Thanks for the staying power for the last session in Room E for the Citizens JMP Life Sciences Conference. We're pleased to have Mirum Pharmaceuticals. We have CEO Eric Bjerkholt here—or CFO, sorry, Eric Bjerkholt—and Head of Investor Relations, Andrew McKibben. And it's been a long day, as you can tell by my pronunciation. Sorry, fellas. But, yeah, so we've been following Mirum from afar for quite some time, and then we picked up coverage, maybe a year, year and a half ago now at this point. And you guys have had a lot of great success and great progress executing really well. But for those that may not be as familiar, can you tell us, you know, high level what your strategy and focus is at Mirum?
Sure. First, let me start by saying thank you for having us at your conference. Thank you for saving the best for last. We very much appreciate being here, and we will be making forward-looking statements through this fireside chat. So please look at our SEC filings for all our risk factors. So Mirum Pharmaceuticals, we are a rare disease company with three approved medicines. We are currently our three medicines are for rare liver diseases, but our goal is to be a rare disease company with medicines in many other indications as well. We have guided to $310 million-$320 million in revenues this year and are on track to accomplish that. So we're very excited about how the year is going so far and excited about continuing to grow the company over the next many years.
Can we spend some time talking about Livmarli, which was your first approved product? Can you talk about the first indication, Alagille syndrome, the opportunity there, and then you recently got approval on a second indication, PFIC? Can you tell us a little bit about, you know, Alagille and then PFIC, and then we can, you know, dig into some details?
Sure. Alagille syndrome, we think the prevalence is about 2,000 patients in the US, and, approximately half of those are what we consider the, the sort of the core addressable market. We launched a couple of years ago. Launch is going really well. We, we think we're about a third penetrated at this point, so there's a lot of room for growth from where we are today. And, internationally, we see a similar opportunity. We at the end of last year, we were, had revenues from 18 countries. We'll continue to expand that this year and be in over 20 countries by the end of this year. So that's going well as also, obviously, you don't get exactly the same price as in the US, but nevertheless, big opportunities. And then PFIC, we think the prevalence is about a third or so of, Alagille syndrome.
We just got approved in April and are in the process of launching in PFIC in the U.S. In Europe, we expect CHMP decision or recommendation, I should say, by the middle of this year and hopefully decision shortly thereafter. And so, we don't expect to see a lot of revenue from PFIC this year, but into 2025 and beyond, we should start to see meaningful contributions.
Can you talk a little bit about how Livmarli works, what you're trying to do for these patients? You guys have done a good job of rolling out real-world data and outcomes and showing, you know, continued benefit. But in the real world, what are you trying to do, and then what is the use case for Livmarli? You talk about pediatric liver disease. Is this something that they're gonna be on for the rest of their life? Do they come on and off? Do you get disease under control? Can you talk a little bit about those dynamics?
Yeah. I mean, so I can start. I mean, generally, it's we see this as lifelong therapy. And the persistence and adherence data that we've seen over the course of its real-world experience is been great. In some ways, you have a built-in mechanism. If you forget to take it, the itch comes back almost immediately. So it's a really strong reminder and I think underscores how impactful that level of pruritus is for these patients in terms of their quality of life. But effectively, what Livmarli does is it helps the body flush out the excess bile that's stemming from cholestasis, which is a theme you'll see across our programs. And that's really what we're trying to do, is minimize that burden of toxic bile acids in the body.
The first thing you see happen when you help flush those out is the pruritus goes away. So, you know, effectively, that's, that's what it's doing. And when you think about over time, you know, we've had patients on therapy for over seven years with, with great outcomes. Beyond pruritus, over time, you do see really nice separation, in terms of, event-free survival. So you, you are having a, a bigger impact, for these patients beyond just managing their day-to-day, quality of life experience.
Yeah. 'Cause I don't wanna call it a loophole, but you guys had a very interesting regulatory strategy. You were able to get approval for these different indications based on pruritus because it's you're improving how patients feel and function, but then you've also tied it to these long-term improvement in event-free survival . So.
Yeah. Exactly.
It's just a really nice, I think, drug development story and strategy you guys are using in your follow-on molecule that we'll talk about shortly. But a question we get quite a bit is there's another, competitive IBAT inhibitor, the same mechanism that's out there as well, Bylvay for the same indications. Can you talk about kind of that dynamic, the interplay, you know, if they're both approved, if they're the same indications, there's the same mechanism, how do people make choices between which one to use?
Yeah. So, I'll start with Alagille and we can talk about PFIC. But in Alagille, Bylvay's been approved for almost a year. I think they were approved in June of 2023. And we really haven't seen much impact post-approval. Our new patient adds and growth has been consistent and strong quarter-over-quarter for the last several quarters. And so expect that dynamic to continue to play out for a couple of reasons. Part of it is that Livmarli has a really profound effect, and you've got that immediate response from a pruritus perspective coupled with the long-term data that we've accumulated, which I think is a really important point that physicians consider when making treatment decisions. The other element is our formulation is just very well suited to pediatric dosing.
