Mirum Pharmaceuticals' Q3 2025: Contradictions Emerge on Dosing Instructions, LIVMARLI Sales, PFIC Growth, Volixibat Pricing, and Study Design Confidence

Date of Call: None provided

Financials Results

• Revenue: $133M, up 47% YOY

Guidance:

• FY2025 revenue expected at $500-$510M, landing at the upper end of prior guidance.
• No additional Takeda (Japan) sales expected in Q4 2025.
• VISTAS (Volixibat in PSC) top-line data expected in Q2 2026.
• VANTAGE (PBC) enrollment expected to complete in 2026; EXPAND enrollment targeted to complete in 2026.
• Cash, cash equivalents and investments $378M as of Sept 30, 2025.

Business Commentary:

* Revenue Growth and Commercial Performance: - Mirum Pharmaceuticals reported third quarter revenue of $133 million, representing a nearly 50% year-over-year increase over the same period last year. - The growth was driven by strong momentum from the US PFIC launch and expanding demand from international markets.

• R&D Progress and Pipeline Advancements:
• The company remains on track for three potentially pivotal readouts over the next 18 months, including the VISTAS phase 2b study in PFIC, with top-line data expected in Q2 2026.

• Advancements in the VANTAGE study of Volixibat in PBC, EXPAND study of LIVMARLI in ultra-rare cholestatic conditions, and the newly initiated phase 2 study of MRM-3379 in Fragile X syndrome are progressing well.

• Financial Strength and Profitability:

• Mirum Pharmaceuticals recognized positive net income for the first time in Q3, demonstrating operating leverage in the commercial model.
• The company's cash balance grew significantly, reaching $378 million at September 30, reflecting financial independence and resources to support expansion.

Sentiment Analysis:

Overall Tone: Positive

• Management reported Q3 net product revenue of $133M (up 47% YOY), GAAP net income of approximately $3M, cash and investments of $378M (up $85M YTD), and said they now expect to land at the upper end of FY2025 guidance ($500-$510M); multiple clinical milestones and enrollment/completion timelines were reiterated.

Q&A:

• Question from Jessica Fye (J.P. Morgan): What are going to be the key drivers of LIVMARLI’s performance as we look at 2026? And can you talk about why the midpoint of the new guidance range now implies 4Q revs flat sequentially from 3Q? I don’t think we saw that dynamic last year.
  Response: US LIVMARLI growth and the ongoing PFIC launch should continue to build in 2026; the implied Q4 flatness is driven by variability in international distributor ordering and the absence of further Takeda Japan sales in Q4.

• Question from Josh Schimmer (Cantor): What trends are you seeing in terms of adoption of the solid tablet formulation of LIVMARLI and what % of sales are for that versus the liquid? And then for Volixibat, what are you thinking in terms of the appropriate price analogs, especially after we’ve seen a significant increase in rare orphan disease prices perhaps over the last year?
  Response: The solid tablet (launched mid-June) showed an encouraging uptake with a substantial proportion of eligible patients switching from liquid; pricing for Volixibat is not finalized but management is benchmarking against PBC analogs (noting ranges like ~$130–150k) while continuing analysis.

• Question from Gavin Clark-Gardner (Evercore): What’s your expectation for Paragraph IV filers? Maybe just helpful to lay out your confidence in your whole IP portfolio, especially around the method patents and including Volixibat.
  Response: The company is quite confident in its IP position—particularly method patents around dosing—and is prepared to defend against any Paragraph IV filers; none have appeared to date.

• Question from James Condulis (Stifel): Shionogi seemed to suggest it’s still an open question around what exactly the best endpoint is for their Fragile X study. Do you have any perspectives on that and implications for your program? And on PSC, given inflammatory comorbidities and IBAT-related GI side effects, any safety signals in blinded data compared to PBC or Alagille?
  Response: For Fragile X, preclinical data and a productive pre-IND FDA interaction support their endpoint strategy and proceeding with the Phase 2; for PSC, the data monitoring committee has raised no safety concerns and the safety profile is consistent with known IBAT effects.

• Question from Joseph Thome (TD Cowen): Now that PSC is fully enrolled, can you describe baseline criteria relative to the interim population? And how important are quality-of-life measures or bile acids, and will those secondary endpoints be provided in the topline release in Q2?
  Response: They will not present granular baseline criteria now; enrolled patients were selected for elevated pruritus and are representative of the PSC population—regulatory focus and the topline will center on the prespecified pruritus primary endpoint, while secondary measures (fatigue, bile acids) are expected to be informative but secondary to the regulatory path.

• Question from Brian Deshnut (Raymond James): What went into the decision to offer BID dosing for the EXPAND study and how would you expect dosing instructions to look on an expanded label? And as a follow-up, any impact from the government shutdown on genetic screening programs?
  Response: BID dosing in EXPAND was chosen empirically based on compassionate-use observations showing strong responses across explored dose ranges; regarding the government shutdown, management has seen no impact to date on genetic screening programs or related operations.

• Question from Manny Murray (Leerink Partners): Can you talk about the pace of new PFIC adds in Q3 versus Q2 and, more broadly, as you start to see consistent positive cash flow, what is your BD strategy for adding more products to the pipeline?
  Response: PFIC patient additions remained healthy in Q3 across infants to adults driven by expanded genetic testing and education; BD will remain active but highly selective—company has no urgency and maintains a high bar for acquisitions.

