Mirum Pharmaceuticals Inc (MIRM) 2025 Q4 法說會逐字稿

Good afternoon, and welcome to Mirum Pharmaceuticals fourth-quarter and full year 2025 conference call. My name is Elliot, and I'll be your operator today.

(Operator Instructions)

I'd now like to hand the conference over to Andrew McKibben, SVP of Strategic Finance, and Investor Relations. Please go ahead.

Thank you, Elliot, and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals fourth-quarter and full year 2025 conference call. I'm joined today by our Chief Executive Officer, Chris Peetz; our Chief Medical Officer, Joanne Quan; and Eric Bjerkholt, our Chief Financial Officer. Peter Radovich, our President and Chief Operating Officer, is unable to join us today as he is attending international commercial event.

Earlier this afternoon, Mirum issued a press release reporting our fourth-quarter and full year 2025 financial results. Copies of the press release and our SEC filings are available in the Investors section of our website. Before we start, I'd like to remind you that during the course of this conference call, we will be making certain forward-looking statements based on management's current expectations, including statements regarding Mirium's programs and market opportunities for its approved medicines and product candidates and financial guidance.

These statements represent our judgment and knowledge of events as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from the results discussed. We are under no duty to update these statements. Please refer to the risk factors in our latest Form 10-K and the subsequent SEC filings for more information about these risks and uncertainties.

With that said, I'd like to turn the call over to Chris. Chris?

Thanks, Andrew, and good afternoon, everyone. 2025 was a year of disciplined execution and growth for Mirium, positioning us for a pivotal 2026. On today's call, we'll recap some of the headlines we announced in January and open the call for questions.

In 2025, we delivered $521 million in net product sales, exceeding the upper end of our guidance range. This was made up of LIVMARLI net product sales of $245 million in the US, $115 million internationally with our bile acid medicines also contributing $161 million. The strong finish was driven in particular by our continued leadership in Alagille syndrome accelerating PFIC uptake and growing demand in our international markets.

Building on this performance, we are entering 2026 with confidence and expect to deliver net product sales of $630 million to $650 million for the year. Beyond commercial performance, we advanced our pipeline through important clinical and regulatory milestones, including the approval of CTEXLI for CTX and a tablet formulation of LIVMARLI and enrolment completion of the VISTAS study of Volixibat in PSC.

We also meaningfully expanded our pipeline with the addition of the Phase III Brelovitug program for chronic hepatitis delta virus, a serious rare disease with limited treatment options. This addition to the portfolio is an excellent fit with our team and the upcoming potential Volixibat launch, creating substantial operating leverage.

Since the closing of the transaction earlier this year, integration has progressed smoothly, and we've welcomed a team that shares our focus on disciplined execution and delivering high-impact medicines for patients with rare disease. With the addition of Brelovitug, we now have four potentially registrational clinical readouts expected over the next 18 months in areas of significant unmet need.

Beginning in the second-quarter, we expect to report top line data from the Volixibat VISTAS in PSC as well as interim results from the AZURE-1 study of Brelovitug in hepatitis delta. The broader Azure Phase III program continues to enrol well, and we expect full top line results from both AZURE-1 and AZURE-4 Phase III trials in the second half of the year.

We're also seeing continued momentum across our other LIVMARLI and Volixibat programs, enrolment in the Phase III EXPAND study in additional rare cholestatic conditions as well as the VANTAGE study in PBC continues to exceed expectations, and we expect to report top line results from EXPAND in the fourth-quarter of this year and from VANTAGE in the first half of next. And finally, the BLOOM Phase II study of MRM-3379 in Fragile X syndrome is also on track for data next year.

Taken together, Mirum is entering a pivotal phase of growth as a leading rare disease company with multiple commercial medicines and several near-term potentially registrational readouts. Our team's strength continues to be its dedication to understanding patient needs and translating that into important medicines. Through this team's insight and hard work, we have now built a portfolio with over $4 billion in potential revenue.

