Q4 2025 Mirum Pharmaceuticals Inc Earnings Call

February 25, 2026

Operator: Good afternoon, and welcome to Mirum Pharmaceuticals' Q4 and full year 2025 conference call. My name is Elliot, and I'll be your operator today. All lines are currently in listen-only mode, and there'll be an opportunity for Q&A after management's prepared remarks. I'd now like to hand the conference over to Andrew McKibben, SVP of Strategic Finance and Investor Relations. Please go ahead.

Speaker #1: 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.

Speaker #1: We'll answer currently in listen-only mode, and there'll be an opportunity for Q&A after management's prepared remarks. And I'd like to hand the conference over to Andrew McKibben, SVP of Strategic Finance and Investor Relations.

Speaker #1: Please go ahead.

Speaker #2: 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.

Andrew McKibben: Thank you, Elliot. Good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals' Q4 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's attending an international commercial event. Earlier this afternoon, Mirum issued a press release reporting our Q4 and full year 2025 financial results. Copies of the press release and our SEC filings are available in the Investors section of our website.

Speaker #2: Peter Radovich, our President and Chief Operating Officer, is unable to join us today as he's attending an international commercial event. Earlier this afternoon, Mirum issued a press release reporting our fourth quarter and full year 2025 financial results.

Speaker #2: 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 Mirum's programs and market opportunities for its approved medicines and product candidates, and financial guidance.

Andrew McKibben: 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 Mirum's programs and market opportunities for its approved medicines, 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?

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: With that said, I'd like to turn the call over to Chris. Chris?

Speaker #3: Thanks, Andrew. Good afternoon, everyone. 2025 was a year of disciplined execution and growth for Mirum, 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.

Chris Peetz: Thanks, Andrew. Good afternoon, everyone. 2025 was a year of disciplined execution and growth for Mirum, 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.

Speaker #3: In 2025, we delivered 521 million dollars in net product sales, exceeding the upper end of our guidance range. This was made up of Liv Marley net product sales of 245 million dollars in the US, 115 million dollars internationally, with our Biolasted medicines also contributing 161 million dollars.

Speaker #3: The strong finish was driven in particular by our continued leadership in Alagille syndrome, accelerating PFAS 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 to $650 million for the year.

Chris Peetz: 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 enrollment completion of the VISTA study of volixibat in PSC. We also meaningfully expanded our pipeline with the addition of the Phase 3 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.

Speaker #3: Beyond commercial performance, we advanced our pipeline through important clinical and regulatory milestones, including the approval of Citexla for CTX and a tablet formulation of Liv Marley and enrollment completion of the VISTA study of Valixabat and PSC.

Speaker #3: We also meaningfully expanded our pipeline with the addition of the Phase 3 BrilovaTug program for chronic hepatitis delta virus, a serious rare disease with limited treatment options.

Speaker #3: This addition to the portfolio is an excellent fit with our team and the upcoming potential of the Valixabat 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.

Chris Peetz: 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 Q2, 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 brelovitug in hepatitis delta. The broader AZURE Phase 3 program continues to enroll well, and we expect full top-line results from both AZURE-1 and AZURE-4 Phase 3 trials in the second half of the year. We're also seeing continued momentum across our other LIVMARLI and volixibat programs.

Speaker #3: With the addition of BrilovaTug, we now have four potentially registrational clinical readouts expected over the next 18 months, in areas of significant unmet need.

Speaker #3: Beginning in the second quarter, we expect to report top-line data from the Valixabat VISTA study and PSC, as well as interim results from the Azure One study of BrilovaTug in hepatitis delta.

Speaker #3: The broader Azure Phase 3 program continues to enroll well, and we expect full top-line results from both Azure One and Azure Four Phase 3 trials in the second half of the year.

Speaker #3: We're also seeing continued momentum across our other Liv Marley and Valixabat programs. Enrollment in the Phase 3 expand study and additional rare cholestatic conditions as well as the Vantage study in PDC continues to exceed expectations.

