Core Insights - Madrigal Pharmaceuticals has successfully launched Rezdiffra (resmetirom) for nonalcoholic steatohepatitis (NASH) in April 2024, achieving net sales of $137.3 million in Q1, surpassing the $100 million per quarter threshold [1] Company Performance - The drug Rezdiffra has shown strong market performance shortly after its launch, indicating a robust demand in the NASH treatment space [1] Market Context - The success of Rezdiffra reflects the growing interest and investment in biotech stocks, particularly those focused on FDA-regulated industries and significant health conditions like NASH [1]

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]

Core Insights - Madrigal Pharmaceuticals announced positive two-year results from the Phase 3 MAESTRO-NAFLD-1 trial of Rezdiffra, showing significant improvements in liver health metrics among patients with compensated MASH cirrhosis [1][2][3] Group 1: Study Results - The study involved 122 patients, with 113 completing two years of treatment, demonstrating a mean reduction of 6.7 kPa in liver stiffness, which is statistically significant [5][8] - 65% of patients with clinically significant portal hypertension (CSPH) at baseline moved to lower risk categories by year two, indicating a positive shift in patient outcomes [4][8] - Among patients with probable CSPH at baseline, 57% transitioned to the no/low CSPH category, further supporting the efficacy of Rezdiffra [4] Group 2: Safety and Tolerability - Rezdiffra was well-tolerated, with a low discontinuation rate due to adverse events; the most common side effects included diarrhea, COVID-19, and nausea [6][8] - Safety data were consistent with previous studies, reinforcing the drug's favorable safety profile [6] Group 3: Mechanism and Future Trials - Rezdiffra acts as a THR-β agonist, which is mechanistically supported to improve outcomes in patients with compensated MASH cirrhosis [7] - A larger placebo-controlled study is anticipated to confirm the benefits of Rezdiffra in this high-risk population, with ongoing trials expected to provide further insights [2][14] Group 4: Market Context - MASH is projected to become the leading cause of liver transplantation in the U.S., highlighting the urgent need for effective treatments [10][11] - An estimated 1.5 million patients have been diagnosed with MASH in the U.S., with Madrigal targeting approximately 315,000 patients with moderate to advanced fibrosis [12]

Group 1 - The article highlights the focus on Madrigal Pharmaceuticals, Inc. (NASDAQ: MDGL), particularly following its first quarter results and the approval of its drug candidate Rezdiffra as the first treatment for a specific condition [2] - The Biotech Forum community is actively discussing lucrative buy-write or covered call opportunities on selected biotech stocks, indicating a trend in investment strategies within the biotech sector [1] - The Biotech Forum offers a model portfolio featuring 12-20 high upside biotech stocks, along with live chat discussions and weekly research updates, showcasing a collaborative investment approach [2] Group 2 - The article does not provide any specific financial data or performance metrics related to Madrigal Pharmaceuticals or the broader biotech industry [3][4]

Core Viewpoint - Madrigal Pharmaceuticals reported a narrower loss in Q1 2025 compared to the previous year and exceeded revenue expectations due to strong sales of its newly launched drug Rezdiffra for metabolic dysfunction-associated steatohepatitis (MASH) [1][2][3] Financial Performance - The company reported a loss of $3.32 per share, better than the Zacks Consensus Estimate of a loss of $3.62, and significantly improved from a loss of $7.38 per share in the same quarter last year [1] - Total revenues for the quarter reached $137.3 million, all from Rezdiffra sales, surpassing the Zacks Consensus Estimate of $114 million [2] - Research and development expenses decreased by 38% to $44.2 million due to reduced clinical study costs and changes in inventory accounting [4] - Selling, general and administrative expenses rose to $167.9 million from $80.8 million year-over-year, attributed to increased commercial activities for Rezdiffra [5] - As of March 31, 2024, the company had cash, cash equivalents, and marketable securities totaling $848.1 million, down from $931.3 million at the end of 2024 [5] Product and Market Updates - Rezdiffra received accelerated FDA approval in March 2024, becoming the first approved therapy for MASH, with over 17,000 patients currently receiving treatment [3] - Madrigal has submitted a regulatory filing in the EU for Rezdiffra, with a decision expected in mid-2025 [8] - Ongoing studies, including the pivotal phase III MAESTRO-NASH biopsy study, aim to provide long-term safety and efficacy data to support full approval of Rezdiffra [9][10] - Positive two-year data from the MAESTRO-NAFLD-1 study indicated a significant reduction in liver stiffness among treated patients, reinforcing the drug's potential benefits [11][12][13] Stock Performance - Year-to-date, Madrigal shares have increased by 8.2%, outperforming the industry, which has seen a decline of 2.2% [6]

