Financial Data and Key Metrics Changes - Madrigal Pharmaceuticals reported net sales of $213 million for Q2 2025, representing a 55% increase quarter-over-quarter [12][33] - The annualized net sales for ResDiffera are now exceeding $800 million, indicating strong demand and execution [12][37] - R&D expenses decreased to $54.1 million from $71.1 million year-over-year, primarily due to lower clinical trial costs [34] - SG&A expenses increased to $196.9 million from $105.4 million year-over-year, driven by higher commercial launch activities [35] Business Line Data and Key Metrics Changes - ResDiffera's quarterly run rate has surpassed $200 million, positioning it among the best specialty launches in the last decade [5] - The number of patients on ResDiffera increased to over 23,000, up from more than 17,000 at the end of Q1 2025 [12] - Physician penetration has reached 80% among the top 6,000 target prescribers, with 60% of a broader 14,000 target prescriber base having written prescriptions by the end of Q2 [14][15] Market Data and Key Metrics Changes - The U.S. market for ResDiffera is expected to expand significantly, with only about 7% of the 315,000 diagnosed F2F3 NASH patients currently being treated [13] - The company is preparing for international expansion, starting with Germany, where it estimates a target population of approximately 370,000 patients [25][26] Company Strategy and Development Direction - Madrigal is focused on maximizing ResDiffera's value and expanding its leadership in the NASH market through geographic expansion and new indications [4][6] - The company has secured a new U.S. patent extending protection for ResDiffera to February 2045, enhancing its long-term growth potential [9][11] - Plans to develop a combination therapy with a newly licensed oral GLP-1 are underway, aiming to optimize treatment for NASH patients [22][23] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing demand for ResDiffera and its ability to maintain growth despite potential competition from GLP-1 therapies [51][52] - The company anticipates that the upcoming GLP-1 launch will raise awareness and drive broader screening, ultimately benefiting ResDiffera [20][21] - Management highlighted the importance of maintaining a disciplined approach to gross-to-net dynamics as the company navigates its launch phase [44][46] Other Important Information - Madrigal has entered into a $500 million senior secured credit facility to support its ongoing launch and business development activities [36] - The company is preparing for a potential launch in Europe, with a focus on Germany, where it has already established a strong foundation [24][26] Q&A Session Summary Question: Can you expand on gross to net and inventory dynamics in the quarter? - Management indicated that gross to net will be choppy early in the launch, with expectations for more impact in the second half of the year [41][44] Question: How do you foresee maintaining growth with the entrance of GLP-1 therapies? - Management expects to continue adding patients and believes that the strong demand will persist through the GLP-1 launch [52][55] Question: Can you provide details on the selection process for the new oral GLP-1? - The selection was systematic, focusing on favorable stability and pharmacokinetic profiles, leading to the choice of SYH-2086 [61][62] Question: What is the expected launch curve in Europe compared to the U.S.? - Management believes that the European launch will benefit from prior preparation and existing guidelines, with revenue recognition expected more in 2026 [79] Question: Can you provide numbers around the gross to net range for specialty drugs? - Management confirmed that the gross to net range is expected to fall within 20% to 30%, based on extensive experience and current contracting negotiations [82][84]

Financial Data and Key Metrics Changes - The company ended Q1 2025 with $150 million in cash, cash equivalents, and short-term investments, an increase from $132 million at the end of 2024 [22] - R&D expenses were $15.8 million for Q1 2025, down from $21.5 million in the same period of 2024 [22] - The net loss for Q1 2025 was $19.6 million, or $0.26 per share, compared to a net loss of $24.4 million, or $0.34 per share, for Q1 2024 [23] Business Line Data and Key Metrics Changes - The company is focused on the development of pemidutide, with significant R&D investments directed towards its clinical trials [8][22] - The IMPACT Phase 2b MATCH trial has enrolled 212 participants, enhancing the study's power compared to the original target [12] Market Data and Key Metrics Changes - The company is expanding into alcohol use disorder (AUD) and alcohol liver disease (ALD), both of which have significant unmet medical needs [8][10] - The market research indicates that a drug like pemidutide, which reduces alcohol consumption and liver inflammation, would be well-received by patients and physicians [17] Company Strategy and Development Direction - The company aims to establish pemidutide as a foundational treatment across multiple fibrotic liver diseases, including NASH, AUD, and ALD [10][18] - The upcoming readout of the IMPACT Phase 2b MATCH trial is expected to be a transformative event for the company, with plans for Phase III trials in NASH following successful results [24] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving the trial's key efficacy and safety objectives for pemidutide, which could become the first therapy to achieve statistical significance on NASH endpoints at 24 weeks [7][13] - The company anticipates 2025 to be a transformative year, with significant milestones expected in clinical development [24] Other Important Information - The company has entered into a credit facility with Hercules Capital for up to $100 million, providing flexibility to support the development of pemidutide [8][20] - The facility includes a $15 million upfront funding and additional tranches available based on milestones [21] Q&A Session Summary Question: Can you provide commentary on the distribution of F2 and F3 in the Phase 2b population? - Management indicated that the demographics of the final qualifying population will be similar to other studies, but precise numbers cannot be disclosed yet [28] Question: What is the ideal population for pemidutide post-IMPACT? - The focus is on treating NASH with obesity, as a significant percentage of NASH patients are obese, which is a key factor in the treatment strategy [30] Question: How are you handling study discontinuations? - Management reported satisfaction with the discontinuation rates and stated that data will be available at the time of the readout [38] Question: How important is weight loss in the study? - Weight loss is crucial, as it impacts the treatment of NASH patients, and the company aims to achieve clinically significant weight loss [41] Question: Will you consider taking a higher dose into Phase III? - The company is strongly considering the 2.4 mg dose for Phase III due to its expected better weight loss outcomes [49] Question: What is the expected range of placebo responses? - The company anticipates a placebo response range of 7% to 13% based on historical data and the trial's design [90] Question: Will you discuss NASH F4 cirrhosis with the FDA? - The company intends to discuss F4 with the FDA and believes it can be successful in this area [80]