Get started. Thank you all for joining us in the room and online for TD Cowen's 46th Annual Healthcare Conference. I'm Joe Thome, one of the senior biotech analysts here on the team at TD Cowen, and it is my pleasure to have with me this morning the team from Mirum Pharmaceuticals for a fireside chat. We have CFO Eric Bjerkholt and SVP of Strategic Finance and IR Andrew McKibben. Thank you both for joining us. Maybe before we get into the individual programs, we'll start off with a little bit of just a high-level overview. Obviously, just came out of earnings, so maybe if you wanna hit the highlights of, you know, 2025 into early 2026 and what investors should be looking at into the rest of the year.
Sure. Thank you, Joe, and thank you to TD Cowen for having us at this conference. Always fun to be here in Boston. We will be making forward-looking statements throughout this session, please look to our SEC filings for risk factors. Maybe just starting off big picture, at Mirum, we're building a rare disease leader by developing and commercializing best-in-class medicines, providing meaningful improvements to patients' lives. Today we have three approved medicines, and we're guided to revenues this year of $630 million-$650 million. Behind that, we have a series of programs in late-stage development that we will have four potentially pivotal trials unblinding over the next 18 months. A very rich pipeline.
What you can expect first in the second quarter is unblinding of our PSC trial with volixibat, then we will also have an interim analysis with the recently acquired brelovitug with 50 patients. In the second half of the year, we will have unblinding of the AZURE-1 and AZURE-4 trials for brelovitug and also unblind the EXPAND trial with LIVMARLI for a series of ultra-rare cholestatic indications.
Perfect. Maybe we'll start on the commercial franchise and then go into the pipeline. With the 2025 product sales that you achieved, it was above the high end of guidance and obviously 2026 guidance was strong, and you exceeded consensus at the time. Maybe what are you seeing in terms of LIVMARLI's continued uptake in Alagille and PFIC, and what's gonna be important to kinda meet the metrics that you set out?
We're expecting continued strong performance of both Alagille and PFIC, both in the U.S. and internationally. In the U.S. for Alagille, we're continuing to add patients both in the prevalent population where we think we're about 50% penetrated, there's also an annual incidence of about 100 patients, and once diagnosed, they typically go on drug. We're getting the vast majority of those, probably 80%+ market share in Alagille. PFIC as you know, has been a pleasant surprise. When we launched in PFIC, we weren't sure what to expect given that BYLVAY had been on the market for several years. We find that we're getting a lot of new patients on therapy, you know, treatment-naive patients. Of those we're at this point, we think getting at least 50% of those.
Because a PFIC patient is dosed twice daily compared to Alagille, which is daily, and they tend to be a little heavier, each patient consumes a lot more drug than an Alagille patient.
Maybe can you talk a little bit about that? It does seem like one of the nice tailwinds is that you're able to almost find these adult patients for PFIC. I guess, A, was that a surprise? B, how many more adult patients do you think you can find? Like how penetrated to that specific market do you think you are?
It's hard to tell because we don't know exactly. We keep finding new patients, we're encouraging physicians to do genetic testing, and through those efforts, you know, a lot of new patients are being identified and coming to therapy. We don't know exactly. You know, like in Alagille, we can confidently say we're about 50% penetrated. That's not the case in PFIC, but we think there's a lot of upside. Every month we're seeing, you know, significant number of new patients coming to therapy.
Can you talk a little bit about the ex-U.S. opportunity? It seems like maybe that is a little bit more, variable quarter-over-quarter in terms of kinda when those orders hit. I guess how much visibility do you have into the ex-U.S. markets?
We have very good visibility where we are commercializing ourselves, so the largest Western European countries. There we're continuing to see growth in Alagille, and we're also just now starting PFIC, so whether we find the same opportunities as in the U.S. remains to be seen. The distributor markets tend to be a little more back-end loaded in a year. In the last few years we've seen lower revenues in the first half of the years relative to the second half, that's a little harder to predict, and there can be more kinda quarter to quarter variations. Although we're in enough countries now with enough distributors that I think some of those dynamics have been muted.