Group 1 - Madrigal reported a quarterly loss of $3.32 per share, better than the Zacks Consensus Estimate of a loss of $3.62, and an improvement from a loss of $7.38 per share a year ago, representing an earnings surprise of 8.29% [1] - The company posted revenues of $137.25 million for the quarter ended March 2025, surpassing the Zacks Consensus Estimate by 20.35%, compared to zero revenues a year ago [2] - Madrigal shares have increased approximately 8.2% since the beginning of the year, while the S&P 500 has declined by 5.3% [3] Group 2 - The current consensus EPS estimate for the coming quarter is -$3.31 on revenues of $137.59 million, and -$12.43 on revenues of $576.53 million for the current fiscal year [7] - The Zacks Industry Rank for Medical - Drugs is currently in the top 23% of over 250 Zacks industries, indicating a favorable outlook for the industry [8] Group 3 - The estimate revisions trend for Madrigal is mixed, resulting in a Zacks Rank 3 (Hold) for the stock, suggesting it is expected to perform in line with the market in the near future [6] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can be tracked by investors [5]

Financial Performance - For the three months ended March 31, 2025, the company recorded $137.3 million in product revenue, net, representing a 100% increase compared to the previous year[134]. - The cost of sales for the same period was $4.5 million, also reflecting a 100% increase due to the sales of Rezdiffra[135]. - Selling, general and administrative expenses increased by 108% to $167.9 million compared to $80.8 million in the previous year[133]. - The total operating expenses for the three months ended March 31, 2025, were $216.6 million, a 42% increase from $152.0 million in the same period last year[133]. - The net loss for the quarter was $73.2 million, a 50% improvement from a net loss of $147.5 million in the prior year[133]. Research and Development - Research and development expenses decreased by 38% to $44.2 million from $71.2 million in the prior year[133]. - Research and development expenses decreased to $44.2 million for the three months ended March 31, 2025, down 38% from $71.2 million in 2024[136]. - The company intends to selectively in-license or acquire rights to programs at all stages of development to diversify its portfolio and enhance its drug development capabilities[118]. Product Approval and Market Potential - The FDA approved Rezdiffra in March 2024, making it the first therapy for patients with MASH, and it became commercially available in April 2024[112]. - The company estimates approximately 1.5 million patients in the U.S. have been diagnosed with MASH, with about 525,000 having moderate to advanced fibrosis[115]. - The company plans to commercialize Rezdiffra in Europe, with a regulatory decision expected in mid-2025 and a potential launch starting in Germany in the second half of 2025[117]. Cash Flow and Financing - Cash, cash equivalents, restricted cash, and marketable securities totaled $848.1 million as of March 31, 2025, down from $931.3 million at the end of 2024, reflecting funding of operations[141]. - Net cash used in operating activities was $88.9 million in Q1 2025, a decrease of 40.3% from $149.2 million in Q1 2024[155]. - Net cash provided by investing activities was $163.9 million in Q1 2025, compared to $98.1 million in Q1 2024, primarily from sales and maturities of marketable securities[156]. - Net cash provided by financing activities was $8.6 million in Q1 2025, a significant drop from $573.7 million in Q1 2024, which included proceeds from a public offering[157]. - As of March 31, 2025, the outstanding principal under the Loan Facility was $115.0 million, with an interest rate of 9.95%[149]. - As of March 31, 2025, the company had drawn $115.0 million under the $250.0 million Loan Facility[160]. Future Outlook and Risks - The company anticipates continued significant losses until sufficient revenue is generated from Rezdiffra and other future products[142]. - The company has the ability to delay certain commercial and research activities due to liquidity concerns until those concerns are alleviated[142]. - There have been no material changes to market risks since December 31, 2024, and no near-term changes are anticipated[164]. - No significant changes to contractual obligations and commitments occurred during the three months ended March 31, 2025, compared to the previous fiscal year[163]. - The company received FDA approval for Rezdiffra in March 2024, with a tiered single-digit royalty payable to Roche on net sales[161]. - The company had approximately $89.1 million of obligations under agreements related to active pharmaceutical ingredients, expected to be paid through December 2027[162].

