Travere Therapeutics, Inc. (TVTX) Earnings Call Transcript & Summary

Okay. Good morning, and welcome to day 3 of the Barclays Global Healthcare Conference. My name is Carter Gould, Senior Biopharma Analyst here at Barclays. Pleased to welcome Travere Therapeutics to the stage. Travere's got a very active 2022 ahead of itself with a number of key regulatory updates and hopefully some new launches. And joining us on stage right now are CEO, Eric Dube; and then Peter Heerma, Chief Commercial Officer. Chris Cline from the IR team is also around here, too. So Eric and Peter, thank you very much for joining us today.

Thank you for hosting us.

Before we jump into Q&A, why don't we just pass it over to you first to maybe make some opening comments and give a little background of the company and we set up the conversation.

Sure. Absolutely. Well, I would first refer you to our SEC filings and our recent 10-K for any of the risk factors and forward-looking statements. Travere Therapeutics is a rare disease company. We are dedicated exclusively to rare disease with a focus in rare liver, kidney and metabolic diseases. And for a company our size, I think we're quite unique in that we have an established commercial infrastructure that has consistently delivered year-on-year organic growth as well as a very exciting clinical stage pipeline, which I'm sure we'll talk more about. And we're well capitalized to continue to invest in the planned launch for sparsentan, I believe, later this year.

Perfect. So the IgAN data last year was clearly the major highlight, at least from our perspective, of events that played out for you guys. Now that you've had the data in hand for closer to, what, 8, 9 months at this point, can you maybe just talk about the reaction of the community to that data and really the sort of profound separation versus the comparator?

Sure. Well, I think the data that we saw from the PROTECT interim analysis last August certainly was consistent with what we see how sparsentan acts in rare glomerular diseases where, in a proteinuric state-like IgA nephropathy, you see a rapid and sustained reduction in proteinuria. That's what we expect and that's what we designed the trial to do. But the degree of reduction in proteinuria was unlike anything that's ever been seen in a non-immunosuppressive in a single agent. And that, I think, has really garnered an incredible response from the nephrology community as well as from the patient community. And so we're really encouraged by what we've seen thus far, and we believe it's going to help in establishing sparsentan as the new standard of care for IgA nephropathy, if approved, and ultimately for FSGS, another rare glomerular disease, also if approved.

Okay. So when we think about the IgAN filing coming up, how should we think about what data is going to be going into the package? Is it going to be largely limited to what data we've already seen? Will it be more mature data? And particularly also on the eGFR side, what data will the FDA be seeing?

Sure. Well, for the NDA that we plan to submit essentially any day now, and we're on track for that submission, we will be providing all of the data that was analyzed at the interim analysis last August. We disclosed a very limited amount of those analyses in August, essentially focused on the reduction in proteinuria. But there are, of course, several analyses looking at eGFR, which we believe is predictive of that difference at 2 years. That will be part of the NDA that FDA will see and we believe is going to be very focused on ensuring confidence in the overall output or endpoint at 2 years. And of course, all of the additional data from the clinical development program including the safety data of the entire database inclusive of the FSGS safety data. So we think that it's going to be a very robust NDA, and we're confident that it should be supportive of an accelerated approval.

So on that front, renal has been somewhat of a tricky group of late with the FDA. And so often, these questions where -- these situations where the companies are going after an accelerated approval strategy. There's oftentimes that question of like well, the eGFR or the outcomes data is not that much further down the road. What's really the urgency to do an accelerated approval here from an FDA perspective when they could just wait X number of months for an eGFR data, I would guess?

Sure. Well, I think first and foremost, these are rare diseases where patients are progressing every day if they have elevated proteinuria. And FDA certainly recognizes that and has communicated to us that they recognize the need for these therapies and the unmet need within IgA nephropathy and FSGS. And there certainly has been a lot of discussion over the years around how these trials are designed, looking at the interim and then shortly thereafter, the confirmatory endpoint. So this has been part of how they've been designed, and I don't know that there's been any reluctance or shift in that strategy, at least in the discussions that we've had with them. And so we're confident that with the data that we're submitting for IgA nephropathy that it should support accelerated approval. And if there is this interest in -- or this concern around what FDA may want to wait, it's not as if we just wait until the confirmatory endpoint next year. In FSGS, it's in the first quarter and in the second half of next year for PROTECT and IgA nephropathy. That essentially means that patients will be waiting well over a year. We'd need to then develop and submit the NDA for full approval and then wait thereafter. So there is a substantial amount of time that patients would be waiting. And we know that they're hearing from the patient community that's driving, I think. It's not going to compromise, I think, their review of wanting a robust file, which we believe that we'll be providing with them very shortly.

