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]

Financial Data and Key Metrics Changes - For Q1 2025, net sales totaled $137.3 million, representing a 33% increase from Q4 2024 [30] - Over the last twelve months, the company generated $317 million in net sales, indicating strong demand and momentum [28][30] - R&D expenses decreased to $44.2 million in Q1 2025 from $71.2 million in Q1 2024, primarily due to changes in accounting for inventory costs and lower clinical trial costs [31] - SG&A expenses increased to $167.9 million in Q1 2025 from $80.8 million in Q1 2024, driven by increased commercial launch activities [32] Business Line Data and Key Metrics Changes - The company has treated over 17,000 patients with ResDiffera, up from 11,800 patients at the end of Q4 2024, indicating strong patient adoption [12] - Approximately 70% of the top 6,000 target prescribers have prescribed ResDiffera, reflecting a strong base of prescribers [15] - The company is focused on a target market of 315,000 diagnosed F2 and F3 MAH patients, with only about 5% currently being treated with ResDiffera [13] Market Data and Key Metrics Changes - The company is preparing for a mid-year regulatory decision in Europe, with plans to launch in Germany in the second half of the year if approved [26] - The company is evaluating additional high-priority global markets beyond Europe [26] Company Strategy and Development Direction - The expansion to treat F4C patients is a key pillar of the company's long-term NASH leadership strategy, with ongoing trials expected to yield data ahead of competitors [25] - The company aims to build a portfolio of differentiated assets to extend its leadership position in the market [27][90] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's positioning within the current macroeconomic environment, highlighting the strong cash position to support ongoing launches [29] - The company expects robust year-over-year net sales growth in 2025, despite anticipated increases in gross-to-net discounts as payer contracts are established [30][31] Other Important Information - The company has recently appointed a new Chief Medical Officer, Dave Sorgel, to lead pipeline development efforts [9][27] - The company is actively evaluating opportunities across multiple mechanisms and stages of development to enhance its product offerings [27] Q&A Session Summary Question: Expectations for growth trajectory for ResDiffera with expanded label - Management expects continued growth in patient numbers and market expansion, with significant potential for new patient additions as the market evolves [39][40] Question: Payer reauthorization requirements and patient persistency - Management is not concerned about reauthorizations, citing strong results and patient feedback, which should support persistency [45][47] Question: Status of European approval and implications for pricing - Management is optimistic about the ongoing review process in Europe and expects to launch later this year, with pricing strategies being evaluated [53][56] Question: Confidence in outcomes benefit on hepatic events - Management expressed confidence in the liver stiffness data translating to clinical outcomes, supported by the mechanism of action of ResDiffera [62] Question: Compliance rates and patient feedback on therapy - Early signs of adherence are promising, with anecdotal evidence suggesting patients feel better on the therapy [66][69] Question: Insights on gross-to-net pricing evolution - Management anticipates a disciplined approach to gross-to-net pricing, with ongoing discussions with payers [106][108]