Welcome everyone to Citi's Biopharma Back to School Summit in New York City. I'm Yigal Nochomovitz, Senior Biotech Analyst at Citi. Our next company we launched on, I guess it was a couple of quarters ago, Mirum Pharmaceuticals. A super interesting story, and I have with me the CEO and founder, Chris Peetz, as well as Andrew McKibben, who is SVP of Finance and IR. Welcome both of you. Thank you very much for joining. Obviously, there's a lot of news flow coming, so maybe we could just start with the cadence of data because you are getting a lot of phase III data and some phase II data. Maybe just walk us through what investors should expect from the catalyst perspective over the next several quarters. Yeah, great. Thanks for having us. First, point out that we make some forward-looking statements, so refer people to the SEC filings for more complete risk factor disclosure. A couple of intro words on the cadence of events over the year for Mirum. We're a commercial stage, rare disease-focused company that just kind of how these programs and readouts that we have tied together is pursuing opportunities in rare disease to bring forward medicines that are generally overlooked. Kind of the overall strategy is finding the small to mid-size medicines that fall off the radar for big pharma, and address real rare disease problems. Recognizing that there's only 5% of rare diseases actually have approved medicines for them. There's just a lot of runway for us to find medicines like that and bring them together in Mirum. A lot of great ones that are making progress this year. On top of revenue of $680 million-$700 million expected this year, several really important readouts ahead of us. Later this month, actually, a phase III readout expected for the brelovitug HDV program. That's one of two phase III readouts. The second one reads out next quarter. AZURE-1 and 4 are those two studies. Together they'll constitute an expected BLA filing in the first half of next year. So, exciting moment for brelovitug and a new therapy for HDV patients as we get to that data readout. We also have later this month a PDUFA date for zilurgisertib and FOP. Zilurgisertib is an ALK2 inhibitor for FOP, and that submission is based on some really impressive phase II data that formed the submission program that we acquired from Incyte earlier this year. We take over at the approval expected later this month. Into Q4, in addition to the brelovitug second phase III readout, we also have a phase III readout for LIVMARLI. So the EXPAND study, looking at a basket of cholestatic pruritus indications, kind of the third leg to LIVMARLI's growth profile, with that study reading out in the fourth quarter. Then into Q1 next year, we also have a second indication for volixibat reading out in PBC. I'm sure we're going to spend time talking about the PSC data and FDA conversation, but another data readout for that program Q1. Well, we'll get to that later, but let's focus on some of the near term. Let's start with HDV, and we can move our way through. I guess a really basic question, what gives you confidence that you're going to show strong data for those two, AZURE-1, AZURE-4? Of course, you had the phase IIb data, which looked really nice. Just help us understand what gives you confidence, and then the two studies are similar, but there's a little bit of a difference between them, if I'm not mistaken. Right. Yeah. The brelovitug program, brelovitug is a HB surface antigen antibody. A really straightforward approach in this co-infection setting to knock down the surface antigen that hep delta relies on for replication and infection. And the phase II data, as you point out, are really clear and strong. Not only the phase IIb data from AZURE-1, which read out earlier this year, there's also a phase IIa study conducted previously by Bluejay Therapeutics, where this program originated, the clinical program originated. And consistent effects overall across the doses evaluated and from one study to the next, where you're seeing very high viral response rates. Most patients, most cohorts reaching 100% virologic response of 2 log or greater reduction, and impressive rates of ALT normalization over time. There's a mix of different time points that have been looked at, week 24 and 48, but it's clear that by week 24, which is the phase III time point, you can get 100% or near 100% virologic response, and the majority of patients achieving or being near ALT normalization. You've done a lot in the diligence leading up to the Bluejay acquisition. Obviously, you've done a lot of diligence on the HDV market. Maybe just help us understand how you see that opportunity. You see it in obviously a very positive way and perhaps understand it in a way that others maybe didn't. Can you go into that a little bit in terms of what the opportunity is in the U.S. and, of course, ex-U.S. as well? This is one of the key things that we were looking at when we were thinking about entering into HDV. It is still, I think, one of the debates that we hear brought to us as a question pretty commonly is on patient finding. It is something that the Mirum team, I think, has done really well in other settings. So, a really strong conviction in what we have seen to date and how we are approaching it. A couple of the observations and estimates we have, we think there is about 15,000 diagnosed insured patients in the U.S. So that is based on some claims data work. Where these patients are, I think, is important to spend a moment thinking about. Because when in interactions with KOLs, you might actually extrapolate to a lower number, because these patients are often more