Mirum Pharmaceuticals, Inc. Q4 FY2025 Earnings Call

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 PSC as well as interim results from the AZURE-1 study of brolobitug in hepatitis delta. The broader AZURE Phase III program continues to enroll 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 are also seeing continued momentum across our other Livmarli and volixibat programs. Enrollment in the Phase III EXPAND study in additional rare cholestatic conditions, as well as the VANTAGE study in PBC, continues to exceed expectations. 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 year. And finally, the BLOOM Phase II study of MRN-3,379 in Fragile X syndrome is also on track for data next year. Taken together, Mirum Pharmaceuticals, Inc. 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 medicine. 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 will 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, 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, Andrew, 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. As 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, I'm just curious as you guys are getting closer to data and potentially commercialization, how you are thinking about the right way to price volixibat and if pricing specifically around the PSC opportunity is on the table or makes sense. Thanks so much.

Thanks, James, for the question. This is something we spend a lot of time thinking about. The PPARs in PBC are a good planning benchmark to consider, but that is not our final guidance or decision. We will take that decision when we have data in hand and are closer to launch. One of the big factors to keep in mind is that unlike in PBC, there are no other approved medicines in PSC, so volixibat would have a unique positioning. We will take the final pricing 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. Do you see that as providing more risk to this study relative to what you are seeing in PBC? And what have you done in the study, whether in terms of the patients you are enrolling or monitoring, to help limit variability? Thank you.

Thanks for the question. A couple things to comment on. I will lead in, and I will let Joanne speak to study design elements. What we find in market research directed at patients and some advanced practitioners is a different perspective on pruritus than what you get from some KOLs who may see patients episodically when there are other complicated factors. In conversations with patients and advanced practitioners, you get a different picture of how persistent pruritus can be and the proportion of patients dealing with it, which can be quite different than the perspective of a KOL at a top center. I will let Joanne speak to what we have seen from screening and the overall operational side.

Thanks for the question. A couple things. We know that pruritus is an issue for a lot of patients, based on work presented at EASL that a large proportion of patients report pruritus, and fatigue is one of the main symptoms associated with their PSC. About half of patients said that pruritus has disrupted their daily life activities, so it is a significant issue. Within the study, we are enrolling patients with persistent pruritus, and we are careful to have that as an eligibility criterion, and therefore we track the pruritus response throughout the study. So I understand the basis for your question, but between study design and understanding the patient population better, we feel comfortable that this is designed to address a significant symptom for patients with substantial impact on 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. You mentioned that you expect to enroll patients with persistent pruritus, but should we expect baseline pruritus scores for the PSC study to be in a similar range to what we saw in the PBC interim data?

Thanks for the question. The commonality is that we are studying cholestatic pruritus, which we have characterized with other indications such as maralixibat. We know how to measure this and implement it in a clinical trial. PSC and PBC are different diseases in etiology, but the commonality is intrahepatic cholestasis and cholestatic pruritus. There is a lot of commonality in how we implement it within the trial. If you look at the PBC interim data, that shows significant pruritus, clearly in the range of moderate to severe at baseline, and that is our expectation. We are selecting patients with moderate to severe pruritus at baseline for both 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?

Thanks for the question, John. Much of this goes back to original pre-IND interactions with FDA. We have subsequently confirmed some of the safety database expectations with them, particularly around PBC, in terms of overall safety database, and with acknowledgment that PSC is a smaller setting. We do expect the current VISTA PSC study to provide a sufficient safety database for that setting. After our top-line data, we will have an interaction with FDA on the submission plan, and we expect to pursue a submission 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.

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?

The overall mix of patients in the study is likely to be approximately half biliary atresia with a longer tail of other settings. We will look at relevant ways to break out the data; biliary atresia is an obvious one. The others are smaller individually. The commonality, as Joanne discussed, is elevated bile acids and cholestatic pruritus. We see treatment objectives and potential responses that we have seen in compassionate use examples as having more in common across settings than different.

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 EXPAND, Chris, I am curious how you think a positive read here 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 will you need to improve diagnoses to drive that additional growth?

Thanks, Ryan. The indication statement in the label will have nuance because EXPAND is a basket defined largely by exclusion. The protocol excludes larger settings where you could run a stand-alone study, such as PSC. Expect that to be reflected in labeling. On the diagnostic piece, particularly in pediatric settings, these conditions are highly symptomatic and therefore well diagnosed. The origin for the study was compassionate use requests, which showed demand for something to help these patients. We view that pediatric population as a readily 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. A question on the guidance: In 2025, sales grew about 55%, and the guidance range implies a 21% to 25% annual growth. Could you provide color on how much of this is driven by Livmarli versus the bile acid portfolio? Thank you.

The growth is more Livmarli-driven. Keep in mind that for Japan, last year we had $22 million in revenues that reflected inventory buildup, and this year we expect lower revenues from Japan, although the launch in Japan is progressing as expected. The bile acid portfolio will continue to grow steadily, but the acceleration we saw in 2025 was primarily driven by Livmarli.

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 wanted to revisit the EXPAND study. Are there any learnings you have taken away from EMBARK that you are applying here based on the high proportion of biliary atresia patients? And could you 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.

Good question. EMBARK looked at bilirubin levels in biliary atresia immediately after the Kasai procedure — a very acute setting where outcomes are heavily influenced by the surgical procedure. What is different in EXPAND is that the biliary atresia patients are those who had a successful Kasai but later have slower progressing or persistent cholestasis, not the acute transplant-driving situation seen in very young patients. The biliary atresia patients enrolling in EXPAND are generally toddler to school-aged children with persistent post-Kasai cholestatic pruritus. From compassionate use, we have seen strong treatment responses in that profile, which inspired the study. Regarding market size, because EXPAND is a basket, traditional epidemiology is harder to apply. From our work in the pediatric setting, there are readily at least 500 patients in the U.S. that would fit this profile, with potential for more. When we look at the total peak Livmarli potential that we see as long-term, EXPAND could represent about 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 talk about the current market for HDV and how you expect it to develop over the coming years? And how much do you expect R&D to increase this year from the HDV studies? Thanks.

I will speak to the market and then pass to Eric on investments. For the current treatment landscape for HDV, there is nothing specifically labeled in the U.S., and one labeled medicine, Hepcludex, is available in Europe and has performed well. We expect the landscape to evolve in the U.S. with potential approvals and other regimens in development. We were excited about brolobitug because, as a single agent, it has shown very impressive response rates and an attractive safety profile — with high virologic response rates at week 48 and strong composite endpoint performance — which could set a high bar for treatment options in delta. We do expect other competitive agents, but we are excited about brolobitug's profile. Eric?

Thanks, Chris. The four Phase III brolobitug studies are enrolling well, which means expenses will be somewhat compressed into this year. We also need to make significant CMC investments to prepare for a filing next year. 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.