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

All right. Good morning, everyone. My name is Richard Law. I'm a senior biotech analyst at Goldman Sachs. It's my pleasure to introduce Chris Peetz, CEO of Mirum. So Chris, why don't we -- why don't you kick us off with some opening remarks before we dive into Q&A.

Thanks, Rich, and thanks for hosting us. We're excited to be here. And yes, a quick overview of Mirum to kick us off. Mirum is a leading commercial rare disease company focused on bringing rare disease products forward that are really an underappreciated settings with high patient impact. Company started about 5 years ago around LIVMARLI, our current lead approved product that's approved in Alagille syndrome and PFIC. And that has been a great way to kind of start and form this company that has huge impact now across a number of rare disease settings where LIVMARLI has been approved in the U.S. for a few years. We are rolling out in Europe and internationally as well, primarily in Alagille syndrome now that have a PFIC label expansion around the corner. We just had a CHMP positive opinion that I'm sure we can talk a little bit about. And then last year took a big step to expand the business by adding 2 more commercial products, CHENODAL and CHOLBAM to the business and have a label expansion opportunity for one of those products coming up as well that we can talk about. And then finally, I think one of the -- one of our nearest term milestones is this month, we are planning to announce interim data for volixibat pipeline agent focused on larger adult settings of cholestasis, evaluating volixibat in primary biliary cholangitis and primary sclerosing cholangitis through exciting adaptive studies that we think can lead to potential approvals in those indications. And I think one other thing just to say, I should have led with going to be making forward-looking statements, so read our SEC filings for all the risk factor disclosures.

Fantastic. So LIVMARLI, a lot that's up happening there, right? So it's approved in Alagille. And it's an IBAT inhibitor now is facing competition from Bylvay which was approved in PFIC and recently Alagille. Can you maybe talk about the differentiation between the 2 and provide some color on the competitive dynamics so far that you see between these 2 products?

Absolutely. And just to start to give a little background on the setting, Alagille syndrome and PFIC. These are genetic cholestatic settings where there is an extreme cholestasis. And in the setting of cholestasis, there's an accumulation of bile acids. These bile acids can not only result in progressive liver damage. So most of these children are on a course to liver transplant without treatment, but also creates a terrible symptomatic burden. So these children generally have very severe pruritus, fatigue, lack of sleep and a huge family impact. That's part of the disease. LIVMARLI as an IBAT inhibitor goes right at that bile-acid accumulation. So LIVMARLI's mechanism of action is to block bile acid reabsorption and deplete those excess bile acids that are causing all of these problems in these cholestatic settings. And for the differentiation and real impact of LIVMARLI we found that the -- over the course of the clinical program that the dosing in these settings is just not obvious in the initial clinical experience. So over time, we've advanced our understanding and have, through the pivotal studies, gotten to higher -- far more active doses of LIVMARLI than were originally studied. And that's resulted in really strong clinical impact. So in the Alagille setting, over 80% of children in the clinical program have a pruritus response. That's the registrational endpoint that's used in the setting. And similarly, in the PFIC study, we saw quite substantial improvements versus placebo, not only in itch, but also in bile acids and other liver markers like bilirubin having a significant difference from placebo.

I see, got it. And maybe a little bit about the market dynamic or the competitive dynamics between the 2. You guys are -- you guys have to defend Alagille as Bylvay comes into the market, and then you guys have to penetrate the other markets that they've been already operating in. But a little bit about sort of the strategy there, how you see these 2 markets play out.

Yes. The -- and I'll speak primarily to the U.S., where we have this dynamic now, where both products are approved for both indications. And for Alagille syndrome in that setting, LIVMARLI continues to perform really well. So we saw a competitive entrant midyear last year. And since then, we've had the continued steady cadence of new patient starts and a healthy dynamic continuing with Alagille syndrome. And quite favorable reception from payers is one thing I would note, where we've seen now an increasing number of policies that actually have LIVMARLI as the first therapy for Alagille syndrome as a step through, frankly, before you can prescribe another IBAT. So that's gone quite well for Alagille syndrome. PFIC is more recent. So we just had our label expansion in March, so really exciting about being able to bring LIVMARLI to PFIC patients. The initial opportunity there is really on rolling over clinical study patients. And again, moving towards on the reimbursement side, that's where we're busy with now in the next couple of quarters to get policies in place. And that's gone really well also. And highlighting the advantages that LIVMARLI brings from a clinical impact, the overall budget impact for LIVMARLI is leading to favorable payer terminations as we go through the rollout of PFIC. And so I'll point it in a quite favorable direction. Maybe bridge to international for a moment as well, where the dynamic is a little bit different. And to date, in Europe and particularly Alagille syndrome, we've been the only product approved there. And just had a positive CHMP opinion for PFIC. And I bring this up to highlight it because something really quite impactful behind getting that positive CHMP opinion, in particular, paired with a positive orphan opinion, which means to get that part of the review is EMA determining that there was a significant clinical benefit over the available therapy for LIVMARLI. That was a big win for us to get that positive opinion and expect the approval to follow in the next couple of months.

