Good morning, everyone. Thanks for joining us for day one of the Citizens Life Sciences Conference. My name is John Wahlberg, analyst here, and we're pleased to have Mirum Pharmaceuticals and CEO Chris Peetz joining us to tell us a little bit more about their story and program. Chris, thanks for joining us. Thanks for hosting. Excited to be here. Mirum's been one of the favorite names that I've talked about the past couple of years, especially when the macro environment was very difficult. You guys were, I'd say, a safe haven 'cause of all the good execution and blocking and tackling you guys have done, and this past year has really come to fruition. You've got now a pipeline with a bunch of stuff going on. Maybe to start with a step back, what do you guys like, what's your strategy at Mirum? What's the overarching focus? Then we can dig into specific programs. Yeah, I appreciate the chance to talk about Mirum. First thing I'd say is, I'll be making forward-looking statements, so refer you to our SEC filings for a full set of risk factors. Diving into a bit of the Mirum story, I mean, we're a rare disease-focused company, so that's the backbone on when you think about the strategy of what we're trying to do is pull together high impact, rare disease medicines that we think we can add value and get them to patients. The setup for this year is a reflection of a lot of work on pulling together all of our programs. On the commercial side, great performance across the board with our three approved medicines on track for $630- 650 million top line for the year, and a pipeline that has four potentially pivotal readouts over the next 18 months. A pivotal year, so to speak, with PSC being the first one up. Later in the year, we'll have bulevirtide phase III data and EXPAND, which is a LIVMARLI indication expansion, and then into the first half of next year, PBC readout for volixibat. We're busy and got a lot of good things going on, and doing this all in a way that, you know, from the strategic standpoint, pulling together these rare disease medicines that you can develop them more efficiently, they turn into a high margin commercially. The business model behind it also is at a real inflection point. In the engine that is helping allow you to do all this, LIVMARLI, can you tell us about the commercial opportunities in Alagille syndrome and PFIC? The sales just keep going up and up. I think early on you guys were saying this could be lumpy, but it seems to keep growing and hasn't quite slowed quite yet consistently. Tell us about where you are in kind of the launch in those two indications and what we should expect as far as, you know, total potential maybe. Yeah. For LIVMARLI, we'll talk about, so the two approved indications and then also EXPAND, which is a label expansion and a basket study with data in the fourth quarter of this year. LIVMARLI, its mechanism is it knocks down circulating bile acid levels, so it prevents absorption of bile acids in the GI tract, very relevant and high impact across these settings of cholestatic pruritus. In Alagille syndrome, in PFIC, and in the basket study for EXPAND, these are patients that have elevated bile acid levels and really severe symptomatic burden. The itching can be really kind of driving their day-to-day experience with fatigue as well being a big factor for these patients. The clinical impact of LIVMARLI for that is quite rapid reductions in pruritus. Given that this is, you know, such a high impact change in symptoms for patients, it's a really, you know, sticky profile for a medicine, right? The adoption that we see, compliance persistence is really strong, and we do expect to continue to accumulate patients over time, given the impact and durable impact that it has for patients. For Alagille syndrome and PFIC, kind of breaking down a couple of the dynamics we see there. You know, Alagille syndrome, we've been in market longer, and see, you know, pretty steady cadence now for several quarters, in terms of what new patient starts look like and what the growth curve looks like for Alagille syndrome. It's kind of a steady accumulation of patients. Mm-hmm ... for LIVMARLI. PFIC has been more dynamic. It's a bit of a different profile for the launch and adoption in PFIC. A lot of that, the difference is what we've come to know and understand for diagnosis of PFIC patients. Mm. The use of genetic testing in adult clinics, in particular, for hepatology and GI, where some of these patients are, is earlier in its adoption. We're seeing an increase in some of the genetic testing that is diagnosing PFIC patients. Adult patients. in adult settings. Wow. That's kind of been a new finding, you know, in the past, call it year of being in market with PFIC, and driven this kind of elevated growth rate. With weight-based dosing, every adult you find is a very valuable patient. They have a higher consumption, but the new starts really is across the board from an age range. Mm-hmm. We're also seeing infants newly diagnosed and starting on drug as well as all the way up to adults. Got it. You mentioned three commercial products. You also have Cholbam and Chenodal, which we are familiar with from their predecessor company. You guys brought that in with a really cool transaction, doing about $100 million a year. That also seems to be finding an inflection point. What's going on there, and what do you expect longer term? It's actually, there's some parallels to how we've grown with LIVMARLI and PFIC. It's just a lot of work on patient finding. For Cholbam and now CTEXLI is the now approved brand name for CTX. We've grown that to over $160 million in the last year. Nice step up really from being out helping to support diagnosis of patients and a lot of, you know, hard work from our commercial team. Awareness, diagnosis, or both? Is it like, "Hey, I knew