Core Insights - Mirum Pharma demonstrates leadership in liver disease innovation by presenting data from its LIVMARLI® and Volixibat clinical programs at AASLD's The Liver Meeting® [1] Group 1 - Mirum Pharma showcases its advancements in liver disease treatment through clinical data [1] - The presentation at AASLD's The Liver Meeting® highlights the company's commitment to addressing liver diseases [1]

Financial Data and Key Metrics Changes - The company reported third quarter revenue of $133 million, representing a nearly 50% year-over-year increase [5][16] - Total net product revenue increased by 47% compared to the prior year, reflecting growth across all commercial medicines [16] - The company achieved positive net income for the first time, generating approximately $3 million in net income [7][17] Business Line Data and Key Metrics Changes - LIVMARLI net product sales totaled $92 million for the quarter, with $64 million in the U.S. and $28 million internationally [9][10] - The bioacquired portfolio, including CHOLBAM and CHENODAL, generated $41 million in net product sales this quarter [10] - The company expects to land in the upper end of its prior full year 2025 guidance range, with projected revenues of $500-$510 million [10] Market Data and Key Metrics Changes - Demand for LIVMARLI in the U.S. remains healthy, particularly in Alagille syndrome and PFIC, with continued growth expected [9] - Internationally, LIVMARLI demand continues to grow, supported by expanding reimbursement and launches in new geographies [10] - The first full quarter of commercialization for Takeda in Japan showed in-market adoption dynamics consistent with LIVMARLI's U.S. launch [10] Company Strategy and Development Direction - The company aims to create and deliver life-changing medicines to patients, focusing on rare diseases [5] - There is a strong emphasis on expanding the commercial portfolio and advancing the clinical pipeline, with three potentially pivotal readouts expected over the next 18 months [6][7] - The company is optimistic about the peak revenue potential for LIVMARLI, Volixibat, and MRM-3379, each exceeding $1 billion [11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's ability to continue executing with focus and consistency, highlighting the importance of patient-centric approaches [5][18] - The company remains well-funded and financially independent, providing resources for expansion and growth [17] - Management noted that while quarterly GAAP profitability is a milestone, it is not yet a consistent expectation as the company continues to invest in growth [17] Other Important Information - The company completed enrollment in the phase 2b VISTAS study in primary sclerosing cholangitis (PSC) and expects to announce top-line data in the second quarter of 2026 [12] - The company is actively monitoring the competitive landscape, particularly regarding pricing strategies for Volixibat [28][68] Q&A Session Summary Question: Key drivers of LIVMARLI's performance in 2026 and guidance for Q4 - Management expects continued growth from the PFIC launch and other existing dynamics, with guidance for Q4 reflecting variability in international sales [20][22] Question: Trends in adoption of LIVMARLI's solid tablet formulation - The solid tablet formulation has seen encouraging uptake, with a substantial proportion of eligible patients switching from the liquid form [26][27] Question: Expectations for Paragraph IV filers and IP portfolio confidence - Management expressed confidence in the overall IP position, particularly regarding method patents for LIVMARLI [32][34] Question: Insights on Fragile X study endpoints and safety risks in PSC - Management is optimistic about the endpoint strategy for Fragile X and noted no significant safety issues in the PSC study [40][42] Question: Impact of government shutdown on genetic screening programs - No impact has been observed on genetic screening programs or business interactions due to the government shutdown [56] Question: Pace of new PFIC adds and business development strategy - The pace of new PFIC adds remains healthy, with ongoing educational efforts to increase awareness among providers [60][63]