dispersed in the community. In particular, in some of the major metro areas, there will be non-traditional for liver care points of care that are more primary care oriented or community clinics that would see most of these patients. A lot of the launch prep work we are doing is profiling who are the physicians that are seeing these patients that are already diagnosed, because that is going to be the first opportunity at launch. The second leg to this is thinking about diagnosis rates. Hepatitis delta, we think is very much underdiagnosed, and there is a story here on incorporating reflex testing for hepatitis delta based on hep B diagnoses. We have seen this play out in Europe over the past four or five years, where they have shifted from what is thought of as at-risk hepatitis delta testing, which ends up being very limited testing for hepatitis delta in hep B patients. As Europe converted to their guidelines and their practices to be more automated tests for delta if you have a positive hep B result, the number diagnosed climbed rapidly. We are hoping that can be deployed against here in the U.S. as we have now already one approved and more coming new medicines for hepatitis delta expect to see a change in some of the practices on how it is tested for. Ultimately, we think there is probably at least 40,000 total patients in the U.S., so the majority of them being undiagnosed. Meaning if you did the math and you know how many HBV there are, and you just do the 5% or low single-digit percent that also have co-infection, you get that 40,000. Exactly. Yeah. Okay. The estimates you see are in the 2%-5% range of HBV Okay would be HDV infected as well. Of course, there are some competitors in the marketplace in HDV, Gilead and Vir. Any comments you want to offer there in terms of how you are differentiated relative to those other options? I think a lot of it comes down to what we're excited about in brelovitug's profile being a single-agent regimen with a fully human antibody. I think is a very favorable tolerability profile. We see that come through consistently in clinic and gets to a really impressive virologic response, 100% of patients having a 2 log or greater reduction. And over time, as we look at some of these maturing data points, we expect to see those numbers continue to improve. So the TND rates, the ALT normalization rates at week 24 is just the starting point, and we do see patients continue to improve their response over time. What do the hepatologists feel as most important when they look at endpoints? What are they focused on? Is it the liver enzyme normalization and the rate, the virologic response? How do they assess efficacy when they're looking at different options? With these new medicines coming to market, I think this is going to set the tone on treatment objectives as they have some tools to work with. When you're looking at some of the longitudinal data from natural history cohorts and in different settings as well, the outcomes are tied to both virologic response and ALT normalization. I think the profile where you can meet both of those objectives logically links to the improved risk for long-term outcomes in this setting. Okay. Assuming you're successful with these two readouts, just very quickly, what's the timeline to file with the FDA and get approved? Yeah. Plan is to submit with FDA in the first half of the year. BLA submitted first half based on the AZURE-1 and 4 data sets. In Europe, we have two other studies, AZURE-2 and 3, that include Hepcludex comparisons. Bulevirtide type comparisons. The European submission would be a bit later, but in the U.S., we'll be planning to file first half of the year. In those European studies, what's the comparison? Are you showing a non-inferiority, or is it a superiority? What's the test that you're doing versus Hepcludex? We're looking at superiority versus two different approaches. One is treatment naive head-to-head. Hepatitis delta patients, and the other is those that have been on Hepcludex and doing a switch versus continued Hepcludex treatment. Okay. Both relevant as you think about the rollout, more relevant in Europe where Hepcludex is more established. Also reads into the U.S. where Hepcludex is recently approved and being launched. Right. Okay. All right. Well, let's move on. You mentioned as well this EXPAND data set, which is sort of an expanded bucket of additional options for LIVMARLI. Talk about what that could imply in terms of expanding the market opportunity, and then also you're getting good traction in PFIC in the adult population. Those two factors hopefully will inflect the trajectory for LIVMARLI even more. Absolutely. The LIVMARLI growth profile has been one that our understanding and expectation in these settings has evolved over time, just as we've been in there and finding where are the patients, how are they diagnosed. PFIC in particular has been an interesting story where in a recent earnings call, we talked about some of the patient-finding efforts, in particular in adult settings where genetic testing is just not as well adopted. There is a lot of opportunity in these adult clinics to change how genetic testing is thought of and incorporated, in particular in patients that are today diagnosed as idiopathic cholestasis, which really is an incomplete diagnosis, right? Getting standard of care to have genetic testing for those patients will bring a more accurate diagnosis and start to find more PFIC patients. We've seen that start to play out in a relatively limited set of centers already for adult hepatology. We see a lot of growth from more expansion into adult liver for PFIC. EXPAND