Mirum Pharmaceuticals, Inc. (MIRM) November 10, 2026 Conference Transcript

Okay, welcome to day two of the Wolf Healthcare Conference. I'm Kalpa Patel. I'm pleased to have here with me the team from Miram, Andrew and Eric. Welcome and thank you for joining us. So, Eric, it's been a pretty eventful few months for Miram over the... In recent times, you've had some positive clinical readouts, launched another commercial medicine, and raised revenue guidance again. So maybe to kick us off, what should we look at over the next 12 to 18 months, and what do you think investors are still underappreciating about where the business is heading?

Thank you, Galpit. And first of all, thank you to Wolf Research for hosting us. And let me remind you that we will be making forward-looking statements, so please look at the risk factors in our regulatory filings. I think it's... Often investors like to get to focus down on the details as they should and really on kind of the news of the day and maybe comparing to other programs, etc. And when you do that, it's often easy to lose. A view of the overall picture, so let me remind you that, you know, less than 5% of orphan diseases have an FDA-approved medicine, and we are trying to change that by bringing to market medicines that have a profound positive impact on patients' lives. To date, we have four approved medicines, with many more to come. Based on all the successes in the clinic we've seen this year, we expect... Five SNDA, NDA, and BLA filings next year, and so within, you know, 18 months, we should have many more medicines approved and indications approved, and with that, we expect very significant revenue growth over the next, you know, five-plus years. Resulting in a very significant cash flow generation, and I think when you focus too much on the details, you lose track of the overall picture and where we are headed.

Okay, and I want to start with Livmarly first, which continues to drive a lot of commercial momentum. You reported about 133 million in third-quarter sales. You've talked about sustaining that to 10 to 15 million roughly in sequential quarterly growth over the next year. How much of that is coming from newly diagnosed adult PFIC patients versus deeper penetration of the existing population or just weight-based dose increases that you would expect? As you go into the adult teaching.

Thank you. Yeah, they're all elements. Allergeal is growing steadily, quarter over quarter. We keep adding new patients. We keep anchoring on being, you know, about 50% penetrated of the treatment-eligible population. Clearly, the big grower is PFIC, where we think it's early days still. We're adding a lot of patients. They're dosed twice a day compared to Allergeal, which is daily dosing. And they tend to be older and therefore heavier and consume more drugs. So that clearly drives the revenue growth. And we think we have a long way to go, which is why we came out with this expectation that our sequential increases of 10 to 15 million should continue for the foreseeable future.

Okay, and what are you learning about how quickly these patients can be found or diagnosed and brought onto therapy?

Yeah, I mean, I think genetic testing is very common amongst pediatric hepatologists, but much less so amongst adult hepatologists and GI docs, and so we are out there trying to educate that community on the importance of genetic testing, and that leads to a number of these patients being found. It is work, but it's work we're doing, and it's very successful, and we're also not the only ones doing it, right? I mean, we do have a competitor, and I think in PFIC, we're probably splitting the opportunity, more or less. And so, you know, between the two of us, I think we're making a lot of progress, and that's resulting in newly diagnosed patients found every month.

And you also had separately a successful expand study recently. We also, we saw a benefit in the biliary atresia patients in that study, and previously you mentioned that about 2,000 BA patients are there in the U.S. and across Europe. Are these patients already concentrated in the centers that you're calling on, and how straightforward is this expansion, or do you need to go out and, you know, find these patients, expand the sales force?

That's a good question. You know, very, very high level of overlap with our pediatric nephrology, I mean, hepatologists, and that's because these are patients are, the biliary atresia patients all get the CASI procedure very early in life, so they're... Already identified, and in total, we think, you know, with about a thousand in the U.S., that would mean it's about the same number of patients as for allergial syndrome, but the dosing is higher, and there shouldn't be any competition here, and so we think the opportunity is at least an allergial syndrome.

Got it. And should we assume that the trajectory is a little faster than what we had seen with LGL and PFIC historically?

You would think so, based on what I've said, but we'll see.

Maybe, Andrew, moving on to PSC. You know, you clearly had a positive trial there, and one of the biggest questions that we get is the uncertainty on the regulatory path for PSC. The FDA had recommended another Phase 3 despite your original trial hitting STAT-SIG. Can you help us understand if anything has changed since your public announcement that the FDA is requiring or asking for another Phase 3? And you presented some data at AASLD this past weekend. Anything from those subgroup analysis that should help drive confidence for this resubmission.

