Good afternoon, and welcome to Mirum Pharmaceuticals, Inc. Fourth Quarter and Full Year 2025 Conference Call. My name is Elliot, and I will be your operator today. All lines are currently in listen-only mode. There will be an opportunity for Q&A after management's prepared remarks. I would 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 would like to welcome you to Mirum Pharmaceuticals, Inc.'s fourth quarter and full year 2025 Conference Call. I am joined today by our Chief Executive Officer, Chris Peetz, our Chief Medical Officer, Joanne M. Quan, and Eric H. Bjerkholt, our Chief Financial Officer. Peter Radovich, our President and Chief Operating Officer, is unable to join us today as he is attending an international commercial event. Earlier this afternoon, Mirum Pharmaceuticals, Inc. 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 would 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 Mirum Pharmaceuticals, Inc.'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 risk factors in our latest Form 10-Ks and subsequent SEC filings for more information about these risks and uncertainties. With that said, I would 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 positioning us for a pivotal 2026. On today's call, we will 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 U.S., $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 Cholbam for CTX, a tablet formulation of Livmarli, and enrollment completion of the VISTA study of volixibat in PSC. We also meaningfully expanded our pipeline with the addition of the Phase III brolobitug 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 have welcomed a team that shares our focus on disciplined execution and delivering high-impact medicines for patients with rare disease. With the addition of brolobitug, 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 VISTA study in…

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, enrollment across all our clinical studies is on track or ahead of previously communicated timelines. Today, I will focus on two of our near-term data readouts for volixibat in PSC, and brolobitug in hepatitis delta. Starting with volixibat in PSC, we are on track to report top-line data from the VISTA study in 2026. The primary endpoint, as aligned with FDA, is pruritus. Safety, change in serum bile acids, 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 the selected 20 mg 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 brolobitug for hepatitis delta, I am pleased to report that all four AZURE clinical studies are progressing well. In the AZURE program, brolobitug 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 two Phase III studies that will form the basis of our FDA registration package, are expected to complete enrollment 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 on the Phase IIb portion of the AZURE-1 study. This study is evaluating hepatitis delta treatment-naive patients randomized to brolobitug or delayed treatment using a 24-week composite endpoint of virologic response and ALT normalization, an 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 enroll an additional 150 patients for the Phase II/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 brolobitug 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 MRN-3,379, 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 are on schedule and expect to report data from this study in 2027. Overall, we are very pleased with the continued progress across our pipeline and look forward to several important updates over the coming year. With that, I turn the call over to Eric to review our financial results.

Thanks, John, and good afternoon, everyone. 2025 was the 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 $330 million the year before, representing 55% year-over-year growth. Total operating expense for the quarter and year ended 12/31/2025 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 non-cash stock-based compensation, intangible amortization, and other non-cash expenses of $95 million. The intangible amortization and other non-cash 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 brolobitug 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 will now turn the call back to Chris for closing remarks.

Thanks, Eric. To close, Mirum Pharmaceuticals, Inc. enters 2026 in a great position. Our commercial business has continued momentum, and our financial position is strong. Our pipeline has four potentially pivotal readouts in the next 18 months, each representing the potential to bring standard-of-care-changing medicines to difficult treatment settings. It is inspiring to work with a team that can achieve this level of impact for patients. It is 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.

Thank you. Star followed by one on your telephone keypad. When preparing to ask your question, please ensure your device is unmuted locally. The first question comes from James Condulis with Stifel. Your line is open. Please go ahead.

Hey, thanks for taking my question, and congrats on all the progress. I actually wanted to ask one on volixibat, and specifically as it relates to the commercial opportunity. You know, obviously, volixibat is coming first and I think generally a lot of people are thinking about pricing in the context of the PPARs in terms of the PBC opportunity, and just curious as you guys are getting closer to data and potentially commercialization, kind of how you are thinking about the right way to price volixibat and if, you know, pricing specifically around the PSC opportunity is kind of on the table or makes sense. Thanks so much.

Yeah. Thanks, James, for the question. This obviously is something we spend a lot of time thinking about. And kind of as you are saying in your question there, the PPARs in PBC really are a good planning benchmark to think about, but that is not certainly our final guidance or decision on it. We will 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, you know, we will take that decision when we are at launch.

We now turn to Joseph Tom with TD Cowen. Your line is open. Please go ahead.

Hi there. Good afternoon, and thank you for taking my question. Maybe one on the upcoming PSC trial. Our KOLs are hinting that maybe the itch associated with PSC patients can be a little bit more episodic. Maybe do you see that as providing a little bit more risk into this study relative to what you are seeing in PBC? And maybe what have you done in the study, whether in terms of the patients that you are enrolling or monitoring, do you think that can maybe help limit any variability there? Thank you.

Yeah, thanks for the question there. A couple things to comment on. I will lead in, and I will let Joanne speak a little bit to some of the study design elements. What we find in market research that is 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 will let Joanne speak to some of the things that we have seen from screening and the overall operational side.

Yeah. Thanks for the question. A couple things. Actually, we know that pruritus is an issue for a lot of patients, and this is really from some work that we did with, you know, Chris Cowley a few years back presented at EASL that a really high proportion of patients do complain of pruritus, and fatigue is one of the main symptoms associated with their PSC. And then perhaps about half of them said that it has disrupted their daily life activities. So pretty significant. Within the study, we are enrolling patients with persistent pruritus, and so we are careful to have that as eligibility, and therefore, we track the pruritus response throughout the study. So I understand the basis for your question, but I think between study design and also understanding the patient population a bit better, we feel comfortable that this is really designed to address a significant symptom for patients with significant impact in terms of their daily lives.

We now turn to Joe Kim with RBC Capital Markets. Your line is open. Please go ahead.

