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© 2026 Madrigal Pharmaceuticals, Inc. All rights reserved. 4Q25 Financial Results Feb. 19, 2026 NASDAQ: MDGL
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Forward-looking Statements This presentation includes “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that are based on Madrigal’s beliefs and assumptions and on information currently available to it but are subject to factors beyond its control. Forward-looking statements reflect management’s current knowledge, assumptions, judgment and expectations regarding future performance or events. Forward-looking statements include all statements that are not historical facts; statements referenced by forward-looking statement identifiers; and statements regarding: potential future growth of Rezdiffra (resmetirom) sales; expected commercial insurance coverage for Rezdiffra; the expected benefit of Madrigal’s intellectual property; Madrigal’s ability to obtain full approval for Rezdiffra in the United States and Europe; expectations regarding Madrigal’s clinical development plans and related timelines; Madrigal’s leadership position in the MASH sector; the potential impact of positive results from the MAESTRO-NASH OUTCOMES trial; the potential benefit of Rezdiffra in patients with compensated MASH cirrhosis; the competitive landscape and market dynamics; estimates of patients diagnosed with MASH and market opportunities; and strategies, objectives and commercial opportunities, including potential prospects or results. Forward-looking statements can be identified by terms such as “accelerate,” “achieve,” “allow,” “anticipates,” “appear,” “be,” “believes,” “can,” “confidence,” “continue,” “could,” “demonstrates,” ”design,” “estimates,” “expectation,” “expects,” “forecasts,” “future,” “goal,” “help,” “hopeful,” “inform,” “intended,” “intends,” “may,” “might,” “on track,” “planned,” “planning,” “plans,” “positions,” “potential,” “powers,” “predicts,” ”predictive,” “projects,” “seeks,” “should,” “will,” “will achieve,” “will be,” “would”, “future” or similar expressions and the negatives of those terms. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: the assumptions underlying the forward-looking statements; risks related to obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections; the challenges with the commercialization of a new product; our history of operating losses and the possibility that we may never achieve or maintain profitability; risks associated with meeting the objectives of Madrigal’s clinical trials, including, but not limited to Madrigal’s ability to achieve enrollment objectives concerning patient numbers (including an adequate safety database), outcomes objectives and/or timing objectives for trials for any product candidate; any delays or failures in enrollment, and the occurrence of adverse safety events; risks related to the effects of Rezdiffra’s mechanism of action or any other product candidate; market demand for and acceptance of Rezdiffra; the potential inability to raise sufficient capital to fund ongoing operations as currently planned or to obtain financing on acceptable terms; our ability to service indebtedness and otherwise comply with debt covenants; outcomes or trends from competitive trials; future topline data timing or results; our ability to prevent and/or mitigate cyber-attacks; the uncertainties inherent in clinical testing; uncertainties concerning analyses or assessments outside of a controlled clinical trial; our ability to enter into strategic transactions and realize the benefits of any such transaction; our ability to obtain, maintain and protect our intellectual property; and changes in laws and regulations applicable to our business and our ability to comply with such laws and regulations. Undue reliance should not be placed on forward looking statements, which speak only as of the date they are made. Madrigal undertakes no obligation to update any forward-looking statements to reflect new information, events, or circumstances after the date they are made, or to reflect the occurrence of unanticipated events. Please refer to Madrigal’s submissions filed with the U.S. Securities and Exchange Commission (“SEC”) for more detailed information regarding these risks and uncertainties and other factors that may cause actual results to differ materially from those expressed or implied. Madrigal specifically discusses these risks and uncertainties in greater detail in Part I, Item 1A of its Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on February 26, 2025, and as updated from time to time by Madrigal’s other filings with the SEC. 2
