Financial Data and Key Metrics Changes - The company is experiencing significant excitement in the NASH space, particularly with the approval of Resdiffera, which has validated the potential for effective treatments in this large market [3][4] - The company anticipates that the market for NASH will expand significantly due to increased awareness and screening, particularly as new mechanisms come into play [5][6] Business Line Data and Key Metrics Changes - The company is focused on both pre-cirrhotic and cirrhotic patient populations, with ongoing studies that are expected to yield significant data in the coming years [8][33] - Pegazifirman is positioned to differentiate itself from competitors based on efficacy, safety, tolerability, and dosing convenience [10][12] Market Data and Key Metrics Changes - The FGF21 class is expected to dominate the advanced fibrosis market, with the company projecting to capture over 50% of this market due to its better safety and tolerability profile [68][71] - The company believes that there is a large market opportunity in advanced fibrosis patients, which includes millions of patients who are at risk of progressing to cirrhosis [69][70] Company Strategy and Development Direction - The company is developing pegazifirman with a focus on advanced fibrosis patients, aiming to prevent progression to cirrhosis while also considering the potential for combination therapies with GLP-1s [67][71] - The company is exploring co-formulation opportunities with GLP-1s, which could enhance its market position and provide additional benefits to patients [72] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of pegazifirman to deliver significant benefits in the treatment of cirrhosis and advanced fibrosis, citing strong data from ongoing studies [36][64] - The company is optimistic about the regulatory environment, having received positive feedback from the FDA regarding its study designs and endpoints [63][66] Other Important Information - The company is actively managing enrollment in its clinical trials, with no significant impact from the approval of ResDiffera reported to date [41][42] - Management highlighted the importance of patient tolerability in clinical trials, as it directly affects patient compliance and study outcomes [39][40] Q&A Session Summary Question: How does pegazifirman differentiate from others in the FGF21 class? - The company highlighted differences in efficacy, safety, tolerability, and dosing convenience as key differentiators for pegazifirman compared to other FGF21 drugs [10][12] Question: What gives the company confidence regarding bone mineral density loss? - Management stated that data through week 48 showed no clinically meaningful changes in bone mineral density or biomarkers, providing confidence in the drug's safety profile [24][25] Question: How has enrollment been impacted by the availability of ResDiffera? - Management reported no significant impact on enrollment due to ResDiffera, with many patients still opting to participate in clinical studies [41][42] Question: What is the company's strategy for the phase three program? - The company is focused on powering its studies based on historical placebo responses and aims for a robust design to ensure statistically significant outcomes [48][50] Question: How does the company view the commercial opportunity for pegazifirman? - Management believes pegazifirman will have a dominant position in the advanced fibrosis market, particularly among compensated cirrhotic patients [67][68]

Financial Data and Key Metrics Changes - For Q1 2025, net sales totaled $137.3 million, representing a 33% increase from Q4 2024 [29][30] - R&D expenses decreased to $44.2 million from $71.2 million in Q1 2024, primarily due to changes in accounting for inventory costs and lower clinical trial costs [30] - SG&A expenses increased to $167.9 million from $80.8 million in Q1 2024, driven by increased commercial launch activities for Risdifa [31] Business Line Data and Key Metrics Changes - Risdifa generated $317 million in net sales over its first twelve months on the market, with Q1 2025 net sales of $137 million [8][29] - The number of patients on Risdifa increased to over 17,000 by the end of Q1 2025, up from 11,800 at the end of Q4 2024 [10][11] - Approximately 70% of the top 6,000 target prescribers have prescribed Risdifa, indicating strong physician adoption [13][15] Market Data and Key Metrics Changes - The target market consists of 315,000 diagnosed F2 and F3 MAH patients, with only about 5% currently being treated with Risdifa [11][12] - The company is focused on expanding its market presence, with plans to launch in Europe in the second half of 2025 [24] Company Strategy and Development Direction - The company aims to expand Risdifa's indication to F4C patients, which could potentially double its market opportunity [23] - Madrigal is also preparing for a mid-year regulatory decision in Europe and evaluating additional global markets [24][25] - The company is looking to build a pipeline of differentiated assets to extend its leadership position in NASH [25][88] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing demand for Risdifa and the company's strong positioning in the current macroeconomic environment [28] - The management team anticipates robust year-over-year net sales growth in 2025, despite expected increases in gross-to-net discounts as payer contracts are established [29][30] Other Important Information - The company has transitioned from an R&D-focused organization to a fully integrated commercial stage company following the approval of Risdifa [6] - The management highlighted the importance of patient education and awareness in driving treatment adoption [84] Q&A Session Summary Question: Expectations for growth trajectory for Risdifa with expanded label - Management expects continued growth and believes the market will expand significantly with the potential approval of SEMA [36][39] Question: Payer reauthorization requirements and patient persistency - Management is not concerned about reauthorizations and expects good persistency due to positive feedback from physicians and patients [42][45] Question: Status of European approval and launch strategy - The company is on track for a mid-year regulatory decision in Europe and is optimistic about the approval process [48][50] Question: Confidence in outcomes benefit on hepatic events - Management expressed confidence in the liver stiffness data and its relevance to patient outcomes [57][60] Question: Compliance rate and patient feedback on therapy - Early signs of adherence are promising, with patients reporting positive experiences on the drug [63][65] Question: Insights on gross-to-net pricing and payer discussions - Management is disciplined about gross-to-net pricing and anticipates it will evolve as payer contracts are established [68][106] Question: Feedback on DTC campaign and business development strategy - Positive feedback on the DTC campaign has been received, and the company is focused on building a pipeline to sustain its leadership position [82][87]