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]

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]

[Executive Summary & Recent Corporate Updates](index=1&type=section&id=Executive%20Summary%20%26%20Recent%20Corporate%20Updates) Madrigal's CEO highlighted Rezdiffra's successful launch and market foundation, with strong Q1 2025 results and key clinical data [CEO's Strategic Vision and Launch Success](index=1&type=section&id=CEO%27s%20Strategic%20Vision%20and%20Launch%20Success) Madrigal's CEO highlighted the successful launch of Rezdiffra, the first FDA-approved MASH treatment, reaching over 17,000 patients and establishing a strong market foundation - Madrigal has executed an exceptional launch of Rezdiffra, the first FDA-approved treatment for MASH, reaching over **17,000 patients** and building a strong foundation with healthcare providers and payers[3](index=3&type=chunk) - Rezdiffra is on track to become the foundational therapy across F2 to F4c MASH[3](index=3&type=chunk) - New Rezdiffra F4c late-breaking data from the MAESTRO-NAFLD-1 trial, showing its effect on the risk of clinically significant portal hypertension, will be shared at the EASL Congress[3](index=3&type=chunk) - A regulatory decision from the European Medicines Agency (EMA) for Rezdiffra is expected mid-year[3](index=3&type=chunk) [Key Highlights of Q1 2025 and Recent Events](index=1&type=section&id=Key%20Highlights%20of%20Q1%202025%20and%20Recent%20Events) The first quarter of 2025 saw significant achievements, including substantial net sales for Rezdiffra, continued patient adoption, and strong cash reserves, alongside key clinical data presentations and corporate appointments **First-quarter 2025 Rezdiffra Net Sales and Patient Adoption** | Metric | Value | | :-------------------------------- | :------------------- | | First-quarter 2025 Rezdiffra net sales | **$137.3 million** | | Patients on Rezdiffra (as of March 31, 2025) | **>17,000** | | Cash, cash equivalents, restricted cash and marketable securities (as of March 31, 2025) | **$848.1 million** | - Two-year compensated MASH cirrhosis (F4c) data from the MAESTRO-NAFLD-1 trial was selected as an oral late-breaker at the EASL Congress (May 7-10)[5](index=5&type=chunk) - David Soergel, M.D., was appointed Chief Medical Officer, and Rebecca Taub, M.D., was named Senior Scientific and Medical Advisor[5](index=5&type=chunk) - Jacqualyn Fouse, Ph.D., was appointed to the Board of Directors[5](index=5&type=chunk) [Clinical Development and Regulatory Updates](index=1&type=section&id=Clinical%20Development%20and%20Regulatory%20Updates) Madrigal provided detailed two-year results from the MAESTRO-NAFLD-1 trial's F4c arm, demonstrating significant reductions in liver stiffness and a consistent safety profile for Rezdiffra - Two-year results from the active-treatment open-label compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial (n=101) showed patients achieved a mean **6.7 kPa reduction in liver stiffness (VCTE)**, which was statistically significant from baseline[6](index=6&type=chunk)[7](index=7&type=chunk) - **51% of F4c patients** achieved a ≥ 25% reduction in liver stiffness, a magnitude associated with reduced progression to end-stage liver disease[7](index=7&type=chunk) - Rezdiffra's safety and tolerability profile in F4c patients was consistent with other clinical trials, with a low discontinuation rate due to adverse events[7](index=7&type=chunk) - Six Madrigal abstracts, including a late-breaking oral presentation on detailed two-year F4c data focusing on liver stiffness, fibrosis biomarkers, and the risk of clinically significant portal hypertension, were accepted for the EASL Congress (May 7-10, 2025)[7](index=7&type=chunk) - Madrigal will host an investor webcast on May 13, 2025, to review the detailed two-year F4c data[7](index=7&type=chunk) [Corporate Governance and Leadership Changes](index=2&type=section&id=Corporate%20Governance%20and%20Leadership%20Changes) Madrigal announced key leadership transitions, appointing a new Chief Medical Officer with extensive experience in metabolic and cardiovascular drug development, and adding an accomplished biotech executive to its Board of Directors - David Soergel, M.D., was appointed Chief Medical Officer in April, bringing over **20 years of leadership