Mirum Pharmaceuticals, Inc. (MIRM) Earnings Call Transcript & Summary

Next up, we have the team from Mirum Pharmaceuticals. So we have Andrew McKibben from the IR side; and Eric Bjerkholt, who is the CFO, hopefully, I pronounced that correctly. Awesome. All right. So before we dive into it, let me just turn it over to you guys for introduction, overview of the company where things stand today.

Great. Thank you, and thank you to Evercore for inviting us to present here today. And as usual, we will be making forward-looking statements. So please refer to our SEC filings for risk factors. So Mirum is a rare disease company. We have 3 approved medicines for rare cholestatic and other diseases. Our guidance for this year is $500 million to $510 million in revenues, and we are cash flow positive, and we expect continued growth from all 3 medicines into next year. And we also have a full pipeline led by volixibat for adult cholestatic diseases, PSC and PBC and then MRM-3379 for Fragile X syndrome, where we announced yesterday that we enrolled the first patient in a Phase II trial. So -- very excited about what our commercial medicines can deliver and also our pipeline.

Awesome. All right. So let's actually start off on the Fragile X side of things, kind of go in reverse order from what we normally do. You've noted $1 billion-plus opportunity for Fragile X. How do you get there?

Relatively simply. I mean there's about 50,000 male Fragile X patients between the U.S. and Europe. From a pricing perspective, if you look at comps, that's -- you kind of get into the 200-ish range. I think that's pretty reasonable looking across other comparable disease settings. And we assume that there's -- while there's nothing approved today, Shionogi has PDE4D in clinic in a Phase III study. So a rough kind of competitive share and the math gets pretty simple. It's quite a sizable opportunity.

Okay. That makes sense. So I guess that's for every 5,000 U.S. patients, that's about $1 billion opportunity, give or take?

Give or take, yes.

Yes. I mean, still early. We'll have more to say, I'm sure in the future, but...

Yes. I mean once -- I mean we're just starting Phase II. So once we have a full understanding of the clinical profile and the competitive profile, all that stuff plays in. But rough math, that's correct.

Awesome. Do you actually know what's the latest with Shionogi's program? I mean on their last earnings, they said they've had the last patient out, but they're discussing the primary with the FDA. Do you have any speculation so what's going on there?

We do have speculation. But I think, generally speaking, based on their comments, it sounds like they're going through the typical motions of validating the NIH toolbox. So if you have a patient-reported outcome, the FDA does require a certain amount of validation for that. And that typically is conducted before you unblind the study. So it sounds like they're kind of going through those discussions right now, getting alignment on MCID and some of those other kind of anchoring measures that are important. But our general expectation is that we'll have a clear answer in Q1.

That makes sense. And you guys are doing an AH toolbox on the CCC domain specifically. I guess like from -- like on that last point, from an FDA clinical outcomes perspective, how validated do you think this measure is?

It needs to be -- I think it's -- there's a lot of great precedent and reason why this end point makes a lot of sense in the Fragile X setting. It does need to be validated, and that's pretty common. I mean we went through the same validation efforts with the ItchRO for the Observer score in the pediatric studies. We're doing the same thing in the adult studies. So pretty standard to do that in parallel in context of a registrational study. So nothing seems out of the ordinary on that front. And from what we've seen from this endpoint versus others, we think this is particularly well suited. And it seems like the FDA agrees with that.

Why did you choose this domain specifically? Maybe it's helpful to kind of walk through what the CCC is testing specifically?

Yes. I mean it's a crystallized measure, right? So it's looking at picture vocabulary, learning memory and some composites of those. What we like about it is that it's calibrated for individuals with cognitive impairment. So that's important. And I think a departure from where -- what you've seen in some of the historical Fragile X studies where you're looking at clinician or caregiver global impressions of change, which you have some real issues with floor-ceiling effects. Because this is completed by the patient, and calibrate it to whether they're getting answers right or wrong, it's a little bit more sensitive and feels particularly well suited for this population.

And I think [indiscernible] data on this measure was pretty strong, too, if I'm not mistaken?

Correct. Yes. I mean, yes, to be very clear, I mean they use this in their Phase II and that definitely informed our approach in terms of pursuit of this mechanism and design of our study.

Awesome. How do you power the Phase II?

Similarly to what we saw from the Shionogi Phase II just as a rough benchmark. I mean that's -- Phase II, the primary endpoint is safety and tolerability. The NIH toolbox is a secondary. And one of many, we're looking at a lot of different other end points, some of the clinician and caregiver change scales, some biomarkers. So we're trying to learn a lot from the study, which would inform subsequent Phase III.

