Summary of Mirum Pharmaceuticals FY Conference Call Company Overview - **Company**: Mirum Pharmaceuticals (NasdaqGM:MIRM) - **Focus**: Rare disease company delivering life-changing medicines to patients with rare diseases - **Key Products**: Livmarli, Volixibat, Chenodal, Cholbam, Brilovatug Financial Performance - **2025 Product Revenue**: Estimated at $520 million - **2026 Revenue Guidance**: Expected between $630 million and $650 million - **Potential Revenue from Pipeline**: Over $4 billion across current commercial and pipeline programs [3][25] Key Products and Pipeline Livmarli - **Indications**: Approved for Alagille syndrome and PFIC, with a third indication expected to read out later this year - **2025 Revenue**: $359 million, with strong growth driven by pediatric patient starts and label expansion into PFIC [8][30] - **Future Potential**: Estimated billion-plus potential opportunity [6][30] - **EXPAND Study**: Aiming for label expansion into other cholestatic pruritic indications, with top-line data expected in Q4 [10][12] Volixibat - **Indications**: Studied for PSC and PBC, targeting a significant unmet need in cholestatic pruritus [12][13] - **Market Size**: Approximately 30,000 patients with PSC, with two-thirds experiencing pruritus [13] - **Upcoming Data**: Top-line data from the VISTAS study expected next quarter, with NDA filing anticipated in the second half of the year [16][25] Brilovatug (Acquisition of BlueJ Therapeutics) - **Indication**: Targeting hepatitis delta, a rare co-infection with HBV - **Market Size**: Approximately 15,000 diagnosed and insured patients in the U.S., with potential for higher prevalence in other regions [22][48] - **Phase 2 Results**: Achieved 100% virologic response, with a 65%-82% response rate on FDA approval endpoints [23][47] - **Phase 3 Program**: AZURE studies currently enrolling, with top-line data expected in the second half of the year [24][25] Market Dynamics - **Livmarli**: Strong growth driven by increased awareness and diagnosis in adult PFIC settings, with a focus on genetic testing [9][28] - **Volixibat**: Positioned as the only potential therapy for PSC, with a significant market opportunity due to the lack of approved therapies [41][42] - **PBC Market**: More competitive with recent approvals of PPARs, but still presents opportunities for IBAT inhibitors [43] Commercial Strategy - **Geographic Focus**: Direct commercialization in North America and Western Europe, with partnerships in smaller countries [5] - **Field Expansion**: Plans to increase the U.S. field force by 30-40 people to target community physicians and GI specialists [44] Risks and Considerations - **Regulatory Risks**: Ongoing monitoring of clinical trial outcomes and regulatory approvals for pipeline products [2][25] - **Market Competition**: Need to navigate competitive landscapes, especially in the PBC market [42][43] Conclusion - Mirum Pharmaceuticals is positioned for significant growth with a strong pipeline and commercial strategy, focusing on rare diseases and addressing unmet medical needs in cholestatic conditions and hepatitis delta. The company anticipates pivotal data readouts in the coming year that could further enhance its market position and revenue potential [25][26].

Core Insights - Saira Ramasastry, a director at Mirum Pharmaceuticals, executed the exercise of 5,000 stock options and sold the resulting shares for a total transaction value of $400,000 on December 22 [2][7]. Transaction Summary - The transaction involved the direct sale of 5,000 shares, with a total value of $400,000, based on a weighted average purchase price of $80.00 per share [3]. - Post-transaction, Ramasastry holds no direct common shares, as the entire transaction accounted for 100% of her direct holdings [8]. Company Overview - Mirum Pharmaceuticals reported a revenue of $471.79 million and a net income of -$41.42 million for the trailing twelve months (TTM) [5]. - The company's stock price increased by 90.71% over the past year, calculated using December 22 as the reference date [5]. Company Snapshot - Mirum specializes in developing therapies for rare and orphan liver diseases, with its lead product being LIVMARLI and additional candidates like Volixibat in its pipeline [6]. Operational Performance - Preliminary results for 2025 indicate net product sales of approximately $520 million, exceeding guidance, with forecasts of $630 million to $650 million in global net product sales for 2026 [11]. - The company ended 2025 with an estimated $392 million in cash and investments and achieved positive operating cash flow, allowing for pipeline expansion and the proposed acquisition of Bluejay Therapeutics [11].