Maybe moving on to the expansion opportunity for LIVMARLI and the basket study that's gonna be reading out, later this year. Can you talk a little bit about the demand that led to initiation of this study initially, and what is gonna be the sort of diagnosis in most of the patients that are enrolled into this basket?
The trial came about because we had about 100 compassionate use requests go into the FDA, and the FDA said, "Well, that's too many. Let's do a trial around it." In collaboration with the FDA, we designed this study, which is a phase III study. It's a basket study, so it includes a number of ultra-rare indications, kind of anything other than the big five. It's enrolled really well. It's there's a long list of diseases that are included. You know, in the enrollment so far, about half the patients have been biliary atresia patients that are post-Kasai, post a successful Kasai procedure, but nevertheless, later in life, still have itch, so.
Did you have to approach the powering assumptions or your expectations for the study any different than PFIC or Alagille given maybe the differences in patients or is itch in this context?
It's the same. It's a, it's a zero to four scale, and clinically meaningful would be a one-point reduction, which is what we're powering for.
How large of an opportunity of, for expansion do you think this subset, these subsets, I guess, could be?
Yeah, we think there's, between the U.S. and Europe, probably, at least 1,000 patients. Although, again, you know, with ultra-rare diseases, until you get in there, once you have an approved therapy, you tend to find more patients. What we've said is that, LIVMARLI overall, we think is gonna peak, at, $1 billion+ , and, that will, kinda be about a third Alagille, a third PFIC, and a third this EXPAND population.
That's about 1,000 pediatric patients. We haven't really quantified patients on the adult side. A lot of the focus of this, the EXPAND study was on pediatric sites, given that's the primary cohort for the endpoint. You know, there are a fair number of adults out there too, which we kinda see as upside.
The one question we do get on the LIVMARLI portion of the portfolio is a little bit on IP and your patent situation. I guess, can you just touch a little bit on your expectations for IP and do any of these trials reading out, you know, could that help bolster that at all?
We expect the IP to be out to 2040. That's the dosing patents that we've talked about, except we also have a tablet patent that goes out to 2043. That's, there's really no update to that. I don't think the EXPAND trial would necessarily lead to new IP. We don't expect that. 2040 is our guidance.
Maybe we'll move on to volixibat. Maybe just at a high level, can you talk about sort of the difference between volixibat and LIVMARLI, in terms of the, you know, differences in one versus the other? Obviously, adults targeting more with the volixibat programs, but any other differences we should be aware of?
I mean, they're chemically distinct, but both designed to inhibit IBAT. I mean, they're doing the exact same thing, but they're just two different compounds. I mean, the reason we're looking at volixibat in the adult settings is these are rare conditions, not ultra-rare like LIVMARLI. You'll, you'd expect differential pricing between two settings like this. Generally speaking, it's an IBAT. You know, what really matters is optimizing the dosing for the indication with that molecule. We learned that and I think achieved that with LIVMARLI in both Alagille and PFIC based on the clinical data packages and are on that track with volixibat here too, from the phase I work to what we saw at the interim, supports that we're at the right dosing levels in PSC and PBC.
Great. Can you talk a little bit about, obviously, we're gonna see the PSC data in the second quarter this year. What are your expectations for what would be, you know, sort of a clinically meaningful difference? Is it that sort of one point above placebo? Additionally, can we use LIVMARLI as a guide, or how should we think about the bar here?
Yeah. Generally in adult settings, we're looking at a zero to 10 numerical rating scale. Typically, what you wanna see from what's considered clinically meaningful is a two-point change from baseline on an absolute basis. Then from a comparative perspective, you wanna beat placebo by at least a point. We've powered both the PSC and PBC studies around a 1.75 placebo-adjusted difference with an assumed standard deviation of three. The PBC interim results were well above that, and just given what we've seen with IBAT inhibition, you know, at the right doses in these settings, think we can do very well there.
Can you talk a little bit about this market? 'Cause it seems one that has a few questions just in terms of the, you know, level of moderate to severe itch, the level of itching. What are you hearing from KOLs as to the proportion of PSC patients that have itch severe enough maybe to seek therapeutic intervention?
