Afternoon, everyone? I'm Lisa Walter, biotech analyst here at RBC Capital Markets. Thanks for joining us at RBC's 2026 Global Healthcare Conference. This session, we have Mirum Pharmaceuticals, and we have the pleasure of hosting Peter Radovich, President and Chief Operating Officer, as well as Andrew McKibben, Senior Vice President, Strategic Finance & Investor Relations. Peter, Andrew, thanks so much for joining us today. How are you both doing?
Doing great, Lisa. Thanks for having us. Great to be here.
Well, it's a pleasure to have you here today. Maybe just to kick things off, can you give us a big picture overview of where Mirum stands today? There's been two clinical data readouts recently. You have an impressive portfolio, three approved assets in rare liver disease, and multiple pipeline assets as well that are brewing. Can you walk us through the latest with Mirum?
Yeah, happy to do it. First, just wanted to remind the audience we'll be making forward-looking statements here today, and of course, we'll refer you to our SEC filings for full disclosures and risk factors. Yeah, Mirum's in a great position today. We're a global, about 430 person strong, rare disease company. We got our start with LIVMARLI, which is a really high-impact medicine for primarily pediatric, but now growing adult population of genetic cholestatic liver diseases, and that product has performed very well. As you noted, we now have three approved medicines. The other two came in through BD transactions and have built a really strong, sustainable, high growth, rare disease business. 2026 is shaping up to be a year where a lot of catalysts are coming together. Just this quarter, we had two really big readouts for the company.
The VISTAS study and primary sclerosing cholangitis pivotal data set read out positive, heading towards a pre-NDA meeting and an NDA submission second half of this year. Really excited about that. Also had a phase II-B readout from our hepatitis delta program, which recently came into the company through acquisition of Bluejay Therapeutics, and that data set read out very much in line with our expectations and earlier data sets. Really excited about that, looking forward to the full phase III readouts there from the AZURE- 1 and AZURE- 4 studies later this year. Finally, we just announced a exciting BD transaction as part of our Q1 earnings result. We can happy to get into more detail on that as we go through, but another high impact, ultra-rare disease medicine that we're excited to put into our infrastructure and bring to patients.
I think that's a great segue to my first question. What is Mirum's approach to BD? You're clearly not shy about doing it.
Yeah.
What is the runway or the firepower that you have for BD after your recent raise as well?
Yeah. The raise is really about addressing existing convertible notes for the 2029 maturity that were on our books and refinancing most of the principal there and taking advantage of a really issuer favorable market, getting a 0% coupon instead of a 4% for most of the debt. Really happy about that, but doesn't really change our fundamental approach to BD. We're very active in BD. We have an active search effort. I think our last several deals that we've done give you an idea of the phenotypes of deals we like. We've done commercial stage deals, very late clinical stage deals like this zilurgisertib that's really in an NDA review now. Done phase III-ready deals and phase II-ready deals.
Really looking at assets that address a high unmet medical need where we have a level of conviction on the biology and the clinical data that's there, and that we think we feel that we can add value to, that we're the right team to own this asset. Critically, we take a very disciplined approach to BD. We're not shy, but we're also highly disciplined. We want to make sure that we have assets where we can create value for patients, but also for our shareholders.
Got it. That's really helpful to get your view on that. I do want to talk about something that affects everybody in biotech and the pharma industry is the recent FDA volatility that we're experiencing with Commissioner Martin Makary stepping down. Are you worried about any impact to any of your late-stage programs? You just mentioned a pre-NDA meeting coming up, filings later this year. You also have a PDUFA date coming up around the corner in September with your newly acquired asset as well. Are there any worries about this? How are you thinking about it?
It's a great question, Lisa. For Mirum, it's really been business as usual in terms of the review teams we're interacting with. We interact across a variety of divisions. A lot of our programs have been in liver, but also rare disease, and now this new program in endocrinology. The review teams and reviewers we're working with on all of our NDA and pre-NDA interactions are largely the same teams we've been interacting with for many years, the programs we've been leading for many years. For us, we haven't seen an impact.