Yeah, it's funny. We get that question a lot, too. But, you know, effectively, I mean, there's no material update to provide. I mean, our conversations are progressing. You know, everything's on plan for a submission in the first half of next year. If something does come out of this interaction that is material or materially changes what we are planning on doing, then we'll tell you. But, you know, so far, so far, so good. The IBD analysis, it's important to note that that was not in reaction to a question from the FDA recently. This was all part of the original design and plan. So back in 2019, this was an area of focus for us and the FDA just to make sure that there was, you know, this is safe in patients with IBD since the majority of PSC patients have that. The analysis that we presented at ASLD shows that. So there's really no exacerbation. And we did everything we could to assess that in the study, and I think it's a pretty reassuring analysis.

How directly do those analyses support what the FDA is asking for?

I believe we've done all we can, and they would acknowledge that.

Moving beyond PSC, you're going to have data for PBC in the first quarter of 2027. How do you think about the opportunity there versus PSC, and what would be a clinically meaningful outcome in your view? I think historically you've mentioned about a two-point placebo-adjusted delta. Sample size gets bigger. Do you expect to see a two-point delta again? What would drive clinical utilization?

Yeah, something in that ballpark would be a win. I mean, obviously, in the interim, we saw a greater than two-point change, which we were very excited about, also saw improvements in sleep and fatigue. We think both the magnitude of the clinical efficacy there and some of these benefits and broader measures of quality of life would translate into a really nice advantage commercially. You know, right now, I believe what's approved has a less than one point placebo-adjusted difference. So, and again, anything in the ballpark of what we saw at the interim would be a great win. And then to your other question on just competitive difference between PBC and PSC, obviously, PSC, there's nothing approved, and so that's kind of a wide-open space for us, one that we're very excited about with the data set that we have. PBC, there's more competition, but it's a really large market. There's over 80,000 patients. The majority of those have pruritus, and a large portion of those are in the frontline setting where they're well-controlled on UDCA, so they're off-label for a PPAR, don't need it, but still have itch. And that's a prime opportunity. And then beyond that, with PPARs, I think you still see opportunity there, too, since those don't fully address the itching in a lot of patients.

Do you think the PBC safety outcome could be useful for the PSE filing, or is that not a gating factor for your submission?

Not a gating factor. I mean, it's obviously something the FDA will look at when they're looking at Volixabat as a compound, but not a gating factor for us.

And how much confidence do you have for the PBC path relative to the PSE path?

More. We've, you know, we've had breakthrough designations since 2024 after the interim analysis. So that's allowed us to have more interaction with the FDA. A lot of that back and forth is oriented towards recognition of this being a pivotal study. So feel much more confident about that.

And then I had one question on PSC for the trial population was a moderate to severe population. Do you expect utilization across the spectrum, broad spectrum of patients, or only in the moderate to severe population, assuming you get approved?

Across the spectrum, you know, grading pruritus is not something that's typically done in a physician's office. It's more of a clinical trial feature to ensure that you have a high enough baseline level of itch to measure a meaningful change. But typically, a physician's not asking a patient, what's your itch on a scale of 0 to 10? It's more a question of do you itch or not, and that's how we'd expect the label to be written, pruritus due to PSC or PBC.

And what's the population size, then, across the spectrum of patients for the U.S.?

We think there's about 50,000 patients, PBC patients, with pruritus in the U.S., and about 20,000 or so PSC patients.

Maybe moving on to the hepatitis D part of this. A lot of data this past weekend. As you look through your own 24-week, 48-week, as well as the two-year experience that you've seen now, what have you learned that you didn't originally appreciate from the Azure One readout?

Yeah, a lot of data this weekend. Very excited about it. I think the most important takeaway is that responses keep getting better over time. You know, we designed our phase threes with a 24-week primary endpoint, which is mostly because you can see separation, statistically significant separation at that time, which is adequate to support a filing, so why do a longer study? But as you follow these patients out to one year or two years, we see a really nice deepening of both viral response, virologic response in terms of TND, target not detected, and ALT normalization, which is a really important measure that goes along with it that I think gets missed because what you want to do from a treatment objective perspective is suppress the virus, and ideally you get rid of it. But the other way to check that, given that your assays are not perfect, is to look at, is the inflammation gone? So if the virus is gone, you'd expect the inflammation to be gone. And we see that playing out over time and get to some really deep responses there.

Got it. And, you know, one of the most important questions we've been getting or more frequent questions we've been getting is people are looking at the TND rates and comparing, making cross-trials comparisons. VIR's data set had a 79% TND at week 48 and 57% at week 24. And I think these are different studies, maybe the assays are different, but anything that you want to highlight that explains the differences between their T and D rates and yours?