Chris Peetz: Enrollment in the Phase 3 EXPAND study and 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 Q4 of this year and from VANTAGE in the first half of next. Finally, the BLOOM Phase 2 study of MRM-3379 in Fragile X syndrome is also on track for data next year. Taking 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've now built a portfolio with over $4 billion in potential revenues.

Speaker #3: 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.

Speaker #3: And finally, the Bloom Phase 2 study of mRN3379 in Fragile X syndrome is also on track for data next year. Taken together, Mirum is entering a pivotal phase of growth as the leading rare disease company with multiple commercial medicines and several near-term, potentially registrational readouts.

Speaker #3: 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've now built a portfolio with over $4 billion in potential revenue.

Speaker #3: And with that, I'll turn it over to Joanne to walk through our pipeline in greater detail. Joanne?

Chris Peetz: With that, I'll turn it over to Joanne to walk through our pipeline in greater detail. Joanne?

Speaker #4: 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.

Operator: Thanks, Chris. 2025 was an important year for our pipeline, and 2026 will be even more significant as multiple programs approach potentially registrational readouts.

Joanne Quan: As Chris mentioned, enrollment 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 and PSC, and brelovitug and hepatitis delta. Starting with volixibat and PSC, we are on track to report top-line data from the VISTA study in Q2 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 pre-specified threshold for efficacy at the blinded interim analysis in 2024 and has proceeded with the selected 20 milligram twice-daily dose.

Speaker #4: Today, I'll focus on two of our near-term data readouts for Valixabat and PSC and BrilovaTug in hepatitis delta. Starting with Valixabat and PSC, we're on track to report top-line data from the VISTA study in the second quarter of 2026.

Speaker #4: 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.

Speaker #4: As a reminder, the study exceeded a pre-specified threshold for efficacy at the blinded interim analysis in 2024 and has proceeded with the selected 20-milligram, twice-daily dose.

Speaker #4: Collectively, the prior clinical data of IBET inhibitors and PSC and the consistent treatment effects seen across other cholestatic diseases, including PBC, all support IBET inhibition as a meaningful therapeutic approach in PSC.

Joanne Quan: 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 two Phase 3 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.

Speaker #4: A disease with no approved therapies. We look forward to sharing the top-line results from this study in the coming months. Turning to BrilovaTug for hepatitis delta, I'm pleased to report that all four Azure clinical studies are progressing well.

Speaker #4: In the Azure program, BrilovaTug is being studied as a single-agent regimen in a broad group of patients with elevated ALT at baseline. Azure One and Azure Four, the two Phase 3 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.

Speaker #4: In the second quarter, we expect to report interim results from the study. This study is evaluating hepatitis delta treatment-naive patients, randomized to BrilovaTug or delayed treatment, using a 24-week composite endpoint of virologic response and ALT normalization—an endpoint aligned with the FDA.

Joanne Quan: In Q2, we expect to report interim results from the phase 2b 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, an endpoint aligned with FDA. The phase 2b 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 3 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 bile, bulevirtide and are designed to support European registration, as well as provide additional long-term safety and efficacy data.

Speaker #4: The Phase 2b 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 3 portion, which has the same study design and endpoints.

Speaker #4: The Azure Two and Azure Three studies are enrolling well. These are active-controlled studies evaluating BrilovaTug in the context of Belebritide, and are designed to support European registration as well as provide additional long-term safety and efficacy data.

Speaker #4: Finally, for mRN3379, our Bloom Phase 2 study in Fragile X syndrome is often an excellent start. The program recently received Fast Track designation from the FDA, recognizing its potential to address a serious unmet need.

Joanne Quan: Finally, for MRM-3379, our BLOOM Phase 2 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.

Speaker #4: 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.

Speaker #4: With that, I'll turn the call over to Eric to review our financial results.

Speaker #5: 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 were $149 million, compared to $99 million the year before.

