDA, we could be looking at a shorter pivotal trial?
Yeah. I would not want to set that expectation.
Sure.
But as you can imagine, that is a key question that we will be asking. I think we will be prepared to do what FDA is looking for.
Yeah.
We will have to evaluate how quickly do we think they could come to that recommendation. We are obviously going to be attending and really monitoring what PARASOL does. One of the key next steps for us is to meet with FDA and see what their expectations are.
Great. Then maybe what does the clinical development cadence look like for sibo in MN, and then as you have talked about other indications as well?
Yeah, I think the pathway with pMN because of the proof of concept is there. With that said, I think we've got a lot of understanding within FSGS to evaluate where and how quickly could we go. We're excited about primary membranous nephropathy and specific immune subsets within FSGS. That's something that we do want to speak with FDA.
But we've not yet said whether that's going to be sequential or whether in parallel development. Things that we are evaluating. But we do recognize that we want to go quickly, but very diligently.
Makes sense. So maybe let's pivot now to pegtibatinase. Your pivotal study is ongoing. Can you walk through the story there and sort of your expectations for the pivotal program?
Yeah. So with HCU, this is a community that we've really come to know and understand, and they're really looking for an approved medicine that is going to directly improve not just their homocysteine levels, but ultimately, to a degree that they could potentially normalize some of their diet. These are patients that have a defective CBS enzyme that healthy CBS levels are able to metabolize protein. For patients that have a defect in their CBS enzyme, you see a toxic accumulation of serum homocysteine that leads to eye problems, bone malformation, ischemic events. Half of these patients will have an ischemic event before their 30th birthday. So a really devastating disease, and one where patients have to have an incredibly strict diet of limited to no protein. So it's one that these patients have not had a lot of options other than vitamin B6 nutraceuticals and diet.
Yep.
In the proof of concept that we saw in our phase II, we saw 67% reduction in homocysteine, and every single patient on pegti were able to get below the target levels that are in the guidelines currently. A real exciting opportunity that we have. We are in phase III now, and we expect to have top-line data from that in the second half of next year.
I guess one of the other questions here is, your total homocysteine surrogate endpoint that you have had agreement on with the FDA for a while now. How confident are you that that agreement holds true, and sort of when was the last time you have talked to FDA about this?
Yeah. We are confident that they would accept a biomarker endpoint of total homocysteine. There is precedent for this, and we have also engaged with FDA. They have aligned on this approach. We have got breakthrough therapy designation, so we have had very active engagement with them. We do not comment on the specific timing of those engagements.
Yeah
But we feel very confident in what they have agreed. We also are excited about one of the unique aspects of our phase III, which is a sub-study for patients that complete randomization, where we can look at are they able to maintain control of total homocysteine levels and introduce additional protein into their diet, which would be considered a clinical endpoint.
I was going to ask, is that a functional endpoint like you would see in other ERT studies? Okay.
That is right. Now it is not required for approval.
Yeah
But it would be something that is incredibly meaningful for patients.
Yeah. Can you talk a little about the size of the patient population in HCU in the U.S. and globally, and how you are thinking about that relative to other ERT type markets?
Yeah. Currently we've estimated about 3,500 patients in the U.S. that are diagnosed and uncontrolled, and under the care of a specialist.
When we look at patients that are not under the care of a specialist, even though they're diagnosed, or patients that have not been diagnosed because they were missed on newborn screening, that number increases pretty significantly. It's a pretty broad range of estimates, but we are doing work to be able to improve newborn screening and find these patients that have really been lost to follow-up because there's been nothing for them. We do expect that the addressable population will grow, as you typically see once a therapy is approved in a rare disease. But at this point, I'd say conservative 3,500 patients.
Obviously a lot of the work that we're doing with the trial sites is helping us to see where these patients are.
I guess, as you think about commercial, what does pricing look like in HCU? I think historically you've had this sort of $300,000-$500,000 a year range for ERTs. One of the more recently approved ERTs from Denali is much, much higher than that.
Where should we think about a reasonable range for HCU?
Yeah. I think looking at the range of enzyme replacement therapies is the right place to start. It's still early for us to be able to narrow that down, and we're going to be very eager to look at the strength of the data coming from phase III. In particular, whether we're able to demonstrate any clinical benefit that could help in supporting the value of this innovation. More to come there, but I think looking within the broad ERT is the right approach.
Great. Then maybe wrapping things up, I wanted to ask about what does your spend trajectory look like next year if you're potentially ramping up sibo, you're coming off of the FSGS development. Should we also expect more BD? How are you thinking about things next year?
Sure. Consistent with the expectations that we set out last quarter, we do expect to have moderate increases in expense as we go forward this year and into 2027. Maybe it's worth breaking down how that looks between SG&A and R&D. From an SG&A perspective, we don't have significant infrastructure that we need to build. We had that done at the end of last year, getting ready for the FSGS launch. So really it's about promotional spend and some of the capabilities that we're going to continue building on. But I don't expect a material change there. On the R&D front, that's where we expect to see a little bit more investment, and that's going to be driven by the fact that we do still have FILSPARI work that's ongoing. DUPLEX and PROTECT, those are rolling off.
But as Eric mentioned, we have the transplant studies that are ongoing and some additional evidence generation. More importantly, you are going to have the full weight of pegtibatinase, the global study that you have all the sites open for and enrolling. Not to mention the continued scale-up of CMC, right? So we have gotten that process optimized, but we need to run the batches to get full scale for commercial launch there. So that is an ongoing investment in parallel. Sibo is the other element where you can envision where it is potential that we have multiple late-stage studies that are ongoing, and we are going to want to move as quickly as we can there. So more to come on how that looks in more detail.
We are in the midst of our budgeting cycle now, but I would anticipate that we will have additional spend next year relative to where we are. Then just on the BD front quickly, we are going to continue looking for interesting assets to layer into the pipeline. I think we have been very disciplined in the past, and we will continue to do that. There is not an urgent need that we are trying to fill. But we do want to continue to leverage the expertise in especially rare kidney and rare metabolics.
Very well. Eric, Chris, really appreciate you joining us today. Thanks so much.
Thank you for having us.