Mirum Pharmaceuticals, Inc. (MIRM) Earnings Call Transcript & Summary

All right. Good morning, everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Michael Ulz, one of the biotech analysts here. And it's my pleasure to introduce Chris Peetz, CEO from Mirum Pharmaceuticals. Before we get started, I just need to read a quick disclaimer for important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. And if you have any questions, please reach out to your Morgan Stanley sales representative. And with that, I'll just turn it over to Chris to give us some introductory comments for people that might not be familiar with the story.

Mike, thanks for having us. I'm going to kick off with also forward-looking statements being made here by me. So I refer you to our SEC filings for full risk factors disclosure. But a quick highlight of Mirum. We are a rare disease-focused company, have 3 approved medicines on track for $490 million to $510 million in revenue this year. So a really strong growing Commercial business, and a very active pipeline in the near term here. Just this morning announced completion of enrollment of the VISTAS Phase IIb study of Volixibat and PSC, and position that as 1 of 3 potentially pivotal studies that we have coming up over the next 18 months with the VISTAS PSC being the first one, expect top line data 2Q next year. . And behind that, a follow-up indication for Volixibat in primary biliary cholangitis and label expansion opportunity for LIVMARLI with the EXPAND study, and Fragile X program behind that. So a lot going on in the company overall. LIVMARLI is really the highlight of the commercial performance recently and with a recent label expansion for PFIC, the second indication for LIVMARLI, we've seen a really nice step-up in growth overall driven by new patient finding, new patient diagnosis and a really strong profile for LIVMARLI, positioning it now as we see line of sight to $1 billion plus for the brand. So exciting moment for the company and really happy with how these high-impact medicines have been rolling out.

Well, great. Thanks for that introduction, and a lot going on. Congratulations on getting your study fully enrolled. And I thought though maybe we could start just with LIVMARLI. Obviously, that's your revenue driver. You touched on this in your prepared remarks that you're seeing some really nice growth there. And a big part of that is PFIC. So maybe just dig into that a little bit more and what's happening there?

So for LIVMARLI, PFIC is what's new. I'd start with actually Alagille syndrome because this is a great base to the LIVMARLI product profile. And what we've seen for LIVMARLI in Alagille syndrome, since its approval, is now a pretty steady pattern of new patient accumulation, really great performance in the U.S., and that continues. So there's a good baseline support from the Alagille syndrome business. Internationally, that's really what's driving most of the performance. It's still Alagille syndrome with PFIC in its early days internationally. In the U.S., the PFIC dynamic since we had that label expansion last year, we've actually been pleasantly surprised about how well we've done from a patient finding standpoint. Unlike Alagille syndrome, there's probably a bigger under-diagnosed pool of patients with PFIC. So we put a lot of focus on getting conversations going about cholestatic patients that maybe haven't had genetic testing, trying to get some of those diagnoses confirmed. And then also, it was kind of worth noting that with our LIVMARLI's flexible formulation, we have a liquid solution for younger patients. Now have recently approved a tablet. It's one tablet per dose for older patients, that's played into some of the performance as well, where for a newly diagnosed patient, that liquid formulation is a little easier and then also a simpler administration for older patients that might want a tablet.

Just for PFIC in terms of identifying the patients? Are you doing anything unique than what you've done sort of in the past with Alagille, for example? Or is it just maybe you underestimated what the initial patient numbers might look?

There's a little bit of each of that, right? So I do think we absolutely underestimated what was the actual patient population out there. And for Alagille syndrome, we're highlighting a difference in presentation where Alagille syndrome is typically better -- we think better diagnosed and earlier diagnosed because of the multi-systemic nature of it. There's facial characteristics, they tend to be more jaundiced in younger age. And so we do think they get picked up more regularly. So the Alagille syndrome population is pretty well defined from what we're seeing. And for PFIC, which really is -- it's a simplifying term for a number of distinct genetic mutations in bile acid-related transporters. So, say PFIC kind of oversimplifies what's going on there. And for some of the specific subtypes, there can be a later onset presentation. So there are a lot more of patients out there that maybe weren't picked up in childhood and start to present with elevated bile acids, elevated liver labs and itch later on in childhood or even in adulthood. And so that's -- so that was kind of what we underestimated. What we've been doing proactively is much more supporting the diagnosis. So we have -- a lot of this through a field medical team, have supported kind of broader awareness of the availability of genetic testing, starting to get, in particular, some of the older patients, the why behind testing for the adult hepatologists, and we're seeing some of the impact of that.