Eric Bjerkholt: Thanks, John, 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 Q4 of 2025 were $149 million, compared to $99 million the year before. For the full year 2025, total net product sales were $521 million, compared to $336 million the year before, representing 55% year-over-year growth. Total operating expense for the quarter and year ended 31 December 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.

Speaker #5: For the full year 2025, total net product sales were $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.

Speaker #5: 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.

Speaker #5: 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.

Eric Bjerkholt: 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 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 Therapeutics acquisition, generating aggregate gross proceeds of $268 and a half million, effectively covering the cash outlays to support the acquisition. In 2025, we achieved positive cash flow from operations.

Speaker #5: 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.

Speaker #5: In addition, we recently completed two private placements concurrent with the closing of the BlueJ acquisition, generating aggregate gross proceeds of $268.5 million effectively covering the cash outlay to support the acquisition.

Speaker #5: 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 BrilovaTug clinical program and manufacturing validation and scale-up in preparation for the anticipated BLA submission next year.

Eric Bjerkholt: 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.

Speaker #5: 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.

Speaker #5: I'll now turn the call back to Chris for closing remarks.

Speaker #6: Thanks, Eric. To close, Mirum Entry’s 2026—and a great position. Our commercial business has continued momentum, and our financial position is strong. Our pipeline has four potentially pivotal readouts for the next 18 months, each representing the potential to bring standard-of-care-changing medicines to difficult treatment settings.

Joanne Quan: Thanks, Eric. To close, Mirum's 2026 ended 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 a team that can achieve this level of impact for patients.

Chris Peetz: Thanks, Eric. To close, Mirum's 2026 ended 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 a team that can achieve this level of impact for patients.

Speaker #6: It's inspiring to work with a 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.

Chris Peetz: It's going to be a very busy year. We look forward to several updates as we go. With that, operator, please open the call for questions.

Speaker #6: And with that, operator, please open the call for questions.

Operator: Thank you. If you would like to ask a question, please press star followed by 1 on your telephone keypad. If you would like to withdraw your question, please press star followed by 2. When preparing to ask your question, please ensure your device is unmuted locally. First question comes from James Condulis with Stifel. Your line is open. Please go ahead.

Speaker #7: Thank you. If you would like to ask a question, please press star, followed by one on your telephone keypad. If you would like to withdraw your question, please press star, followed by two.

Speaker #7: When preparing to ask your question, please ensure your device is unmuted locally. First question comes from James Condulis with Stifel. Your line is open.

Speaker #7: Please go ahead.

James Condulis: 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's 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. Just curious, as you guys are, you know, getting closer to data and potentially commercialization, kind of how you're 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.

Speaker #8: Hey, thanks for taking my question and congrats on all the progress. I actually wanted to ask one on Balixabad, and specifically as it relates to the commercial opportunity.

Speaker #8: Obviously, Balixabad is coming first, and I think generally a lot of people are thinking about pricing in the context of Balixabad around 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're thinking about the right way to price Balixabad and if pricing specifically around the PSC opportunity is on the table or makes sense.

Speaker #8: Thanks so much.

Speaker #5: Yeah, thanks, James, for the question. This is obviously something we spent a lot of time thinking about and kind of as you're saying in your question there, the PPARs and PBC really are good planning benchmark to think about, but that's not certainly not our final guidance or decision on it.

Chris Peetz: Yeah, thanks, James, for the question. This obviously is something we've spent a lot of time thinking about. Kind of as you're saying in your question there, the PPARs and PBC really are a good planning benchmark to think about, but that's not, certainly not our, you know, 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. 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'll take that decision when we're at launch.

Speaker #5: 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.

Speaker #5: And so really unique positioning for Balixabad but we'll take that decision when we're at launch.

Speaker #8: Makes sense. Thanks so much.

James Condulis: Makes sense. Thanks so much.

Chris Peetz: Okay. Thanks for the question.

Speaker #5: Thanks. Thanks for the question.

Speaker #7: We now turn to Joseph Thom with TD Cohen. Your line is open. Please go ahead.

