STIFEL 2026 HEALTHCARE CONFERENCE - MIRUM PHARMACEUTICALS INC

Welcome, everyone, to the next session here. Happy to be joined by Miriam Pharmaceuticals. We have CFO Eric Bierkolt and Andrew McKibben, SVP Strategic Finance and IR. A lot going on at Miriam, so we can jump right in. But maybe, you know, Eric or Andrew, if you just want to kind of give like a brief overview of recent quarter, you've had a lot of data going on, so maybe just kind of like set the stage and then we can dive in. Sure. First, thank you for having us. Thank you to Stifel for organizing the conference. We will be making forward-looking statements, so please refer to our risk factors in our SEC filings. So we now have four approved medicines. We're experiencing really rapid revenue growth. We've guided to revenues of $715 to $720 million for this year, with strong momentum going into next year. we see growth from all our medicines and next year we expect significant contributions from atrebiros in fop which was very recently approved we've guided to being cash flow positive in 2027 um we were cash flow negative last year cash flow passive first half of this year but And second half of this year, we have a heavy R&D lift in part with significant investments in CMC for the expected filing of, you know, Berlovitag next year, as well as for Velixibat. So sets us up really well for continued growth and good financial performance next year. Great. Makes sense. And maybe we can just start off with some of the, you know, pipeline assets. Obviously, you guys have had kind of a lot of updates recently. You know, I think PSC naturally remains kind of the focus for folks. So maybe it would be helpful just to kind of like lay out sort of like some of the context there and sort of your kind of continued perspectives on sort of the path forward there. It's Andrew's favorite topic. You know it's funny. No one asks us about this. Yeah. Thank you. Yeah. So just to make a little bit of context, you we're planning to file in the first half of next year. We received feedback in July from the FDA at our pre-NDA meeting. They recommended a phase three, but noted that we could file at our discretion. Based on our understanding of where that review team was, and it was a new review team, we felt that it would behoove us to take some turns to interact with them with our breakthrough designation before we put that submission in just to bring them closer to the data set. There was no specific issue that they were pointing at behind their recommendation or specific recommendations around what a phase three should look like, which tells us that there was just lack of familiarity with the program and a review team that was a bit newer to the program. So taking a couple iterations to interact and get them closer to what we've done, it's a very robust data package. Before we put that submission in, we thought it would be prudent. So that's where we are. uh if anything changes in this in this kind of back and forth with them between now and submission that's material that changes our plans we would certainly update you but you know right now everything's on track sounds good um and and you may not be able to answer this but uh want to ask it just in terms of do you think there's like sort of an alignment that's going to happen before you submit or is it going to be more like we'll just have to kind of like see throughout through you just like curious if you think there's the latter is a win right and rarely do you know i wouldn't expect them to say i'm sorry we love you please submit like that this doesn't that's not a thing the fda does it's usually moving the conversation to a review issue which is where we think a lot of this should be yeah makes sense um and then at asld this past weekend um you guys shared some like additional data for for psc maybe just kind of like recap that that kind of briefly and sort of the importance of that data and kind of Like rounding out the the broader clinical profile for Fervalix about? Yeah, it kind of goes back to the start of the program. I mean, as you know, there's a high degree of IBD in PSC patients, around 70% have IBD. And so going into the program, we were concerned that there's some potential for IBD exacerbation. We discussed that with the FDA. What we see is there's not. So it's a pre-planned analysis from the get-go giving us reassurance that, you know, there's going to be no exacerbation in PSC patients with IBD. So really, really reassuring. Yeah. Yeah, makes sense. You know, maybe just like while we're on PSC, totally understand, you Know, totally get your confidence kind of going forward. And on the regulatory front, maybe on just like commercial kind of remind us the right way to think about that opportunity, kind of how many patients are out there, and how many you think are, like, truly addressable in terms of this, you know, addressing itch? Yeah, for PSC, we believe there's about 50,000 patients in the U.S. About 60%, we believe, have significant itch that would warrant treatment. So that's a very significant patient population, probably a similar number outside of the U。