That makes sense. For the 3 doses that you're testing, do you know how much CNS concentration, CNS inhibition, I guess, that you're getting compared to [indiscernible]? Specifically, I know [indiscernible] is using a 25-milligram dose in both of the studies, I think. Like, how do your 3 doses kind of bracket that?

We're, generally speaking, at their level or more exposure.

Yes. All right. That makes sense. All right. Over the PSC side then looking ahead to next year, which is going to be one of the big binary events. Maybe it's just helpful to kind of recap what you guys have said on powering and variability, kind of what you're seeing for the ongoing trial to set the stage there.

Yes. So we had an interim analysis about 1.5 years ago, which was blinded to us, but it was set up where the committee that looked at the unblinded data had the 3 possible outcomes. One was to continue the study without any change, and that would be the outcome if what they saw in terms of efficacy and safety exceeded predefined thresholds that would predict a positive trial. The second option would be to supersize the study, increase the size. And the third would be to tell us to unblind because it wasn't working. And the outcome was the best possible, meaning the first option, which is they said, continue the study unchanged. We also, in the first portion, had 2 different doses plus a placebo, so 3 arms. And they were to select which dose to take forward, and they picked the 20-milligram dose as the one with the best therapeutic window.

Awesome. Have you talked about the baseline pruritus scores at all? I'm just trying to kind of mix and match versus the prior VANTAGE study, which is on the PB side for what you've shown. Like, was the baseline pruritus here generally similar seen there?

Yes. baseline pruritus in the VANTAGE study was -- for the interim was a little over 6 on a 0 to 10 scale, and I expect the same in PSC.

Awesome. What about minimal effect size from a statistical perspective, right? Because you talked about how you powered it, especially variability is tracking a bit on the lower side, which is good. Like, at what pruritus effect size do you start to run into troubles from the statistical perspective?

The limit of detection. I actually don't know the answer to that, but I mean in PBC, GSK had a positive study with a 0.7 difference, placebo adjusted. And I mean, they have more patients, but I don't think it would take a lot more than that to achieve statistical significance with our number of patients in PSC.

Makes sense. What about beyond pruritus, like the quality of life, fatigue, sleep, very important secondaries that you guys are measuring? Should we expect those to be statistically significant in this study? If they are statistically significant, what does that do for you commercially?

We didn't power obviously for these, right? I mean we've seen a really nice interesting signal in the PBC interim on fatigue. And just worth pointing out that fatigue and sleep are different things. Fatigue is not just being tired, it is characterized as a brain fog or kind of this inability to get off the couch, always wanting to sleep, but not the same thing as "I didn't sleep well last night." And is next to pruritus, one of the most burdensome symptoms that patients discussed in both PSC and PBC settings. So very encouraged by what we saw in the PBC side. It's certainly a nice to have if we can get it, and I think would be very meaningful for patients. But I don't think we've -- we didn't set the study around a stat sig for fatigue or sleep. But clearly, when you address the itch, you see improvements in sleep, that's been pretty consistent across the pediatric settings, and we'll learn more on fatigue when we see the final data.

Makes sense. All right. Thinking about the tolerability safety side, and this applies to PBC also. Just one investor question we've gotten, and I'll just paraphrase it, is if you have some rates of diarrhea, GI events that you've seen with just the IBAT inhibitor class, why trade itch for diarrhea? And I know it's not quite like that, but I'll phrase it to get your response.

Yes. I mean, I think this kind of minimizes how bad the patient experience is, and it's really important -- and we've heard this a lot, it is just itching. And when you actually talk to a patient and understand what this actually means for them and how much it impedes their ability to live a normal life, it is significant. The diarrhea that you see with IBAT is very much on target. That's how you clear the bile acids out of the body. And it's typically mild and transient. It's very easy to manage with simple imodium, if you even have to do that. So it is -- it seems to be a very easy trade. And if you just look at our studies and participation in the extension portions, the degree of participation we're seeing is indicative of a patient choice and that's, I think, important.

More importantly, I would say, look at our experience in real life, we have now many hundreds of patients treated with LIVMARLI and very, very rarely does somebody discontinue for diarrhea or other side effects.

Yes. That makes sense. It's just back to the quality of life and other measures beyond pruritus alone. If some of those other secondaries hit, does that change how you think about things from a pricing access perspective?

Maybe. I mean, the more attractive the profile is, obviously, the more value the medicine will deliver. And so we'll -- that would be one of the factors we consider when deciding what the right price is.

Yes. Switching gears, going over to the PBC side of things. For the VANTAGE study. How many patients are on UDCA or PPARs on that study?