I see. Got it. And how much of the -- of your sales guidance, your $310 million to $320 million sales guidance for 2024. How much is that driven by LIVMARLI and also the -- how much of it is also from the debt growth expansion?

For the $310 million to $320 million sales guidance, that -- I mean, that's driven by growth across all products is the first statement I'd make. The majority of it is LIVMARLI. We haven't broken it out more specifically by product, but LIVMARLI continues to be kind of the larger product of the portfolio and a lot of great growth dynamics, in particular, as we get later into the year and start to see some PFIC impact?

I see. Okay. So now alongside with the approval in PFIC, you guys submitted an sNDA to support a lower age cutoff from 5 years of age to 3 months, which is in line with your Alagille indication of [ Bylvay ] PFIC indication as well. So what's driving the confidence that you can make that change? And what impact would that have for PFIC?

So the current label for PFIC is for patients 5 years and older. And as part of the review, with FDA as FDA requested us to introduce a different formulation for those younger patients. And it's one that was used in the clinical study. So this is something that's easy to accommodate. As mentioned, it's already submitted. The label expansion for PFIC, we expect it to be 2 steps. So this first submission is to introduce the formulation from the PFIC study to bring us down to 12 months. And that's the same age that was used in the pivotal study. So that's where the confidence comes from that this is largely administrative to bring out the formulation that is a higher concentration for these younger patients. The next step we're planning to have a subsequent filing take us down to 3 months of age. This is the same strategy we followed with Alagille syndrome, where the pivotal study was 12 months and older, and then we had a follow-up following to bring down the age for infant patients based on a separate study. That's already been conducted for PFIC. It just has not yet been submitted to FDA.

I see. Got it. So why don't we switch gears to volixibat, your second IBAT inhibitor. So why do you need to develop another IBAT inhibitor, why can't you just use LIVMARLI and going to other indications?

So from a first statement, I mean, volixibat is, from a mechanistic standpoint, has a lot in common with the other IBATs. It's minimally absorbed. It's a very attractive profile to have a minimally absorbed, highly active drug like this. It's also quite potent against the target. The reason for having differentiated development here, though, is that these settings are very different. And the PSC and PBC indications are much larger. They are adult settings, and having the liquid pediatric formulation for that ultra-rare pediatric setting and price point, we can have a differentiated product for the adult setting that's more appropriate for that larger indication and the adult patients.

I see. Got it. And maybe a little bit about the unmet need for PSC and PBC as well.

Yes, there's some quite significant differences in how we talk about the treatment landscape between the two. And I'll start with PSC because in some ways, the competitive landscape and current treatment alternatives are pretty easy to describe because there just are no approved therapies. So this is a really challenging setting where the progressive liver damage and symptomatic burden be quite severe with many of these patients going to transplant over a 10-year course. And along the way, having this quite significant symptomatic impact from pruritus and fatigue, both being highlights of that. So the drug development in this setting has been challenging historically because of endpoints to bring any kind of therapy to these patients. That's because some of the biochemical markers are quite variable, alkaline phosphatase, for example, ALP has been used a lot in the other adult setting that we're going to talk about in PBC. But it's too variable in PSC to be reliable for a surrogate endpoint. And so what we've done with our program is kind of jumped over all of that, and we're going straight to the outcome that matters most for the patients, which is the symptoms. So similar to the pediatric settings, we're using itch as the outcome as the primary endpoint for our program and also an outcome that can lead to -- potentially to an approval. So the PSC setting for volixibat are really unique in that we've landed on alignment on a pivotal design pivotal endpoint for a setting that has no other therapies. And if you can't impact the symptoms really challenging to find an endpoint for approval.

And that's always been difficult to kind of be the first 1 to go into new setting. So while we're anxiously waiting for the Phase IIb interim data in PSC and also for PBC, that's coming out in June, right? Maybe walk us through the clinical design a little bit more and then the patient population for these 2 trials?