Yeah. I mean, it's certainly changing as they start to ask about it. I mean, that's been one of the, you know, most, you know, common dynamics that we saw early on when we were planning the study was that, you know, most physicians weren't talking to their patients about it. When you actually spend time with the patients and the patient support groups, you get a very different answer. Fostering that discussion really helps elucidate the symptomatic burden that these patients experience. You know, one of the reasons that's not talked about is there's nothing to give them. That's, that's in play a bit. Yeah, we haven't really seen that come through on an enrollment perspective. I mean, the studies have enrolled, you know, quite well and, you know, frankly, you...
The main reason for screen fail is not qualifying itch, it's actually fluctuating liver labs or compliance with the diary.
Very rarely does a patient not make it in for not having meaningful itch.
I mean, we don't expect that our clinical data will show that itching is intermittent, and I think this will be an important data set that we can use to really educate physicians and the market in general.
Great. After positive data, maybe how long would it take to kind of finalize the regulatory submission? Maybe can you just remind the audience your conversations with the FDA on sort of the outcome of this study is sufficient to be the sort of the pivotal registration also?
Yeah. Yeah. Aligned with FDA on the endpoint, pruritus is an outcome supporting full approval. It checks the box of feels, function, survives, alignment on the statistical analysis plan and study size from a safety database perspective. All of those pieces were clear. We'd expect to file an NDA in the back half of this year.
Maybe moving over to PBC, which is going to come, you know, towards the beginning part of 2027. You've passed an interim here. Maybe what have you learned from that interim, and how does that set your expectations for the final readout?
I mean, feeling very good about the final readout based on what we saw at the interim, which, you know, The interim was based on about 30 patients, about 10 per arm, so low-dose volixibat 20 milligram twice daily AD versus placebo. Each arm was stat sig compared to placebo, with a, you know, 2.3-2.5 placebo-adjusted difference. Really strong pruritus benefit that was, you know, rapid and maintained throughout the study. You know, we also saw and presented at AASLD some improvements in fatigue and sleep, which is, you know, also important part of the symptomatic burden that these patients experience. Really like the setup going into the kind of part two of the PBC study.
You know, clearly the size of it is much larger, and that's really about just getting to the right safety numbers. You know, clearly based on the interim, you don't need a large study to show stat sig, but from a safety perspective, the FDA has the standards they typically look for, so we're orienting to that.
Can you walk us through a little bit how you determine the optimal dose to take forward into the sort of pivotal portion of the study? What were you seeing in terms of activity and balancing that with any AEs that we should be thinking about?
Yeah, we don't see a lot of difference in the AEs. I mean, you know, you typically see, you know, treatment emergent, mild, diarrhea, sometimes moderate, usually mild. Pretty well tolerated by the patients, and that's directly on mechanism. That's how the body gets rid of the excess toxic bile acids, and from a, you know, patient perspective, seems to be quite well-tolerated. I mean, we don't see a lot of discontinuations for this. In the real-world setting, with LIVMARLI, it has not been an issue. I mean, it's a very easy trade-off for patients to make, you know, this constant debilitating itch versus some easily managed, transient, mild diarrhea. Across doses, don't see a big difference there.
It's really about making sure that you are maximizing the level of IBAT inhibition, so you're effectively clearing as much bile as you can. At the 20 milligram dose that we tested in the study, we thought we were at those levels. That 80, that higher dose was more of a just in case because we do know there's this kind of, you know, sigmoidal or plateauing dose response curve, and it's really important to not get fooled by that plateau and dose through to the maximal efficacy point. We thought 20 was there, and that's how it played out. If you look at the response curves in the PBC interim, the 20 and 80 are overlapping.
Perfect. If this therapy is approved, how do you expect it to fit into the treatment paradigm? We have the PPARs out there, and we're getting some questions as to, you know, sort of would physicians reach for one first? Can you do combination approaches here? How are you thinking about that?
Well, it depends on where the patient is, right? If you're diagnosed with PBC, you receive UDCA, and that works really well at controlling alkaline phosphatase for most patients. If it doesn't, you're eligible for a PPAR. That's kind of the roughly a third or so. You know, PPARs are trying to move up in that ladder, but generally speaking, there's a very large portion of patients who have well-controlled disease but have itch and nothing for them. That's, I think, priority one. The second area where you kind of overlapping with the PPARs, you certainly can dose them together. You can certainly consider an IBAT in lieu of a PPAR if itch is the predominant symptom. You know, PPARs do have some benefit on itch, but what we see is that it's not universal.