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

Speaker #9: 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 NPSC patients can be a little bit more episodic.

Joseph Thome: 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, in PSC patients can be a little bit more episodic. Maybe do you see that as providing a little bit more risk into this study versus what you're seeing in PBC? 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? Thank you.

Speaker #9: Maybe do you see that as providing a little bit more risk into this 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 were enrolling or monitoring, do you think that can maybe help limit any variability there?

Speaker #9: Thank you.

Speaker #5: Yeah, thanks for the question. There are a couple of things to comment on that all lead in, I'll let Joanne speak a little bit to the some of the study design elements.

Chris Peetz: Yeah, I think. Thanks for the question there. A couple things to comment on, that I'll lead, and I'll let Joanne speak a little bit to some of the study design elements. 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.

Speaker #5: 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 saying the patient episodically when there are other more complicated factors.

Speaker #5: 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.

Chris Peetz: 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, you know, might be the perspective of a KOL at a top center. On study design, I'll let Joanne speak to some of the things that we've seen from screening and the overall operational side.

Speaker #5: 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.

Speaker #10: Yeah, thanks. Thanks for the question. A couple of 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 Chris Cowley a few years back, presented at ESIL, that a really high proportion of patients do complain of pruritus and fatigue as the main symptoms associated with their PSC.

Joanne Quan: Yeah, thanks. Thanks for the question. A couple things. Actually, we know that pruritus is an issue for a lot of patients. This is really from some work that we did with, you know, Christopher Cowley a few years back, presented at EASL, that, you know, a really high proportion of patients do complain of pruritus, and fatigue is the main symptoms associated with their PSC. Perhaps about half of them said that it's disrupted their daily life activities. Pretty significant. Within the study, we are enrolling patients with persistent pruritus. You know, we're careful to have that as eligibility, and therefore, we track the pruritus response throughout the study.

Speaker #10: 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.

Speaker #10: And so we're careful to have that as eligibility, and therefore we track the pruritus response throughout the study. So, I understand kind of 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.

Joanne Quan: You know, understand it's kind of the basis for your question, but I think, you know, 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 and significant impact in terms of their daily lives.

Joseph Thome: That's perfect. Thank you so much.

Speaker #9: That's perfect. Thank you so much.

Speaker #5: Next question.

Chris Peetz: Thanks for the question.

Speaker #7: We now turn to Joe Kim with RBC Capital Markets. Your line is open. Please go ahead.

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

Speaker #11: Hi, 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 VISTAS and the VANTAGE study designs. You mentioned that you expect to enroll patients with persistent pruritus, but I was 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.

James Condulis: Hi, 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 VISTAS and the VANTAGE study designs. 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.

Joe Kim: Hi, 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 VISTAS and the VANTAGE study designs. 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.

Speaker #11: Thank you.

Speaker #10: Yeah, 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 from arilixibad, for instance.

Joanne Quan: Yeah. Thanks for the question. I think, you know, the commonality is that we're really studying cholestatic pruritus, which is something that we know well and have characterized, you know, with the other indications that we have for maralixibat, for instance. You know, we know how to measure this. We know, you know, how to implement that within a clinical trial. You know, 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. There's a lot of commonality in terms of how we implement it within the trial.

Speaker #10: 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.

Speaker #10: So there's 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.

Joanne Quan: I think, you know, probably the best guide in terms of what the baseline pruritus is if you look at the PBC interim. That shows significant pruritus, I mean, with clearly within the range of moderate to severe pruritus for baseline. 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.

Speaker #10: And that shows significant pruritus. I mean, clearly within the range of moderate to severe pruritus for baseline. So I think that's kind of our expectation.

Speaker #10: We're selecting patients with moderate to severe pruritus at baseline to study in both of these studies.

Speaker #11: Thank you.

Joe Kim: Thank you.

Speaker #5: Next question.

Chris Peetz: Thanks for the question.

Speaker #7: We now turn to John Wallenben with Citizens. Your line is open. Please go ahead.