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Accelerating U.S. MASH Market Growth Building an Industry-Leading MASH Pipeline Delivering on Best-in-Industry Rezdiffra Launch 4Q25 Earnings Call Agenda 3
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4 2024 FDA Approval for First MASH Medicine 2025 Building the Foundational Therapy 2026+ Shaping Our Future Landmark FDA approval of Rezdiffra on March 14, 2024 Rezdiffra net sales of nearly $1B in first full year of launch New U.S. Rezdiffra patent extends value to 2045 Rezdiffra global expansion starting with Germany Rezdiffra + oral GLP-1 As the Market Leader, We are Shaping Our Future and the Future of MASH Maximizing Rezdiffra Building our pipeline 1. Pending successful completion of MAESTRO-NASH OUTCOMES trial and FDA approval. F4c indication could double opportunity (2027 readout) 1 Accelerate Rezdiffra evidence generation Rezdiffra + DGAT-2 inhibitor Rezdiffra + siRNA targets (6) Drive and shape a growing MASH market Robust Rezdiffra net sales growth expected in 2026 Continue to build pipeline through BD
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$14.6M $62.2M $103.3M $137.3M $212.8M $287.3M $321.1M 2Q24 3Q24 4Q24 1Q25 2Q25 3Q25 4Q25 5 Net Sales: Continuing to Generate Strong Uptake Net Sales: Continuing to Generate Strong Uptake First full year of launch: $958.4M in net sales 4Q25 net sales $321.1M $958.4M FY25 net sales Generated nearly $1 billion in net sales in first full year of launch Rezdiffra: Executing on Best-in-Industry Launch
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6 Successfully Building a Specialty Market and a Mega Blockbuster Brand First MASH medicine; best-in- disease profile Wired the system practice by practice to establish care pathways Built the right team; executed with long- term mindset; educated prescribers Secured first-line access through disciplined contracting strategy
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<12% Significant Opportunity in 315,000 Target Market2 >2,000 >6,800 >11,800 >17,000 >23,000 >29,500 >36,250 2Q24 3Q24 4Q24 1Q25 2Q25 3Q25 4Q25 Steadily Adding Patients in a Market Positioned for Significant Expansion 7 1.Specialty pharmacy and distribution dispense data; 2. Forian claims data. Patients on Rezdiffra: Steadily Adding Patients1 Penetrated in F2/F3 MASH as of 4Q25
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U.S. F2/F3 MASH Population has Increased Nearly 50 Percent Since YE 2023 8 MASH Market Growth Since YE 20231 315K 460K 46% Key Drivers of MASH Market Growth Since Launch Increasing diagnosis Increasing patients under specialist care Increasing disease awareness Diagnosed MASH Pop. Diagnosed w/ F2/F3 F2/F3 Target Market YE 2023 YE 2025 1.9M 525K 680K 315K 460K 1.5M 1. Estes et al. (F2/F3 staging); Forian claims data. F2/F3 Target Market
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MASH is Similar to Other Large Therapeutic Categories Where Additional Therapies Grow the Market Over Time Source: Evaluate Pharma; IBD: Inflammatory bowel disease; RA: Rheumatoid arthritis. 9 Total Global Sales by Therapeutic Category in 2024 ~$0.2B ~$23B ~$26B ~$28B Therapeutic Category MASH IBD RA Psoriasis # of approved therapies in 2025 2 19 13 14 Year first therapy was approved 2024 1998 1999 2004
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Rezdiffra is the Foundational Therapy in MASH Driven by its Compelling Profile 1. Harrison SA, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024;390(6):497-509; T2D: Type 2 diabetes. 10 10 Rezdiffra Mechanism of Action Liver-directed MASH Efficacy Consistent across patient subtypes (e.g., T2D) 1 Tolerability Well-tolerated1 Adherence High1 Route of Administration Once-daily pill; no titration
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Expansion into F4c has the Potential to Double the Opportunity for Rezdiffra1 F4c outcomes trial data expected in 2027 Estimated addressable U.S. patient population ~245,000 Rezdiffra tracking to be first to market No treatments available today 2-year OLE data provides confidence in MAESTRO- NASH OUTCOMES 2 Higher urgency to treat given 42x higher risk of liver- related mortality Significant Unmet Need in Compensated MASH Cirrhosis (F4c) 1. Pending successful completion of MAESTRO-NASH OUTCOMES trial and FDA approval; 2. 2-year OLE data are from the F4c cohort of the Phase 3 MAESTRO-NAFLD-1 trial; OLE: Open-label extension. 11
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Madrigal is Shaping the Future of MASH • Treatment available in F2/F3 • Treatment available in F2-F4c • Combination therapy strategies undefined • Combination therapies to drive better outcomes and tailored treatment approaches • Low awareness, diagnosis and treatment • Market in infancy • Awareness and screening expand diagnosed and treated patient population is the foundational therapy MASH Treatment Today MASH Treatment in the Future MASH is a complex, heterogeneous disease with a broad spectrum of comorbidities. Its future will include multiple therapies, combinations and personalized regimens. 12