Just about all patients are on UDCA. I mean, that is the kind of underlying therapy that if you have PBC, you are treated with UDCA. Very few patients end up intolerant to UDCA. So you typically see that as the mainstay. And for the portion of the patients where UDCA doesn't work that well, you typically layer on typically not PPAR, what used to be Ocaliva. So just about everybody is on UDCA. With PPARs, I'd say maybe a handful. I mean it's certainly part of the inclusion criteria that if you're on a stable PPAR, you can continue that into the study. We had several patients who were on fibrates in the interim, which I think is an interesting point. PPARs do have some benefit on price, but it's not universal. And seeing patients meet the inclusion criteria for Vantage while on a PPAR is kind of indicative of that.

So I guess with that said, how do you expect the label to read assuming it's a positive study per the last data that you've put out?

Treatment of cholestatic pruritus in PBC.

Yes. For like all backgrounds, different ALP status?

Yes, there's no alk phos cutoff for the study, so that we're agnostic.

Awesome. All right. Working our way commercial, but one before we get there on the expand side of things for the next expansion of LIVMARLI. Like what's the mix of patients that you're seeing come in to that study because you allow a few different groups.

Roughly half the patients have biliary atresia and the rest is a smattering of different extremely rare cholestatic conditions.

How is the age also skewing for the trial?

Well, we've got a pediatric cohort, and there's also a separate adult cohort. So the primary endpoint will be based on the pediatric cohort that's the ItchRO Observer Scale. So there's slightly different ways of measuring itch between peds and adults. So that's why you break them up. Typically, though, in the pediatric side, these patients are 7, 8, 9 in that range. I mean, there's a spectrum for sure, but I'd say, on average, pretty typical.

Maybe it's worth asking like given you're seeing a high mix of VA patients as expected, can you call out how that's different from the population that was studied to EMBARK?

Very different. Yes. I mean the EMBARK study was incident biliary atresia. So these are right after these children are born, they're diagnosed with biliary atresia. They have an emergency Kasai procedure and then would be enrolled in the study. This population that we're looking at and expand, these are patients who've had a successful Kasai, and 2, 3, 4, 5 years later, they developed cholestasis and the resulting pruritus. So you can't predict which patients who do have a successful Kasai will go on to develop cholestasis, but we do see a fair number that do -- and it's a fairly activated patient population, which is why we aren't surprised to see such a good participation and expand.

Awesome. All right. So turning to the commercial business. Thinking about 2026, maybe just kind of frame like if we step back on 2025, what drove so much growth? And especially in the PFIC side, was it more on the population being larger than you expected? Was it more that they skewed a little bit heavier, maybe there was a different pricing mix than you expected. Maybe it's a little bit of both. But really the question is, you'll have that base in revenue given your high retention that you've talked about before. What's the right way to think about growth heading into 2026?

Sure. So I mean we expect continued growth from all 3 medicines and also both U.S. and international. This year, the reason we so dramatically outperformed our original guidance at the beginning of the year was primarily related to PFIC, where we found more patients that were naive to treatment much more than we thought. And that's, I think, a combination of probably there being more PFIC patients. than we had originally thought, but also more patients that had yet to see treatment. And we've been very successful through our various efforts at getting a good share of those patients to treatment, and we expect that to continue.

I mean like next year, do you think there's still more upside versus your original expectations? Or do you think you've kind of recalibrated at this point to a more reasonable view?

It's hard to tell. We keep being surprised to the upside of how many patients we can get to therapy, and hopefully, that will continue.

Awesome. I think I asked this question at least once a year, maybe a good time to ask again. The reweighing dynamic that you see as patients stay on therapy as they get older and grow. What do you see on that front?

That's definitely a dynamic that's playing out, and we're seeing the average dose creep up, albeit slowly. And the reason it slowly is because on average, a patient will see a dose adjustment every other year. And the difference between each dose span or one dose span and the next is about 10% to 15%. So that's a dynamic. But we have some discontinuations usually to transplant is the most common. And those patients are then -- if you look at the whole pool usually replaced by infants that are diagnosed to Alagille syndrome, and they weigh a lot less and so bring down the average weight. But over time, as the pool of prevalent patients gets larger, you definitely see more of that dynamic play out.

Awesome. And then just on the Paragraph IV side of things. Maybe you could just like quickly frame your IP estate and like which patents you put more weight on internally? Like I know, for example, the 2040 method of use patent was something the company was founded on right out of the gates, and there's basically why you got the assets. So there's some interesting findings within that patent. But maybe you could just kind of walk through that.

Yes, that's definitely still our -- I think, our most important patent out to 2040. And this Paragraph IV filings were completely expected on the date, no surprises, and we were prepared for that. So we have a very good legal team ready to vigorously defend our patents.

Awesome. Well, it's right on time. So I think we'll wrap it up there. But thanks so much for joining.

Thank you.

Thank you for having us.