Summary of Mirum Pharmaceuticals Conference Call Company Overview - **Company**: Mirum Pharmaceuticals (NasdaqGM:MIRM) - **Acquisition Target**: BlueJ Therapeutics - **Focus**: Rare diseases, specifically Hepatitis Delta Key Points from the Conference Call Acquisition Announcement - Mirum announced a definitive agreement to acquire BlueJ Therapeutics for a total of $620 million, consisting of $250 million in cash and $370 million in stock priced at $71.21 per share, plus up to $200 million in sales-based milestone payments starting at $500 million in annual sales [2][17] - The acquisition aims to expand Mirum's rare disease portfolio and enhance its late-stage pipeline [2][4] Product Details - The acquisition includes tegovibart, an anti-hepatitis B surface antigen monoclonal antibody for chronic hepatitis delta virus, which has shown promising Phase II results [4][5] - Tegovibart has received FDA Breakthrough Therapy and PRIME designations in the EU, indicating its potential to significantly change the standard of care for Hepatitis Delta patients [5][9] Clinical Data - Phase II study results showed a 100% virologic response rate in 47 adults with chronic hepatitis delta, with 65%-82% achieving a composite endpoint of virologic response and ALT normalization [8][9] - The ongoing Phase III Azure program is designed to meet registration requirements in both the U.S. and EU, with final data expected in the second half of 2026 [10][11] Market Opportunity - There are an estimated 40,000 prevalent Delta patients in the U.S. and over 230,000 in the U.S. and EU combined, with a significant number undiagnosed [13][14] - Mirum anticipates a global revenue potential of at least $750 million for tegovibart, with the majority expected to come from the U.S. market [14][42] Commercial Strategy - Mirum plans to leverage its existing commercial infrastructure, which is expected to deliver $500 million-$510 million in sales in 2025, to support the launch of tegovibart [14][17] - The company aims to expand its field teams modestly to cover areas like infectious disease and internal medicine practices where Delta patients are managed [15] Financial Position - Mirum has a solid balance sheet and expects to return to cash flow positive status in 2027, with no change to its 2025 guidance despite the acquisition [17][18] - The acquisition is seen as a disciplined approach to capital allocation, expanding the rare disease portfolio without compromising financial independence [18] Competitive Landscape - The competitive dynamics include the potential entry of Gilead's Hepcludex in the U.S. market, which could enhance market development for Hepatitis Delta [22][24] - Mirum believes that the unique profile of tegovibart, with its high response rates and favorable safety profile, positions it well against competitors [46] Regulatory Path - The Azure One and Azure Four studies are designed to support U.S. registration, with clear buy-in from the FDA [23][55] - The Azure Two and Three studies are superiority studies aimed at supporting EMA registration [61] Future Outlook - Mirum is optimistic about the upcoming catalysts, including four registrational stage readouts in the next 18 months, which could significantly enhance its value creation potential [19][20] Additional Important Points - The acquisition process was competitive, with other interest in BlueJ's program, but Mirum had been following the program for over a year [52] - The company is focused on the Delta program and does not plan to invest in BlueJ's HBV pipeline agents [37] This summary encapsulates the key aspects of the conference call, highlighting Mirum Pharmaceuticals' strategic acquisition, product potential, market opportunity, and future outlook in the rare disease sector.

Summary of Mirum Pharmaceuticals FY Conference Call Company Overview - **Company**: Mirum Pharmaceuticals - **Industry**: Rare disease pharmaceuticals - **Key Products**: Three approved medicines for rare cholestatic diseases - **Revenue Guidance**: Expected revenues for the year are between $500 million and $510 million, with the company being cash flow positive [4][48] Core Points and Arguments - **Pipeline Development**: - The company has a full pipeline led by Volixibat for adult cholestatic diseases (PSC and PBC) and MRM-3379 for Fragile X syndrome, with the first patient enrolled in a phase two trial [4][5] - **Fragile X Opportunity**: - Estimated market opportunity for Fragile X is over $1 billion, with approximately 50,000 male patients in the US and Europe. Pricing is expected to be around $200, based on comparable disease settings [5][6] - The company is currently in phase two trials, with expectations for a clearer understanding of clinical and competitive profiles in Q1 [11][9] - **Clinical Measures**: - The NIH Toolbox is being used for clinical outcomes, which is considered well-suited for the Fragile X population due to its sensitivity to cognitive impairment [12][14] - The primary endpoint for the phase two trial is safety and tolerability, with secondary endpoints including various clinical measures [17][28] - **PSC and PBC Trials**: - An interim analysis indicated that the ongoing PSC study should continue unchanged, with the 20 mg dose selected for its therapeutic window [20][21] - Baseline pruritus scores are expected to be similar to previous studies, and statistical significance for secondary measures like fatigue and sleep is not powered but would be meaningful if achieved [22][28] - **Patient Experience**: - The company emphasizes the significant impact of pruritus on patients' quality of life, arguing that the trade-off between itching and mild gastrointestinal side effects is manageable [30][32] Additional Important Insights - **Market Dynamics**: - The company has seen a larger-than-expected patient population for PFIC, contributing to revenue growth. Continued growth is anticipated from both U.S. and international markets [48][49] - The average dose for patients is gradually increasing, reflecting the dynamics of patient aging and treatment duration [50] - **Intellectual Property**: - The company holds important patents, including a method of use patent expiring in 2040, which is crucial for its market position. The company is prepared to defend its patents against Paragraph IV filings [51][52] This summary captures the key points discussed during the conference call, highlighting Mirum Pharmaceuticals' current status, future prospects, and strategic focus within the rare disease pharmaceutical industry.

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]