is kind of that last piece of the LIVMARLI profile where the idea for the study actually came from the hepatology community, and what we saw was demand and interest for treating a range of patient types that had cholestatic pruritus, but from a variety of different reasons. Biliary atresia is the most common for what we saw. We have some presented case studies that inform our confidence in the upcoming readout, where you see a nice response profile and compassionate use examples of biliary atresia treatment. Given the amount of interest in these other cholestatic settings, with FDA, we designed a protocol to put them together in a basket protocol. That is the EXPAND study. Now fully enrolled and on track for data next quarter. What we see in that patient population in the study, it's about half biliary atresia, so that's prospectively written in as a secondary endpoint to look at the biliary atresia cohort independently after the full study is analyzed. The other half of the study really is kind of a mix of many different types of cholestatic disease. Post-procedural secondary sclerosing cholangitis, a number of other genetic causes of cholestasis. It's quite a broad mix. Would this study be sufficient to support an sNDA for this broader set of opportunities, or do you have to do some further clinical work? That's the plan in the discussion with FDA, was to have this be label-enabling, and really came from FDA reaching out about the volume of single-patient IND and compassionate use requests that they wanted us to put a protocol together around it. In that interaction, we discussed how to make that label-enabling. This is pointed towards an sNDA in the first half of next year. Our estimates are that in the pediatric setting alone, there's probably at least 500 patients in the U.S. that fit this profile. There's an adult opportunity here as well that's a little harder to characterize and haven't gotten our hands fully around what the size of that could be. But it's a nice addition to the addressable patient population for LIVMARLI. Just remind everyone, if adding Alagille and PFIC, what's the addressable, just so people can get a sense of the scale when you would include the 500 from EXPAND, just roughly. How these have evolved over time, and we have to kind of undo some of the prior statements we've made about how the relative sizing of these indications are. We originally thought Alagille was the bigger opportunity. What we've seen in PFIC has kind of proven that wrong. For Alagille, the original estimate was that for addressable patients were probably 1,000 or just over 1,000 Alagille patients. In PFIC, when you combine the pediatric and adult, you're probably towards 2,500. For EXPAND, when we're looking at the pediatric, that 500 or more, it's a sizable addition to what's already there. But I don't think we really have our head around how many are out in the adult settings either. We'll have to get out there with the label that we end up with before we have a firm estimate of that. Yeah. I think in our model, we preserve that as an upside for the EXPAND population. We'll have to model that once we see the data. Yeah, and I think that's fair. Each rare disease, if you know one rare disease, you know one rare disease. As we get into each setting, understanding where the patients are and being able to go out and promote against it is how you find the actual size of the patient population. Start with an estimate, and we like to be conservative on how we're thinking about these early benchmarks and- Okay product sizing estimates, and see if we can find more impact once we get out there. Okay, let's spend a few minutes on what I guess is the most proximal catalyst, which is at the end of the month, the PDUFA date for FOP. I guess you're in the very final stretches now. I gather you're maybe in the labeling conversations. What can you say there? And I believe there are a few other products that are in the market. So how do you differentiate with your drug? Yeah. The FOP landscape is kind of recently evolving. Historically, only one medication was approved, Sohonos, that from community feedback and treatment experience was kind of an overall difficult drug to take, and many patients actually opted for clinical study instead, which helped bring these recent two programs along. Regeneron has recently launched a new medication for FOP. Looking at that as a new entrant provides some direction on, frankly, price points to consider as well. Our program, zilurgisertib, in the review with FDA has gone well. Nothing really to comment on. Late cycle comments didn't raise any issues, and I think we're tracking towards approval at the PDUFA date. We're ready for launch in Q4. zilurgisertib is an oral daily ALK2 inhibitor, so targets what is the overactive receptor that's a driver of disease in FOP. Excited about the mechanism, the clinical data that was the basis of the NDA, really strong, showing stopping the compared to placebo, a dramatic difference in volume of new ossifications. Great data to have out there supporting the launch next quarter. How are you positioning zilurgisertib as a frontline option instead of Regeneron or the other one you mentioned, or would it be used after? How does that shake out? Overall, I think it's to be seen how physicians look at the two medications. What we're doing is leading with our profile and our data, which I think is quite attractive. One important thing to note from the clinical program for zilurgisertib is that the phase II program that's the basis of the submission started at age 12. So we can treat some of the younger patients. We fully enroll the