Makes sense. You also mentioned sort of the strength in your international markets. So maybe talk about some of those markets you recently launched? And then sort of looking ahead, what are the additional markets you'll be looking out for?

International performance has played out nicely. I think we still, as mentioned, early days because what we're seeing to-date is largely Alagille syndrome-driven. I note on how we approach the international commercialization. We're direct in a shorter list of countries. So Canada and Western Europe. That's where it's Mirum people on the ground. So we call those our direct markets. And beyond that, get closer to global reach using distributors and partners, so kind of the partner markets. And what we see in the direct markets, really echoes a lot of what the U.S. is seeing for Alagille syndrome. So a nice steady growth over time and new patient starts. And distributor markets, we continue to get access in new countries. So we're now over 30 countries with reimbursed product. Real highlight from the second quarter, first and second quarter, frankly, is Japan. So our partner Takeda is off to a great start with their recent approval. That was a big factor in our Q2 numbers, some of their first orders get recognized. And so more to come from the international rollout as we get more distributors up and rolling and then also ahead, we'll have a PFIC expansion as well for the international markets.

Great. maybe we can just flip back to Alagille syndrome for a minute in the U.S. and kind of that's been sort of your initial launch there. So it's been several years. You keep growing that. Sort of where are you in that sort of process and how much room is left, I guess?

So when we're thinking about the patient population here that we think LIVMARLI can be it applicable for, there's both the prevalent pool of patients that, as mentioned, we do think are pretty well diagnosed. And we think we're probably about half penetrated into that prevalent pool of patients. But on top of that, new diagnoses every year, call it about 100 is what is typical new Alagille cases diagnosed. So 100 infants that present in any given year. And so those -- we think we do even better than that 50% because the treatment decisions are just a lot more straightforward, frankly, at that new diagnosis time point. And the question that always follows is like, so where is this going? Like how high does that 50% go? And we certainly see it moving higher. So we do continue to see new starts in the prevalent population even this far into the launch. And what's behind that, that we've talked about before is the physician-patient conversation and decision on who's a patient for eligible for treatment and who's a LIVMARLI treatment candidate. A lot of that's somewhat subjective conversation about what is the burden of my pruritus, what is my symptomatic burden that I'm dealing with. And so there's a lot to unpack to get those conversations to happen from both the physician side and from the patient or family side. So that's how we see that 50% continuing to go higher over time.

Makes sense. And in your sort of introductory comments, you sort of mentioned you recently increased your sort of peak sales expectations for LIVMARLI to $1 billion plus. Maybe you can just talk about, maybe a different components of that and I don't know if you're willing to go there, but the breakdown of those components?

Happy to give a very high-level picture of it. It's not something that we've really kind of detailed out by indication. But the three big pieces here, Alagille syndrome which we now have a clear line of sight, steady trends, kind of have a good view of where that's going. That's certainly the biggest component from how we look at it, so call that roughly 40% or so of where we see the peak getting to. And then the other two pieces probably somewhat equivalent as well. So between PFIC and the EXPAND indication. So we'll note that we're still learning as we go on those two pieces. So PFIC, as noted, there's been more out there than we initially thought. For EXPAND, we're starting trying to be pretty conservative in terms of what that population is. It's a long tail of different causes of cholestasis. But initial performance from the clinical study, enrolling and conversations with investigators and physicians, it's at least the size of PFIC in terms of patient population.

Maybe in terms of the EXPAND study, if you can just sort of remind us, the rationale there and how you started to head in that direction for those rare conditions?

It's an interesting program. So the EXPAND study is a basket study. And there are several different causes of cholestasis. So different diseases or postsurgical complications or implications that cause cholestasis. And with that comes elevated systemic bile acids, the pruritus that shows up in Alagille syndrome and PFIC, quite similar in how it develops in these other causes of cholestasis. And so we were initially seeing a lot of just compassionate use demand for patients that kind of fit in the long tail. These could be older biliary atresia patients. That's a big portion of it. Secondary sclerosing cholangitis, a number of kind of more rare occurrences of cholestasis, that are secondary to other diseases. And given the volume of compassionate use that we saw, FDA actually requested us to put a protocol together around it. That kicked off a conversation to develop this protocol and strategy, to gather these otherwise hard to study indications because each one on its own is just too rare to run a stand-alone study. So that allowed us to put them into a pooled population. So call it, at least 500 patients in the U.S. that fit the criteria that we have here and on track to complete enrollment next year.