Financial Data and Key Metrics Changes - The company reported third quarter revenue of $133 million, representing a nearly 50% year-over-year increase [4][16] - Total net product revenue increased by 47% compared to the prior year, reflecting growth across all commercial medicines [16] - The company achieved positive net income for the first time, generating approximately $3 million in net income [5][17] Business Line Data and Key Metrics Changes - LIVMARLI net product sales totaled $92 million for the quarter, with $64 million from the US and $28 million from international markets [7][9] - The bioacquired medicines, CHOLBAM and CHENODAL, generated $41 million in net product sales this quarter [9] - The company expects to land in the upper end of its prior full year 2025 guidance range, with projected revenues of $500-$510 million [9] Market Data and Key Metrics Changes - Demand for LIVMARLI in the US remains healthy, particularly in Alagille syndrome and PFIC, supported by expanded diagnosis and increased genetic screening [8] - Internationally, LIVMARLI demand continues to grow, with significant contributions from new geographies and expanding reimbursement [9] - The company noted variability in international partner and distributor ordering patterns affecting revenue projections [9] Company Strategy and Development Direction - The company aims to advance its clinical pipeline with three potentially pivotal readouts expected over the next 18 months [5] - The focus remains on building a high-growth, cash flow positive rare disease company with a broad pipeline and global footprint [6] - The company is actively looking for underappreciated programs to add to its pipeline, maintaining a high bar for new product acquisitions [50] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the continued growth potential across the portfolio, with peak revenue potential for LIVMARLI, Volixibat, and MRM-3379 each exceeding $1 billion [10] - The company highlighted the importance of sustained engagement with the medical community to drive incremental gains in genetic testing and diagnosis [8] - Management emphasized the strength and scalability of the business model, viewing quarterly GAAP profitability as a milestone rather than a consistent expectation [17] Other Important Information - The company completed enrollment in the phase 2b VISTAS study in primary sclerosing cholangitis (PSC) and expects to announce top-line data in the second quarter of 2026 [11] - The VANTAGE study continues to progress well, with interim data showing statistically significant improvements in pruritus and other key measures [12] - The company initiated a phase 2 study of MRM-3379 for Fragile X syndrome, with promising preclinical data supporting its efficacy [13] Q&A Session Summary Question: Key drivers of LIVMARLI's performance in 2026 and guidance for Q4 revenue - Management expects continued growth from the PFIC launch and noted that international revenue may show variability due to large distributor orders [20][22] Question: Trends in adoption of LIVMARLI's solid tablet formulation and pricing for Volixibat - The solid tablet formulation has seen encouraging uptake, with a substantial proportion of eligible patients switching from the liquid form [25][26] - Pricing for Volixibat is still under analysis, with comparisons to other PPARs in the market [26] Question: Expectations for Paragraph IV filers and confidence in IP portfolio - Management expressed confidence in the overall IP position, particularly regarding method patents for LIVMARLI [30] Question: Insights on Fragile X study endpoints and safety risks in PSC - Management is optimistic about the endpoint strategy for Fragile X and noted no significant safety issues in the PSC study [33][37] Question: Impact of government shutdown on genetic screening programs - No impact has been observed on genetic screening programs or business interactions due to the government shutdown [46] Question: Pace of new PFIC adds and business development strategy - The pace of new PFIC adds remains healthy, with ongoing educational efforts to increase awareness among adult providers [48] - The company continues to seek underappreciated programs for its pipeline, maintaining a high standard for new acquisitions [50] Question: Competitive dynamics in PBC with recent market entrants - Management highlighted the unique positioning of Volixibat in the PBC treatment landscape, emphasizing its potential in both first and second-line settings [52]

Financial Performance and Guidance - Mirum Pharmaceuticals expects net product sales of $500-510 million in 2025[7, 100] - The company had a strong financial position with $378 million in cash balance[8, 101] - Mirum anticipates achieving positive cash flow in 2025[8, 100] Approved Products and Pipeline - Mirum has 3 approved ultra-rare medicines[7, 9] - LIVMARLI is approved for Alagille Syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC)[9, 14] - CHOLBAM and CTEXLI are bile acid replacement therapies for rare genetic diseases[9, 26] - Volixibat is in development for Primary Sclerosing Cholangitis (PSC) and Primary Biliary Cholangitis (PBC) with positive interim analysis[9, 44] - MRM-3379 is a PDE4D inhibitor in Phase 2 development for Fragile X Syndrome (FXS)[9, 78] Clinical Trials and Milestones - EXPAND Phase 3 study is enrolling patients with ultra-rare cholestatic pruritus, excluding PSC, PBC, ICP, ALGS and PFIC, with enrollment completion expected in 2026[9, 39, 42] - VISTAS study (PSC) expects confirmatory topline data in Q2 2026[9, 63] - VANTAGE study (PBC) expects enrollment completion in 2026[9, 72]

Business Overview - Mirum Pharmaceuticals projects net product sales of $310-320 million for 2024[9, 17] - The company has three approved rare disease products and three additional indications in late-stage development[8, 13] - Mirum's cash balance is $303 million, positioning it to execute its strategy[14] LIVMARLI (maralixibat) - In Alagille Syndrome (ALGS), 93% of participants experienced at least a 1-point reduction in ItchRO[Obs] in cholestatic pruritus[30, 95] - In ALGS, 83% of patients with a >1-point reduction in ItchRO[Obs] remained transplant-free 6 years after starting LIVMARLI[30, 100, 102] - In Progressive Familial Intrahepatic Cholestasis (PFIC), 62% of patients achieved minimal to no itch after 26 weeks of treatment[34, 35, 104] CHENODAL - CHENODAL addresses Cerebrotendinous Xanthomatosis (CTX), with a US prevalence of approximately 1,000-2,000 patients[13, 49] - RESTORE Phase 3 study showed a 20-fold increase in urine 23S-Pentol (bile alcohol) after placebo withdrawal (p<0.0001)[122] - RESTORE Phase 3 study showed a 50-fold increase in plasma 7αC4 after placebo withdrawal (p<0.0001)[122] Volixibat - Primary Sclerosing Cholangitis (PSC) affects approximately 54,000 patients across the US & EU, with ~65% experiencing active pruritus[13, 59] - In a CAMEO study, patients with PSC experienced a 70% mean reduction in pruritus and a 40% mean reduction in bile acids after 14 weeks of treatment with an IBAT inhibitor[61]