Got it. Well, maybe let's dive down into some of your commercial programs. Let's start with LIVMARLI. You already alluded to it. Launch has been going well. Q1 2026, you had $114 million in net sales. You had 55% growth year-over-year, you also raised the full year guidance to $660 million-$680 million. I guess, can you take us through what's driving this momentum with LIVMARLI? Is it volume, pricing, international expansion, or a combination of all of those?
Thanks for the question, Lisa. The Q1, we were really happy with the performance and, as you noted, beat and raised the big drivers demand and the biggest driver of higher than expected demand is the PFIC dynamic. The second indication for LIVMARLI just kind of continues to outperform our expectations. We're finding many patients who are later onset PFIC are often adolescents or even adults. It's a kind of newer clinical entity that wasn't something that was considered by the field even some couple of years ago. That's kind of a market development effort or a new diagnosis effort that's kind of working out really well. Also, our international sales for LIVMARLI did better in Q1 than we thought.
Usually, we expect a meaningful decline in Q1. There's a little bit of a phenomenon in our international LIVMARLI business where in Q4 we see some distributor name patient sales markets kind of buy in bulk for individual name patients. You're kind of working through that demand in Q1. The underlying demand was strong. That was kind of better than expected.
Got it. Maybe more importantly, what penetration levels are we at in the ALGS and PFIC indications, are we getting close to peak penetration, or is there still room to grow?
Yeah. Each indication is a little bit different dynamics. In Alagille syndrome, we're about 50% penetrated into the addressable sort of prevalent population. Still, I think a lot more to go. We are the kind of the dominant share of IBAT of the two, kind of us and our competitor BYLVAY. We really dominate the share in Alagille syndrome. The primary kind of competition there is, if you will, activating patients who are eligible but haven't yet come to therapy. We see those patients even though FDA approved our product over four years ago, every quarter, every month, a continued kind of steady accumulation of adds in the U.S. and other developed countries, in the Alagille market. It's been on a steady cadence of adds for a couple of years now.
See that being a kind of rare disease dynamic where that kind of continues to build throughout the life cycle. The PFIC indication, if you kind of think about two separate groups there, if you think about the pediatric onset PFIC, the kind of classic PFIC, we're probably, collectively the class is probably even higher than 50% penetrated there. That second entity I talked about, the later onset or the adult PFIC, it's very early days there. In fact, most adult professionals, most adult prescribers are just now starting to do genetic testing. The majority of them still don't. I think we made a lot of progress, and that's what's driven the growth.
I think there's more progress to come with the more adult providers we can get becoming curious about genetic cholestasis and taking the next step to do the genetic testing and then diagnose PFIC, that we think there's a lot of growth to come on that runway.
You mentioned the competing drug, BYLVAY. What is the market share dynamic in PFIC between BYLVAY and LIVMARLI?
Yeah. In PFIC in the U.S., I think it's probably 50/50 at this point, roughly. Pretty much split in the market, whereas Alagille we're considerably higher.
Got it. Well, I do want to touch on the EXPAND study. This is a phase III study that's ongoing that could open up a new market in ultra-rare cholestatic pruritus. Top-line data is around the corner in Q4. How should we think about the addressable market here? What is the opportunity, and how much incremental revenue could EXPAND add to drive LIVMARLI forward to potentially becoming a billion-dollar blockbuster drug?
Yeah. We think it's a significant contributor. The read will be in Q4, and we kind of talk about LIVMARLI being over $1 billion in peak potential and really see Alagille, PFIC, and then this kind of EXPAND basket indication as roughly being equal components of that. When we talk about the opportunity, we've traditionally looked at the pediatric opportunity, so that's about 1,000 patients across U.S. and Europe, and that's where we have good line of sight to patient populations. Just out there with prescribers, you can see who they have, that's patients that are Alagille, PFIC, and then also this other bucket. That doesn't really factor in the opportunity on the adult side of things where we have a bit less visibility. As we're out there and encouraging genetic testing for PFIC, we are seeing more of that.