S. So really excited about what this could mean for us. Okay. Sounds good. And I'll talk about PBC in a little bit. But obviously, a lot's been going on in the HDV space as well recently. Maybe just kind of like recap some of the data from, you know, Azure One. You just had Azure Four as well. And, you Know, I think you presented some longer term data recently as well, so maybe just kind of like set the stage with all that's happened. Yeah, I mean, a whole lot of really exciting data coming out of the Berlowituk program. So just to recap, Azure one and Azure four, the two phase three studies that will form the basis of our BLA submission. Both of those studies met the primary endpoint, which we looked at at 24 weeks, looking at, you know, treatment versus delayed therapy. So very clear signal very early on. You're getting really nice rapid viral suppression and normalization of ALT. I think taking a step back and looking at the full picture of data that we presented at ASLD over the weekend, what we also showed was those responses continue to deepen meaningfully over time. which is as expected. You know, 24 weeks is enough to see a signal and, you know, support a filing, but we're tracking these patients out to 96 weeks. And the longest term data that we presented, I think, is the most exciting. We're at up to 108 weeks, and this is data from our phase 2A extension. You're seeing 100% ALT normalization, 100% virologic response, greater than 70% rates of TND, which, you now, is, I ultimately, a nice objective to shoot for, But from a clinical and outcomes perspective, you know, not that differentiated from the primary endpoint that we're looking at. But overall, I think it's a great profile, well tolerated, too, which was nice to see that confirmed in all these data sets. Yeah, yeah, no, totally makes sense. And, you Know, just sort of like on that point, there's a lot of different endpoints here, different veer logic response sort of endpoints, assays. you know for for docs maybe just help us understand in the in the real world you know what matters most um as it relates to sort of thinking about how docs will view sort of these different efficacy measures like what do you think is most important yeah i mean it's a really good point i think it's easy to kind of get lost in the the nuances of assays and different sensitivities i mean ultimately you know what you're seeing with you know these antibody approaches and srna approaches, is you're getting virus down to almost negligible levels. And that's what's important. I mean, this is a very progressive disease. So getting the virus under control and normalizing that liver inflammation are kind of the two main objectives you'd look for in a treatment. When you talk to physicians, I think there's a lot of interest in potential for finite therapy and a cure. And I think that is the right objective for any kind of viral disease is curing it. It will take some time for us to see if that's achievable here. Ultimately, the current recommendations are to get to TND, which is the lowest level of viral load we're able to measure, and ALT normalization and maintain that for 96 weeks or so before even experimenting with withdrawal. And part of the reason is that what we know about TND is that you can have it for some time and then if you withdraw therapy the virus rebounds so it's tnd is not elimination it's just the lowest level of objectively virus we can measure or in this case can't measure with the assays yeah yeah it makes sense and you know i think naturally obviously you know veer had their data this weekend as well and people are trying to you know like draw comparisons um between the two data sets from an efficacy perspective obviously some differences in terms of like timelines, patient populations are kind of like slightly different. I think the assays are slightly different, maybe just sort of like, help us kind of understand maybe the caveats and trying to draw like direct comparison between the two data sets. I Think it's important to draw back up to the big picture, which is that we are likely to have two highly effective therapies that both get approved and that both companies out there will develop what is likely to be a very significant opportunity to help, you know, thousands of patients with a significant unmet need. And so, you Know, there's many situations where it helps to have several companies out there develop a new market. This is definitely going to be one of those patient finding situations where we need to improve the levels of reflex testing. That's going to help identify many more hep B patients that have hepatitis D. And, you know, some patients might do better on our drug. We think we have some very significant advantages and other physicians might prefer to prescribe the drug. But I think, you Know, we're going to be very successful here. Yeah, yeah, makes sense. And, and I think, you know, one thing with that study, there was a cap around the baseline ALTs. Can you maybe just sort of like help us understand what proportion of your study may have been excluded from from that VEER study? About 20%. 