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Madrigal is Uniquely Positioned to Extend its Leadership in MASH Deliver transformational outcomes data, securing full approval from F2-F4c Advance combination therapies anchored by Rezdiffra Invest in new modalities, including those that enable patient-specific care Execute disciplined, capital-efficient clinical development (quick go/no-go) Our R&D strategy is to build the industry-leading MASH pipeline through targeted business development and internal innovation, leveraging Rezdiffra as the foundational therapy 13
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14 Reducing CSPH Risk, Lowers Liver Related Events; Rezdiffra 2-Year F4c OLE Data Support its Potential in F4c 1. Alkouri, N et al. Treatment with resmetirom for up to two years led to improvement in liver stiffness, fibrosis biomarkers, fibrosis scores and portal hypertension in 122 patients with compensated MASH cirrhosis [Presentation], EASL Congress, May 7-12, 2025, Amsterdam, the Netherlands; CSPH: Clinically significant portal hypertension; OLE: Open-label extension. Clinical Significance of CSPH as an Indicator of Outcomes in F4c • CSPH responsible for most severe complications of cirrhosis (F4c); precursor to decompensation • Event rates are higher once patients have CSPH • Lowering risk of CSPH reduces liver-related events • 2-year OLE F4c data demonstrate 65% of Rezdiffra patients with CSPH at baseline shifted into a lower-risk category • Similar patient populations in OLE and MAESTRO-NASH OUTCOMES Rezdiffra shifted patients from CSPH to lower risk categories, supporting the potential clinical benefit of Rezdiffra in F4c No/Low CSPH 34% No/Low CSPH 42% Probable CSPH 24% Probable CSPH 23% CSPH 100% CSPH 41% CSPH 35% Baseline Year 1 Year 2 1
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Image adapted from: Noureddin M. MASH clinical trials and drugs pipeline: An impending tsunami. Hepatology. 2025;82(5):1325-1340. We’re Building Our Pipeline with the Most Promising Targets Brain Heart Stomach Kidney Pancreas Intestines Adipose Liver LOXL2 inhibitor ASK1 inhibitor Mitochondrial pyruvate carrier Pan-caspase inhibitor Targeting lipotoxicity & cell death Targeting inflammation Targeting fibrosis Citrate G3P ACL Acetyl-CoA ACC Malonyl-CoA FASN SCD Fatty acyl-CoA DGAT-2 MoGAT2 TG Targeting lipid carbohydrate metabolism ACC inhibitor FASN inhibitor SCD1 inhibitor DGAT-2 inhibitor FGF21 FGF19 CCR2/CCR5 inhibitor Mitochondrial uncoupler SGLT1/2 inhibitor GLP-1/GIP GLP-1 GLP-1/glucagon dual agonists FXR agonist Galectin-3 inhibitor Mechanisms of action MASH asset MASH Disease Pathways and Potential Mechanisms Hepatoprotective Structurally engineered fatty acid Genetically focused drugs (e.g., siRNA) PPAR agonist THR-beta agonist Cyclophilin inhibitor 15
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Adding a New Modality to Our Portfolio: siRNA Targets for the Treatment of MASH GalNAc: N-acetylgalactosamine; IND: Investigational new drug. Development Stage Preclinical Mechanism of Action Precisely degrade mRNA thereby reducing protein production associated with steatosis Rationale • siRNA is validated in MASH; offers broad efficacy or more tailored approaches • GalNAc-siRNA modality well- established; highly liver targeted • Combine with resmetirom to develop next-generation combination MASH therapies Route of Administration Injectable Small Interfering RNA (siRNA) Next Steps: Initiation of IND-enabling activities 16
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Oral DGAT-2 Inhibitor (Ervogastat) Rationale and Next Steps Development Stage Completed Phase 2b1 Mechanism of Action Blocks final step of triglyceride assembly to reduce steatosis Rationale • Complementary mechanisms; potential to address production and clearance of liver fat • Phase 2b data demonstrate impressive MRI-PDFF reduction and clean safety profile • Combine with resmetirom to drive better anti-fibrotic efficacy Route of Administration Oral Next Steps: DDI study in 2026; Phase 2 combination study anticipated to start in 2027 following regulatory discussions DGAT-2 Inhibitor (ervogastat) 17 1. Ervogastat monotherapy Phase 2b study completed by Pfizer; drug-drug (resmetirom/ervogastat) interaction study expected to initiate in 2026; DGAT-2: Diacylglycerol O-acyltransferase 2; MRI- PDFF: Magnetic resonance imaging-proton density fat fraction; DDI: Drug-drug interaction .