You know, 30%-40% of patients have a nice response on a PPAR, but you flip that, and that's 60%-70% are not optimizing for their itch. That's where you consider an IBAT, but I think that'll be a physician, you know, patient-based decision.
The company's indicated that volixibat could also be sort of a billion-dollar-plus opportunity for the company. How do you see that splitting up between PBC and PSC? 'Cause some of the things we talked about PSC might be a little bit of a smaller overall indication, but obviously the competition we just spoke about too.
There's also a lot more.
Perfect. Are the current going to be sufficient execution registration as well? Have you had those conversations?
We believe. We have not had those conversations yet. We want to get through and then discuss the data set with the EE.
Perfect. The company folded in Bluejay Therapeutics recently in their hepatitis delta program. I guess maybe just at a high level, what was the strategic rationale for being in Bluejay at this point?
A huge clicks, highly synergistic with we're building, and so it fits into strategic rationale that I started with. You know, how we go about building early to a rare disease there. Very excited at this opportunity. We think negotiated a price, and we're excited the data we're gonna generate this year.
Talk a little bit about the patient size. This is a question that is coming up with our, with our KOLs, and obviously not really anything out there in the U.S. to treat hepatitis delta. Is this gonna be a market that evolves over and can you solidify the market?
Based on kind of the research we've done to date, we're very confident at least 15,000 patients are diagnosed and under the care of physicians. If the prevalence is 40, what happened in Europe once IBATs was approved that you started more reflex testing and the percentage of hepatitis B patients that were identified as all having hepatitis D went up. We think something similar will happen here with therapies, more reflex testing, and you'll see the diagnosis rate go up. They could be much larger than 40,000 over time.
Can you talk a little bit about how the therapy compares the data that you've seen so far? Maybe A, what got you excited about it, and how would this compare to an emerging standard of care worldwide? Obviously we have the Vir compounds that are out there also in late-stage development. How do you think this will fare competitively in that investors out obviously the bonds, but also some of the data that we're seeing.
Yeah. I mean, I think from a, you know, comparative perspective pair is very, I mean, what you're looking at is efficacy composite, which is the combo of viral response and ALT normalization. We see really of that. You also have convenience and tolerability, and who I think brelovitug has a bit of an advantage. It's we expect to commercialize with a once weekly at-home dosing, so very convenient, and see a lot of flu symptoms when you sing with this, which is also, I think, a benefit. Finally, there's no ALT limitations in our phase III. We're enrolling patients, you know, above five times up with a little bit of normal ALT, which, you know, represents about 10%-20% of the population and those with the most severe need.
A number of competitive points that I think will be differentiating for brelovitug. I mean, that said, Vir's program works, and we expect it to get approved. I mean, it's showing nice viral response. We just think we have a bit of an edge.
Great. We're gonna see some interim data here in the second quarter, and then obviously the final pivotal data from one and four later this year. Can you kind of set the stage for what you wanna see first in the interim and maybe how that could feed into the data later this year?
The interim is really looking at the first 50 patients at 24-week primary endpoint. And it's the 24-week data, so it's a little bit different than what was presented at AASLD last November, which is 48 weeks. Typically, you see responses deepen over time, so expect to see something that's, you know, tracking to what we saw at the 48-week data point, but overall strong response. The second piece of the study, this 150 patients, really the phase III, one of two phase IIIs that will form the kind of basis of the BLA submission, that'll be in the second half of the year and basically same time point, just more patients.
Maybe can you talk a little bit about how the therapy, if it is approved, can filter into your current marketing footprint for your currently approved agents? How much will you need to build this out for the HDV opportunity, but maybe also if PSC is as successful as well?
Yeah. I mean, we're already planning to expand for volixibat, so both PSC and PBC. You know, generally speaking, you know, we're already covering the top tier hepatologists, so the expansion for volixibat was really focused on kind of the community gastro/ heps about, you know, 35 or so additional reps. Those two tiers cover part of HDV as well. The only third piece that would require some additional expansion and really at the margin would be in, you know, certain centers because this is very highly facility, Chicago, L.A., maybe have reps that are focusing more on like the practitioners that are seeing patients there. Highly synergistic with the efforts that we already have underway.