Very clear. In terms of -- based on your discussions, any hints yet that there will be an ADCOM? Clearly, Nefecon was able to get approved without one. At this point, what's your guys thinking on that side?

Well, it's certainly a question that we asked in our pre-NDA meeting with the FDA. And they had indicated that based on the review of the data thus far from them that they did not see a need for an advisory committee. So we don't anticipate there would be one. We certainly will ask with FSGS once we have the additional data to share with them. And if their plans change, and they do want to have an ADCOM, we'll be ready. But at this point, based on our feedback from them, we don't anticipate one.

Perfect. Peter, maybe help frame the commercial opportunity in IgAN for us and think about the dynamics that are really going to drive adoption here.

Yes. First of all, I think building on what Eric was mentioning earlier, there's a high unmet need in this patient population in both IgA nephropathy as well as FSGS are among the most rapidly progressive kidney disease patients. I think the opportunity is real. And in particular, for those patients that have a consistent high proteinuria level higher than 1 grams per gram. Where we see really the opportunity and what we hear from our thought leaders as well as from the market research is that physicians are most excited about sparsentan because it has the opportunity to become the new standard of care, really replacing ACE inhibitors and ARBs that is currently the standard of care. Basically over 95% of the patients get those treatments. But most of the patients are not being treated to the targeted level. And so physicians are now kind of like forced to go to the steroid path, and there is a high level of reluctance both from the patient community as well as from the nephrology community. And that's why sparsentan has a potential to become like a new standard of care, having the significant higher efficacy that we have seen in the interim analysis for PROTECT, without going -- having to go to the path of the steroids. And that's how we see the commercial opportunity. And I think that's being reinforced what we hear both from the patient community as well as from the nephrology community.

So our research is big on case studies when we think about launches. I guess the 2 questions that pop up. First one, any -- I know it's early days, but in terms of early lessons from Tarpeyo and sort of their go-to-market strategy. And secondly, more broadly, when you think about potential benchmarks or comps to think about with the launch of IgAN, how -- any insight there might be helpful.

Yes. It's a great question. I think overall, in nephrology, I haven't seen a lot of innovation over the last 20, 30 years. I think it's very rewarding to see that innovation is coming to nephrology right now. I think a few years ago, we saw this with Otsuka. Last year with Aurinia, with ChemoCentryx, now with Calliditas. So innovation is coming to nephrology. And I think that is good for patients. It's good for the industry as well. With regards to benchmarks and early marks, I mean, we monitor those very closely. We have a good sense of like how the uptake is looking. I think for budesonide from Calliditas, I think it's too early. I mean, product availability, they got the PDUFA December 15th. Product availability became available in January 30th. So it's out about 6 weeks right now. But there is clearly an unmet need. And I think that investment will have its place, but I think it's more later on in the intervention cascade to sparsentan. We see the additional sparsentan clearly different than an add-on therapy like [indiscernible].

So maybe 2 more questions. First is on just the importance of KDIGO guidelines in terms of driving adoption and maybe some sense on how quickly that may or may not be updated.

Yes, that's a great question. I think in addition to what you mentioned earlier, like there's a lot of innovation coming to nephrology. I think also the recent KDIGO update on glomerular diseases is an additional catalyst, I think, in the marketplace. New guidelines, as you may know, were published last fall. I think also there, you see like a higher level of reluctance in the use of steroids, and it's also something that we are seeing right now in market research that is taking up. There is more reluctancy of using steroids in IgA nephropathy, in particular. So I think that is a good thing for sparsentan. With regards to your other question, like how fast will sparsentan be included, not yet, but other than in the past, KDIGO didn't implement new medications once they became available. They have now changed their processes. So once you have the published data, that will be -- it will be integrated in the guidelines. So I think good developments on the KDIGO front as well.

And then just the back half of that question, just when you think about sort of the segmentation here between academic and community centers, any stats you can give us on that side. And I guess, following on your earlier point in terms of reluctance on steroids, any kind of real divergence there we should keep in mind or differing approaches to the disease?

Yes. So it's -- with regards to the uptake of medication, it's early. With regards to implementation of KDIGO guidelines, I think overall, you see pretty good reference to KDIGO guidelines. When you ask physicians like what are guidelines that you are following? I think across academic as well as community hospitals and physicians that is followed quite well. I think what you see other than other rare diseases where you have more like expert centers, centers of excellence that have very focused treatment centers, nephrology, it's more diverse. And I think the community hospitals, the community prescribers will be important for us in that respect as well.