And with that, I'll turn it over to Joanne to walk through our pipeline in greater detail. Joanne?

Thanks, Chris. 2025 was an important year for our pipeline, and 2026 will be even more significant as multiple programs approach potentially registrational readouts. As Chris mentioned, enrolment across all our clinical studies is on track or ahead of previously communicated timelines.

Today, I'll focus on two of our near-term data readouts for Volixibat in PSC and Brelovitug in hepatitis delta. Starting with Volixibat in PSC, we are on track to report top line data from the VISTAS study in the second-quarter of 2026. The primary endpoint, as aligned with FDA is pruritus. Safety, change in serum bile acids and other symptoms and quality of life measures will also be evaluated.

As a reminder, the study exceeded a prespecified threshold for efficacy at the blinded interim analysis in 2024 and has proceeded with a selected 20-milligram twice-daily dose. Collectively, the prior clinical data of IBAT inhibitors in PSC and the consistent treatment effects seen across other cholestatic diseases, including PBC, all support IBAT inhibition as a meaningful therapeutic approach in PSC, a disease with no approved therapies. We look forward to sharing the top line results from this study in the coming months.

Turning to Brelovitug for hepatitis delta, I'm pleased to report that all four AZURE clinical studies are progressing well. In the AZURE program, Brelovitug is being studied as a single agent regimen in a broad group of patients with elevated ALT at baseline. AZURE-1 and AZURE-4 the 2 Phase III studies that will form the basis of our FDA registration package are expected to complete enrolment soon with 24-week top line data anticipated in the second half of the year.

In the second-quarter, we expect to report interim results from the Phase IIb portion of the AZURE-1 study. This study is evaluating hepatitis delta treatment-naive patients, randomized to Brelovitug or delayed treatment using a 24-week composite endpoint of virologic response and ALT normalization and endpoint aligned with FDA.

The Phase IIb portion of the study will include the first 50 patients evaluated at the week 24 time point. The study is continuing to enrol an additional 150 patients for the Phase III portion, which has the same study design and endpoints. The AZURE-2 and AZURE-3 studies are enrolling well. These are active controlled studies evaluating Brelovitug in the context of bulevirtide and are designed to support European registration as well as provide additional long-term safety and efficacy data.

Finally, for MRM-3379, our BLOOM Phase II study in Fragile X syndrome is off to an excellent start. The program recently received Fast Track designation from the FDA, recognizing its potential to address a serious unmet need. We're on schedule and expect to report data from this study in 2027.

Overall, we're very pleased with the continued progress across our pipeline and look forward to several important updates over the coming year.

With that, I'll turn the call over to Eric to review our financial results.

Thanks, Joanne, and good afternoon, everyone. 2025 was a year of accelerating financial performance driven by growth across our three commercial medicines. Total net product sales in the fourth-quarter of 2025 was $149 million compared to $99 million the year before. For the full year 2025, total net product sales was $521 million compared to $336 million the year before, representing 55% year-over-year growth.

Total operating expense for the quarter and year ended December 31, 2025, was $153 million and $543 million, respectively. Full year operating expense includes R&D expense of $186 million, SG&A expense of $257 million and cost of sales of $100 million. Expenses for the year included noncash stock-based compensation, intangible amortization, and other noncash expenses of $95 million. The intangible amortization and other noncash item expenses of $24 million are reflected in our cost of sales.

The Commercial cash contribution margin in 2025 was approximately 55%, a significant increase from the prior year. We ended 2025 with $391 million in cash, cash equivalents, and investments, up from $293 million at the end of 2024, reflecting our solid operating performance. In addition, we recently completed two private placements concurrent with the closing of the Bluejay acquisition, generating aggregate gross proceeds of $268.5 million effectively covering the cash outlay to support the acquisition. In 2025, we achieved positive cash flow from operations.