That was gonna be part of my next question was just on the geographical differences. If it seems like in the U.S. at the major centers, I guess when you look worldwide, I guess, are there any target markets that you're particularly going after? Maybe along with that, obviously, the clinical development program is built in a little bit differently for the worldwide approvals. Can you talk about that a little bit?
Yeah, definitely, more patients outside of the U.S. than in the U.S. by a wide margin. As you said, they are concentrated in certain pockets and, we know where they are. Once we have the results, we'll be, you know, developing, trying to commercialize the drug globally, either ourselves where that makes sense or through distributors like we have LIVMARLI.
Obviously did this transaction, what's your appetite to do sort of additional BD deals in this sort of rare liver disorder landscape?
Yeah, it goes beyond rare liver, really. It's, you know, going back to where I started, we're trying to build a rare disease leader. We have a lot on our plate right now near term, wanna make sure that anything we bring in, we can execute really well and successfully. We will continue to look, but continue to be very, very disciplined. I think we are. You know, the first question we always ask ourselves, which I feel like companies should ask more often, is, you know, why are we the right owners of that asset? If we can handle that conveniently and see how we can add value to our , and it's a question of diligence and terms.
Maybe jumping over to Fragile X for the phase II that you just off the dose study. Talk us through about why MRM-3379 active likes based on what you've seen, then obviously we've seen some, if you wanna put that context too?
Yeah. I mean, mechanistically, you know, based on what we understand in Fragile X, there is deficiency like AMP is part of this FMR1 mission. We understand how the working and, I mean, that trans preclinical work and models and with clinic phase II study, like the mechanism and with MRM-3379, it's like that there's a higher brain to ratio. You're getting more of what you want, where you want it, and potentially limiting some of that. Ultimately is emesis that you see at higher doses. We recently published some phase I work that shows that, you know, we do eventually see that at higher doses, but the therapeutic range that we're looking at and exploring in the phase II is much lower.
You know, then it kind of comes down to does this hypothesis play out? Based on what we've seen, you know, we're confident this will have an effect. You know, how that differentiation differentiates from Shionogi is TBD, and I know we're waiting on their phase III data. You know, would expect those studies to work based on what we've seen so far.
It seems like Shionogi is having a little bit of an issue with validation of the endpoint that they're using with the FDA. I guess, what are the steps to finding, A, the right endpoint for this patient population and then validating it that it kind of moves along with the disease, progression or other markers? How should we think about that?
Yeah, I mean, there's, you know, hard to say what their conversations and approach has been. It's something that we've done a lot of. I mean, with our the Itra obs or the adult Itra across our PSC, PBC, and pediatric studies, we've done a lot of validation work, and we're doing a lot of validation work. It's, you know, a very familiar dialogue for us with the FDA. We have started those conversations in the context of the phase II. We've got the NIH Toolbox, which is our kinda key secondary and a host of other things that we'll be looking at that against as part of, you know, any kind of confirmatory validation for a phase III.
I'm sure we'll learn a lot from Shionogi's experience too in terms of what, you know, to do or not to do, but, you know, that's kind of TBD.
Are there other indications where this mechanism might make sense that you'd wanna explore?
Go ahead.
Absolutely. Let's get through this phase II trial first and see what we have, make sure we understand the profile and, in parallel, we are thinking about where else we could take this.
Great. Maybe for the last question, we'll circle back to the rest of the commercial portfolio with the bile acid therapies. Maybe how is that portion of the franchise progressing, and how has patient finding been going post the CTEXLI approval?
It's. We continue to be pleasantly surprised. We're finding new patients. Not huge numbers, but we never thought we would find huge numbers. We're continuing to kinda exceed the thesis we had when we acquired these assets. You know, this year we should continue to see, you know, double-digit percent growth in revenues, and we'll be very happy with that.
Awesome. Well, great. Well, thank you for a nice discussion, and have a good rest of the week.
Thanks for having us.
Thank you.