experience** in metabolic and cardiovascular disease drug development[7](index=7&type=chunk) - Rebecca Taub, M.D., Madrigal's founder and former CMO, transitioned to Senior Scientific and Medical Advisor[7](index=7&type=chunk) - Jacqualyn Fouse, Ph.D., an accomplished biotech executive with over **30 years of biopharmaceutical and financial leadership experience**, was appointed to Madrigal's Board of Directors in March 2025[7](index=7&type=chunk) [First-Quarter 2025 Financial Results](index=3&type=section&id=First-Quarter%202025%20Financial%20Results) Madrigal reported $137.3 million Q1 2025 product revenue, with higher operating expenses from launch and reduced cash [Revenue and Operating Expenses](index=3&type=section&id=Revenue%20and%20Operating%20Expenses) Madrigal reported its first product revenue of $137.3 million in Q1 2025, a significant increase from the prior year, with operating expenses rising due to commercial launch activities for Rezdiffra **Three Months Ended March 31, 2025 vs 2024 (in thousands)** | Metric | 2025 (in thousands) | 2024 (in thousands) | | :-------------------------------- | :------------------ | :------------------ | | Product revenue, net | **$137,250** | $0 | | Cost of sales | $4,513 | $0 | | Research and development | $44,172 | $71,237 | | Selling, general and administrative | $167,876 | $80,800 | | Total operating expenses | $216,561 | $152,037 | | Loss from operations | $(79,311) | $(152,037) | | Interest income | $9,370 | $8,334 | | Interest expense | $(3,297) | $(3,838) | | Net loss | $(73,238) | $(147,541) | | Basic and diluted net loss per common share | $(3.32) | $(7.38) | - Research and development expenses decreased by **$27.1 million** year-over-year, primarily due to a change in accounting for inventory costs following FDA approval of Rezdiffra in March 2024 and a reduction in clinical trial expense[11](index=11&type=chunk) - Selling, general and administrative expenses increased by **$87.1 million** year-over-year, primarily due to increases for commercial launch activities for Rezdiffra, including a corresponding increase in headcount, and an increase in stock compensation expense[11](index=11&type=chunk) [Balance Sheet Highlights](index=3&type=section&id=Balance%20Sheet%20Highlights) Madrigal's cash, cash equivalents, restricted cash, and marketable securities decreased to $848.1 million as of March 31, 2025, primarily due to funding operations **Balance Sheet Highlights (in thousands)** | Metric | March 31, 2025 | December 31, 2024 | | :------------------------------------------------ | :------------- | :---------------- | | Cash, cash equivalents, restricted cash and marketable securities | **$848,068** | $931,251 | | Total assets | $996,629 | $1,042,247 | | Current liabilities | $167,237 | $169,277 | | Long-term liabilities | $118,755 | $118,587 | | Stockholders' equity | $710,637 | $754,383 | | Total liabilities and stockholders' equity | $996,629 | $1,042,247 | - The decrease in cash, cash equivalents, restricted cash and marketable securities from **$931.3 million** at December 31, 2024, to **$848.1 million** at March 31, 2025, was attributable to funding of operations[11](index=11&type=chunk) [Conference Call Details](index=3&type=section&id=Conference%20Call%20Details) Madrigal hosted a conference call and webcast on May 1, 2025, to review its financial and operating results and provide a general business update - Madrigal hosted a webcast on May 1, 2025, at 8 a.m. EDT to review its financial and operating results and provide a general business update[9](index=9&type=chunk) - The webcast was accessible via the investor relations section of the Madrigal website, with an archived version available post-event[9](index=9&type=chunk) [Disease Overview: MASH](index=3&type=section&id=Disease%20Overview%3A%20MASH) MASH is a severe liver disease progressing to life-threatening complications, with a significant patient population targeted by Madrigal [Understanding MASH and its Progression](index=3&type=section&id=Understanding%20MASH%20and%20its%20Progression) Metabolic dysfunction-associated steatohepatitis (MASH) is a severe liver disease that can lead to life-threatening complications, including cirrhosis and liver failure, and is projected to become the leading cause of liver transplantation in the