I think as we get closer and get out there, we'll probably evolve the opportunity.
Got it. No, that's helpful. I do want to shift to volixibat and the VISTAS study. You recently announced the phase IIb met its primary endpoint, and you're expecting to present data, the full data at EASL later this month. What should we expect to see in your EASL presentation and that you haven't already shared?
Yeah. Really excited about this data set, and just to recap, a statistically significant improvement in pruritus, which is the primary endpoint.
For the EASL presentation, we've disclosed the material data, the primary endpoint improvement, safety, some of the key secondaries. We'll have some incremental data on responder rates and be able to show a kind of time course of pruritus improvement. Very much what you'd expect from an IBAT. It's very rapid and sustained, and if not improving over time, pruritus curve. We are excited to get that out there. It's an oral late breaker and should close out the late breaker session on Saturday. It is nice to get this out there soon, too.
Got it. We look forward to just seeing that data at EASL. I just want to touch on the opportunity with volixibat. You've flagged it that previously that it could reach a billion-dollar in revenue. Are there any changes to that number since the VISTAS study results were announced?
Not really. We've talked about it also being over a billion opportunity. The PSC results are in line with what we expected. We expected to see a benefit on itch, just like you see with IBAT in other settings of cholestasis, and we've shown that here. No immediate change to the opportunity. It's pretty easy when you look at the market opportunities across PSC and PBC to get to some large numbers. Right now, I think where we've kind of set the bar is reasonable, and hopefully there's upside to that.
Got it. Well, let's talk about PBC. One of the risks in these pruritus trials is having a high placebo response. Your VISTAS study design incorporated this screening period, these placebo run-in periods to specifically address this issue. I guess, how effective do you think those design elements were in reducing noise in the VISTAS study? More importantly, for the VANTAGE study in PBC, are you seeing the same level of noise reduction with these screening run-in periods incorporated into that trial as well?
Those are elements of study design. There's also elements of conduct where you're training both the patients and sites around the use of the ItchRO tool. Credit to our study team in terms of their execution there. Those do seem to be effective. You saw it in the PBC interim. You're always going to see a placebo response, but you want to mitigate that. Now in both of these settings, we've seen these approaches be pretty effective.
Are you seeing roughly the same percentage of screening failures in VANTAGE versus VISTAS?
Let's see. It's generally comparable, maybe a little bit higher in PBC. Generally, where you see screen failures is not for qualifying itch, but more for fluctuating liver labs. These patients have active liver disease, and that tends to be the main reason. The second reason would just be compliance with the diary, so just not filling it out consistently enough. That's important because that is the basis for your endpoint, so you want to make sure you have compliance with the diary going into the study.
Got it. Given the positive results in PSC, does this make you more confident with the VANTAGE study and the potential there for a positive outcome?
The interim results in the VANTAGE study made us quite confident. This certainly helps reinforce that. In a 30-patient interim analysis, seeing such clear separation between treatment and placebo across both those groups was very encouraging and expect to replicate that in the phase III.
Is the bogey here for VANTAGE really just to beat GSK's, Alfasigma's Lynavoy, which showed a 0.72 delta on the pruritus score versus placebo? Is that kind of the bar to beat?
Generally. I think we can do better than that. We were over a two-point improvement from placebo in the interim, and so anything in that ZIP code is, I think, going to be really differentiated from a commercial perspective.
Got it. For pricing, do you have any idea why Lynavoy hasn't been priced yet? What's the hold-up?
GSK sold it to Alfasigma. They had to go through with HSR, there's probably some just logistics of transfer and from one sponsor to another. We're actively watching for it and would expect them to launch soon, given that it's approved.
