Good afternoon, and thanks for joining us at the Fourth Annual Nasdaq BioConnect event. My name is Swayampakula Ramakanth, or RK, Senior Analyst at H.C. Wainwright Healthcare Team. Thank you for joining us to have a conversation with Peter Radovich , President and COO, and Andrew McKibben, the SVP of Strategic Finance and IR of Mirum Pharmaceuticals, ticker MIRM, a $6 billion commercial company. That's focused on commercializing novel therapies for rare debilitating diseases of the liver. Their commercial portfolio is made up of LIVMARLI for cholestatic pruritus and bile acid sequestrant therapies. However, the pipeline is quite exciting with, you know, a best-in-class therapy, brelovitug, volixibat for primary sclerosing cholangitis and primary biliary cholangitis.
They also have zilurgisertib for FOP genetics, and to discuss their commercial portfolio and also their developmental pipeline. I welcome both Peter and Andrew to this fireside chat. Peter , just to get started off, give us a little bit of a background of Mirum and showing the corporate strategy. Also, as we think about how this company has grown in terms of net sales across that were five years ago, you were $10 million. Your recent guidance for 2026 is at the range of $660 million-$780 million. The target for cash flow positive end of next year, which is a tremendous growth the company has achieved. If you can give us a little bit of highlight as well as what the strategy is as the company continues to grow.
Thanks for the question, RK, and thanks for the invite. It's great to be here. Appreciate you and the organizers including Nasdaq. Just want to say we will be making forward-looking statements, so of course refer you to the risk factors in our disclosures filed with the SEC. On Mirum. Mirum is a rare disease company focused on developing and commercializing high impact rare disease medicines for children and adults living with a variety of rare diseases, which you have named in the outset there. In terms of your question about capital allocation and kind of how we think about that as we go forward, you know. We think about capital allocation at Mirum through the lens of how do we build a high growth, sustainable, durable, rare disease company that can serve patients' interests and return value to shareholders.
That's kind of the way we think about it. You know, really nice line of sight, as you mentioned, to top line growth with another beat and raise and increase in guidance in Q1. We were actually cash flow positive last year, and we're cash flow positive in Q1, although our guidance is this year. We expect to probably not be cash flow positive, returning to cash flow positivity next year, as we work through investments in our phase III pipeline, especially with the recent addition of brelovitug for hepatitis delta virus. That's the kind of high level lay of the land and how we think through capital allocation.
Fantastic. You know, in the next 12 months, you know, have potentially four registrational top line readouts, starting from VISTAS, as you mentioned before, the EXPAND and also VANTAGE. You know, plus you're gonna have, you know, PDUFA on September 26th on, for zilurgisertib. How does management think about, you know, all these various value drivers? And, you know, what is your internal investment, you know, being sequenced so that, you know, you can de-risk some of these events?
Y eah, I can take that. I mean, you know, ultimately we are really excited about the setup. All of these programs have some measure of de-risking associated with them. You know, for HDV, we just announced the phase II-B top line a couple weeks ago with a very clear effect. PBC, you've seen the interim data, you know, we feel really good about this. You know, from a kind of investment staging perspective, we're moving forward, you know, with all of these in parallel, right? There's very clear synergies on the liver side of the business between build for volixibat and the build for HDV. With zilurgisertib on FOP, that fits right in the bag of our team who's on kind of rare genetic diseases. That they're currently marketing CHOLBAM and CTEXLI.
Not a lot of incremental investment there. From an investment perspective, it's all kind of moving together, which is great. Finally, just rounding out with EXPAND, I mean, that's LIVMARLI's extension.
Yeah.
We're already kind of doing that.
Now your portfolio, you know, spans across various categories in clinic, from the rare cholestatic liver disease, HDV, Fragile X syndrome, I mean, Fragile X neurology, and also FOP genetics. You know, with this broad, how do you know, how do you move that, you know, from LIVMARLI and move on to scale, what scale of revenue do you think, you know, you will create formal franchises between these structures?