second cohort of patients that brings that age potentially lower, so looking to move towards generating the data for potential sNDA already to even improve on that 12 and older patient population, and trying to get at where the desire to treat these patients as early as possible, to prevent some of the accumulation of these ossifications over time. Just to clarify, the other two drugs, their label is only for 18 or older, or adults, or how do they structure theirs? That's correct. Right. Okay. That's what I thought. Okay, so that's coming up. Then there's the PBC top line data in the first quarter of 2027, so that's a phase II study. Just walk us through the data that supports a positive outcome there for volixibat. Yeah. The VANTAGE study for volixibat is an adaptive phase II study with pivotal intent. Similar to the VISTAS study, we discussed this program at length with FDA when we were designing it and had the opportunity to actually have further discussion with them in written correspondence last year. As a reminder, the VANTAGE study had an interim analysis a couple of years ago with really strong data coming out of that, seeing quite pronounced improvements in pruritus versus placebo. That was the basis of breakthrough therapy designation in PBC for volixibat for treatment of cholestatic pruritus in PBC. With the breakthrough designation, we had some back and forth with FDA confirming some of the NDA components. It had clear direction on what FDA wanted if we were to consider VANTAGE a pivotal study. We've incorporated that all into the upcoming readout in Q1, so do see this as a pivotal program for volixibat and PBC. Worth commenting a little bit on the treatment landscape because there's been a lot of progress in PBC over the past few years, where we've seen two PPAR agents approved in, think of it as a second-line PBC setting, those patients not controlled by UDCA. Those PPARs have now been on the market for getting on a couple of years. The most recent evolution is another IBAT inhibitor that was approved for treatment of cholestatic pruritus in PBC. See some precedent out there on the regulatory approach. I know that comes up as a question. Very clear that cholestatic pruritus is an approval path for PBC. Overall, I think our dosing for volixibat in this setting is going to lead to some impressive headline data. So excited about getting to that data readout and what it means for treating cholestatic pruritus across all lines of therapy in PBC. We're addressing both those first-line patients controlled on UDCA and also the second-line patients where you see PPAR use as well. It doesn't really address pruritus for all patients. Okay. There's one more which we can spend 30 seconds on, the Fragile X, if you want to comment. I know that's more of a high risk, high reward opportunity, but any brief comments there, and then we can spend a little bit of time on the topic you mentioned at the beginning in terms of the FDA feedback on PSC. In Fragile X, we are running a dose-ranging phase II study of a PDE4D inhibitor for trying to improve cognitive scores and some of the behavioral scores in Fragile X patients. A lot of what informed and got us excited about this program was data that came out of a PDE4D inhibitor at Shionogi, that from what they have announced did not replicate some of their phase II data. There is a little bit of a question on what informed the study design. I think one of the things to keep in mind is that the dose-ranging work we are doing is different and more fully explores what we expect to be the target therapeutic dose. MRM-3379, our program, has a much higher CNS penetrance compared to the Shionogi program. It is differentiated, and we are asking some different questions here. While unfortunately the signal we were following didn't play through, it is going to be an interesting data set to look at next year. Okay. Then, obviously there was a lot of debate around the FDA feedback on PSC and their surprising request for phase III when you had had alignment. Can you update us in terms of what the state of play is there with regard to the FDA interactions and what we may expect now and into the next year in terms of a resolution or clarity on filing the NDA for PSC? Yeah. Overall, no update or change to the status of things. Just to recap where we sit today, had our pre-NDA conversation with FDA. Subsequently, we were granted breakthrough designation, and now our strategy is to bring FDA closer to the data, right? The original feedback was based on a pretty standard briefing book, which doesn't have the full data sets, doesn't have a full safety analysis, clinical study report, all the validation work that would be part of an NDA package. We see an opportunity to get some of that in front of the review team and work towards a multidisciplinary conversation with them. That is part of being granted breakthrough designation is the expectation to have a conversation like that. This data set is very convincing, right? It's a highly persuasive data set showing a clear improvement of pruritus versus placebo in PSC patients. The study has confirmatory evidence built into it. There's a second cohort of patients with milder itch that were also significant in their improvements versus placebo, and the profile from safety standpoint looks like an IBAT. We think this is a data set that's absolutely sufficient for review and labeling, and our strategy is to work with FDA towards an NDA submission. In terms of guidance and what we can share publicly, our guidance is that we do plan to submit in the first half of next year. Do not expect there will be much to update along