Summary of Madrigal Pharmaceuticals (MDGL) Conference Call on May 13, 2025 Company Overview - **Company**: Madrigal Pharmaceuticals - **Focus**: Development of treatments for Non-Alcoholic Steatohepatitis (NASH) and related liver diseases - **Key Product**: Risdipla (Resmeterome), FDA approved for NASH with moderate to advanced fibrosis (F2 and F3) Industry Context - **Disease**: Compensated mass cirrhosis (F4C) is a high-risk stage of NASH with no FDA approved treatments - **Market Opportunity**: Expansion into F4C could potentially double the market opportunity for Risdipla Core Points and Arguments 1. **Understanding F4C**: F4C patients are severely ill but still retain some liver function, facing serious risks once clinically significant portal hypertension (CSPH) develops [5][6][8] 2. **Clinical Data Presentation**: New findings from the two-year open-label MAESTRO NAFLD-1 trial were shared, showing Risdipla's broad and consistent effects [6][10] 3. **Pivotal Phase III Trial**: The MAESTRO NASH outcomes trial is designed to evaluate Risdipla's ability to reduce liver-related events in F4C patients, with results expected in 2027 [7][48] 4. **Efficacy of Risdipla**: In phase three trials, Risdipla halted or improved liver stiffness in 91% of patients, with over 17,000 patients treated by Q1 2025 [9][10] 5. **Mechanism of Action**: Risdipla targets fat, inflammation, and fibrosis through THR beta activation, which is crucial for liver metabolism [12][24] 6. **Clinical Outcomes**: The trial showed that 65% of patients with CSPH at baseline moved to a lower risk category after treatment, indicating a significant clinical benefit [19][57] 7. **Safety Profile**: Risdipla was well tolerated, with common adverse events similar to non-cirrhotic populations, and a low discontinuation rate of 2.5% [41][43] Important but Overlooked Content 1. **Patient Population Characteristics**: The trial included patients with lower platelet counts, indicating a more advanced disease state, which is critical for understanding the treatment's impact [55][68] 2. **Long-term Outcomes**: The potential for sustained improvement in liver stiffness and reduction in CSPH risk categories over time is emphasized, with a focus on preventing decompensation [69][70] 3. **Comparison with Competitors**: The call highlighted the importance of Risdipla's unique mechanism compared to other treatments in development, such as FGF21s, and the need for further education among community gastroenterologists [60][81] Conclusion - **Future Outlook**: Madrigal Pharmaceuticals is positioned to lead in the treatment of NASH and F4C, with Risdipla showing promising clinical data and a strong safety profile. The company aims to solidify its role as a foundational therapy for patients across the spectrum of liver disease [48][49]