Yeah, it's not apples to apples. There's differences in the baseline populations, which matter. If you look at our Azure 4 data, which we just announced this morning, over half the patients had a six-log HDV RNA level. And I think that's part of the challenge is you talk about these things in logs because a log scale because the virus levels are so high. So that's basically about 1.2 million. Viral units per ml, which is a lot of virus. And, you know, if you compare that to like a 5.4 log, for example, that's 200,000. So you're looking at how half the patients in the study had 4x the viral load as some of the other studies that are done. So they've got a lot, they've got a longer way to come down before they get to TND. And that's, you know, aside from, you know, differences in assays, right? These assays are all pretty sensitive, but at the end of the day, you're debating between 5 or 10 units per ml in terms of their sensitivity. And so these threshold analyses can kind of mask the fact that both therapies are getting patients to a great level of suppression. And that's why you, you know, you have to think about ALT, and if you're thinking about trying to get rid of the virus, how does that play into things?

Anything in the baseline demographics that you guys want to mention, differences between your study and their study?

I mean, the viral loads is one, so significantly higher. ALT is also higher, about 30% higher.

What do you think that most people don't really think about logarithmic math and the primary endpoint is a two log reduction, which is a 99.9% reduction in the viral load. And when we talk about LLQ less than 10, that's a 99.98% reduction. And so it's important that people don't get too hung up on, you know, small differences in percentages when When, you know, any agent that's going to get approved is going to show a really dramatic reduction in the viral load.

Across all the metrics in HTV, what do you think matters the most for physicians when they're evaluating a new therapy?

It's a good question. I think that given how progressive this disease is, you really want to get the virus under control. And... By extension, the inflammation. The inflammation is what causes cancer and some of these liver-related outcomes. So both of those pieces, getting those to very low levels or normal levels, is critical. And then maintaining that. Right? You don't want to see viral rebound. You want to see that improve over time. And it's actually interesting at ASLD this last weekend, the expert panel guidance around HDV treatment, the objective is to look for, obviously, as low as viruses you can get. So TND is like the best standard that we have, and ALT normalization. If you can maintain that for 96 weeks, they recommend experimenting with treatment withdrawal. I think the key is the duration. You want to get this down, low, and suppressed, and maintain that for as long as possible.

Have you looked at your samples and tested with the other assays, or are you planning to test it, make an apples-to-apples comparison?

I mean, to Eric's point, no. Yeah, they're basically doing the same thing, and it doesn't really make a difference.

One of the more frequent questions we get also in HEPD is that are there really that many patients? These investors do doc calls and they say HEPD is very rare in the community, hard to find these patients. What do you say to these investors when you get pushback like that?

I mean, we see a much different population. I mean, claims data supports that. These are patients who have multiple visits, undercare, insured. I think the challenge when you call a physician in Boston is there's not a lot of hepti in Boston. You know, you do see it concentrated in certain geographic centers, predominantly in community settings in these urban areas. So New York, Chicago, L.A., you know, there's large communities there. You see some in, you know, Minnesota, for example. But it's not going to be picked up in your standard dot call, per se.

They're not really in tertiary centers, they're much more in the community, and so you have to...

Okay, and you recently increased the peak sales guidance to a billion-plus for HEP-D. Has anything over the past weekend changed the thinking around that billion-dollar number?

No, no. I mean, the increase in guidance was driven more by HEP-CLUDIC's pricing, which was significantly higher than what the prior guidance was anchored on, so I'm patient. The numbers haven't really changed, although I noticed that Gilead came out recently and said there's 40,000 to 80,000 patients, and here in their presentation yesterday or over the weekend said 61,000 or something like that. We're obviously being more conservative and trying to end your promise a little bit.

Yeah, but we do see upside if testing increases, and currently there's very little testing that's done. I think less than 5 to 10 percent of Hep B patients are actually tested for hepatitis delta. So if you see that change, and I think the guidelines are moving towards that, that could find more, too.

Do you guys think this is a chronic treatment, or is there a possibility of fixed-duration treatment based on the results we're seeing?

There's certainly a possibility for some patients. I think that would, if you talk to most physicians, that would be the ideal option, right, is a finite therapy. Frankly, that's the best thing for patients, so that makes sense. Right now... There's still questions to be answered about what that looks like and how to do it. I think they've taken a first step in their recommendations for maintaining TND and ALT normalization for about 96 weeks before you experiment with it. The data shows that you can have that withdraw therapy and then the virus rebounds. So, you know, I think we still have some work to do there, but it's certainly, I think, a good objective.

So the $1 billion peak sales does not assume a finite duration.

It assumes chronic therapy, and I think that, you know, in a lot of these patients, you're going to have at least multiple years of therapy before, in some, you get to a treatment.

Can you talk about the decision to go for once weekly regimen versus once monthly? I think the data zooming out seem to be pretty similar, at least when you go and expand into longer durations of treatment. So, just curious on the thinking there.