Operator: We now turn to Jonathan Wolleben with Citizens. Your line is open. Please go ahead.

Jonathan Wolleben: 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'll need and what that means for timing of a potential NDA submission?

Speaker #12: Hey, thanks for taking the question. Piggybacking on the PSC questions—can you talk a little bit about your interactions with the FDA around safety database requirements for Valixabat, and what follow-up you'll need, and what that means for timing of a potential MAA submission?

Speaker #5: Yeah, I can jump in on this one. 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.

Chris Peetz: Yeah, I can jump in on some. Thanks for the question, John. A lot of this kind of what 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. What we do expect that the current VISTAS study has the sufficient safety database for the setting. 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.

Speaker #5: 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.

Speaker #5: 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.

Speaker #5: 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.

Speaker #12: Great. Thanks, Chris.

Jonathan Wolleben: Great. Thanks, Chris.

Speaker #5: Thanks for the question.

Chris Peetz: Thanks for the question.

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

Speaker #7: We now turn to Ryan Deshna with Raymond James. Your line is open. Please go ahead.

Speaker #5: Thanks a lot. Congrats on a big year. Looking forward to 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 end of the second, end of other secondary by indication?

Joe Kim: Thanks a lot. Congrats on a big year. Looking forward to a busy cadence of catalysts this year. For the EXPAND readout coming later in Q4 this year, are you expecting to break out the data on pruritus by and other secondaries by indication? 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 syndrome? Thanks.

Ryan Deschner: Thanks a lot. Congrats on a big year. Looking forward to a busy cadence of catalysts this year. For the EXPAND readout coming later in Q4 this year, are you expecting to break out the data on pruritus by and other secondaries by indication? 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 syndrome? Thanks.

Speaker #5: 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 allergy?

Speaker #5: Thanks.

Speaker #9: Yeah, I mean, 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.

Chris Peetz: Yeah, overall, there's the mix of patients in this study. Just as a reminder, we think it's probably ultimately gonna end up being approximately half biliary atresia and then a much longer tail of other settings. You know, we'll look at, you know, whatever the most relevant ways to break it out are. Biliary atresia is an obvious one. The others are just much smaller, each of them individually. 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. We see kind of the treatment objectives and the potential for response that we've seen in compassionate use examples, having more in common than different across various settings.

Speaker #9: So we'll look at whatever the most relevant ways to break it out are biliary atresia is an obvious one. The others are just much smaller.

Speaker #9: 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.

Speaker #9: So we see kind of the treatment objectives and the potential for response that we've seen in compassionate use examples. Having more in common than different across various settings.

Speaker #5: Thanks very much.

Joe Kim: Thanks very much.

Ryan Deschner: Thanks very much.

Speaker #9: Thanks for the question.

Chris Peetz: Thanks for the question.

Speaker #7: We now turn to Manny Faruha with LegalRank Partners. Your line is open. Please go ahead.

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

Speaker #13: Hey, guys. Do you have Ryan on for Manny? Thanks for taking our question, and congrats on the quarter. Maybe just sticking with expand. Chris, I'm curious how you think a positive readout here kind of plays out in terms of the label expansion, given it's more of a basket trial.

Ryan Deschner: 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'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. When we think about biliary atresia and the other indications, like, how well diagnosed are these? Is this gonna be more of a PFIC setting where you're gonna have to improve diagnoses to really drive that additional growth?

Ryan McElroy: 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'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. When we think about biliary atresia and the other indications, like, how well diagnosed are these? Is this gonna be more of a PFIC setting where you're gonna have to improve diagnoses to really drive that additional growth?

Speaker #13: 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 diagnoses to really drive that additional growth?

Speaker #5: Thanks for the question, Ryan. Yeah, the thinking around label indication statement and the label, as you point out, it has some nuance because it's a basket.

Chris Peetz: Thanks for the question, Ryan. Yeah, 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, the way that the protocol is written is it excludes the larger settings where you could run a standalone study to look at cholestatic pruritus and PSC, for example, as we're doing with volixibat. Expect that to be reflected in the labeling. Could you remind me of the second part of your question?