Yes. So for PSC, starting there, and I'll bridge back to give some color on PBC treatment landscape and design. PSC VISTAS study is a randomized Phase IIb study with an adaptive dose selecting element to it. That's what's going to be happening at this interim that's coming up is a dose will be selected and the study will continue into the confirmatory portion of it. The study will target in total about 120 patients, but this interim coming up is in the first 45 that have passed the 3-month time point in the study is the way to think about it. The interim for the VISTAS PSC study is it's somewhat unique. I try to describe it as kind of the inverse of a futility analysis. It's actually confirming activity for the study to continue. So there is an efficacy threshold that the data monitoring committee will review to ensure that the separation from placebo is happening, that they're seeing this treatment effect at a minimum threshold that we think predicts the full study working. If that's the case, the data monitoring committee has instructions to select the dose and continue with the study remaining blinded, which gets us to that potentially pivotal data faster. I think the reason for doing that. You can -- those patients in the first portion out in the final analysis. So you're heading into a somewhat derisked like pivotal readout because you know the drug is working in some of those patients.

And how often do they monitor that?

So this is a onetime interim analysis to select the dose and move forward. The measure that's being looked at is the itch in patients in the second half of the study, in months 4, 5 and 6. If you look at itch over time, which helps reduce some of the variability in the endpoints and in a way, add power to the final analysis.

I see. Got it. So your VISTA -- VISTAS interim will be blinded. So what should we expect to hear? And what should we expect the study to continue as a blinded -- on a blinded basis?

That's the great outcome that we're hoping to see, and the announcement would be study continues as planned. That means that there is a separation from placebo that we think it's on track for a positive readout. And we'll also share some kind of guidance on time lines to complete enrollment so that we have a sense of time to pivotal data.

I see. Okay. Got it. And what should we expect from the interim analysis for VANTAGE?

So VANTAGE, quite different setting. Maybe I'll take a step back and talk a little bit about PBC as an indication first. Kind of a high-level summary numbers to think about it. PBC is probably about 100,000 patients in the U.S. and you divide that further into about 60,000 patients of that likely controlled with Urso (sic) [ UDCA ], and that's the standard first-line therapy and controlled on their biochemical endpoints, not their symptoms. So many of those patients while they aren't looking for some of the second-line treatment agents, they are having symptomatic burden in potentially progressive disease. In the second-line setting, it's about 40% of those patients. That's where the recently approved PPAR and potentially another one coming like OCA. That's the treatment setting where you hear a lot of discussion about new competitive entrants. Also an opportunity to treat pruritus in those patients as well. So they do have more treatment options to consider once the biochemical progression has started. The VANTAGE study is going after both settings. We're including first- and second-line patients. We have no baseline alkaline phosphatase criteria to provide something that physicians can use for any PBC patient that has symptomatic burden. That's the goal. That's the product profile that we're targeting. The interim analysis will look at the first kind of readout on those symptoms. So we're going to -- we'll share top line data on Itch, not powered for significance, but it's meant to be a dose selection analysis looking at the 2 doses of volixibat compared to placebo on Itch. We'll also look at bile acids and safety obviously.

I see. Got it. And then going back to the VISTAS program, I think you mentioned there's a threshold for stopping the study because you don't see the separation with placebo or the futility of the study. Is there a separate threshold where you do stop it because you see overwhelming effect as well? And how do you define that?

So the threshold is to unblind, not to stop the study. So if we don't meet that activity threshold, we'll unblind and look at the data. Yes, because there could be an opportunity to potentially adjust the study and let it roll into the confirmatory portion enriched in some other way. Because of our -- from our discussion with the FDA because of the safety database that they want, there's no automatic stopping criteria in the other direction. As we know we need to get to that approximately 120 number because of what FDA wants for the full safety data set. We didn't want to stop the study early for high activity.

I see. Got it. Okay. So why don't we talk about the commercial opportunity in PSC versus PBC. What's the burden of pruritus in these settings? And how do you view the market opportunity for both?

It's quite substantial. I mean it's the lead-in comment for it. Putting some numbers behind it. In PSC, we think there's about 30,000 patients in the U.S. is kind of a rough number to put on it. 1/3 of those patients will have pruritus as a part of their disease. So there will be some level of pruritus. And many of them can have quite severe impactful pruritus. But that 2/3 of the market is what we see as the target on-label population for PSC. And it's somewhat similar for PBC as well. Just the numbers are larger, right? So 100,000 patients in total and about 2/3 of them have pruritus. And it does seem to be somewhat consistent between the 2 settings, though there may be a bit of elevation and severity as you see disease progress. Pruritus is present in both first and second line at similar rates.

