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]