20%? Okay. I mean, I think there's notable differences on baseline ALT and baseline viral load. You know, viral loads are measured in a log scale. And when you're looking at those numbers, sometimes it doesn't look like there's a big difference. But comparing a 6.1 log to a 5.4 log on absolute terms is a 4x difference in viral load, and we see our patients and our studies starting substantially higher. So there's that to take into account, too. Yeah, makes sense. You know, obviously, we've talked a lot about efficacy. From a safety perspective, maybe just kind of like help us understand how important that is in terms of treatment decisions in the real world, as it relates to things like flu like symptoms and some of the other kind of, like, safety dynamics in this space, just like, you know, curious how important that is relative to some of these efficacy nuances. We think it's important. I mean, we know, like, how a patient feels matters. And we, like live that, you know, with Liv Marley and see that with Felixabat. So I think that will come into, like part of the decision making. You know, we have pretty low rates of flu-like symptoms and a really nice tolerability profile. So that may matter for some. Yeah. Okay. Maybe just in the context of the commercial opportunity. So, you know, I think there's just some inherent or, you know, some skepticism on this market in general, not even as it relates to kind of the, the, you know, competitive dynamics here. You know, I think you, you guys point to 15,000 patients that are like addressable in, in the sense of being diagnosed under care, et cetera, maybe just sort of walk us through kind of how you kind of arrived at that sort of epi number. And again, just sort of your confidence in that being like a addressable patient population kind of like relatively quickly. Yeah. So that's looking at claims data that and by doing that, we found 15,000 patients or so that are diagnosed with insurance and under care of a physician. So we think that's a pretty solid number that forms kind of a baseline or a minimum, if you want. We do think that today, a very small portion of hepatitis B patients are being tested for a hepatitis delta. And that once testing becomes more common, which is likely to happen or will happen now that there's one, but soon to be, I think, three approved medicines, that's going to change. And a good example is what happened in Europe, where before the Gilead drug, Hepcludex was approved. They were doing risk-based testing, which is generally what's happening here as well. But with the approval of Hepcludex, they started doing more reflex testing and ended up finding many, many more patients. And we think the same dynamic is here, going to happen here. So is it 2%, 3%, 4% of hepatitis B patients? We don't know. But there's probably about 2 million or so hepatitis B patients in the US. So you could easily see getting to a very meaningfully larger number than the 15,000 baseline. Yeah. And you guys recently raised your guidance here to greater than $1 billion for Prolovitug, I think, versus 750 million previously. maybe just sort of like walk through kind of what drove that change and and sort of you know maybe some of the underlying assumptions that that kind of gets you there that was really to be honest entirely driven by the fact that uh hepcludix was priced more highly than what we had assumed when we put out the 750 million so that difference just drives us to a billion plus but uh you know as often is the case uh with us we over time lean more to the plus than the than the base number so we'll see yeah makes sense um and i presume you have um you know competitive assumptions in sort of that billion dollar guide as it relates to not just veer but also um gilead yeah absolutely i mean we'll see how it plays out i do i do think that uh um between us and we're gonna dominate this market and uh exactly how the market shares uh split ends up is way too early to speculate on yeah makes sense and maybe just you know gilead's been launched for a little bit now is there any sort of like insights you guys have on kind of that initial launch and you know this market or any key learnings i think it's too early and you know it looks like it's not a very high priority for them but let's see how the next few quarters play out yeah and maybe just like help us remind what that drug has done x us um in terms of like a revenue number just to like again put some some context around you know what this opportunity may look like yeah i mean i think uh four years into the launch they were at about a $200 million run rate ex-U.S., so it just points to how meaningful the opportunity is. And that's obviously at a price level that's far below what the U.S. price would be. Yeah, makes sense. Great. Anything else on HTV to specifically highlight or any specific questions on HTC? I think we've covered it. Sounds good. So, you know, back to Velixabat, we have PBC coming in, in 1Q27, you know, maybe just in the context of some of the PSC updates, um, if you could just kind of like lay out your confidence and sort of your alignment on that study, obviously we saw GSK's drug get approved on, on pruritus, but just, you Know, curious your confidence, you, you know, what you can sort of share in terms of your like alignment there on PBC. Yeah, so we had interim data in 2024, a really nice signal, over two-point improvement in pruritus and improvements in sleep and fatigue. Based on that, we received breakthrough designation from the FDA, which has allowed us more interaction and dialogue with them. So between then and now, there has been more communication around this program. The analysis plan feel much more confident in, you know, how they're viewing this and as viewing as a pivotal study. And I think there's a lot more precedent in PBC, too. The design size approach is very much in line with other programs. So feeling pretty good about that. Makes sense. And, you know, I think there's a general sort of investor view that that study is a high POS, obviously, your interim, you know, just the consistent kind of efficacy with this mechanism across these different etiologies. But, you know, just sort of curious if you could