I see, okay. So how are you thinking about the regulatory time lines and potential filing? And also have you thought about pricing for these communications?

From a pricing standpoint, we look to the other PVC agents as kind of benchmarks, and we haven't shared anything on our pricing plan specifically. But you see other agents at $100,000 or higher per year per patient is what the benchmarks are that we'll look at. In terms of the regulatory time lines, for PSC, it's probably a year or so to complete enrollment. And so we'd have pivotal data in kind of 18 to 24 months from now is roughly where we think we're at. We'll give a refined view of that when we announce the interim update.

I see. And then going back to pricing a little bit. So you have LIVMARLI, which is also another IBAT inhibitor we talked about. How do you -- I mean, when you factor in pricing, do you also look at LIVMARLI or you just treat this as completely separate product?

They're totally independent products in their own indications. And you have to establish dosing in the clinical effect of that dosing in these different settings. Being that they're products that require prior authorization. And we don't -- we see them really largely being used only in the settings where they're approved as we bring additional the second IBAT to market.

I see. I think we mentioned before that LIVMARLI also there's some compassionate use in these 2 new indications as well. Do you -- like how do you factor that in? Is that going to continue? You think you're going to -- how would that dynamic change?

Yes. When we have an actually an indicated product for PSC, we'd expect that to be the product of choice for physicians. So the volixibat has the answer for PSC patients when it comes to market. So I will circle back to the compassionate use dynamic for LIVMARLI. We do see outreach on a growing number of different kind of less common cholestatic presentations, PSC being one of them. And that tends to be a couple of examples we have are patients who didn't meet eligibility criteria for the study and the physicians urgently looking for a treatment alternative. And the reports back are that there's quite dramatic responses in terms of drive this improvement. The quote I've heard recently is that they feel like they get their lives back because they can sleep again and can go out and get a job again, things like that. But we see it across other indications as well. So we're looking at ways that we could maybe build a program around some of these other indications just driven by the demand that's out there that we're seeing.

I see. Okay. So a lot of future, I guess, expansion with these products.

Yes, I think there's an opportunity to continue to develop into other cholestatic settings.

Fantastic. Okay. So why don't we switch gears? I think we only have about 10 minutes left, to your other 2 products that you recently acquired last year, which is CHENODAL and CHOLBAM. Remind us on the history of these 2 assets and the rationale behind acquiring them.

Yes. So CHENODAL and CHOLBAM are bile acid replacement products. So these are synthetically made bile acids to replace specific bile acid types in settings where there's been a genetic disruption in the ability to synthesize bile acids. So the settings, these are used are in are a number of quite rare different disruptions in that signaling cascade to synthesize new bile acids called bile acid synthesis disorders, Zellweger spectrum disorder, another one that's recently emerged with new data for CHOLBAM is Smith-Lemli-Opitz syndrome and CTX for CHENODAL. So quite a long list of different specific genetic -- genetically driven disruptions, but they all have a commonality where there's something disrupted in that bile acid synthesis cascade, the signaling goes haywire, and they tend to have toxic accumulation of intermediaries in that synthesis cascade. So these products have been generally standard of care for a number of these indications. CHOLBAM has been on the market for 8 or 9 years at this point used in a number of these indications. So with steady kind of patient accumulation over that time period. So it's a healthy business for an ultrarare setting like this. We do think there's a growth opportunity with this emerging data in Smith-Lemli-Opitz and so we're exploring more investigation around that. But we talk more about growth opportunity for the bile acid programs is with CHENODAL for CTX. And we're talking about that one for a moment because it's a quite unique regulatory background here, where CHENODAL's approved indication is for treatment of gallstones, but it's really -- it's entirely used today off label for CTX.

I see.

And we completed a Phase III study looking at CHENODAL in CTX with an eye towards getting a formal approval largely so we can go do more patient finding and also have exclusivity, orphan exclusivity for the program. The progression of CTX without treatment results in irreversible neurocognitive impact. And we think by finding and treating patients earlier, you can really have a dramatic impact on the course of that condition. But to date, it's been all passive because it's not labeled formally for the indication. So we think there's an opportunity to go out, find more patients. There's -- it's probably about 10% diagnosed. And so what we're doing now is to work on how can we go out and help support physicians who might be able to catch these patients early on when the symptoms are starting to build.

