Executive Summary / Key Takeaways

• Mirum Pharmaceuticals ($MIRM) is rapidly establishing itself as a leader in rare cholestatic liver diseases, transitioning to a high-growth, cash flow-positive entity with a robust commercial portfolio and a promising pipeline.
• The company delivered strong financial performance in Q3 2025, reporting $133.01 million in total revenue, a 47% year-over-year increase, and achieved GAAP profitability for the first time, signaling significant operating leverage.
• LIVMARLI, the company's flagship IBAT inhibitor, is a key growth driver, with strong U.S. demand in Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC), expanding international uptake, and the recent FDA approval of a convenient tablet formulation with patent protection extending to 2043.
• Mirum's pipeline, featuring volixibat for primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), and MRM-3379 for Fragile X Syndrome (FXS), is advancing rapidly with multiple pivotal readouts expected by mid-2027, each holding over $1 billion in peak revenue potential.
• Despite facing competition and inherent risks in drug development and commercialization, Mirum's specialized technology, strategic acquisitions, and disciplined execution position it for sustained long-term growth in underserved rare disease markets.

A Focused Vision: Mirum's Ascent in Rare Disease Therapeutics

Mirum Pharmaceuticals, Inc. was founded in May 2018 with a clear mission: to transform the treatment landscape for debilitating rare and orphan diseases. From its inception, the company strategically built its foundation, notably through an Assignment and License Agreement with Shire (later Takeda Pharmaceutical Company Limited (TAK)) in November 2018, securing exclusive global rights to its lead product candidates, Livmarli and volixibat. This initial step laid the groundwork for a focused approach, emphasizing innovative therapies for underserved patient populations. Mirum's strategy is deeply rooted in commercial execution, scientific innovation, and financial discipline, aiming to leverage its specialized expertise to deliver life-changing medicines globally.

The company's history is marked by strategic portfolio expansion. In May 2022, Mirum acquired Satiogen, streamlining royalty obligations for Livmarli and volixibat. A more significant move came in August 2023 with the acquisition of the Bile Acid Medicines portfolio from Travere Therapeutics , adding Cholbam and chenodiol (now Ctexli) to its commercial offerings. These acquisitions were pivotal, transforming Mirum into a company with three approved medicines and a rapidly advancing pipeline. This strategic growth has enabled Mirum to establish a unique market position as a specialized challenger in rare disease, distinguishing itself from larger, more diversified pharmaceutical players.

Technological Edge: IBAT Inhibition and Beyond

Mirum's core technological differentiation lies in its expertise with ileal bile acid transporter (IBAT) inhibitors, exemplified by Livmarli (maralixibat) and volixibat. These orally administered, minimally-absorbed agents are designed to reduce the reabsorption of bile acids, thereby alleviating cholestatic pruritus—a severe and debilitating symptom in various rare liver diseases.

Livmarli, the company's flagship product, demonstrates the tangible benefits of this technology. It is approved for cholestatic pruritus in patients with ALGS and PFIC in the U.S. and internationally. In clinical trials, Livmarli has shown significant improvements in pruritus and, in PFIC, has demonstrated positive impacts on growth and bilirubin levels, which are critical outcomes for these pediatric populations. The company's commitment to innovation extends to drug formulation; in Q1 2025, the FDA approved a convenient single tablet formulation of Livmarli, which launched in mid-June 2025. This tablet is expected to be a highly attractive option for eligible patients over 25 kilograms (typically older children, adolescents, and adults), enhancing persistence and adherence due to its single-tablet-per-dose format. This new formulation is protected by an allowed patent expected to grant soon, extending coverage to 2043, significantly bolstering Livmarli's competitive moat.

Beyond Livmarli, volixibat represents another promising IBAT inhibitor in Mirum's pipeline, targeting adult cholestatic liver diseases like PSC and PBC. The mechanism's consistent efficacy across multiple cholestatic settings, as observed with Livmarli, underpins confidence in volixibat's potential. Furthermore, Mirum is diversifying its technological approach with MRM-3379, a brain-penetrant PDE4D inhibitor for Fragile X Syndrome (FXS). Preclinical data from a mouse FMR1 knockout model of Fragile X showed MRM-3379 reversed the disease phenotype across multiple behavioral assessments, highlighting the importance of this pathway in learning and memory. This strategic expansion into genetic neurology leverages Mirum's rare disease capabilities and opens up a wide range of potential indications beyond FXS, all associated with intellectual disability.