U.S - MASH (formerly NASH) is a serious liver disease that can progress to cirrhosis, liver failure, liver cancer, need for liver transplantation, and premature mortality[10](index=10&type=chunk) - MASH is expected to become the leading cause of liver transplantation in the U.S. and is already the leading cause among women[10](index=10&type=chunk) - Patients with moderate to advanced liver fibrosis (F2-F3) have a **10 to 17 times higher risk** of liver-related mortality, while those who progress to cirrhosis (F4) face a **42 times higher risk**[11](index=11&type=chunk)[12](index=12&type=chunk) - MASH is also an independent driver of cardiovascular disease, the leading cause of mortality for patients[12](index=12&type=chunk) [MASH Patient Population and Unmet Need](index=4&type=section&id=MASH%20Patient%20Population%20and%20Unmet%20Need) An estimated 1.5 million patients are diagnosed with MASH in the U.S., with Madrigal specifically targeting approximately 315,000 patients with moderate to advanced fibrosis who are under the care of liver specialists - An estimated **1.5 million patients** have been diagnosed with MASH in the U.S[13](index=13&type=chunk) - Madrigal is focused on reaching approximately **315,000 patients** with moderate to advanced fibrosis who are under the care of liver specialists[13](index=13&type=chunk) - The number of diagnosed patients with MASH with moderate to advanced fibrosis is expected to grow as disease awareness and prevalence increase[13](index=13&type=chunk) [Product Information: Rezdiffra](index=4&type=section&id=Product%20Information%3A%20Rezdiffra) Rezdiffra is an FDA-approved MASH treatment for moderate to advanced fibrosis, with critical safety information and potential side effects [Rezdiffra Indication and Usage](index=4&type=section&id=Rezdiffra%20Indication%20and%20Usage) Rezdiffra is an FDA-approved prescription medicine, used in conjunction with diet and exercise, for adults with MASH and moderate to advanced liver scarring (fibrosis), excluding those with cirrhosis - Rezdiffra is a prescribed medicine used along with diet and exercise to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver[14](index=14&type=chunk) - The indication is approved based on improvement of NASH and liver scarring (fibrosis), with ongoing studies to confirm the clinical benefit[14](index=14&type=chunk) - It is not known if Rezdiffra is safe and effective in children (under 18 years old)[14](index=14&type=chunk) [Important Safety Information and Side Effects](index=4&type=section&id=Important%20Safety%20Information%20and%20Side%20Effects) Patients considering Rezdiffra must inform their healthcare provider about existing medical conditions and all medications due to potential drug interactions and serious side effects, including liver injury and gallbladder problems - Patients should inform their healthcare provider about all medical conditions, including liver problems (other than NASH), gallbladder problems, pregnancy, and breastfeeding plans[15](index=15&type=chunk)[17](index=17&type=chunk) - Patients must disclose all medicines, including prescription, over-the-counter, vitamins, and herbal supplements, especially gemfibrozil, cyclosporine (not recommended with Rezdiffra), clopidogrel, or statins[15](index=15&type=chunk)[17](index=17&type=chunk) - Serious side effects include liver injury (hepatotoxicity) with symptoms like tiredness, nausea, vomiting, fever, rash, jaundice, or abdominal pain, and gallbladder problems (e.g., gallstones, inflammation) with symptoms like nausea, vomiting, fever, or severe abdominal pain[16](index=16&type=chunk)[18](index=18&type=chunk) - The most common side effects of Rezdiffra include diarrhea, nausea, itching, stomach (abdominal) pain, vomiting, dizziness, and constipation[18](index=18&type=chunk) [About Madrigal Pharmaceuticals](index=5&type=section&id=About%20Madrigal%20Pharmaceuticals) Madrigal Pharmaceuticals develops MASH therapeutics, with Rezdiffra as its first FDA-approved medication for moderate to advanced fibrosis [Company Overview and Product Focus](index=5&type=section&id=Company%20Overview%20and%20Product%20Focus) Madrigal Pharmaceuticals is a biopharmaceutical company dedicated to developing novel therapeutics for MASH, a liver disease with high unmet medical need, with Rezdiffra