I see. And I think you guys are filing an NDA submission for that -- for CHENODAL or for CTX?

Correct. We just had a pre-NDA meeting with FDA that went well. There were a few nonclinical items to complete for that package. The discussion with the FDA went well, and so that submission is imminent.

I see. So if it's already being used in an off-label setting and I think the FDA recognizes it, why do you need to get that sNDA? Why not just you already -- it's already being used in the market? I mean how -- like what would that do for you from a commercial perspective?

Two reasons why there's a lot of value in pursuing an NDA here. The first is in patient finding, like you can help really change the course of disease for these patients that don't get diagnosed until they're in their 30s or 40s. And that's the average age of diagnosis today. And while CHENODAL is standard of care for patients who are diagnosed. Most patients are not diagnosed. So that's where the real opportunity is and to be able to be active promoting given the reason why physicians should be looking for these patients is why we think it's worth getting the formal approval. The second reason to point to is exclusivity. So CHENODAL has orphan designation for CTX. So we'd be able to have orphan exclusivity for the indication.

I see. That make sense. Okay. How has the commercial transition been since you guys acquired them? And why do you guys think that you guys are better parent for these 2 drugs?

Yes. First of all, I'd say I think Travere did a great job with them. The -- so I wouldn't use the word better, but I do think they're a great fit with us. And that has resulted in a very smooth transition to bring them in. They -- there's a lot of overlap in the prescriber base. We actually have an overlap in a lot of the vendors that support distribution. So that's all gone quite smoothly. And we've seen that play out in just really in the numbers, right, in terms of what we've seen for patient starts compliance, the persistence has all remained steady and healthy through the transition.

I see, got it. We have 5 minutes left. So if the audience have any questions, please raise your hand and we'll get to you. Okay. So why don't we continue on -- talk a little bit about high-level strategy and BD. Maybe give us a state of the affairs of your financial position? And how are you thinking about profitability going forward?

So the overall financial position of Mirum is quite strong. We're -- with that $310 million to $320 million of revenue that we're tracking for this year, that puts us in a position where on kind of an operating cash flow basis into the back half of the year. We're at breakeven or better is the direction that it points towards really strong financial position with over $300 million cash on hand as well. And this kind of self-sustaining growing commercial business. So very solid and attractive footing from a financial standpoint. And that speaks to the efficiency of the business. And as we brought in the bile acid programs that synergy and overlap on the commercial platform has played out well. In terms of the overall strategy going forward, we look to do more of the same in terms of what made Mirum possible from the beginning in finding these overlooked rare disease opportunities where we can add value and might help get them across the finish line to patients.

I see. Got it. And maybe speak a little bit about your tick on BD in terms of you guys acquired these 2 assets. How should we think about your strategy from a BD versus organic growth?

For that, we start with looking at first, where have we been effective at, what are our strengths that we can then apply to future products. And really across the rare pediatric spectrum, there's a lot of places where I think we could add value, particularly with the now expanded business, and we have a presence in almost all major pediatric have direct interactions across not only medical genetics will further cement that and expand path across other pediatric rare settings where the Mirum team could bring a lot. Also on the clinical regulatory side, the regulatory strategies for ultrarare are that's a skill set that we've developed inside the company.

I see. I have a blue sky question for you. So what's the long-term aspiration for Mirum? And what would the company look like in 10 years from now?

When I've answered that question before, just to give the shortcut here, most people say, "Oh, you want to be the next horizon, which I think that's a fair way to think about it. We see ability to leverage commercial expertise and late-stage clinical expertise to find programs that we can build value from and have both a dynamic growing healthy commercial business, but also adding clinical programs that can be really value creating over...

In about partnerships, commercial partnerships based on some of these interim readouts you are coming up?

Today, there's been no need. I mean Mirum's been able to build out efficiently directly in the U.S., Canada and Western Europe. We'll leverage that as volixibat comes across the finish line and for other rare pediatric programs would already fit with our team. So we're in a position where we can retain all the value from these programs rather than needing to partner. And that's been by design for the type of products that we've pulled together here. They're ones that we wanted to be able to keep all of the value in Mirum.

Fantastic. I think we're running out of time. So I'll leave it to you, Chris, for the final remarks.

Well, I just want to say thanks again for hosting and exciting time at Mirum heading towards a $310 million to $320 million with 3 growing commercial products. And look forward to an update soon on the volixibat interims where we take those into the next leg of their journey.

Right. Fantastic. Thank you so much again, and thanks, everyone.