kind of like lay out your perspectives and kind of what you're you're hoping to see there. And if there should be anything different versus what we saw in the interim, anything in that ballpark, you know, we saw, I think, a two slightly over a two point placebo adjusted itch benefit. It's a smaller population in the interim analysis, but anything there, I think, would be a win from our perspective. The competitive bar is, we think, relatively low, so we're in a pretty good position here. Yeah, makes sense. And I think there's some debate around the opportunity here, specifically in the context of the PPARs. And, you know, maybe what do you think investors are kind of like missing as it relates to this commercial opportunity and how, you know, if Elixabat could be positioned within this treatment paradigm? Yeah, it's a very large patient population. So 80,000, at least, you Know, possibly 100,000 patients, a third of those patients are well controlled on UDCA, but still have itch and those patients Are off label for a PPAR. So, you Now, that third alone is a meaningful opportunity. And then you look into the patients that are suboptimally controlled or not controlled, where the PPARs, you see most of the PPARA use. And, you know, we expect share there as well. PPARS are not a universal, don't universally address itch. We have patients on PPAR in our study with moderate to severe pruritus. So, you Know, ultimately, you don't need a large share of this population to make the opportunity meaningful. And we think we'll have a fantastic option. yeah and presumably the you know data are positive in one queue like the the review sort of timelines are probably like relatively similar for pbc and psc with felix about is that right well we'll after data we'll still have to submit yeah so like the psc will be ahead yeah and pbce will be following but there may be some overlap yeah and i just said like in that context how are you thinking about pricing with with felixa that tbd yeah we'll have to look at the data, look at how the competitive dynamics evolve. But, I mean, there is one line of thought that we would prioritize PSE, where we would be the only approved therapy. But that would probably lead to several step-throughs into the PBC opportunities. So we'll have to give that a lot more thought and think very carefully about what the right approach is. Yep. Makes sense. Great. Well, let's dive into, you know, the existing commercial business, Live Marley. Definitely want to talk about FOP quickly, but maybe just Live Marly. You've raised, and just kind of on your base business, you've raised guidance multiple times this year. It continues to go really well. Like, what are really kind of the key growth drivers here? And as we look, you know, next year, the year beyond, you know, where are we in terms of the kind of, like, Live Marley launch? Like, is there at all a plateauing coming in terms of AllerGeal's PFIC and all the opportunity you have here? No plateauing. Let's address that. So we have two approved indication, AllerGEAL and PFIC. AllerGEO is a steady grower, I would say. We're probably slightly north of 50% penetrated of the opportunity, but we keep adding patients every quarter, every month. And there's also a weight-based dosing dynamic that's at play. So that's growing very nicely. But the main engine behind the rapid growth has been PFIC, both pediatric but also adult PFIC. We think there's at least 2,000 adult PFIC patients in the U.S. And so of those, a small minority are diagnosed today, so a very significant upside. And to fully capitalize on that opportunity, we're expanding our sales force both for adult PFic but also for Brilovitag and Valixibat. So we're adding about 40 reps. They should all be in place around year end this year and excited about having them in the field and seeing what they can do. Yeah. And so kind of the PFIC experience to date thus far is kind of without that specific investment in sort of like the adult sales force. We're probably only calling on the top decile of adult hepatologists at this point. So a lot of room to grow. Yeah. And I think the other interesting thing that, you know, you guys have talked about in the past, and it's kind of been discussed in sort of the community is genetic testing, and specifically in these like adult hepatology clinics. Has that even like really happened yet? And is that why we're finding more PFIC patients? Or is that still like down the road for that to come? It's early days. It's not something that we see gastros and on the adult side very familiar with. Obviously, on the pediatric side, they do that all day. But we are seeing growing interest and adoption. And obviously, that's something that me and Ipsen are doing to help facilitate. We both sponsor genetic test panels. We think that that is helping, and you're seeing more interest in genetics at the adult liver conferences as well. So I'd say early days, and, you know, we're doing what we can to accelerate it. Yeah. And so, you know, 2000 adult PFIC patients in the US, small minority are diagnosed today. Like, what do you think that number? Do you think half those adults get diagnosed over the next five years? Or, you're just curious, we can kind of like help us understand kind of the pace with which this market is going to be built over the coming years. I think it's hard to quantify. I don't really have an opinion on the pace, except that I think it's going to continue to grow. And it's actually an example