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]

Summary of Mirum Pharmaceuticals FY Conference Call Company Overview - **Company**: Mirum Pharmaceuticals (NasdaqGM:MIRM) - **Industry**: Biopharmaceuticals focused on rare diseases - **Products**: Three commercialized small molecule drugs: LIVMARLI, CHOLBAM, and CHENODAL [1][2] Financial Performance - **Revenue Guidance**: Management raised revenue guidance for 2025 to a range of $490 million to $510 million, reflecting robust revenue gains in the first half of 2025 compared to 2024 [1][2] - **Cash Flow**: The company is operating cash flow positive and has a strong balance sheet [2] Product Details LIVMARLI - **Indications**: Approved for Alagille syndrome and PFIC (Progressive Familial Intrahepatic Cholestasis) [3] - **Market Growth**: The PFIC indication has shown unexpected growth, particularly in adult populations, leading to increased patient identification [4][5] - **Clinical Profile**: LIVMARLI has a differentiated clinical profile, showing benefits in pruritus, growth, and bilirubin improvements [4] CHENODAL - **Indication**: Approved for CTX (Cerebrotendinous Xanthomatosis) with seven years of orphan exclusivity [3] CHOLBAM - **Indication**: Approved for bile acid synthesis disorders [3] International Expansion - **Partnerships**: Strong performance from international business, particularly in Japan with partner Takeda, who received approvals for Alagille and PFIC [6] Clinical Pipeline EXPAND Trial - **Objective**: Expanding the label of LIVMARLI to include additional settings of cholestatic pruritus, targeting at least 500 pediatric patients in the U.S. [7][8] VISTA Study - **Indication**: Evaluating volixibat for PSC (Primary Sclerosing Cholangitis) with an expected top-line readout in Q2 of the following year [9][10] - **Market Size**: Approximately 30,000 patients in the U.S., with a significant unmet need for effective treatments [9][10] AVANTAGE Study - **Indication**: Evaluating volixibat for PBC (Primary Biliary Cholangitis) with positive interim data showing significant improvements in pruritus and fatigue [17][18] MRM-3379 - **Indication**: Targeting Fragile X syndrome, a genetic mutation leading to autism spectrum disorder, with a market opportunity of around 25,000 patients in the U.S. [22][23] - **Phase 2 Study**: Expected to start in Q4 of the current year, focusing on different age groups [25] Competitive Landscape - **Volixibat Positioning**: Positioned as a first-line treatment option for pruritus in PBC, differentiating from existing therapies that primarily target second-line settings [20][21] Future Outlook - **Clinical and Commercial Catalysts**: Continued growth of all three medicines, initiation of Phase 2 in Fragile X, and upcoming data readouts for PSC and PBC expected in 2026 [27] - **Portfolio Expansion**: The company is actively looking for opportunities in the rare disease space, focusing on adding value and ensuring alignment with current capabilities [28][29]

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]