I had this patient, didn't know there was a drug," or, "I'm finding new patients," or both? There's a little bit of each. You know, for Cholbam and CTEXLI, it's actually a fairly long list of different very rare conditions that these medicines are indicated for, and so they each present in a slightly different way. You have a little bit of some of this is awareness, and some of the settings where you know, a setting like Smith-Lemli-Opitz syndrome. Mm-hmm. It's more about awareness of the use of Cholbam and the benefits that it could potentially bring for patients. In a setting like CTX, this is really a diagnosis play where these patients are generally diagnosed pretty late into adulthood, so many of them being diagnosed in their 30s. Mm-hmm. If you can build more genetic testing into some of the settings where some of their symptoms might show up, you can help find those patients earlier. I think you mentioned, I think, guidance $630-650 for 2026? That's right, and that's across all brands, 630-650, so adding more than $100 million to the top line. Just very nice consistent growth, which is very nice to see when we have many years under the belt and all those products. Moving to the pipeline, you mentioned four pivotal readouts. Maybe since we were just talking LIVMARLI, it's not the nearest term, but maybe talk about EXPAND and what that could mean for the LIVMARLI franchise. Yeah, the EXPAND study for LIVMARLI is evaluating cholestatic pruritus, so same endpoint that we've used in the prior two indications for LIVMARLI. The idea of this study was a basket of the very ultra-rare kind of settings that each individually is hard to study because there just aren't that many cases, but in aggregate, it's actually quite a substantial clinical issue that physicians are dealing with. The idea for the study actually came to us through the volume of compassionate use requests for patients that fit this profile. So we structured a study around it in dialogue with FDA to capture you know, just kind of a definition, a basket defined by exclusion. By excluding the larger indications of Alagille syndrome, PFIC, PSC, PBC. Mm-hmm. Cholestasis of pregnancy also excluded. That study will look at 45 patients, placebo-controlled, looking at itch as the primary endpoint and expect data towards the end of this year. What, timing of the endpoint? The primary endpoint? Primary will be Q4 this year. Okay. We know LIVMARLI works. We know how well it works. When you're talking about a basket study, any concern about the heterogeneity of the patient? Does the etiology matter, or is it if you have elevated serum bile acids, we know LIVMARLI will work? That will be one of the things to analyze there. What we've seen across some of the compassionate use examples and really now across all of the indications where IBAT has been studied is that there's a really consistent change in itch in patients with elevated bile acids and in pruritus with this cholestatic pruritus. Yeah, we're confident that you'll see a consistent effect across the settings, though that's something that'll be evaluated. Within the patients enrolled, what we're seeing and this is kind of in line with expectations, biliary atresia is probably the biggest and will be the biggest indication of the basket. Hmm. You know, maybe as much as half of the study. You get into, you know, very small numbers of patients per other etiology. I imagine you're gonna have to break out by whatever the diagnosis is, what that looks like. There'll be some. You know, we're looking at how when the final enrollment is together, how those get grouped. That looks like. The one to call out, the biliary atresia does stand out because it's a bigger proportion. Mm-hmm. That definitely will be one that we look at. You guys have talked about this. What does the EXPAND mean for the top line potential for LIVMARLI? It's all part of, you know, our guidance that we think LIVMARLI is a billion-dollar brand. It's about a third of that. Okay. Each indication kind of roughly speaking is about a third contributor to that total top line. Just backing out the math we were talking about earlier, so you're about 450-500 for PFIC, Alagille today, right? Yeah. Okay. Yeah. Growing. Growing pipeline. You mentioned bulevirtide, your most recent addition. Hepatitis D, everyone remembers Hepatitis C and the boon that was. Hepatitis B kinda had its moment and has hit its challenges. What about Hepatitis D? We had some late stage candidates. Now you guys are one of them. It's not an opportunity we hear about, like, from a commercial perspective because there hasn't been too many success stories, but how should we think about the unmet need and opportunity? Then we can talk a little bit about data. Yeah. I mean, the setting is. You know, Hepatitis D is known as the most progressive form of hepatitis. It is a rare disease, so we think there's probably 40,000 cases in the U.S. 15,000 of them is our estimate of that are insured and in care for their disease. It's, you know, a scary setting. Hepatitis D is more progressive liver condition that can lead to higher rates of liver cancer, cirrhosis, liver failure, transplant, death, so huge unmet need there. The virus is dependent on Hepatitis B, so it only occurs in a co-infection with Hepatitis B because the delta actually relies on the envelope from the Hepatitis B. That's how bulevirtide works. It's actually targeting the hepatitis B surface antigen. Mm-hmm That then makes it impacts the replication and spread of Hepatitis D. Is there a reason why it wouldn't work in Hepatitis B as well? Well, it does impact the levels of hepatitis B, but it's far more active on delta. Interesting. I can't keep my timeline straight anymore. You guys brought that in recently, but, like, what did you see that triggered your enthusiasm to bring that in-house? Talk