Okay. And how, I guess, enrollment is tracking sort of as you expected? Or is it faster maybe or...

Yes, as expected, I mean the -- in terms of what we're seeing out there, the patients are there, and it's really about getting sites open and the families engaged with the clinical trial. It is a study that's open to children and adults. Worth noting that the focus analysis and the real primary endpoint is in the pediatric patients. So we do see adult interest in it as well. So our screening and enrolling adult patients into it. So the target 45 patients that we talk about is in the pediatric population.

Got you. And maybe just last question on LIVMARLI before we move on, maybe just touch on current IP? Or is there more IP coming that we should be looking out for? Or what's the status there?

For IP, we point to a key family of patents that are 2040 family that are directed towards LIVMARLI indications and dosing. There is more around that, including formulation and some other applications that extend a bit beyond out to 2043. But as we look at it, we plan on 2040 is really the key patent family.

Great. Maybe we can move on to just the bile acid portfolio. You had 2 programs there. You added them a few years ago, and you're seeing some nice growth. So maybe just give us a little background and kind of what's driving the growth there?

Yes. So Cholbam and CTEXLI are the 2 bile acid replacement drugs that we acquired a couple of years ago now. And we've been able to do quite a bit with them, really across both brands on identifying patients as well as the real highlight of the work we've done has been getting to the approval of CTEXLI. A lot of great work started from Travere, the company that we acquired these from, and we were able to go to the final NDA to get CTEXLI a formal label for the treatment of CTX. So what we've been doing to grow these products has been execution on patient finding for CTX, in particular, pretty substantially under-diagnosed. So we've been iterating on different programs on supporting genetic testing in different specialties. These patients do present in a number of different settings and generally can be quite advanced into adulthood, before they're found. So that's where we've been seeing early traction. I expect it to be continued build over time as we iterate through some of these different programs. And we've done really well. When we -- our first quarter with these, they were about $25 million a the quarter and recently, Q2 was at $40 million. So a lot of good impact over time and see it growing -- continue to grow in the future.

Yes, definitely making nice progress there. And maybe now we just shift to Volixibat. And maybe just start with PSC since that's sort of more advanced in development, maybe talk about the market opportunity there and the unmet need?

So Volixibat for primary sclerosing cholangitis, PSC. Really exciting program. PSC is one of the larger adult cholestatic indications and really historically has been really challenging from a drug development standpoint, where there's not really been an attractable surrogate endpoint. It's a lot of work on trying to find different alternatives, but unlike some of the other liver settings, there isn't as predictable of serum measures that you can use for drug development. Now what we've done with the approach for Volixibat is to target symptoms. And that actually gives us an attractable near-term outcome that can be used for registrational purposes. So the VISTAS study for Volixibat in PSC is the primary endpoint of pruritus in patients with PSC and designed to use that as the registration pathway, similar to what we've done in the pediatric setting. Now I mean what the -- how that maps on to the patient population and the impact we can have there, probably about 30,000 PSC patients in the U.S. Those that have itch is probably about 2/3 of that. And when you start to have conversations to understand what the impact of this means for patients. It's a potential game changer for them. The day-to-day burden of itch and fatigue as well, is another one of the symptomatic burden that's a real highlight in this setting is the day-to-day burden of this disease that these patients are facing. So feedback we've gotten from response stories from Volixibat, and LIVMARLI as well, I should note have some case studies. Feedback has been very positive on what that means for the patients day-to-day.

You mentioned coming up with an endpoint for this disease has been a bit challenging. You sort of focused more on the symptoms and you've seen some nice impact there. But I guess from a regulatory perspective, are there any issues or hurdles you need to sort of clear to sort of make that an approvable endpoint? Or is that -- are we there already?

It's a pretty straightforward approach and using a itch endpoint with the 0 to 10 NRS scale, and that's what the ItchRO scale is in this study. It's a pretty typical approach. There's a standard validation work that goes into any PRO endpoint, and that's all baked into our program. And so otherwise, while it's novel for PSC, it is otherwise a pretty standard approach to using itch as an outcome.

Makes sense. And I think it was last year, you gave some sort of interim analysis. So maybe walk us through that and kind of how to think about that.