Perfect. So usually, when we talk to investors, we get a lot -- we talk a lot about IgAN. And then the other thing that people obviously want to try to understand is just the updates that will come on the FSGS site and then the potential ramifications as we think about IgAN. So I guess, first, when we think about FSGS, maybe just you can remind us -- clearly, you have the data and the interactions with the agency that played out last year. At this point, how should we then think about additional data and interactions with the agency that will play out over the earlier part of this year?

Sure. Well, I think against the backdrop of what we've disclosed in our FSGS program, we certainly had a very positive Phase II study that was essentially replicated in the interim analysis of our ongoing Phase III program, the DUPLEX Study, where we set a very high bar in the measurement of proteinuria, the partial remission endpoint, which is correlated with longer-term renal outcomes. And we saw a very significant difference in that analysis of partial remission. When we look at the overall data with FDA, they were looking for a more mature analysis and a more mature data set when it comes to that confirmatory endpoint of eGFR. And eGFR is a longer-term assessment of renal function. And typically, that's how nephrologists think about that is over the long term. And so when you have a data set that is much more heavily weighted to earlier study visits, which is what we saw, essentially because of the enrollment trends, like FDA wanted to see a bit more data in order for them to feel confident that, that 2-year confirmatory endpoint would be demonstrated. And so we have an agreement to meet with them and share additional -- an additional analysis in the middle of this year. We're on track to be able to do that. And essentially, what we're going to be doing with that analysis is looking at the eGFR once all patients in the study have at least 1-year study visit and 50% of patients have 2 years, so that whole confirmatory endpoint for 50% of the patients. That's certainly going to be much more mature and actually more mature than the eGFR analysis that was done in IgA nephropathy next year. So we think that, that's going to certainly provide the questions that FDA is looking around eGFR. And if we see what we're expecting, then we believe that FDA would provide a greenlight for submission for accelerated approval. Again, we're on track. We're not going to be able to provide any incremental updates from here on out. We'll be able to provide an update once we've met with the agency. But again, one of the important things about sparsentan is just how consistent it has behaved over the clinical development program.

So I'm going to ask a couple of annoying questions you're probably not going to answer, but when we think about how that's going to play out just in terms of scheduling that meeting or I guess, first off, collecting that data, internally analyzing it, then submitting it with the agency, what will be sort of like the last horse for you and then you guys will kind of go radio silent on that front? And how should we think about that?

Sure. Well, I would say, on our quarter 4 earnings call earlier this month, we'd indicated that essentially, we're going to be not providing any additional updates. What I can say is that we will be prepared to provide an update on the timing and pathway for regulatory submission for FSGS once we've met with the agency. And essentially, the way that process works is you get -- we're on track to look at the data the first half of this year. We then will request a meeting. We'll meet with them. And then once we have done so, and typically, we'll wait for minutes, then we will provide an update externally. But at this point, there's no value in providing any additional information because essentially, we're going to need to wait to share data with the agency.

Okay. Perfect. And when we think about the potential implications of the FSGS data on the ongoing IgAN submission, are there any -- how do you think about that? Are they going to be reviewed by -- assumed by different review teams at the FDA? Is there any -- under the scenario where maybe FSGS looks to be less good, could that potentially impact IgAN? Any thoughts there?

So we don't see any particular read-through here in our 2 programs. We have worked with the same review team to date, and so we believe that it will be the same review team that will be looking and reviewing the NDA for IgA nephropathy and FSGS. They have separate INDs, and they will be separate NDAs. And so we don't know that there's going to be any direct read-through. We certainly can't speak for the agency and how they're going to be reviewing them. But they have been very independent in how the FDA has looked at them. They wanted to look at the correlation between proteinuria, eGFR renal outcomes independently for each of those diseases. And the good news is that correlation and that relationship exists in the data. So now we just need to ensure that we're demonstrating that in both of our ongoing programs. And we'll make sure that we have a strong NDA for both.

Perfect. Why don't we switch gears to homocystinuria, another quality data set you had last year. We've done a lot of work on that prior to the data reading out. I guess the one thing that we kind of spent a lot of time trying to understand is how is clinical significance going to be defined for a therapy here? Is it really around getting below a threshold? Is it the magnitude of reduction of the relevant the metabolite here? Can you just kind of help us understand how you guys are thinking about more -- I guess, more importantly how the field is thinking about [indiscernible].