Commercial Engine: Driving Robust Revenue Growth

Mirum's commercial execution has been a significant driver of its recent success. The company reported total revenue of $133.01 million for the three months ended September 30, 2025, marking a substantial 47% increase over the same period in 2024. For the nine months ended September 30, 2025, total revenue reached $372.38 million, a 57% increase from the prior year. This robust performance is a direct reflection of the growing demand for its approved medicines.

Livmarli net product sales totaled $92.235 million in Q3 2025, a 56.0% increase year-over-year, and $253.619 million for the nine months ended September 30, 2025, representing a 69.9% increase. In the U.S., Livmarli demand remains healthy in both ALGS and PFIC. Management notes that more PFIC patients are being identified than initially anticipated, driven by increased disease awareness and broader genetic testing, including cases presenting later in childhood or adulthood. This expanding recognition of PFIC's variability and the importance of genetic testing across age groups has been a core focus of Mirum's launch strategy. The company estimates U.S. ALGS market penetration is approaching 50% of the eligible treatment population, with continued growth expected from further penetration, new infant diagnoses, and dose adjustments due to weight-based dosing. Internationally, Livmarli demand is also robust, with $28 million in net product sales in Q3 2025, supported by expanding reimbursement and launches in new geographies. Q3 2025 marked the first full quarter of commercialization for Mirum's partner, Takeda, in Japan, with adoption dynamics consistent with the U.S. launch.

The Bile Acid Medicines, Cholbam and Ctexli, also contributed significantly, generating $40.775 million in net product sales in Q3 2025, a 30.8% increase year-over-year, and $118.761 million for the nine months ended September 30, 2025, a 35.3% increase. The FDA approval of Ctexli for CTX in adults in February 2025, which carries seven years of orphan exclusivity, is expected to drive increased patient finding efforts across specialties like neurology, ophthalmology, and GI, leading to a gradual increase in new CTX patient diagnoses.

Financial Strength and Operating Leverage

Mirum's financial position has strengthened considerably, reflecting its disciplined operating model. As of September 30, 2025, the company held $378 million in unrestricted cash, cash equivalents, and investments, an $85 million increase from the beginning of the year. This robust liquidity position provides ample resources to fund ongoing operations and strategic initiatives.

The company achieved a significant milestone in Q3 2025, reporting positive net income of $2.90 million. While management views this as a milestone rather than a consistent expectation given ongoing growth investments, it underscores the inherent operating leverage in Mirum's commercial model. Cash operating margins have consistently improved, with the commercial business's cash contribution margin exceeding 50% in Q2 2025.

Total operating expenses for Q3 2025 were $130.41 million, including $42.96 million in R&D and $61.91 million in SG&A. The increase in R&D was primarily due to volixibat and MRM-3379 programs, while SG&A rose due to increased personnel and commercialization efforts. Notably, the company recognized a benefit from income taxes in Q3 2025 due to the One Big Beautiful Bill Act (OBBBA), which eliminates the requirement to capitalize domestic research and experiment costs. Mirum expects to be cash flow positive for the full year 2025.

Pipeline Catalysts: Fueling Future Expansion

Mirum's pipeline is poised to deliver multiple high-impact catalysts over the next 18 months, further solidifying its long-term growth trajectory.

• Volixibat in PSC (VISTAS Study): Enrollment for the Phase 2b VISTAS study in PSC was completed in Q3 2025, with topline data anticipated in Q2 2026. This program passed its blinded interim analysis for efficacy and safety in 2024, with a recommendation to maintain the current sample size, suggesting a strong signal. PSC represents a significant unmet need with no approved therapies, and early compassionate use data with maralixibat in PSC patients has shown meaningful pruritus reductions.
• Volixibat in PBC (VANTAGE Study): The VANTAGE study in PBC is progressing well, with enrollment expected to complete in 2026 and topline data in H1 2027. Interim data presented in Q2 2025 demonstrated a rapid, deep, and statistically significant improvement in pruritus, with a 3.8-point reduction from baseline and a 2.5-point placebo-adjusted reduction. This led to a Breakthrough Therapy Designation from the FDA in October 2024. Volixibat is positioned to address pruritus in both first and second-line PBC patients, including those with stable alkaline phosphatase on UDCA.
• LIVMARLI EXPAND Study: The Phase 3 EXPAND study, evaluating Livmarli in additional ultra-rare cholestatic conditions, is enrolling well and is on track for completion in 2026. This study aims to broaden Livmarli's label, targeting a patient population estimated to be at least the size of PFIC (approximately 1,000 patients in the U.S. and Europe), representing a meaningful label expansion opportunity.
• MRM-3379 in Fragile X Syndrome: The Phase 2 study for MRM-3379, a brain-penetrant PDE4D inhibitor, initiated in Q3 2025 following FDA feedback and IND clearance. The study will enroll approximately 52 male participants (16-45 years old) with full mutation FXS, with a key secondary efficacy endpoint focused on cognitive measures. Management sees a substantial U.S. market opportunity exceeding $1 billion for FXS alone, with further upside in other intellectual disability conditions.