Yes, the interim analysis design for VISTAS, part of what gives us -- makes us so excited about where we're at now. And I'll tie in a little bit of the VANTAGE PBC study here because these were designed really to help inform each other. And last year, we conducted interim dose selecting analyses for both of these studies. For the VISTAS study in PSC, it was designed to help the independent monitoring committee follow an algorithm to make a dose selection decision and keep the study blinded assuming all was within the target effect size. So for the VISTAS study, interim analysis stayed blinded. There was a potential outcome there where the effect size was close to the boundary that we had designed. There could have been a recommendation to upsize, that didn't happen. So it makes us feel confident on where we're at and that was designed to be predictive of a positive outcome for the overall study. So really kind of an interim analysis designed to give us confidence in the final primary data that we're going to see next year. For VANTAGE, however, because PBC is a more common indication, and we're targeting overall a larger safety database, we could unblind that data. So the VANTAGE study had an unblinded interim analysis that was announced and subsequently presented. And that gives us confidence in the dose selection as well. So both of these selected the lower dose to move forward and the unblind VANTAGE analysis, we think, helps us understand what was potentially happening in the VISTAS study.

Have you mentioned what the threshold was in VISTAS for the interim on pruritus or...

It was designed as a threshold based on the statistical effect size. So think of it more as a curve. We haven't disclosed what the exact numbers are, but it's basically a curve looking at the placebo-adjusted difference, the variability within the data set. So -- and with that curve then, there was a boundary area. We know we were above the boundary area.

And then maybe just on pruritus in general, like what's considered a meaningful difference? And then remind us what you showed in the VANTAGE?

So this measured on, as mentioned, is 0 to 10 scale, and it's expected that a 2-point change would be clinically meaningful. And in the VANTAGE analysis, we saw a 3.8 change from baseline. So really strong, clinically meaningful effect coming out of that interim analysis.

Great. And maybe just sticking with VISTAS and again, you complete enrollment that you announced today, and now you're heading towards data in the second quarter of next year. So maybe just talk a little bit about what to expect from that readout and kind of what you're looking for and what's sort of a positive readout in your view?

So the study was designed to really look at the pruritus as the primary outcome. As mentioned, from looking at VANTAGE, I think that this dose level is highly active. So we're confident that we'll be seeing -- that effect size that it's going to be meaningful for patients. The analysis is really just looking at placebo adjusted difference on that itch score, so that the top line, expect to be announcing that. And from the tolerability profile, at this point, we have a pretty good handle on what IBAT looks like in clinic. And the most common treatment-related effect is actually mechanistic, right? So there is a diarrhea related to flushing the bile acids out of the body. And we found that if you're coaching and helping patients expect it, it can be very manageable. So it's not something that we see as a real barrier, in particular, if there's good awareness around it. So that's another thing we'll be looking at, is the headline kind of GI adverse event rates.

Okay. And then maybe just shifting to PBC and maybe just a similar questioning market opportunity there, unmet need?

Yes. So for PBC, it's a much larger indication, but it's busier from a competitive standpoint, where PSC because of the endpoint issues, there are no approved therapies. In PBC, there has been a surrogate using alkaline phosphatase as an endpoint for recent approvals. So to break it down, think about in lines of therapy and probably about 100,000 patients in the U.S. roughly is the rounded way to make the math is pretty easy to follow. And in that -- of that 100,000, maybe 1/3 or 40% have progressive alkaline phosphatase levels. So they are eligible from these more recent approvals of Seladelpar and Elafibranor, the PPARs that were recently out there. And the Volixibat's role really goes across all of these lines of treatment. So we see pruritus in PBC really happen at similar rates in both first line and second line. So we kind of are approaching the market segmentation quite differently from the recent approvals. That means that in the first-line setting, right now, there's no other approved therapies. We have one other IBAT that has a PDUFA date next year. So there will be one other product out there that we can surely touch on their relative positioning. The IBAT role in PBC really cuts across all lines of therapy. Similar to the other indications, probably about 2/3 of patients have pruritus. So that's nearly 60,000 patients roughly is the target market for launch.

And just for the VANTAGE study, can you just remind us the current status there in terms of where you are in enrollment and kind of time lines around that?

Yes. So expect to complete enrollment next year. We -- and that would put us on track for top line data in the first half of '27. We'll look to try to refine that as we get closer, but that's the rough guidance that we have at this point. And study conduct is going well. As mentioned, for PBC, we're looking for a bigger total safety database. And so it just takes a little bit more time than the VISTAS study to enroll to get to that target patient number. And I'd point that out because the size of the study really is not about efficacy powering right? As we saw from the interim analysis, it's highly significant, even with only a 30-patient analysis. So this is really about sizing up for the safety database.

