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]

Mirum Pharmaceuticals (MIRM) 2025 Conference Summary Company Overview - **Company**: Mirum Pharmaceuticals - **Focus**: Rare disease therapeutics with three approved medicines - **Current Revenue Guidance**: $490 to $510 million, cash flow positive, financially independent [2][76] Key Products and Market Insights LIVMARLI - **Current Market Penetration**: Approximately 50% in the U.S. and mature European markets for Alagille syndrome [14] - **Patient Population**: Estimated 2,000 to 2,500 prevalent cases in the U.S., with 75% experiencing pruritus [18] - **Incidence Rate**: About 1 in 50,000 births [19] - **Newborn Screening**: Not necessary as most patients present with neonatal jaundice [16] SATEXLY - **Patient Identification Strategy**: Focused on identifying patients with CTX through a dedicated sales team and screening efforts [4] - **Diagnosis Rate**: Literature suggests only about 10% of patients are diagnosed [4] - **Newborn Screening Efforts**: Ongoing pilot projects to include CTX in newborn screening, with promising results from New York [9][10] PFIC (Progressive Familial Intrahepatic Cholestasis) - **Target Demographic**: Older children, adolescents, and adults [27] - **Patient Identification**: Focus on gastroenterologists and hepatologists to identify patients with idiopathic cholestasis [30] Financial Performance and Projections - **Revenue Recognition Model**: Revenue recognized upon family signing for LIVMARLI, reflecting demand sales [17] - **Takeda Partnership**: Significant revenue generation from Japan, with a scaling down of royalties expected over time [35][36] - **Future Profitability**: Potential for Mirum to become a very profitable company in the coming years, assuming successful product launches [76] Research and Development - **Pipeline**: Four clinical trials from three different product candidates, with three believed to be registration trials [2] - **Expanded Basket Study**: Aimed at treating patients with cholestatic pruritus beyond Alagille and PFIC, with an estimated 500 or more patients targeted [49][61] Strategic Planning and Risk Management - **Long-term Strategy**: Discussions on cash flow deployment and potential acquisitions are anticipated as profitability increases [78] - **Risk Appetite**: Expected to evolve with increased profitability, with a focus on validated mechanisms and lower biology risk [80][82] Core Competencies - **Strengths**: Late-stage clinical development, regulatory expertise, and strong commercial capabilities in rare diseases [85][88] Additional Insights - **Market Dynamics**: The company is optimistic about the potential for growth in the rare disease market, particularly with ongoing education and awareness efforts among healthcare providers [70][71] - **Patient Engagement**: Emphasis on building relationships with physicians and patient advocates to enhance product visibility and adoption [85][88]

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]