Speaker #5: It's really defined by exclusion, right? I mean, the way that the protocol is written, it excludes the larger settings where you could run a standalone study to look at cholestatic pruritus and PSC, for example, as we're doing with Volixibat.

Speaker #5: So expect that to be reflected in the labeling. And could you remind me of the second part of your question?

Speaker #13: Yeah, 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 hand-holding and physician education to drive further uptake in these additional settings?

Ryan Deschner: Yeah, just kinda like when you think about these additional settings, like, how well diagnosed are these? Or do you think it's gonna really take a lot of handholding and physician education to drive further uptake in these additional settings?

Ryan McElroy: Yeah, just kinda like when you think about these additional settings, like, how well diagnosed are these? Or do you think it's gonna really take a lot of handholding and physician education to drive further uptake in these additional settings?

Speaker #5: And thanks for that. Yeah, 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.

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

Speaker #5: And that's really what the origin for the study was, compassionate use requests. So we see the demand is out there for something to help these patients.

Speaker #5: So I do see it as a pretty well-tracked patient population.

Speaker #13: I appreciate it.

Ryan Deschner: I appreciate it.

Ryan McElroy: I appreciate it.

Speaker #5: Yeah, thanks for the question.

Chris Peetz: Yeah. Thanks for the question.

Operator: As another reminder, if you'd like to ask a question, please press star one on your telephone keypad now. We now turn to Charles Wallace with H.C. Wainwright. Your line is open. Please go ahead.

Speaker #7: That's another reminder. If you'd like to ask a question, please press star one on your telephone keypad now. We now turn to Charles Wallace with HC Wainwright.

Speaker #7: Your line is open. Please go ahead.

Speaker #14: Hi. Thanks for taking my question. This is Charles on for RK. So I guess a question on the guidance from me. So in 2025, the sales grew about 55%.

R.K. Handa: Hi. Thanks for taking my question. This is Charles on for R.K. I guess a question on the guidance from me. 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.

Raghuram Ram Selvaraju: Hi. Thanks for taking my question. This is Charles on for R.K. I guess a question on the guidance from me. 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.

Speaker #14: 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.

Speaker #14: Thank you.

Speaker #9: Yeah, I mean, the growth is definitely more Liv Marley driven. Keep in mind, though, that for Japan last year, we had 22 million in revenues which was inventory buildup.

Eric Bjerkholt: Yeah, 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 well.

Speaker #9: 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.

Chris Peetz: 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.

Eric Bjerkholt: 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.

Speaker #9: Not accelerating the way the Liv Marley growth has been in the last few years.

Speaker #13: Fantastic. Thanks for taking my question.

James Condulis: Fantastic. Thanks for taking my question.

Speaker #5: Thanks for the question.

Chris Peetz: Thanks for the question.

Speaker #7: We now turn to Brian Scorni with BED. Your line is open. Please go ahead.

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

Brian Skorney: 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've taken away from EMBARK that you're going to be applying here based on the high proportion of biliary atresia patients? 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.

Speaker #15: 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've taken away from EMBARK that you're going to be applying here based on the high proportion of biliary atresia patients?

Speaker #15: 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?

Speaker #15: Thanks.

Chris Peetz: 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. Think of that as a, 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, that, you know, the surgical procedure directed at bile flow actually is most determinative of outcome in those young patients. What's 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.

Speaker #9: Thanks for the question. And that'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 CASAI procedure.

Speaker #9: 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 CASAI procedure that the surgical procedure directed at bile flow actually is most determinative of outcome in that in those young patients.

Speaker #9: Now, what's 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.

Speaker #9: 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 thinking of as toddler to school-aged that have a persistent post-CASAI cholestatic pruritus.