a little bit about that deal. Yeah. The phase II data is really striking for bulevirtide in Hepatitis D. This data was presented. The 48-week analysis was presented at AASLD last year, where at the 48-week time point, you're seeing 100% virologic response. Importantly, there's the composite endpoint that is the FDA approval endpoint is virologic response with ALT normalization, saw 65%-82% across the doses studied, in a setting where there's nothing approved. That is a really strong data set that got us excited. As we've brought this in, I think the excitement from the KOLs really shows up in the enrollment. Mm-hmm where we've completed enrollment in the U.S., registration studies already. AZURE-1 and AZURE-4 are the studies that'll be the basis for the FDA filing. Those enrolled so fast. A really exciting program, and the time to bring it in lined up well with the rest of our pipeline. To recap, because we have so much going on, the timelines for bulevirtide AZURE-1, which is the bigger of the 2 phase IIIs in the U.S., has an interim, a phase II portion that we expect to analyze in the second quarter, and then the full data set will be in the second half of the year. These are programs you inherited. Can you walk through the rationale for the interim? Is that something you would have done as well, and what are we gonna learn? What data are we gonna get in 2Q? I mean, the primary purpose for that was to have an early readout and keep excitement around the program. Yeah. It's not really needed from a statistical standpoint, because the effect size is expected to be so strong. The powering of these studies is really, and the sizing is really more about the safety database for FDA. Mm-hmm. It doesn't really serve a purpose from a statistical standpoint or, you know. It's a no change. Change in study conduct or anything like that. Okay. The final analysis excludes these patients from the interim. It's on the balance of the enrolled patients in the study. The interim is on the first 50 and there's another 150 patients in the study. Got it. that make up the phase III portion. Got it. There are some other late-stage candidates. How do you guys stack up against what else is in the field? Yeah. There are a couple of other programs. One that's actually approved in Europe, that as we talk about the registration strategy between the US and Europe, it's a key factor in why there's different studies. And the bulevirtide profile we think is really competitive and appealing in this setting. Getting those 100% response rates on virologic response, doing it with a single agent that the safety profile has been really clean. It's a fully human antibody. It's really clean safety profile. And we think it's gonna be a compelling product even with this, the competition. The, you know, two agents, two programs that are kinda later stage is Gilead's Hepcludex, which is approved in Europe, and we expect approval this year in the US. There's also another program that's HB surface antigen combined with an siRNA, and we like the simpler single agent approach that we've taken. I'm a very big keep-it-simple guy. I'm with you on that one. Interim readout second quarter and then full data from the U.S. study is fourth quarter. How about the EMA progress? Second half of the year. Yeah. 'Cause the timing will be a little bit different between AZURE-1 and AZURE-4, over the second half of the year. Okay. Yeah. The two other studies, do you guys have guidance on those readouts? Two other studies expect to complete enrollment next year. They include comparisons to Hepcludex, either a switch or a head-to-head with new therapy. Those are directed at European approval. Mm-hmm Because Hepcludex is approved in Europe. The response rates that we're seeing we think will be really compelling compared to the historical data for Hepcludex. It's about a year or more behind the U.S. data. Got it. Okay. The other second quarter readout you have that we're doing a lot of homework on is for primary sclerosing cholangitis with volixibat. This has been an opportunity that the industry's talked about for quite some time, and it's been a tough nut to crack. Can you talk a little bit about PSC, that opportunity, and then how your drug works? Yeah. For volixibat and PSC and we see this as a really unique program. The challenge for PSC really has been one of endpoints for drug development. Some of the other liver settings like PBC has an acceptable surrogate endpoint that's used for approvals has been used in the past. It's too variable to look at alkaline phosphatase, and histology has been tried. That also is quite variable and patchy in the PSC patients. What's novel about our approach is using symptoms, using pruritus as a registration endpoint. It's really taking the playbook from LIVMARLI, right? That's how we were able to get LIVMARLI approved for Alagille syndrome in PFIC patients. Doing that in the adult setting with PSC is the novel approach here. No approved medicines for PSC patients. It's a setting with really high symptomatic burden. Pruritus and fatigue is really worth emphasis as well, as part of the day-to-day burden for PSC patients. Using that as an endpoint, highly relevant. This is what patients and physicians are looking for, and it's driven a lot of excitement around the program. Volixibat is an IBAT inhibitor, similar, the same mechanism as LIVMARLI, and we're looking to knock down the excess bile acid levels in PSC patients to drive improvement in pruritus. Precedent data for IBAT doing this in compassionate use examples. Mm-hmm in a small phase II study, so we're excited about the promise for volixibat in the VISTAS study. Any sense on, you know, number of patients and how many are affected by itch that would be good candidates? In the U.S., the PSC epidemiology, we think there's about 30,000 patients