Would you think of pricing at a premium to Lynavoy ? How are you thinking about volixibat?
That's certainly one of the options. That's one of the debates that we have a lot is that do you price for PSC, which will be first, or do you price more for PBC? Certainly recognize that pricing for PSC, you have potentially more pricing power given it's a smaller population, and there's nothing approved in this setting. That's one bookend. Another bookend would be pricing closer to the PPARs in PBC. Ultimately, we'd want to see where Lynavoy prices. We'd like to see the final profile of volixibat in PBC, which we'll have before we have to set pricing Q1 of next year with the VANTAGE readout. A few more cards to turn over. Suffice to say, our goal will be to maximize access and value around volixibat.
Thanks for bringing up the PPAR agonist, which Gilead has one, Ipsen has one, already approved for PBC. These two drugs have a different mechanism of action versus IBAT. How should we think about PBC here with these other drugs that are already approved, is there a possibility for combo treatment? Is it going to be one drug versus the other? How are you thinking about the market opportunity here for PBC?
There's certainly room for combo dosing. We already have patients on PPARs in our studies. Typically, it's the fibrates, which are effectively PPARs, and you do see use in these settings. In PBC in general, though, you see similar rates of pruritus across lines of therapy. Even patients who are doing just fine on Urso still experience this moderate to severe pruritus. That's the prime area of focus for us in PBC, where these PPARs would be off-label. In the second line setting, PPARs have an effect in some patients but not others, and so those are clearly opportunities where IBAT can play a role.
Got it. Very helpful. I do want to talk about hepatitis D and Brelovitug. The phase II-B interim results were quite striking, but they left us with, or left me with some questions. We saw 100% virologic response in the 300 mg weekly dose, and 45% at that dose achieved the primary endpoint, versus 0 responders in the placebo arm achieved the primary endpoint of virologic response and ALT normalization. However, the 900 mg, the monthly arm, this didn't quite fare as well as the 300 mg arm, which was dosed weekly. How should we think about the slight disconnect between the two when arguably patients should, in theory, be getting exposed to the same level of drug?
Yeah, I can take that one, Lisa. Our take there, I think your final point is correct. The exposure between the two, the pharmacokinetic profile between the two different doses is pretty comparable. Maybe slightly higher for 300 mg, not meaningfully. Probably any differences we're seeing between the arms and efficacy is due to small numbers. In fact, some of those patients in the 900 mg monthly arm that just missed the 2-log viral reduction cutoff, they might have been at 1.5 or 1.7, they're clearly getting a meaningful response. Likely, if you looked at instead of at week 24, if you look at the next time point, maybe week 36, you're going to see them cross that threshold. I think it's small numbers and just response kinetics is probably what we're seeing here.
Does the AZURE-1 interim increase your confidence for the pivotal readouts in AZURE-1 and AZUR-4 that are coming later on in second half?
Yeah, I'd say so. We already had pretty high conviction based on the phase I-B data that were presented last year at AASLD. Those were the data we had in hand when we entered into the acquisition of Bluejay, and then it was really nice to see that get replicated here, of course. I'd say that both data sets have given us the confidence on the full phase III.
Got it. What about competition here in the hepatitis D space? You have Vir. They have a dual approach with a monoclonal antibody and an siRNA, and you have Gilead in there, and Hepcludex, which is already approved in the EU but not in the U.S. How are you thinking about positioning Brelovitug if there's other competitors in the United States?
Yeah. Thanks for the question. I'd first say it's great news for patients, especially in the U.S. There's been nothing to treat these patients with other than interferon, which most people don't want to give. It doesn't work very well. There's a lot of toxicity. It's great that you have, I think, three drugs regimens coming to the market soon that are going to make a big difference for people with the most deadly form of viral hepatitis. Excited to be a part of that, and I think all of them are active regimens. I think with Gilead, going chronologically, we expect, as we understand it, a PDUFA date and a potential action this quarter.