These kids can't swallow pills, and so we have a liquid formulation to help dose them, which also matters. And then I think the other factors come down to physician experience with us. I mean, we've spent a lot of time developing our capabilities to make sure that the way that we support physicians and patients in terms of coming to care is really tailored to this, the specific needs in the ultra-rare disease setting. So they have a lot of experience, and we make the process easier for them. And then finally, there's a pricing element too, and that Livmarli is, I think, more favorably priced than Bylvay. So all those factors kind of come into play. And, you know, when you look at the last several quarters, that's really how it's played out.
So, don't really see a lot of differentiation in terms of preference. Anecdotally, we've heard that, you know, some of older, older patients might prefer a capsule that they can swallow.
But that's been anecdotal at best, and those have been few and far between. That said, it's, you know, a patient preference that, you know, we recognize, and that's something that we're working on.
How about in PFIC? I mean, is it the same docs treating the same types of patients so they know they have their experience in Alagille syndrome and can understand it translates to PFIC? 'Cause you're second to the party there. Is it gonna be a similar dynamic where maybe Bylvay has more entrenched position that you have to take share from them, or how does the PFIC dynamic look?
Yeah. So it's a little bit different. You know, so I'd say that, you know, not every Alagille physician sees PFIC patients.
But every PFIC physician sees Alagille, just because it's a smaller population. And you're right about some of the entrenched share. You know, Bylvay had positive data, and, you know, we do expect it to work in a portion of the PFIC population. And so if you're on something and it's working, we don't expect a patient to switch. If it's not working optimally, that would be a candidate to switch to Livmarli, where we've shown broader and deeper responses within our MARCH PFIC Phase III study. And I think importantly, another element where we expect to be competitive is just in the subtypes. So PFIC is an umbrella term for a series of different types of mutations that all ultimately result in cholestasis. We studied a very broad set of those subtypes in our study.
When you think about how that translates to reimbursement, some payers are restrictive to the data that you have. So having a broad set of data will be an advantage for some of the rare PFIC subtypes. But kind of tying it all together, strength of clinical data, these really profound response rates in our study, that, you know, we're really happy to set the bar up there, breadth of patients as well, and also the experience piece matters.
Have you guys said how big of an opportunity Livmarli can be between the two indications?
Yeah. I mean, in the US, we think about Alagille syndrome as having, you know, peak potential in the $500 million range and that PFIC, as we said, would be about a third of that.
Internationally, we haven't really said it would be smaller, but still a very meaningful opportunity.
And then how do we think about launch expectations for this year in PFIC? 'Cause you just got the approval in April, I believe. So, what kind of blocking and tackling do you have to do to make sure that's set up for success? And is it any easier because you already have approval in a different indication?
Our first goal is, we have about 25 PFIC patients on clinical study, and our goal is to convert as many of those as possible into commercial drug. We think about 20 of the 25 meet the current label, and so we're starting to convert them, but typically it takes a few quarters to achieve that. And then we're also hoping to, towards the end of this year, to have made enough progress on the reimbursement front to start to generate, you know, new patients as well. So we don't think of the 310-320 that we're guiding towards this year. PFIC will be a very small part of that, but into 2025, we hope to have a good momentum and for it to be a more meaningful part of our growth story, starting next year.
Okay. So launch is going well. We have expansion to PFIC. Wanna spend some time talking about volixibat, though, your second-generation IBAT inhibitor, 'cause you have some interim analysis coming up soon from two trials, in PBC and PSC. Maybe to start, can you talk a little bit about those two conditions and unmet need?
Yeah. So, these are larger settings of cholestasis. So PSC in the U.S. is around 30,000, 30,000 patients, potentially more. You, if you look at the literature, the diagnosis rate or the incidence rate, I should say, is increasing, actually. And PBC is significantly larger. Over 100,000 estimates kind of put the diagnosed population in the 80,000-100,000 range. But like you see across cholestatic settings, that accumulation of bile acids and the symptomatic burden of pruritus is, you know, very much there and affects the majority of those patients. You know, our estimates kind of put it around 60% of patients who, you know, have active pruritus and are seeking treatment for it.
Okay. And maybe PSC is a little bit more straightforward 'cause there's nothing approved. Something's in development. Maybe can you talk about how volixibat could compare to, you know, other drugs that are in development for PSC, and then we'll jump to PBC?