of an opportunity where I think it helps to have two people out there developing the market. I think, you know, Bilve and Liv Marley are both used to treat PFIC patients. We probably have about a 50-50 shares. And, And, you know, I think we both benefit from that dynamic. Yeah. And do you think it will kind of stay around that 50-50 over time? Hopefully we can continue to do a great job. And they've had a large sales force out there for a while, right? And we're just expanding our sales force. So maybe we can increase that over time. But we'll have to prove that. Yeah. No, it makes sense. And, yeah, I think it's an interesting point you mentioned around not only the upside or opportunity with Live Marley, but sort of the leverage you'll get as it relates to HDV, presumably PSE and PBC, as you kind of expand this adult sales force. So it's kind of across your whole portfolio. Is that the right way to think about it? Exactly, yeah. Great. Well, also with Liv Marley recently, you had, you know, the EXPAND data that were, you know, positive, maybe just help us understand, you know, if there's any specific like labeling implications or regulatory implications, but more just sort of like how big that opportunity can be. Yeah. I mean, it was really, really happy with that phase three readout, very clear benefit in the overall population and then the subset of biliary atresia patients, which represented about half of the study. TBD on what the label ends up looking like. I mean, that'll obviously be a conversation with the FDA. But the way we've talked about the opportunities, if you just look at biliary Atresia alone, there are at least a thousand addressable patients in the U.S. So that's with their native liver and and pruritus um so that's you know comparable in size to algeol the dose is a bit higher so it's about 1.5 times the dose of algeo patient um but ultimately a comparable opportunity at a minimum at a and then kind of think about the other bucket as as upside to it and you know ibsen failed their biliary atresia study so there's you know no competition within sort of the biliary atresia setting um makes total sense in your study about half of it like you said was biliary attresia is it's the real world in terms of what the right way to think about the size of that tail of other cholestatic indications is that like sort of right proxy as well in the real word it's our best guess yeah you know we had a study with multiple sites open for you know a little over a year and we got half and half Yeah. Okay. And I guess outside of biliary atresia, I know that study specifically was more focused around pediatrics, but do you think those other cholestatic diseases tend to be more like adult patients or is it going to be pediatics? No, there'll be some. I mean, this was a heavily focused pediatric study, but kind of going back to the conversation around PFIC and diagnosing PFIC, you're looking at idiopathic cholestasis. We think about 20% of those patients have underlying PFIC genetics that other, you know, 70 to 80%, some of those could be expand patients. Yeah, makes sense. And I guess maybe Eric just, you now, seems like there's so many tailwinds here and still so much room for Liv Marley. You know, is the street and models kind of like right over the coming years as it relates to what Live Marley can become, or do you think people are still missing what this ultimate opportunity is? I still... I mean, I think most street models don't quite correctly appreciate the opportunity long-term, but maybe that's okay for now. No, makes sense. Okay, maybe just last question quickly on Live Marlay. I think just as more people have started to do a little bit more work just given how well it's gone um ip has come up a little but more recently so maybe just kind of lay out sort of your ip and just sort of the confidence as it relates to kind of like what the length of protection here may look like yeah we feel very good about our uh dosing patents portfolio going out to 2040 um we have uh also a solid dose, a patent going out to 43. And, you know, those patents came from an insight that there's kind of a strange dosing mechanic in iBAT and particularly with Limarly where it tends to plateau and you have to the efficacy plateaus and you Have to dose through that to get to the efficacy we're seeing. And so we think those patents were, you know, highly prosecuted and issued and are very solid. And in terms of some of like the paragraph four, is there any sort of like timelines or catalysts related to some of this IP stuff or? And this next step is Markman hearing, which I think is around next summer. And then there'll be, you know, several years after that and before you know could take a while before this resolves makes sense um great maybe just in the last 20 seconds fop i think it obviously gets or tends to get less you know attention um relative to some of the other stuff you got going on you got to greater than like 200 million maybe just like briefly kind of characterize how you think about that opportunity and the strength of the data that you've seen yeah there's about 900 patients worldwide at least 300 maybe a little bit more in the U.S., highly engaged population, diagnosed. This is not a patient finding exercise. And we're really encouraged by what we've seen in the first few weeks of the launch and have high expectations going forward. Great. Well, thanks both for being here and thanks for everyone listening in. Thanks for having us.