I think that'll be really helpful to have an option out there that motivates clinicians to do screening, as right now, a very low percentage of hepatitis B patients ever get tested for delta. I think Gilead has proven they're quite adept at developing viral hepatitis markets over the years. I think that'll be a positive dynamic for the overall market and growing the number of diagnosed patients, increasing the interest in treatment. I think when we compare profile to Brelovitug versus Bulevirtide, their Hepcludex, we feel there's advantages probably on efficacy, safety tolerability, and convenience, a more active regimen. Instead of a daily sub-Q with reconstitution, it's a weekly self-administered sub-Q. Feel really good about the profile there. Of course, Vir also has a really nice regimen that's making a big improvement for patients. This will be a competitive market.
When we look at our profile, we feel really good about how we perform on the composite endpoint that FDA and EMA are focused on, which is both the 2-log viral load reduction together with the liver inflammation, ALT normalization, as both of those together are what's most associated with improving outcomes in this setting, whether that's liver cancer, liver decompensation, transplant. I think that's really strong. We've also enrolled a really broad population. Some of the other programs have excluded more advanced patients with higher ALT or meaningful cirrhosis, and that's about 20% of the population and the most high-need population that will be on-label for us and not for some others. Finally, just a really simple single-agent monoclonal antibody that's very well-tolerated.
We have a very low rate of flu-like symptoms, which from the feedback we've received from the patients, flu-like symptoms are important to them, and for a chronically administered medicine, it's obviously desirable to have as low of a rate of that as possible.
Well, I do want to touch on one more thing with hepatitis D. You've outlined potential for a $750 million opportunity for Brelovitug. How do we get there? Do we need both U.S. and ex-U.S. approvals to hit that number?
That is a global number. If you look at even just the U.S. and you assume we don't improve the number of diagnosed patients and just stick with the number that are diagnosed today, which is 15,000 patients. If you start there and you assume a competitive split of the market, which is the way we modeled it when we acquired the program and just assume it's competed, there's competitive shares, and you have rare disease pricing, it's pretty easy to get towards those numbers, even just with the U.S. We do have a development plan and a regulatory plan to make this available broadly around the world.
Got it. Well, I do want to talk about the FOP program. This is the asset that you recently acquired from Incyte. What is the opportunity here, and how do you plan to compete versus Ipsen SOHONOS, which is already approved, and potentially Regeneron's drug as well, which could be launched maybe a month ahead of zilu?
It's a little assertive. It's a tough one to say. We're really excited about this program. FOP is just a devastating condition, where patients essentially form a second skeleton every time there's an insult to their soft tissue or connective tissue. It's really just a horrific, ultra-rare setting. About one in a million is the epidemiology for it, so about 300 patients in the U.S. with this. Only a small proportion of the FOP patients are on SOHONOS. The profile is quite limited, both from an efficacy and safety tolerability perspective. We think that both this program as well as the Regeneron monoclonal antibody are major advances for patients from an efficacy standpoint.
For our program, it's an oral once-daily profile, which for these patients who any little thing, including an IV-infused monoclonal antibody, can actually cause ossifications for them, we think that'll give it a nice position in the market.
Well, maybe last question from me in the 2- seconds we have left here. Peter, I guess for Mirum, how are you thinking about balancing profitability versus investing in more BD to build out the pipeline further and potentially the top line?
Let Andrew take the closer.
Our focus is on value creation, and we've taken a really disciplined lens towards that. Less about profitability, and I think our priority right now is value creation through our pipeline and commercial business. BD is a big part of that. We'll continue to stay disciplined. We will also continue to stay financially independent. Profitability is not the goal, but the business is in a really strong financial position, and we aim to keep it that way.
Well, Peter, Andrew, thank you so much for joining me this afternoon. It's been a pleasure to host you both, and I hope you have a great day.
Thanks, Lisa.
Thank you.