Looking ahead, we expect R&D expense to increase in 2026 driven primarily by investments in the Brelovitug clinical program and manufacturing validation and scale-up in preparation for the anticipated BLA submission next year. This increase in R&D spend is fully funded. We expect a return to positive cash flow in 2027. We have scaled the business while maintaining spending discipline and a strong balance sheet positioning us to advance our pipeline without compromising financial strength.

I'll now turn the call back to Chris for closing remarks.

Thanks, Eric. To close, Mirium enters 2026 in a great position. Our commercial business has continued momentum and our financial position is strong. Our pipeline has 4 potentially pivotal readouts in the next 18 months, each representing the potential to bring standard of care changing medicines to difficult treatment settings. It's inspiring to work with the team that can achieve this level of impact for patients, and it's going to be a very busy year.

We look forward to several updates as we go. And with that, operator, please open the call for questions.

(Operator Instructions)

James Condulis, Stifel.

Congrats on all the progress. I actually wanted to ask one on Volixibat and specifically as it relates to the commercial opportunity. Obviously, Volixibat is coming first and I think generally, a lot of people are thinking about pricing in the context of Volixibat around the PPARs in terms of the PBC opportunity. I'm just curious as you guys are getting closer to data and potentially commercialization kind of how you're thinking about the right way to price Volixibat? And if pricing specifically around the PSC opportunity is kind of on the table or it makes sense.

Thanks, James, for the question. This obviously is something we spent a lot of time thinking about. And kind of as you're saying in your question there, the PPARs in PBC really are good planning benchmark to think about, but that's not -- certainly not our final guidance or decision on it. We'll take that as we have data in hand and are closer to launch to make the final decision. And one of the big factors to keep in mind here is that unlike in PBC, there are no other approved medicines. So really unique positioning for Volixibat, but we'll take that decision when we're at launch.

Joseph Thome, TD Cowen.

Maybe one on the upcoming PSC trial. Are KOLs are hinting that maybe the itch associated with in PSC patients can be a little bit more episodic. Maybe do you see that as providing a little bit more risk into the study versus what you're seeing in PBC? And maybe what have you done in the study, whether in terms of the patients that you're enrolling or monitoring, do you think that can maybe help limit any variability there?

Yes. Thanks for the question there. A couple of things to comment on. I'll lead in and I'll let Joanne speak a little bit to the -- some of the study design elements. And what we find in market research that's more directed at patients and some of the advanced practitioners that maybe spend more time with patients is a different perspective on pruritus than what you get from some of the top KOLs who may actually just be seeing the patient episodically when there are other more complicated factors.

And in conversations with patients and some of the advanced practitioners, you do get a different picture of how persistent the pruritus can be and also just the proportion of patients that are actually dealing with it being quite different than might be the perspective of a KOL at a top center. But then on study design, I'll let Joanne speak to some of the things that we've seen from screening and the overall operational side.

Thanks for the question. A couple of things. Actually, we know that pruritus is an issue for a lot of patients. And then this is really from some work that we did with Chris Kowdley, a few years back presented at EASL that a really high proportion of patients do complain of pruritus and fatigue as the main symptoms associated with their PSC. And then perhaps about half of them said that it's disrupted their daily life activities. So pretty significant.

Within the study, we are enrolling patients with persistent pruritus. And so we're careful to have that as eligibility and therefore, we track the pruritus response throughout the city. So I understand kind of the basis for your question, but I think between study design and also understanding the patient population will be better. We feel comfortable that this is really designed to address a significant symptom for patients with a significant impact in terms of their day with lives.

Kim, RBC Capital Markets.

I wanted to dig more into the study design for PSC. If you could highlight some of the key similarities and differences between VISTAS and the VANTAGE study designs. And you mentioned that you expect to enrol patients with persistent pruritus, but just wondering whether we should expect the baseline pruritus scores for the PSC study to be in a similar range to what we saw in the PBC interim data.