Sure. Well, homocystinuria is a defect of the CBS enzyme that when working fully functionally, it metabolizes homocysteine levels. And in patients with homocystinuria, you have varying degrees of CBS activity, quite low where you see increases in homocysteine levels over time. And those become related to some of the sequelae that you see in patients with HCU thrombosis, which is oftentimes fatal and the most severe, but you have bone, cognitive and eye defects as well. And those are all related to the buildout of homocysteine levels. That is important to understand how the field thinks about this disease and what would be modifying for these patients. And in the clinical guidelines, you see that patients really are targeted to have total homocysteine levels below 100 and -- 100 micromole. And that's really driven by some of the literature showing that once patients are below that level, they are at lower risk of some of these clinical sequelae. Patients -- some patients are responsive to high doses of vitamin B6 and they are able to -- as vitamin B6 is a cofactor to the CBS enzyme, are able to get to some lower levels of homocysteine. For those patients, the target in guidelines is to get below 50 micromole. Our goal was to be able to see whether pegtibatinase is able to get patients at high levels and that are not responsive to vitamin B6 below that threshold of 100. We were very pleased in our ongoing Phase I/II study where patients at baseline of 180, which is quite high, were able to get very quickly, within 2 weeks, below 100 and sustain that over 12 weeks. So it's very encouraging and we believe is related to how clinicians think about the goal for homocysteine.

And when we think about the sort of the cadence of data emerging from this program over the course of 2022, there's a couple of things pop up. One, when will we see the initial cohorts presented? And two, maybe just kind of remind us around that additional dose cohort, what's being evaluated there and when we might see some data?

Sure. Well, we have submitted the data from cohorts 1 through 5 to a medical meeting. That should be in the next couple of months, and we'll certainly provide updates at the right point. And we also have a sixth cohort at a higher dose level, studying the similar endpoints to see whether patients are able to get further below 100 on their total homocysteine levels. And that's going to help inform how we think about the dose going forward into a Phase III. Those data, we expect to be able to provide on that cohort 6 sometime later this year, but it's all going to depend on the enrollment rates for that cohort. But you can see additional data from cohort 5 in the coming months.

At this point, what's your thinking on kind of what would be a regulatory endpoint? Or is it likely to be that biomarker? Or would you need to show some outcomes data or other kind of clinical measures?

Well, our view is that total homocysteine is an ideal biomarker. It's the most proximal to the enzymatic defect, and it really has, I think, some precedent in PKU, which we know is something that we're evaluating from a regulatory standpoint. We're -- one of the key goals for us this year is to align with regulators on the use of a biomarker such as total homocysteine. Those discussions are often iterative, and we're pleased with how the discussions have gone thus far, and we believe this data should support the use of that. But we'll certainly continue and provide updates when we've aligned.

And Peter, it's probably a good segue to you. He stole my comp question. But when you think about just help frame the opportunity in homocystinuria relative to whatever other rare disease or what sort of might be easiest.

Yes. I mean what we hear consistently is that there's about 3,500 patients under the care of physicians in the U.S. and probably the same amount of patients in Europe. We're further informing ourselves on the patient journey and with what symptoms those patients appear and what physicians are treating those patients. I think if you talk about like benchmarks, what other disease areas could you compare yourself with, I think PKU is probably the most relevant benchmark.

Okay. Perfect. And when you think about how that might complement the existing commercial franchise, can you talk about that for me?

Yes. I mean that was one of the reasons we in-licensed pegtibatinase because I think we have a -- that rare -- ultra-rare infrastructure already with our hepatology -- pediatric hepatology infrastructure. So we have a field force in there, and I think it's a very nice fit with regards to geneticists, ophthalmologists. So I think we have that infrastructure in place. So I think it's a very nice fit and very complementary to our current portfolio.

Okay. Coming back to Eric. Just a bigger-picture strategic question. The pegtibatinase acquisition certainly looks very sexy in the rearview mirror so far. You've also got clearly a lot on your plate with launching sparsentan. What role is BD going to play for the company going forward? Is that still going to be an active effort? Or how should we think about you balancing that with clearly a lot already on your plate?

Sure. Well, our goal is to continue to be a leader within the rare disease space, and we look for opportunities like pegtibatinase, where there's innovation externally that there may be a need for a partner like ourselves, who can do the late-stage clinical development and commercialization. That's really where we see our role. Business development is going to be critical for us to continue to build and grow this organization, but it's not going to detract us from our #1 priority, which is the successful launch of sparsentan, which hopefully could come later this year.

Perfect. Well, with that, we're out of time. Eric, Peter, thank you very much for joining us today and have a good conference.

Thanks, Carter.

Great. Thanks, Carter.