Yeah. So, you're right. There's nothing approved in PSC, which is why we're very excited about this opportunity. We can talk a bit about our regulatory strategy there, but what makes volixibat unique in this setting is directly targeting the burden of cholestasis. So we're addressing the bile acid accumulation and the resulting pruritus as part of that. Other agents in development, and this has kind of been traditionally the case. If you look back a decade over the course of development history in this setting, have focused more on the inflammation and fibrosis that is a result of the cholestasis.
and there's some interesting data out there, but the regulatory pathway, if you're pursuing that type of outcome, is less clear and has traditionally been a real challenge in this setting, just because of lack of alignment and/or prohibitive requirements from the FDA, which is why the strategy that we're using with pruritus, which is an outcome, how a patient feels and functions, is unique and, you know, from our view, really excited about potentially bringing the first therapy to patients in PSC.
Is there any key differences between Livmarly and volixibat as far as how they work or translatability between the mechanism between what you're seeing in pediatric patients and these adult conditions?
No, not a lot of difference. Different formats. So volixibat is a capsule that you swallow. But beyond that, they're both IBAT inhibitors. They're doing the exact same thing. It's really about just getting the dosing right for the indication. And we spent a lot of time on that, going into both the PSC and PBC programs to make sure that we were optimizing the dose.
And PBC, a little bit of a different animal. The standard of care, UDCA front line. We have obeticholic acid from Intercept that was approved second line, selling, you know, pretty well for a drug that, you know, works minimally and has, you know, significant safety concerns. And then recently, we just had Gilead's acquisition of CymaBay, I believe, for $4.3 billion for a Phase III PBC asset. How do you think about volixibat's opportunity and how that could be different than, you know, what's available and then what could be coming soon?
Yeah. It's a great question. And there's, there's a lot more, I think, a, a more of a competitive dynamic in the PBC setting, which is obviously much larger. You know, from, from our perspective, the way we're looking at PBC is w-we don't have a criteria for disease state. So there's no alk-phos cutoff in our study. We're looking at patients who are well controlled on UDCA and have pruritus, of which there are many, as well as patients who may not be adequately controlled, and who are on second-line therapy, which is currently Ocaliva and in the future is likely gonna be, also include PPARs. So seladelpar, elafibranor, those are both under review by the FDA. So when you think about the opportunity from our perspective, what's really differentiating is the breadth of focus here.
And the first-line setting is 50%-60% of the patient population that is not gonna have an option for their pruritus, beyond some of the other benefits that IBAT inhibition could provide in this setting. In the second-line setting, you do see a nice impact on pruritus from the PPARs, but I will say it's not universal, you know, based on the data that's been shared. About 30%-40% of patients have a really nice response, which leaves 60%-70% that may not be having an optimal pruritus response. So we do see opportunity in both lines of care, which is why we structure our study to take patients from both.
Do you know, the front lines PBC setting, you know, what percentage of patients suffer from pruritus?
Yeah. It's about 60%. It's pretty consistent across lines of therapy. It's not as correlated to disease setting or disease stage.
Yeah. Similar to Alagille and PFIC, do you expect that, you know, long-term IBAT inhibition will improve, you know, different outcomes, be disease-modifying as well, or is this, pruritus is a key symptom for these diseases that you guys are relieving?
Well, pruritus is the key symptom, and that is the regulatory strategy, which, you know, allows for a more efficient clinical development path. But certainly, that's something that we'll be looking at. I mean, from just a scientific rationale, you do see elevated bile acids very clearly correlated with inflammation, fibrosis, and they're predictive of progression to outcomes. Some really nice data sets on that in PSC. And so we structured our studies to look at pruritus over a 28-week period, but we have long-term extensions for both to generate some of that long-term data where you should see more of that. It's hard to see movement in a very short term, but that's why you follow patients over a longer period.
I think it was last week you guys gave us your first quarter results, maybe two weeks ago. It's all a blur, but you gave us some more color on the interim analysis we'll be getting. Can you talk about, let's start with PBC, that interim analysis, what you're looking for, what you're gonna tell us about, and what that means for the program?
Yeah. So, I mean, in both these settings, there is really great precedent data showing that IBAT is doing exactly what it should be doing in terms of lowering serum bile acids and pruritus. And so for both programs, what we really wanna do is make sure we've got the right dose. So the PBC interim analysis, it's an open analysis, so we will be sharing top line. That will include pruritus, safety, and other biomarkers like serum bile acids. And so our focus there is making sure that we've got the right dose going into the potentially pivotal portion of the study. It'll be about 32 patients, so randomized, across the two volixibat doses and placebo, one to one to one, which we feel is sufficient to see, one, give us a sense of efficacy and, two, make a decision on dose.
Is there a threshold of pruritus reduction you'd wanna see to continue the trial, or is it if you see a trend, that's good? Like, how important is dose response? What are you thinking about the actual result could be?
Yeah. From a dose response perspective, and I'll start with that. With the low dose that we are going into in the study, we expect that to be enough. The high dose is really a just-in-case, you know. We've seen that when you push the dose higher, you can drive, you know, broader and deeper responses. And so we wanted to make sure that our starting dose in this study, or the low dose, was on the kind of maximum end of that curve, and the higher dose is really a just-in-case.