in total. You know, probably two-thirds of them are dealing with itch. Mm-hmm. That's what we talk about as the launch population, so that 20,000 PSC patients dealing with pruritus. You mentioned this, you know, so it's a pivotal trial readout, but Volixibat hasn't been studied in a trial in PSC, so what gives you confidence that this is gonna work? Some of it's in the unique design of the VISTAS study itself. VISTAS is an adaptive phase IIb study that had an interim analysis built into it for dose selection, and really to make sure that there was a treatment effect at the dose that was being taken forward. The interim analysis, which happened in 2024, was a blinded analysis reviewed by the data monitoring committee, that from that analysis, we know that there was some level of treatment effect and a dose selected that had that treatment effect. Really kind of built into the study design, we know there's activity. Okay. In parallel, you're running the VANTAGE trial. VANTAGE, right, is PBC. Mm-hmm. Primary biliary cholangitis, where you do have some data. We have two PPAR agonists approved. We had an FXR agonist that's been pulled. PBC is a market that people may understand a little bit more, so how are you going to attack and address an unmet need there? Yeah, it's using the same endpoint we are for VISTAS, so we're using pruritus as the primary endpoint, going after symptomatic improvement for PBC patients. Huge issue for PBC patients. Again, like, two-thirds of the PBC population deals with pruritus as well, so a highly relevant issue to address for patients. By using that endpoint, we actually can approach the treatment regimen in a very different way from where the other recent approvals have been. The PPARs, the most recent launches, I really think of them as a second-line agent, so these are patients that have been on UDCA without being able to control their alkaline phosphatase levels, which is probably about a third of the market- Mm-hmm that have this elevated alkaline phosphatase and would be on-label for a PPAR. For the VANTAGE study and volixibat, there is no baseline alkaline phosphatase criteria, so actually two-thirds of our study enrollment is estimated to be in that front-line setting. They have control of their alkaline phosphatase with UDCA but still have symptomatic burden, because UDCA is, in general, not active on itch. There's a lot of our patients are actually in that front-line setting. How should we think about the opportunity set for you then? Because I, if I recall, the PPAR agonists are, you know, the label for failed or intolerant to first-line treatment with UDCA. Do you guys think you'll have to show that, or are you gonna have a broader label that you can address everybody? The enrollment criteria and expected label is broader. Mm-hmm. We expect it to be for treatment of pruritus in PBC patients without the kind of, you know, any kind of background therapy, UDCA or a PPAR even. You know, enrolled in our study actually, some of the second-line profile patients in VANTAGE who have a background PPAR, so bezafibrate or fenofibrate being the more common ones. The numbers get big pretty quick. The PPAR agonists are projected to do, you know, $1 billion in sales. I think seladelpar, it might have been 3.7, 3-something billion. How do you not get over your skis on the opportunity when you're gonna be going after a broader PBC population, then you throw in PSC? How do you think about the opportunity for volixibat, and how do we, you know, stay in reality? I mean, the way we talk about is volixibat, you know, being at least a billion-dollar brand. There's a lot of ways to get to that. I mean, starting with just being, you know, conservative about what the opportunity is in front of us. The PSC launch first, making the most of that is our focus. PBC will come later. I think that's the thing that I would emphasize is that for the PSC opportunity, no approved therapies, volixibat's gonna be standing alone from a competitive standpoint, and excited to get that out there. For the foreseeable future, right? Yeah. There isn't much coming down the pipeline that can come in PSC. That, that's right, yeah. We've seen a couple of companies talk about starting liver outcome studies recently, but those are pretty long studies to enroll, so we believe we'll have the market to ourselves for several years. In the last minute or so, can you talk a little bit about, you know, capital allocation, cash position? You guys got a lot of money coming in the top line. How do you think about maximizing, getting back to profitability or investing the pipeline or both? Like, strategically, how do you think about the priorities? Our focus as a company is to really build value and bring new medicines to patients. From a transactional standpoint, you know, if we find a misunderstood or program or something that we think we can add value to, we'll absolutely pursue it. Still wanna be active on the BD front. Continue to do it in a very disciplined way. You know, financially right now, we're in an excellent position. You know, we're operating cash flow positive last year. This year's a big investment year, bringing bulevirtide and the four pivotal studies across the pipeline. Expect from an operating cash flow standpoint to dip a little bit negative but return to cash flow positive next year. Really don't need to dip into the balance sheet substantially. You know, excited about how it all comes together. That's why we like the name so much, because it's the best of both worlds, and it's something that investors can watch grow but also have the upside potential from the pipeline coming soon. You've got a lot to do, Chris. We appreciate you coming and spending time with us and telling more about the story. Yeah. Thanks again for hosting and exciting year ahead. Looking forward to it.