Thanks for the question, RK. I think even today we're already moving towards organizing our business in two different units. I think as Andrew alluded to, if you look at our business today, LIVMARLI is a rare liver disease product. Most of the business is coming from pediatric liver doctors, but growing in the adult side with adult PFIC. That platform will have volixibat added on top of it for PSC/ PBC, as well as brelovitug for hepatitis delta to have kind of a fully functional, you know, liver unit that can reach both pediatric and adult liver prescribers. The rare genetic side of the business today is comprised of CTEXLI and CHOLBAM. Those are, you know, important products for us that are growing nicely.
When we, you know, announced the in-license of zilurgisertib for FOP, you know, one of the things we noticed there as we did the diligence is that a very high proportion of the prescribers are at the same exact accounts as our CTEXLI and CHOLBAM team. You get a lot of synergy there. Some different prescribers, maybe some different specialties, some of it's medical genetics, but you also pull in endocrinologists with FOP and bone diseases, but it's the same accounts. We get a lot of leverage. That product becomes kind of immediately accretive to us. That's kind of the way we think we can serve the products and patients in our portfolio now as we come around those two different units.
Looking into the future, you know, let's say three to five years down the line, currently LIVMARLI, you know, is above all other leads. We've got additional leads, like brelovitug and volixibat, and with that all of these can be certainly, you know, a big message a year down. When we look across these, you know, how should we think about what sort of revenue contribution will we get from all these drugs? And is there a way for us to kind of rank order these things?
Yeah, good question. We always get asked which of our children we like the best. It's hard to say because we like them all. I think in terms If I was trying to, you know, rank order, I mean, you know, you might. One way to focus on that might be where we have clearest line of sight to both the clinical and regulatory profile as well as the commercial potential. With that, with that kind of framing, I think you'd start with LIVMARLI, obviously. It's been approved by FDA for about five years and two indications, clinical profile, label, all very well described. Several quarters of sales trends that you can look at that are available to give you kind of line of sight to what we see as at least a billion in peak sales for LIVMARLI.
T hat's kind of obviously the bedrock of the company and, you know, could, you know, quite a bit of visibility there to the profile. I think if you move from there, you know, volixibat, we just sort of reported this quarter our pivotal PSC data. You know, now we have kind of line of sight to, you know, an NDA and what that profile kind of looks like as we disclosed the top line readout. You know, between PSC and PBC, a lot of ways to see that opportunity for volixibat as being a billion-dollar peak opportunity with the much larger TAMs you're talking about in the adult settings there. As you move from there, I think brelovitug is really interesting.
Obviously, we don't have pivotal data yet in hand there. Two different phase II data sets, a phase I/ II data set that was reported last year at AASLD. Just this quarter, as I think Andrew alluded to, randomized phase II-B AZURE-1 data. I think in virology we see pretty good replication between phase II and phase III. We have pretty high conviction there that'll be at least a $750 million opportunity. You know, potentially more, depending on how successful we can be at developing the market, which we're pretty optimistic about. Finally, zilurgisertib, you know, really excited about that. I mean, we pegged that as at least a $200 million opportunity.
Recognize that it's kind of hard for the investment community to assess that because there's no clinical data in the public domain yet, but hopefully that will come very soon. Suffice to say, we were excited enough to enter into the license agreement, based on what we saw, and of course, FDA has accepted that with priority review and a PDUFA date in September. Maybe that tells you a little bit about the profile, but understand you'll get more visibility hopefully very soon when that data are released.
In terms of the clinical updates that, you know, you seemingly provided, thinking about VISTAS, you know, that delivered a 1.64 placebo-adjusted, you know, sBA reduction, with a 55.6%, you know, responder rate, in the moderate to severe, primary cohort. You know, and you're looking out for the two-year open extension, data et cetera to come. You know, in thinking through the durability and also, you know, what sort of, depth, you know, and consistency of maintenance data do you think the FDA would require in terms of approval? You know, what sort of a label are you expecting from them?