• Question from Mike Olds (Morgan Stanley): With the recent Linerixibat PDUFA for GSK, how do you see the competitive dynamics playing out in PBC?
  Response: Volixibat targets both first- and second-line PBC patients (VANTAGE has no baseline ALP entry criterion), and interim data showing a strong placebo-adjusted itch signal support a favorable competitive profile versus Linerixibat.

• Question from John Wallerman (Citizens): Are you anticipating disease-modifying effects over time with Volixibat similar to those seen with LIVMARLI in PSC and PBC, and if so what's the timeframe and importance for adoption?
  Response: It’s too early to assess disease-modifying effects; near-term regulatory and launch focus is on pruritus improvement, while potential longer-term disease-modifying outcomes would require extended follow-up and take much longer to evaluate.

Contradiction Point 1

Dosing Instructions and EXPAND Study Design

It pertains to the dosing instructions for the EXPAND study and the background behind its design, which could impact the interpretation of study results and patient outcomes, as well as regulatory approval.

What factors influenced the decision to use BID dosing in the EXPAND study? How will the expanded label specify dosing instructions for cholestatic pruritus patients? - Brian Deshnut (Raymond James)

2025Q3: BID dosing decision was based on empirical observations from compassionate use settings. The expanded label for cholestatic pruritus patients will be informed by the EXPAND study. - Chris Peetz(CEO)

Are any eligible patients currently using Livmarli via compassionate use or other exceptions? - Josh Schimmer (Cantor Fitzgerald)

2025Q2: The EXPAND study came around because we had a lot of requests for [compassionate] use in these patients with cholestatic pruritus from these other settings. And so we're taking patients who have not previously been treated in order to assess the treatment response in this setting. - Joanne M. J. Quan(CMO)

Contradiction Point 2

LIVMARLI Sales Growth and International Distribution

It involves differing expectations for LIVMARLI sales growth and international distribution, which are crucial for revenue projections and competitive positioning.

What are the key drivers for LIVMARLI's performance in 2026? Why does the new guidance midpoint imply flat Q4 revenue sequentially, a dynamic not seen last year? - Jessica Fye (J.P. Morgan)

2025Q3: We expect LIVMARLI performance to be driven by PFIC launch both in the US and internationally. Growth in guidance reflects PFIC launch and international sales timing. - Chris Peetz(CEO)

What steps are needed before initiating the Phase 2 study in the back half for MRM-3379? - Jessica Fye (JPMorgan)

2025Q1: We continue to expect LIVMARLI US sales to grow sequentially in Q2 and Q3 as we expand commercial reach to unused Alagille and PFIC patients. - Chris Peetz(CEO)

Contradiction Point 3

PFIC Patient Growth and Market Penetration

It reflects differing perspectives on the growth and market penetration of PFIC patients, which directly impacts revenue projections and market presence.

Can you discuss the pace of new PFIC adds in Q3 compared to Q2? - Manny Murray (Leerink Partners)

2025Q3: PFIC adds have been consistent, and we've added about 30 or so in Q3. - Peter Radovich(COO)

What is our current market penetration in Alagille, and how will U.S. growth be driven? - Mani Foroohar (Leerink Partners)

2024Q4: PFIC adds have been consistent, adding about 60 to 70 in Q4. So now we're near 200 PFIC patients. And obviously, we expect that to be a different number when we report in Q1. - Christopher Peetz(CEO)

Contradiction Point 4

Volixibat Pricing Strategy

It involves pricing strategy for Volixibat, impacting market positioning and price competitiveness.

What trends are you seeing in the adoption of LIVMARLI’s solid tablet formulation, and what percentage of sales does it represent compared to the liquid formulation? What pricing analogs do you consider appropriate for Volixibat, especially given the recent significant price increases in rare orphan diseases with lower prevalence than PBC but similar to PSC? - Josh Schimmer (Cantor)

2025Q3: We're still in the process of analyzing the data and we'll have more to say in the future. - Chris Peetz(CEO)

Can you discuss the additional Volixibat PBC data in the EASL abstract and share any insights? - Gavin Clark-Gartner (Evercore)

2025Q1: Volixibat in PBC incorporates both first and second-line therapies, and its dose level is highly effective, strengthening its competitive position. - Chris Peetz(CEO)

Contradiction Point 5

IMPACT Study Design and Endpoint Confidence

It involves differing levels of confidence and clarity regarding the study design and endpoint for the Fragile X study, which is crucial for the development and approval of MRM-3379.

Shionogi recently indicated uncertainty about the optimal endpoint for its Fragile X study. Does this raise concerns for your program initiated this year, and what are the implications? - James Condulis (Stifel)

2025Q3: We feel confident also in the Fragile X study design and endpoint, having, as I mentioned, strong preclinical data and community engagement. - Joanne Quan(CMO)

With the stock above the conversion price, does this affect your approach to BD and capital allocation? - Gavin Clark-Gartner (Evercore ISI)

2024Q4: Shionogi seems to suggest it's still an open question around what exactly the best endpoint is for their Fragile X study. - James Condulis(Stifel)