And maybe you can touch on the competitor in the space or the recent data we've seen and kind of how you're positioned there?

So the other IBAT that's been developed in PBC is coming out of GSK, and they have a PDUFA date next year, first half of next year. What they saw from their Phase III data really looks like an IBAT, right? So they're seeing improvements in pruritus. Their approval strategy and kind of patient population is really similar to kind of how we're approaching it. But in some of their -- from what we've seen from their dose selection, they did not take their highest dose forward. And we think that really shows up in the headline effect size. The VANTAGE study in its interim analysis, the effect size we saw there was just really striking. And so I think that puts us in a position, assuming it holds up in a similar range in the final data set be a fast follower with a much stronger effect size.

Makes sense. Maybe we can just shift quickly to your [ FXS ] program. Maybe just talk about that a little bit, how it's differentiated and kind of next steps there?

MRN-3379 is the PDE4D that we're starting a Phase II study now for Fragile X. Really unique program here. And again, we're going to come back and talk about endpoints is kind of what's got us excited about diving into this program. So in Fragile X, there's been a number of different studies, largely looking at behavioral tools, so surveys from the caregivers. And these studies because of the -- we think in large part to the end point, have had a lot of noise in the final data sets. And there was a key data set that actually came out of Shionogi from a competing program where they used a cognitive tool called the NIH toolbox. It was really designed for settings of cognitive impairment. And so it adjusts to provide a scale for the level of where the patient's at. And that resulted in a pretty striking Phase II result for their program. We think the MRM-3379 program has a differentiated CNS penetrant. So it gets more of the drug where you want it to be and is a compelling profile compared to that program, and looking to play that out in the Phase II study.

And maybe just quickly remind us where you are in the Phase II. Is it started yet? Or when will you start it?

We just cleared the IND. So after in-licensing the program, we did some work on having formulation and drug product ready to go conversation with FDA confirming their view on endpoints, what they wanted to validate this NIH toolbox. I feel great about that being the viable registration endpoint. So we want to have all that squared away before we started the study, and kicking it off now. So it'll be 3 doses versus placebo, to do that dose-ranging work to understand where we're at on playing out this, we think the stronger drug profile for 3379. I want to make sure we do the dose-ranging work to figure that out.

Maybe in the last few minutes, we can talk about some of these macro issues. We're asking a couple of questions to all our companies at the conference. So maybe if we just start at the top with the first question, China's rise in biotech innovation, how are you thinking about your competitive position here? And will this influence your R&D or BD strategy?

So overall, I mean, the most relevant for BD strategy for us, where the more potential drug candidates out there, that's our business model is to go find kind of underappreciated programs, and maybe reposition a mechanism or find something that data set was misunderstood that we can take it forward. I'd say from rare disease competition, we haven't seen as much of that out of China. They've been -- these companies have been focused on bigger indications. It doesn't mean that might not happen over time. But what the result of that is more product candidates that are available for us to go try to bring into the company.

Maybe next question, how are you currently leveraging artificial intelligence or thinking about AI's future disruption potential in your business?

Yes. So all the Mirum employees out there listening, make sure you're logging in and using it. That's the -- we've been trying to roll it out for really a lot of kind of first round drafting of documents, as all the work that we're doing here, there's a lot of writing on the regulatory side, on data review, on analytics and having some of these tools as a first path to add efficiency, we think will help us helps out quite a bit. And it's really about adding efficiency for the team we have. We're ambitious about bringing in more programs and doing more. So it's not necessarily that we're trying to replace people's jobs, just trying to make our strong team even stronger.

Got you. And then maybe last question, just what's been most impactful for Mirum on the regulatory side in terms of would it be FDA? Would it be MFN, if you have any impacts there or tariffs?

Mostly, it's been about how much time we have to answer questions about it. That's been the biggest impact for us so far. With Mirum -- from how our business is set up, I feel like we have somewhat less exposure on a lot of these topics. And we certainly track them. But for the FDA interactions, continue to be constructive and direct our teams that we deal with are all here. We've had 2 approvals and recent interaction on multiple programs. That's all gone smoothly. So no impact there. On the other ones, MFN, I think hard to tell where that one goes. But our relative pricing in the European markets, it's really not that far off of where our U.S. government price is already, frankly. So overall, we're -- I think we're pretty well positioned.

Great. Looks like we're just about out of time. So why don't we end it there. Chris, thanks so much. Appreciate it.

Yes. Thanks for the time.