Competitive Landscape: Differentiating in Rare Diseases

Mirum operates in a highly competitive biopharmaceutical industry, but its specialized focus provides a distinct advantage. While larger players like Gilead Sciences (GILD) boast superior financial resources and broader portfolios (Gilead's TTM Net Profit Margin is significantly higher than Mirum's -8.78%), Mirum's agility and deep expertise in rare cholestatic liver diseases allow for targeted innovation. Ipsen (IPSEY), with its IBAT inhibitor odevixibat (Bylvay/Kayfanda) for PFIC and ALGS, is a direct competitor. However, Mirum's volixibat program in PBC, with its strong interim data and Breakthrough Therapy Designation, aims for a "highly preferred position in the market without meaningful competition" in PSC, where no approved therapies exist. Mirum's Livmarli tablet formulation, with its extended patent protection to 2043, also provides a competitive edge in patient convenience.

Against niche competitors like Travere Therapeutics (TVTX), Mirum's focused R&D and commercialization strategy in liver diseases can lead to more efficient execution and potentially "materially stronger patient outcomes" in its core indications. While Travere also targets rare diseases, Mirum's specialized knowledge in cholestatic conditions offers a unique value proposition. The market for PSC, for instance, is characterized as "very unsatisfied" with existing off-label therapies such as UDCA, cholestyramine, and rifampin, which are perceived as standard of care despite lacking FDA approval. This creates a significant opportunity for volixibat to capture market share upon approval. Furthermore, Mirum's strategic acquisitions, like the Bile Acid Medicines portfolio, demonstrate its ability to consolidate and grow within its specialized niche, leveraging existing commercial infrastructure.

Barriers to entry in this segment are high, including substantial R&D costs and complex regulatory hurdles, which protect Mirum's position. However, the company faces risks from generic competition for its Bile Acid Medicines due to a lack of patent exclusivity, and from other IBAT inhibitors in development, such as GSK (GSK)'s linerixibat for PBC. Mirum's strategy to provide samples to generic manufacturers, compliant with the CREATES Act, reflects its proactive approach to managing potential competition.

Risks and Challenges

Despite its strong momentum, Mirum faces inherent risks common to the biopharmaceutical industry. The company anticipates continued net losses for the foreseeable future as it invests heavily in clinical trials and commercialization efforts, despite achieving quarterly GAAP profitability. Revenue variability, particularly from international partner and distributor orders, can impact quarterly results. The reliance on third parties for manufacturing and distribution, including sole-source suppliers, poses supply chain risks. Clinical development is lengthy and uncertain, with potential for delays in patient enrollment or failure to demonstrate safety and efficacy, as seen with the Livmarli EMBARK study in biliary atresia. Extensive and evolving regulatory requirements, including potential changes in EU exclusivity rules and U.S. healthcare reforms like the IRA and OBBBA, could impact pricing and market access. Geopolitical and macroeconomic developments, such as inflation, high interest rates, and trade tensions, also present potential headwinds.

Conclusion

Mirum Pharmaceuticals has rapidly transformed into a high-growth, cash flow-positive rare disease leader, driven by a compelling commercial portfolio and a robust pipeline. The company's strategic focus on underserved cholestatic liver diseases, underpinned by its differentiated IBAT inhibitor technology and expanding into areas like Fragile X Syndrome, positions it for sustained long-term value creation. Strong financial performance, marked by significant revenue growth and the achievement of GAAP profitability, reflects effective commercial execution and operating leverage. With multiple pivotal pipeline readouts anticipated by mid-2027 and a clear path to over $1 billion in peak revenue potential for its key assets, Mirum is poised to capitalize on substantial market opportunities. While challenges such as competitive pressures and regulatory complexities persist, Mirum's technological leadership, disciplined strategy, and patient-centric approach make it a compelling investment in the evolving rare disease landscape.