Everyone, thanks for taking my question. I wanted to dig more into the study design for PSC. If you could highlight some of the key similarities and differences between VISTA and the VANTAGE study designs. And you mentioned that you expect to enroll 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. Thank you.

Yes. Thanks for the question. I think the commonality is that we are 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 therefore cholestatic pruritus. So there is a lot of commonality in terms of how we implement it within the 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, clearly within the range of moderate to severe pruritus for baseline. So I think that is our expectation. We are selecting patients with moderate to severe pruritus at baseline to study in both of these studies.

We now turn to John Wolleben with Citizens. Your line is open. Please go ahead.

Hey. Thanks for taking the question. 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 will need and what that means for timing of a potential NDA submission?

Yeah. I can weigh in on this one. Thanks for the question, John. You know, a lot of this goes back to some of the original pre-IND interactions we have had with FDA. We have subsequently actually confirmed some of the safety database 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 we do expect that the current VISTA PSC study has the sufficient safety database for the setting. So the idea is after our top-line data, we will have an interaction with FDA on the submission plan. And I think that we will track to get it submitted in the second half of the year.

Great. Thanks, Chris.

Thanks for the question.

We now turn to Ryan Deschner with Raymond James. Your line is open. Please go ahead.

A lot. Congrats on a big year. Looking forward to a busy cadence of catalysts this year. For the EXPAND readout coming later in April this year, are you expecting to break out the data on pruritus and other secondary endpoints by indication? And how are you looking at the pruritus bar in general compared to what was shown in PFIC and Alagille?

Yeah, the overall mix of patients in the study, just as a reminder, we think it is probably ultimately going to end up being approximately half biliary atresia and then a much longer tail of other settings. So we will look at whatever the most relevant ways are to break it out. Biliary atresia is an obvious one. The others are just much smaller, each of them individually. But I would come back to the comment that Joanne was making earlier just on the commonality here being that these are settings with elevated bile acids and cholestatic pruritus. So we see the treatment objectives and the potential for response that we have seen in compassionate use examples as having more in common than different across various settings.

We now turn to Mani Foroohar with Leerink Partners. Your line is open. Please go ahead.

Hey guys, you have Ryan on for Mani. Thanks for taking our question and congrats on the quarter. Maybe just sticking with the EXPAND, Chris, I am curious how you think a positive read here kind of plays out in terms of the label expansion given it is more of a basket trial. And when we think about biliary atresia and the other indications, how well diagnosed are these, or is this going to be more of a PFIC setting where you are going to have to improve diagnoses to really drive that additional growth?

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

Yeah. Just when you think about these additional settings, how well diagnosed are these, or do you think it is going to really take a lot of hand-holding and physician education to drive further uptake in these additional settings?

Thanks for that. Yeah, actually, we think that, in particular in the pediatric settings, it is highly symptomatic, so it is diagnosed. And that is really what the origin for the study was: compassionate use requests. So you see the demand is out there for something to help these patients. So I do see it as a pretty well-tracked patient population.

We now turn to Charles Wallace with H.C. Wainwright. Your line is open. Please go ahead.

Hi. Thanks for taking my question. 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. I was wondering if you could provide some color on how much of this is driven by Livmarli versus the bile acid portfolio. Thank you.

Yeah, 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 is more kind of steady growth, not accelerating the way the Livmarli growth has been in the last few years.

We now turn to Brian Skorney with Baird. Your line is open. Please go ahead.

Hey, guys. Thanks for taking the question. Congrats on a great quarter and year. I just wanted to revisit the EXPAND study. Are there any learnings that you have taken away from EMBARK that you are 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.

Thanks for the question. And that is an important distinction from EMBARK actually to point out. As a reminder, the EMBARK study was looking at bilirubin levels in biliary atresia immediately after the Kasai procedure. So think of that as 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 the Kasai procedure that the surgical procedure directed at bile flow actually is most determinative of outcome in those young patients. Now what is different in EXPAND and in the biliary atresia patients in 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 the biliary atresia patients that are enrolling into EXPAND are going to be, think of those toddler to school-aged, that have a persistent post-Kasai cholestatic pruritus. So from the learnings there, it comes back to what we saw in compassionate use: there are examples of patients being highly responsive to Livmarli treatment with that profile. So that is what inspired us to pursue the study, 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 is hard to use traditional epidemiology, so you cannot look at literature or incidence rates, so to speak, because this is a long list of different potential causes of cholestatic pruritus. From the work we have done in the pediatric setting, it is clear that there are readily at least 500 patients in the U.S. that would fit the profile of this, with potential for more. When we look at the total peak Livmarli potential of that billion-plus that we see as the long-term potential for the brand, EXPAND could represent a third of that overall.

We now turn to Mike Ulz with Morgan Stanley. Your line is open. Please go ahead.

Hi, this is Rohit on for Mike. Thanks for taking our questions. 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? Thanks.

Yes, I will 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 nothing specifically labeled in the U.S., and then one labeled medicine, Hepcludex, in Europe that actually has been performing well. We do expect that to evolve in the U.S. given Hepcludex is up for review and potential approval in the U.S., and then also another dual-agent regimen looking at an HBsAg and siRNA approach in hepatitis delta. So this will be an evolving landscape. But what got us excited about brolobitug as a potential for best-in-class profile is that with a single agent, you are seeing really impressive response rates and a very attractive safety profile. A 100% virologic response at week 48, you know, that is 65–82% composite endpoint, has a chance to really set the bar for treatment options in delta. So we do expect to have other competitive agents in the market. Just excited about what brolobitug can do compared to those. Pass over to Eric on the P&L.

Thanks, Chris. So the good news is the brolobitug 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 brolobitug we anticipate roughly a $150 million increase in R&D spend tied to this program, with about half being CMC.

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

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

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