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Oral GLP-1 (MGL-2086) Rationale and Next Steps IND: Investigational new drug; SAD: Single ascending dose. Development Stage IND complete Mechanism of Action Indirect; decreases caloric intake thereby reducing free fatty acid delivery to the liver Rationale • Strong real-world use supporting combo of GLP-1s and resmetirom • Resmetirom patients with ≥5% weight loss see enhanced antifibrotic effect • Combine so the right amount of weight loss potentiates resmetirom’s anti-fibrotic effect Route of Administration Oral Next Steps: Phase 1 SAD study to begin 2Q26 Oral GLP-1 (MGL-2086) 18
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MOA Indication Preclinical Phase 1 Phase 2 Phase 3 Launched THR-β agonist MASH F2/F3 THR-β agonist MASH F4c Ervogastat/resmetirom combo1 Oral DGAT-2 inhibitor MASH MGL-2086/resmetirom combo2 Oral GLP-1 receptor agonist MASH siRNA combo/resmetirom combo siRNA (6) MASH Additional MASH Assets in varying stages of development Exploratory oral assets (3) MASH Advancing an Industry-Leading MASH Pipeline to Transform Patient Care 1. Ervogastat monotherapy Phase 2b study completed by Pfizer; drug-drug (resmetirom/ervogastat) interaction (DDI) study expected to initiate in 2026; Phase 2 combination study expected to initiate in 2027 following regulatory discussions; 2. MGL-2086 Phase 1 single ascending dose (SAD) study expected to initiate in 2Q26; MOA: Mechanism of action. 19
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Consolidated Statement of Operations: 4Q25 20 1. In thousands except for basic and diluted loss per common share and average number of common shares outstanding; 2.Operating expenses include $25.8 million and $17.7 million of non-cash stock-based compensation expense in 4Q25 and 4Q24, respectively and $98.1M and $79.9M in FY25 and FY24, respectively. Basic and diluted weighted average common shares outstanding not inclusive of convertible preferred stock (2,369,797) and warrants (pre-funded and other; 3,625,244). Three Months Ended Dec. 31 (in thousands)1 2025 2024 Revenues: Product revenue, net $321,083 $103,320 Operating expenses: Cost of sales $24,448 $3,445 Research and development $116,268 $25,648 Selling, general and administrative $239,976 $141,224 Total operating expenses2 $380,692 $170,317 Loss from operations ($59,609) ($66,997) Interest income $9,459 $11,079 Interest expense ($8,297) ($3,498) Other expense, net ($128) -- Net loss ($58,575) ($59,416) Basic and diluted net loss per common share ($2.57) ($2.71) Basic and diluted weighted average number of common shares outstanding 3 22,829,067 21,929,425 Strong Balance Sheet $988.6M in cash, cash equivalents, restricted cash and marketable securities as of Dec. 31, 2025
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Madrigal is Well-Positioned for Continued Value Creation in 2026 and Beyond 21 $958.4M In first full year of launch Data anticipated in 2027 could double the opportunity1 Leading the Fight Against MASH Rezdiffra F2/F3 Launch F4c Outcomes Indication Expansion Building Our Pipeline Pipeline programs >10 1. Pending successful completion of MAESTRO-NASH OUTCOMES trial and FDA approval.
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© 2026 Madrigal Pharmaceuticals, Inc. All rights reserved. 4Q25 Financial Results Feb. 19, 2026 NASDAQ: MDGL