Yes. So thanks for the question. So I think the commonality is that we're really studying cholestatic pruritus which is something that we know well and have characterized with the other indications that we have for maralixibat for instance. So we know how to measure this. We know how to implement that within a clinical trial. PSC and PBC are different diseases in terms of the etiology. But we think the commonality here is the fact that there is cholestasis, intrahepatic cholestasis and then, therefore, cholestatic pruritus.

So there's a lot of commonality in terms of how we implement it within trial. I think probably the best guide in terms of what the baseline pruritus is, is if you look at the PBC interim and that shows significant pruritus, I mean, with -- clearly, within the range of moderate-to-severe pruritus for baseline. So I think that's kind of our expectation. We're selecting patients with moderate-to-severe pruritus at baseline to study in both of these studies.

Jon Wolleben, Citizens.

Piggybacking on the PSC questions. Can you talk a little bit about your interactions with FDA around safety database requirements for Volixibat and what follow-up you'll need and what that means for timing of a potential NDA submission?

Yes. I can jump in on thanks for the question, John. A lot of this kind of goes back to some of the original pre-IND interactions we've had with FDA. And we've subsequently actually confirmed some of the safety database questions with them, in particular, around PBC in terms of what they want for overall safety database and with acknowledgment that PSC is smaller. And so what we do expect that the current VISTAS PSC study has the sufficient safety database for the setting.

So the idea is after our top line data, we'll have an interaction with FDA on the submission plan and think that we'll track to get it submitted in the second half of the year.

Ryan Deschner, Raymond James.

Congrats on a big year, looking forward to a busy cadence of catalysts this year. For the EXPAND readout coming later in 4Q this year, how are you -- are you expecting to break out the data on pruritus by and other secondaries by indication? And are you looking at the pruritus bar here? How are you looking at the pruritus bar in general compared to what was shown in PFIC and Alagille?

Yes. I mean the -- overall, there's the mix of patients in the study, just as a reminder, we think it's probably ultimately going to end up being approximately half biliary atresia and then a much longer tail of other settings. So we'll look at whatever the most relevant ways to break it out. Our biliary atresia is an obvious one. The others are just much smaller each of them individually.

But I'd come back to the comment that Joanne was making earlier, just on the commonality here being these are settings with elevated bile acids and cholestatic pruritus. So we see kind of the treatment objectives and the potential for response that we've seen in compassionate use examples having more uncommon than different across various settings.

Mani Foroohar, Leerink Partners.

You have Ryan on for Mani. Maybe just sticking with EXPAND, Chris, I'm curious, how you think a positive readout here kind of plays out in terms of like the label expansion, given it's more of a basket trial. And when we think about biliary atresia and the other indications, like how well diagnosed are these? Or is this going to be more of a PFIC setting where you're going to have to improve diagnosis to really drive that additional growth?

Thanks for the question, Ryan. The thinking around label -- indication statement in the label, as you point out, it has some nuance because it's a basket. It's really defined by exclusion, right? I mean we're -- the way that the protocol is written as it excludes the larger settings where you could run a stand-alone study to look at cholestatic pruritus in PSC, for example, as we're doing with Volixibat. So expect that to be reflected in the labelling. And could you please remind me of the second part of your question?

Yes. Just kind of like when you think about these additional settings, like how well diagnosed are these? Or do you think it's going to really take a lot of handholding and physician education to drive further uptake in these additional settings?

Yes. Actually, we think that -- I mean, what we're seeing, in particular in the pediatric settings is it's highly symptomatic. So it is diagnosed. And that's really what the origin for the study was a compassionate use request. So we see the demand is out there for something to help these patients. So I do see it as a pretty well tracked patient population.

(Operator Instructions)

Charles Wallace, HC Wainwright.

This is Charles on for RK. So I guess a question on the guidance for me. So in 2025, the sales grew about 55% and the guidance range implies a 21% to 25% annual growth, so I was wondering if you could provide some color on how much of this is driven by LIVMARLI versus the bile acid portfolio.