Chris Peetz: That is not the kind of acute transplant-driving situation you see in the very young patients. Those the biliary atresia patients that are enrolling into EXPAND are going to be think of as toddler to school-aged that have a persistent post-Kasai cholestatic pruritus. 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. That's kind of what inspired us to pursue this study, is seeing actual strong treatment responses in those older biliary atresia patients. In terms of bridging that to market size, because this is a basket, it's hard to...

Speaker #9: 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 Liv Marley treatment with that profile.

Speaker #9: 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 or incidence rates so to speak because this is a long list of different potential causes of cholestatic pruritus.

Chris Peetz: You can't use traditional epidemiology, so you can't 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've done in the pediatric setting, it's clear that there's readily at least, you know, 500 patients in the US that would fit the profile of this, potential for more. When we look at kind of the total peak LIVMARLI potential, that billion-plus that we see as the long-term potential for the brand, EXPAND could represent a third of that overall.

Speaker #9: 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.

Speaker #9: Potential for more. When we look at kind of the total peak Liv Marley potential that billion-plus that we see as the brand, expand could represent a third of that overall.

Speaker #15: Great. Thanks for taking the question.

Brian Skorney: Great. Thanks for taking the question.

Speaker #5: Yeah. Thanks for the question.

Chris Peetz: Yeah. Thanks for the question.

Speaker #7: We now turn to Mike Oles with Morgan Stanley. Your line is open. Please go ahead.

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

Michael Ulz: 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? How much do you expect R&D to increase this year from the HDV studies? Thanks.

Speaker #16: 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?

Speaker #16: And then how much do you expect R&D to increase this year from the HDV studies? Thanks.

Speaker #9: Yeah. I'll speak to the market and pass it over to Eric to comment on the investment side. For the current treatment landscape for HDV, there really isn't there is nothing specifically labeled in the US.

Chris Peetz: Yeah, I'll speak to the market and pass it over to Eric to comment on the investment side. You know, for the current treatment landscape for HDV, there is nothing specifically labeled in the US. There's one labeled medicine, Hepcludex, in Europe that actually has been performing well. We do expect that to evolve in the US, given 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 a HB surface antigen and siRNA approach in hepatitis delta. This will be an evolving landscape.

Speaker #9: And the one labeled medicine Hep Cluedex 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 Hep Cluedex is up for review and potential approval in the US.

Speaker #9: 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.

Speaker #9: But what got us excited about Brilovatug 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 that's 100% viral response at week 48 that's 65 to 82 percent composite endpoint has a chance to really set the bar for treatment options in delta.

Chris Peetz: What got us excited about brelovitug as a potential for a 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 a 100% viral response at week 48, and the 65% to 82% composite endpoint has a chance to really set the bar for treatment options in HDV. Though, 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.

Speaker #9: Though there will be—we do expect to have—other competitive agents in the market, just excited about what Brilovatug can do compared to those.

Speaker #9: Pass it over to Eric on the P&L.

Speaker #5: Thanks. Thanks, Rick. So the good news is Brilovatug for Phase 3 studies are enrolling really well, which means that the expenses will be somewhat compressed into this year.

Eric Bjerkholt: Thanks. Thanks, great. The good news is that brelovitug for Phase 3 studies are enrolling really well, which means that the expenses will be somewhat compressed into this year. Means we need to make significant CMC investments to prepare for a filing next year. They are compressed, and in total, related to brelovitug, we anticipate, you know, roughly a $150 million increase in R&D spend tied to this program, with, you know, about half being CMC.

Speaker #5: Also means we need to make significant CMC investments to prepare for filing next year. So they are compressed and in total related to Brilovatug, we anticipate roughly 150 million dollar increase in R&D spend tied to this program with about half being CMC.

Michael Ulz: Good. Thank you.

Speaker #16: Yeah. Thank you.

Speaker #5: Thanks for the question.

Chris Peetz: Thanks for the question.

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

Speaker #7: This concludes our Q&A. I'll now hand back to Chris Petes, CEO for any final remarks.

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

Speaker #9: Great. Thank you all for joining today. Really excited about the year ahead, and hope everybody has a great afternoon.

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

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