Any kind of safety concerns of pushing the dose higher or things to be looking at?
No, not that we've seen. I mean, you typically see mild and transient treatment-initiated diarrhea, which is basically the IBAT doing exactly what it should be doing. That's how the body gets rid of the excess bile acids. But we have not seen a big difference in our dose-finding work between lower and higher doses.
How about in PSC? What's that interim analysis gonna look like?
So PSC, it's a bit different. It's a blinded interim analysis. So ultimately, we will not be sharing top line. We won't see top line if under a certain scenario. So effectively, this allows us to keep the study efficient if the drug is working. So we've set a threshold for efficacy that, if met, a blinded or an independent DMC can make a dose decision and continue the study. So if the drug is working, we don't wanna stop that. And if it's not, if it doesn't meet that threshold, this converts to a standard interim analysis where we unblind, look at top line data, and share that with you. But this allows us to accomplish a couple of things. You know, one, it allows us to see if we're seeing a meaningful effect. Two, it allows us to select dose.
You know, most importantly, if we continue the study on a blinded basis, that allows us to include those patients from the interim as part of this potentially pivotal analysis set. So you've got a head start on your pivotal data, and you already know that there's a treatment effect in there that is predictive of a positive outcome.
What is that, that threshold that's predictive? What's that therapeutic benefit that you, you're targeting to see?
Yeah. We haven't disclosed the threshold, you know, in part just to protect the integrity of the study. That's, and in some ways, a regulatory requirement. But ultimately, we don't wanna continue a study that we don't think has a good shot at being successful. So we've set a bar that would reassure us if we cross that, we are tracking in the right direction.
An important point I think we might have glossed over is that both of these trials will serve as registrational trials if continued to completion.
Yeah. That, yeah, a lot of conversation with the FDA at the outset to position these studies to support that goal.
Can you remind us when the interim analyses are happening?
they'll be in June.
In June. And at the same time, different times?
Yeah. We'll announce at the same time.
It's gonna be a lot for us to chew on that day.
Yeah.
And I think a really nice deal you guys did, I guess maybe last year, bringing on Chenodal and Cholbam, two products that we covered for years when they were at Retrophin, but a really nice, I think, commercial acquisition. Can you talk a little bit about how that fits into your portfolio and what that means for, you know, top line growth?
Yeah. It fits in perfectly. They are also in pediatric liver disease and generate, you know, they've been steady growers in the low- to mid-single digits. This year, you know, probably generate somewhere around $110 million or so. And contributing probably about 60%, sort of on our commercial operating cash operating margin. So very good cash flow that allows us to continue to invest in our business. We expect them to continue to grow at those rates and continue to be meaningful contribution contributors to us.
How big is the commercial organization then? Did you have to add anything when you brought those products in?
Yeah. I mean, in terms of pure sales force, we for Alagille syndrome and now PFIC, it's about 12 to 15 salespeople. And then in addition to that, obviously, you have the whole sort of reimbursement infrastructure and marketing and all of the support functions. And when we added the bile acid portfolio, we added a second sales force that's about the same size, about 12 people that are calling on pediatric ophthalmologists, geneticists, and pediatric neurology folks because CTX, for example, is a neurologic manifestation. So that's where those patients are typically identified and treated.
I have one big picture last question, but before that, this is typically where I ask about cash runway, but you're in an enviable position with your balance sheet. So maybe can you talk a little bit about cash position but also potential path to profitability?
Yeah. So we ended the first quarter with $302 million in cash. And we're not quite operating cash flow positive yet, but we're getting close. And in absence of new business development transactions, you know, we should be cash flow positive or close to that by the end of this year. And so, you know, we don't need to finance in absence of new business transactions.
And that's a perfect segue 'cause my ears perked up earlier when you said rare liver disease, but we're a rare disease company. You know, what does this look like long term? What other, you know, potential rare diseases could make sense? Is there anything completely out of bounds, or are there specific areas that you think would make sense with what you guys have shown you're excellent at delivering?
I think, what's out of bounds is probably oncology, you know, more genetic type treatments, gene therapies, et cetera. But there's more in bounds than out of bounds. And so we're looking for things that are a good fit where we think there's data that we can believe in, have confidence in, where we think we can add some value either through development or commercially. And that would accelerate our growth.
Late stage, early stage, commercial, all the above?
All of the above, I would say.
Interesting. Okay. Well.
But I would say we don't think we have to do something so we can be. There's a high bar for what we end up doing.
You guys are plenty busy. So I thank you for taking the time to join us, and we're looking forward to seeing the updates in June and then learning a lot more about volixibat. So thanks, guys. Appreciate the time.
Yes. Thank you. Great questions.
Thanks for having us.