Core Insights - GSK plc announced that the European Medicines Agency has accepted its marketing authorization application for linerixibat, an investigational IBAT inhibitor, aimed at treating cholestatic pruritus in patients with primary biliary cholangitis [1][7] - The MAA for linerixibat is based on positive results from the phase III GLISTEN study, which demonstrated significant improvement in symptoms compared to placebo [4][7] - GSK aims for linerixibat to be the first approved therapy for itch associated with PBC, addressing a significant unmet medical need in the market [5][6] Company Developments - A regulatory filing for linerixibat is under review in the United States, with a final FDA decision expected on March 24, 2026 [2] - Year-to-date, GSK's shares have increased by 13.1%, contrasting with a 3.3% decline in the industry [2] Competitive Landscape - The PBC treatment market is seeing increased competition, with other companies like Gilead Sciences and Mirum Pharmaceuticals developing their own therapies [6][8][9] - Gilead's seladelpar received accelerated approval from the FDA and conditional marketing authorization from the European Commission for PBC treatment [8] - Mirum is currently evaluating volixibat in a phase IIb study, with enrollment expected to complete in 2026 [9]

Financial Data and Key Metrics Changes - Total net product sales for 2024 were $336.4 million, a 88% increase from $178.9 million in 2023 [24][27] - Fourth quarter 2024 net product sales were $99.4 million, representing a 43% year-over-year increase from $69.5 million [24][25] - The company ended 2024 with cash, cash equivalents, and investments of $293 million, an increase of approximately $7 million from the start of the year [27] Business Line Data and Key Metrics Changes - LIVMARLI's total net product sales for 2024 were $213.3 million, a 50% increase compared to 2023 [25] - Bile acid medicines achieved total net product sales of $123.1 million for 2024, with fourth quarter sales of $35 million, representing approximately 25% growth over the fourth quarter of 2023 [25][26] Market Data and Key Metrics Changes - The company expects to add close to $100 million to its top-line in 2025, with anticipated net product sales between $420 million and $435 million [12][27] - The market for MRM-3379 in Fragile X syndrome is estimated at $1 billion, primarily focusing on the 50,000 male patients in the US [39][40] Company Strategy and Development Direction - The strategic priorities for 2025 include global growth of commercial medicines, advancing the pipeline, selectively pursuing product acquisition opportunities, and maintaining scientific and financial discipline [8][9] - The company aims to expand LIVMARLI's label and drive Volixibat towards pivotal data in adult cholestasis [8][14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strong demand for LIVMARLI in Alagille syndrome and PFIC, anticipating continued growth [10][12] - The company is positioned for sustained growth in the rare disease market, leveraging its financial position for potential acquisitions [33][34] Other Important Information - The FDA approved CTEXLI for cerebrotendinous xanthomatosis (CTX) in adults, which is expected to enhance promotional efforts and patient reach [12][51] - The company reported being cash flow positive in 2024 and expects to maintain this status in 2025 [27] Q&A Session Summary Question: Strategic implications of convertible notes and capital allocation - Management highlighted the unique position of the company in the rare disease market, allowing for potential acquisitions and value creation opportunities [33][34] Question: Market penetration and competition for MRM-3379 - The market potential for MRM-3379 is based on a 50,000-patient market in the US, with substantial upside beyond the initial estimate [39][40][42] Question: Alagille market penetration and growth drivers - Current penetration for eligible treatment population in the US is around 40%, with growth driven by new diagnoses and increased patient starts [46][48] Question: Impact of CTX approval on sales trajectory - Management expects a gradual increase in patient diagnoses and treatment conversions to CTEXLI, impacting sales positively over time [51][52] Question: Patient mix for LIVMARLI in Q4 2024 - Most LIVMARLI patients are currently from Alagille syndrome, but there has been a notable increase in PFIC patient starts [56][58] Question: Commercial team expansion for LIVMARLI - No significant expansion of the commercial team is anticipated, as the same prescribing universe will be leveraged for the potential label expansion [62] Question: Timeline for topline data from Volixibat study - Topline data is expected approximately six months after enrollment completion, which is targeted for the second half of 2025 [84][85] Question: Patient experience in the EXPAND study - Positive treatment outcomes have been observed in biliary atresia patients treated through compassionate use, supporting the need for the EXPAND study [90][91]