Yeah, the feedback that we've had from just a commercial perspective is the once weekly is much more convenient and preferred for that reason. I mean, I think there's some debate on it. I mean, obviously, you can have patients that would refer once monthly, but by and large, we think the once weekly will be the better option.

You posted data for Azure 4 today. Talk to us about those results. Anything different versus Azure 1 that you want to highlight?

Not really. It's very, very consistent, you know, other than some of the baseline characteristics that I mentioned earlier in terms of baseline viral loads. But, you know, data consistent, no new safety signals. So we're on track to file our BLA in the first half of next year. So very excited to move this forward. This is a reminder of Azure 1 and Azure 4 where the two studies needed to support the BLA package.

One billion-plus peak sales expectation you have, is that U.S. plus Europe, or is that U.S. only? Moving on to FOP. I wanted to touch on, you know, the patients there, your initial launch expectations following September's approval. You've had, I think you've mentioned recently, you've had strong engagement with prescribers. There could be stronger adoption than Livmarly's original launch. What gives you that confidence? You know, is it the concentration of the known patients, the severity of the disease, or anything else that you're expecting a strong launch there?

Yeah, I'd say both of those. So it's a very severe disease. Patients are well identified, and we have a therapy that is really impactful. So all three of those factors, we think, would support a different launch profile than what we saw with Livemarly.

It's a highly engaged patient community. Just to give you an anecdote, the day we got approved overnight, we got a congratulatory email from the family in Turkey. So this is a patient population and families that are really paying attention and are really desperate for treatment options.

And the $10 to $15 million sequential growth that you guys cited on the third quarter earnings, does that include contribution from? The EXPAND study from this launch, what exactly does that $10 million to $15 million include?

Yeah, it's meant to be for the portfolio overall, and to be clear, I mean, you know, we just wanted to put that out there so people could, you know, have some sense of where we're headed. But as usual, you know, in early January, we will be pre-announcing revenues for the year and also give more specific guidance for revenues for 2027.

Do you guys expect to be positive cash flow next year, operating cash flow?

Absolutely, yes. We were cash flow positive last year. We were cash flow positive first half of this year. But as we've signaled, because of the somewhat heavy R&D lift driven by Brelovitard for both clinical studies as well as manufacturing, we expect it to be somewhat cash flow negative. In the second half, and in the third quarter, it was minus 4 million. So not a lot, but a little bit. But we absolutely expect to return to be cash flow positive next year.

And talk to us about the spending trajectory. You had some temporary phase three increases, as well as OPEX increases, as well as for manufacturing activity. How much of that should we expect to replicate in 2027?

Yeah, so let me give you kind of the, again, the big picture. So the commercial cash contribution margin has been in the high 50s percent for the last few quarters. We expect it to continue at that level. But once we get. More revenue and new medicines launched that will expand well past 60%. On the R&D side, because of this heavy lift, it's been about 50% of revenues, but will trail down significantly over the, you know, probably stay at that level another quarter or two. But then after that, really trail down quite significantly as a percent of revenue. And then for kind of non-commercial, GNA is also trailing down as a percent of revenue.

Andrew, how should we think about additional BD activity versus just monetizing what you have in the pipeline today? Historically, you guys do a lot of transactions, so I'm curious to hear what's next.

Yeah, well, I mean, I think just kind of going back to where Eric started, you know, only 5% of orphan diseases have an approved therapy. So there's a lot of opportunity out there for us. And, you know, our team is always active. You know, we're always looking. I think that there's, you know, that's coupled with a lot of discipline. We have a high bar for bringing something in. It has to make sense for us to be the owners of it. It has to be transactable. It has to make sense financially. And we've got a lot of great things in the portfolio, so that gives us the luxury of being able to be disciplined.

Got it. Okay. Andrew, if we're having this conversation another year from now, what are two or three milestones that, you know, you want to highlight that would demonstrate that Mirim is a successful company in transitioning from a small rare disease company into a multi-billion dollar franchise?

Yeah, I mean, I think continuing on the trajectory that we've been on and getting all these medicines I talked about approved, you know, Brilovitag, Elixabat in two indications, the SNDA for the expanse study in biliary atresia, younger population approved for Artebrios, we think we can achieve all of that, and That's our goal, and we want to be held accountable to achieving all of that, and that's going to really benefit patients and expanding patient populations, take us into much larger patient populations, and that will, from a business standpoint, result in very strong revenue growth for many years, and as I said, also generate a lot of cash.

Investors. That's all they have. Anyone in the audience has any questions for the team? Happy to take questions.

Thank you. Thanks for having us.