Well, the easy part to start is, you know, from a label perspective would be treatment of cholestatic pruritus due to PSC, similar to what we've seen for ALGS and PFIC. In terms of, you know, the response and durability, we expect it to be quite durable throughout the extension. If you look at, you know, other IBAT settings, it is a very durable response that tends just to incrementally improve over time. Expect to see that here and already kind of seeing that in the long-term data. you know, we're obviously excited to share that and when we can, I think you'll see what we're talking about. From an FDA perspective, I mean, what they're really looking at is, you know, the stat sig improvement on pruritus.
I think we've got a very clear data set and very significant effect on that on pruritus in this setting, which you look at other approvals this is, you know, very much clearing that bar.
The other major update that you recently provided on the brelovitug, you know, the new one, phase II-B, interim data. Can you discuss a little bit about the data itself and, you know, how, you know, you're looking at the 300 mg loading dose, and also looking at once in four weeks dose. How I'm not asking what you favor, but what do you think is generally commercially relevant, you know, dose? I mean, where do you think the science stops?
Yeah. I mean, I can address that one. The reminder of the phase II-B AZURE-1 study has the delayed treatment arm, the 300 mg subcutaneous self-administered, and then the 900 mg monthly healthcare professional administered. You know, the feedback we get universally from physicians, from patients, level providers, even payers, is that the self-administered option is preferred. People, you know, wanna be able to administer their medicine. Burden of interacting with the healthcare professional. That would be kind of the preferred approach. Of course, the phase II and III program have optionality built into it. This is the kind of first of three real looks we'll get at that. We'll also, when the AZURE-1 and AZURE-4 study read out second half of this year, we'll have another look at it.
You know, I think what you saw in this readout was, you know, comparable, maybe numerically a little bit better for the 300 mg. If it looks like that in the end, we'd probably end up proposing the 300 mg self-administered approach for labeling, but we'll have to see how the final action go.
Thinking about, as you have two and I think three studies with the same drug, you know, the field is, already approved in Europe and, you know, did you feel that you could design that instead? You know, what sort of, implementable efficacy, or convenience, because it's a daily subcutaneous, do you think is meaningful in terms of knowing that, but also in terms of pricing?
Yeah. You know, these studies are designed with the European market in mind. You know, the feedback we've received, primarily for the reason you mentioned, the difference in convenience and maybe even tolerability already, you know, quite different. A daily subcutaneous that requires 30 minutes-45 minutes of reconstitution versus a, you know, a potential weekly self-administered, ready to inject, liquid and vial kind of approach. That you wouldn't really need to see large differences in efficacy for, you know, the preference to be towards brelovitug from payer and physician interactions. You know, you can certainly look at the published phase II data that we have, and we're pretty confident about those readouts we think should compare favorably.
Regarding the HDV opportunity. HDV was, it was a precondition for it that the patient has to be co-infected with HBV. How do you envision therapy itself? You know, do they have to be combined with some other HBV therapies? If they have to be combined, are there certain preferred therapies? Obviously, there are multiple, you know, drugs which have been approved for the patient. You know, depending on the combination, does that change the market size?
I don't see it impacting the market size too much. I mean, we expect them to be treated for their hepatitis B. Generally speaking, though, you know, you're seeing some emerging data around functional cures in hepatitis B, which is a question that we get a lot. That's a very different patient profile than the co-infected patient. Specifically, you're seeing some achievement of functional cure in hepatitis B patients with low viral loads, so in the 1,000-3,000 range. The, you know, baseline surface antigen levels in a co-infected patient are, you know, around 10,000 +. Very different setting. You know, in short, expect these patients to be treated for their hepatitis B, but don't see the functional cure is really impacting the market opportunity for the co-infected patients.
Getting the reminder, I'm looking at VISTAS and EASL presentation, which is coming up. It is actually a very big presentation. What sort of data should we expect to see there? You know, how should we think about clinically meaningful data coming from that particular presentation?
I mean, we've disclosed the material update. You'll have incremental data at EASL, you know, thinking about like responder rates and things like that. I think you know the headline. That is a clinically meaningful headline, this 1.67 placebo-adjusted response. We think that that sets us up well from a, you know, in terms of positioning this with the FDA and risk-benefit perspective.