as its flagship FDA-approved product - Madrigal Pharmaceuticals, Inc. is a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH)[20](index=20&type=chunk) - Rezdiffra (resmetirom) is Madrigal's once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH[20](index=20&type=chunk) - Rezdiffra is the first and only medication approved by the FDA for the treatment of MASH with moderate to advanced fibrosis (consistent with stages F2 to F3)[20](index=20&type=chunk) - An ongoing Phase 3 outcomes trial is evaluating Rezdiffra for the treatment of compensated MASH cirrhosis (consistent with stage F4c)[20](index=20&type=chunk) [Forward-Looking Statements & Disclaimers](index=5&type=section&id=Forward-Looking%20Statements%20%26%20Disclaimers) Forward-looking statements are subject to risks and uncertainties, advising against undue reliance and directing readers to SEC filings [Nature and Risks of Forward-Looking Statements](index=5&type=section&id=Nature%20and%20Risks%20of%20Forward-Looking%20Statements) This section clarifies that the press release contains forward-looking statements subject to various risks and uncertainties, including regulatory approvals, financial performance, clinical trial outcomes, market demand, and competitive factors - The press release includes "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995[21](index=21&type=chunk) - Forward-looking statements are subject to risks and uncertainties, including those related to obtaining and maintaining regulatory approvals, potential operating losses, meeting clinical trial objectives, market demand for Rezdiffra, capital raising, debt compliance, competitive trials, cyber-attacks, and changes in laws and regulations[21](index=21&type=chunk)[22](index=22&type=chunk) - Undue reliance should not be placed on forward-looking statements, and Madrigal undertakes no obligation to update them[22](index=22&type=chunk) - Readers are directed to Madrigal's SEC filings (Form 10-K and 10-Q) for more detailed information regarding these risks and uncertainties[22](index=22&type=chunk) [Financial Statements](index=7&type=section&id=Financial%20Statements) Madrigal's condensed consolidated statements of operations and balance sheets for Q1 2025 detail financial performance and position [Condensed Consolidated Statements of Operations](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) This statement provides a summary of Madrigal's financial performance for the three months ended March 31, 2025, compared to the same period in 2024, detailing revenues, operating expenses, and net loss **Condensed Consolidated Statements of Operations (in thousands)** | Metric | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :------------------------------------------------ | :-------------------------------- | :-------------------------------- | | Product revenue, net | $137,250 | $0 | | Cost of sales | $4,513 | $0 | | Research and development | $44,172 | $71,237 | | Selling, general and administrative | $167,876 | $80,800 | | Total operating expenses | $216,561 | $152,037 | | Loss from operations | $(79,311) | $(152,037) | | Interest income | $9,370 | $8,334 | | Interest expense | $(3,297) | $(3,838) | | Net loss | $(73,238) | $(147,541) | | Basic and diluted net loss per common share | $(3.32) | $(7.38) | | Basic and diluted weighted average number of common shares outstanding | 22,061,214 | 20,001,560 | [Condensed Consolidated Balance Sheets](index=7&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This statement presents Madrigal's financial position, including assets, liabilities, and equity, as of March 31, 2025, and December 31, 2024 **Condensed Consolidated Balance Sheets (in thousands)** | Metric | March 31, 2025 | December 31, 2024 | | :------------------------------------------------ | :------------- | :---------------- | | Cash, cash equivalents, restricted cash and marketable securities | $848,068 | $931,251 | | Trade receivables, net | $61,428 | $53,822 | | Other current assets | $78,483 | $47,854 | | Other non-current assets | $8,650 | $9,320 | | Total assets | $996,629 | $1,042,247 | | Current liabilities | $167,237 | $169,277 | | Long-term liabilities | $118,755 | $118,587 | | Stockholders' equity | $710,637 | $754,383 | | Total liabilities and stockholders' equity | $996,629 | $1,042,247 |