the way. While we will be having interactions with FDA, do not plan to provide updates on those conversations unless something materially changes in terms of the feedback that they give us or our plans for that first half submission. The team's hard at work in prepping some of these data sets, analyses, and follow-ups for FDA and working with them towards the submission. Okay, based on what you're saying and also what you mentioned earlier in the year at the earnings call, sounds like you have a solid degree of confidence that you will be able to work collaboratively with the FDA to get them to understand what you've achieved in the VISTAS trial and obviously not have to run a phase III, which would by all indications seem totally superfluous. Yeah, that's our thinking as we've considered the recommendation for a phase III and looking at what you would try to answer. Based on what's in VISTAS, we don't know what other question would be asked. I think this data set is definitive for cholestatic pruritus treatment. While we can't control FDA's ultimate thinking on it, what we can do is work through making the case on how clear this data set is. By the way, you mentioned VANTAGE and PBC, so can you clarify that was obviously with pivotal intent, and you have breakthrough for that one as well. Is there clarity there from the FDA that they understand that that is a pivotal trial, or is there still something to work out with the FDA so they're on board considering it as a new group that's taking a look? We think there's better alignment there. Yeah. Based on some of the written correspondence last year, that's the current under the same leadership of the division last year as this year. There's, I think, good consistency of the people that we're interacting with and did have clear feedback in those written correspondence on what they recommended we do for this to be considered pivotal. There was some thought, or there was an idea that perhaps you could include some of the PBC data in supporting PSC, but what is the latest on that? It seems like that may not be necessarily the way it is going to go. The readout in Q1, we think is not necessary. The interim analysis already from VANTAGE is supportive evidence, supportive data. We are pairing that with a scientific explanation and write-up of how cholestatic pruritus between these two indications is similar. While the underlying disease is different, the cause of cholestasis is different, the cholestatic pruritus driven by circulating bile acids is common. Right. That is the indication statement that the interim data from VANTAGE already is supportive data. The supplemental cohort within VISTAS already is supportive data. We really see there is already enough here. As the timeline plays forward, there is a scenario where we would consider if VANTAGE should be included, but that is not currently the plan. The original interim from VANTAGE, did that get put in the NDA for PSC in some respect or not? It was brought into the discussion Oh, okay. with FDA in the pre-NDA meeting. Okay. Yeah, and I think to be clear on that, the initial conversation was debating how related the indications are. Looking at PBC versus PSC being different underlying diseases and distinct, so kind of downplaying the role of that as supportive evidence. We think that is not really supported, actually. The cholestatic pruritus indication that these are addressing is quite related. So we're building that case as one of the pieces of what we're taking back to FDA. So it's another one of the arguments that we're working on for the PSC conversation. Okay. I guess final question, which is change of topic here. We're asking everyone, so forgive me, but the AI question, how are you leveraging AI at your organization? Either just to make things faster, to get to answers quickly, analyze data, operational efficiencies, drawing conclusions, helping with submission of filings. Yeah, we've rolled it out company-wide, so at Mirum, employees have access to it in a kind of integrated AI system. I think it's being adopted for many different use cases. It's actually kind of exciting to hear how people are using it in different ways. So we have different programs to help people use it to improve the speed and quality of drafting analytical documents. Our corporate development team uses it extensively for BD analysis, for diligence analysis, for understanding even down to molecule design as we're looking at other programs. So we've rolled it out in a lot of different ways. I'd describe it as letting the company organically find the places where individuals can use it best to streamline their day-to-day work or improve their productivity. Is there a certain flavor that you're focused on, like Claude versus Gemini versus something else, or you just use all of them? We have a couple of options all through Copilot. Okay Actually, and have loved how Copilot integrates across the other file sources and structures in the company. Okay. Personally, I find it helps me find files so much faster, and now I don't need to bug other people. I can actually just ask my Copilot, Claude. Where you save everything other than say- Okay Where is that attachment that somebody sent me 3 months ago? I think it was about this or that." And it pops right up. I need to learn how to do that. Okay. All right. Great. Well, thank you very much. Great to be obviously formally covering you guys. Looking forward to a lot of important updates starting in basically 2 weeks, I guess, the PDUFA date, so. Yeah. Exciting stretch, and thanks for making time to talk about it. Of course. Okay. Thanks for hosting. Great. Thank you.