You know, this is looking at cholangitis, especially in the PSC population, where there's no good therapy today. What's the expectation for having an advisory committee meeting on this? Also, you know, in terms of getting to the commercial launch, which potentially could be, you know, it could be next year probably?
From an advisory committee perspective, you know, we have five IBAT indications approved, right? LIVMARLI has two, Bylvay has two, Lynavoy has one. For all five of those reviews, we haven't seen an advisory committee yet, so that's probably the best thing we could point to in terms of guiding expectations. In terms of timeline for launch, the NDA submission, we've got in second half of this year. We'll request priority review and of course, we know at the time of filing if that's granted or not. It would seem to us like PSC, for the reasons you already said, RK, would likely, you know, meet the criteria for a priority review. If that were to be the case, that would point towards a launch mid-next year.
Okay. The VANTAGE is that there's the next exciting study where, you know, the interim data certainly showed 2.4 and 2.6 placebo-adjusted reductions on the itch-related scale for the 20 mg and the 80 mg. How do you position, you know, volixibat against linerixibat, which is already approved? You know, what sort of, you know, what is the VANTAGE that volixibat has against linerixibat? You know, whether it is clinical or, you know, or on the commercial front?
Yeah. I mean, definitely the efficacy profile is differentiated. I mean, we're working off of our interim data set. You know, when you look at that placebo-adjusted benefit on itch, it's significantly higher than what linerixibat showed. Some of that, you know, we believe comes down to dosing. We are dosing at more effective levels of IBAT inhibition with volixibat, which is where you see deeper and broader responses. Same story has played out with LIVMARLI too, analogy with PFIC. The clinical efficacy perspective, I think, is where we differentiate the most.
Okay. The recent in-licensing of zilurgisertib stuff, with a $16 million upfront and a pre-payment in terms of approval. You know, I'm just trying to understand, you know, the logic and the commercial strategy to do that. You know, how should we think about your general business development plan from here onwards, you know, keeping that as a base case into the next two to three years?
Yeah. We're really excited about that as a profile or phenotype of BD deal, you know, we looked at it. It's a late-stage program with a PDUFA date in September. We see a $200 million at least peak sales opportunity, and the opportunity to license that for $16 million upfront, you know, for us is, you know, really attractive. Not to mention, immediately accretive program that kind of fits in the fad of our existing infrastructure. We like that profile. You know, zooming out broader BD, I mean, we look for, you know, high impact medicines that can make a big difference on, you know, patients with high unmet needs. Of course, we're looking at probability of success.
I think the deals we've done probably give you a sense of the, you know, the kinds of things we look at. We looked at late-stage things like this. We've, you know, with brelovitug, we got involved right as the phase III studies were kind of getting up and going. We've done the Fragile X program, which is much smaller upfront, but a phase II-ready program, where there's some strong rationale, but yet to establish a proof of concept, so more high-risk, high-reward kind of phenotype. That probably gives you a sense of what we looked at. Ultimately, we build a durable, high-growth rare disease company.
As we're getting, I think we're past the time, so as we're getting close. Andrew, you know, you're entering a very busy period for the rest of 2026. You know, what are the major catalysts that, you know, you think investors should be on the lookout for?
Well, you know, as Peter kind of mentioned, it's hard to pick your favorite children. Just from a sequence perspective, you know, we'll have the HDV readouts, EXPAND, and then PBC. I think those are big ones for us. We're excited about all of those for different reasons. That kind of fits into the growth of our liver business. That's kind of foundationally LIVMARLI right now. You know, EXPAND is expanding that into a broader setting, cholestatic pruritus that we're very excited about. I think it's kind of missed sometimes by investors just because it's a little bit harder to do the epi on this kind of long tail of other diseases and causes of cholestasis.
Then with volixibat and brelovitug, I mean, that's expanding from a really pediatrics to adults. Frankly, it's synergistic with what we're doing with PFIC. You know, really excited about that setup. It's hard to pick a favorite, but it's, you know, as you said, we're gonna be busy.
Thank you. Thanks for joining us.
Thanks. Appreciate it. Great to be here.