Yes. I mean the growth is definitely more LIVMARLI driven, Keep in mind, though, that for Japan last year, we had $22 million in revenues, which was inventory buildup. And this year, we expect, therefore, lower revenues from Japan, although I should clarify that the launch in Japan is going as expected. In terms of the bile acid portfolio, we do expect continued growth, but it's more kind of steady growth, not accelerating the way the LIVMARLI growth has been in the last few years.

Brian Skorney, Baird.

Congrats on a great quarter and year. I just wanted to revisit the EXPAND study. Are there any learnings that you've taken away from EMBARK that you're going to be applying here based on the high proportion of biliary atresia patients. And could you just kind of help us contextualize the market represented by the expand basket relative to PFIC and ALGS in terms of size as well as the dose you anticipate using in this population?

Thanks for the question. It's an important distinction from EMBARK actually to point out. As a reminder, the EMBARK study was looking at bilirubin levels in biliary atresia patients immediately after the Kasai procedure. So think of that as it's just a very acute setting where the goal would be to try to improve the immediate transplant rates. What we learned is in that very young infant setting after Kasai procedure, the surgical procedure directed at bile flow actually is most determinative of outcome in that -- in those young patients.

Now what's different in EXPAND and in the biliary atresia patients and EXPAND is those are all patients that had a successful Kasai, and then over time, they have what seems to be just a much slower progressing or persistent cholestasis that is not the kind of acute transplant driving situation you see in the very young patients. So those -- the biliary atresia patients that are enrolling into EXPAND are going to be think of as toddler to school age that have a persistent post-Kasai cholestatic pruritus.

So from the learnings there, it really comes back to what we saw in compassionate use is that there are examples of patients being highly responsive to LIVMARLI treatment with that profile. So that's kind of what inspired us to pursue the study is seeing actual strong treatment responses in those older biliary atresia patients.

And in terms of bridging that to market size, because this is a basket, it's hard to -- you can't use traditional epidemiology, so you can't look at literature incidence rates, so to speak, because this is a long list of different potential causes of cholestatic pruritus.

From the work we've done in the pediatric setting, it's clear that there's readily at least 500 patients in the US that would fit the profile of this and potential for more. When we look at kind of the total peak LIVMARLI potential of that $1 billion plus that we see as the long-term potential for the brand, EXPAND could represent a third of that overall.

Mike Ulz, Morgan Stanley.

This is Rohit on for Mike. Can you just talk about the current market for HDV and how you expect it to develop over the coming years? And then how much do you expect R&D to increase this year from the HDV studies?

Yes. I'll speak to the market and then pass it over to Eric to comment on the investment side. For the current treatment landscape for HDV, there really is -- there is nothing specifically labelled in the US. And the one labelled medicine Hepcludex in Europe that actually has been performing well. We do expect that to evolve in the US given from what we're seeing is that Hepcludex is up for review and potential approval in the US and then also another dual agent regimen looking at HB surface antigen and sRNA approach in hepatitis delta. So this will be an evolving landscape. But what got us excited about Brelovitug as a potential for best-in-class profile is that with a single agent, you're seeing really impressive response rates and a very attractive safety profile.

It's 100% viral response at week 48, and that 65% to 82% composite end point has a chance to really set the bar for treatment options in delta. Though there will be -- we do expect to have other competitive agents in the market. I'm just excited about what Brelovitug can do compared to those. Pass over to Eric on the P&L.

Thanks, Peetz. So the good news is that Brelovitug four Phase III studies are enrolling really well, which means that the expenses will be somewhat compressed into this year. It also means we need to make significant CMC investments to prepare for a filing next year. So they are compressed and in total related to Brelovitug, we anticipate roughly $150 million increase in R&D spend tied to this program with about half being CMC.

This concludes our Q&A. I'll now hand back to Chris Peetz, CEO, for any final remarks.

Great. Thank you all for joining today. We're really excited about the year ahead, and I hope everybody has a great afternoon.

Ladies and gentlemen, today's call has now concluded. We'd like to thank you for your participation. You may now disconnect your lines.