Madrigal Pharmaceuticals : Rezdiffra Approval Presentation

Rezdiffra (resmetirom)

FDA Approval

Conference Call

March 2024

NASDAQ: MDGL

© 2024 Madrigal Pharmaceuticals. All rights reserved.

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: Rezdiffra (resmetirom) and its expected use for treating NASH with moderate to advanced fibrosis; the initiation of the commercial launch of Rezdiffra including statements regarding commercial insurance and the anticipated time to fill prescriptions; estimates of patients diagnosed with NASH and market opportunities; the relationship between NASH progression and adverse patient outcomes; the estimated clinical burden of uncontrolled NASH; analyses for patients with NASH with moderate to advanced fibrosis concerning potential progression to cirrhosis, decompensated cirrhosis, liver transplant or death; cardiovascular risks, comorbidities and outcomes; health economics assessments or projections; indicating Rezdiffra has been shown to improve the fibrosis that is associated with progression to cirrhosis and its complications and resolve the underlying inflammation that drives the disease; projections or objectives for obtaining full approval for Rezdiffra (resmetirom), including those concerning potential clinical benefit to support potential full approval; regarding post-approval requirements and commitments; reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality; treatment paradigm; improved liver enzymes, fibrosis biomarkers and imaging tests; the potential efficacy and safety of Rezdiffra (resmetirom) for noncirrhotic NASH patients and cirrhotic NASH patients; possible or assumed future results of operations and expenses, business strategies and plans (including ex-US. Launch/partnering plans); research and development activities, the timing and results associated with the future development of Rezdiffra (resmetirom), the timing and completion of projected future clinical milestone events, including enrollment, additional studies, the potential to support an additional indication for Rezdiffra (resmetirom) in patients with well-compensated NASH cirrhosis; optimal dosing levels for Rezdiffra (resmetirom); potential NASH or NAFLD and potential patient benefits with Rezdiffra (resmetirom), including future NASH resolution, safety, fibrosis treatment, cardiovascular effects, lipid treatment, and/or biomarker effects with Rezdiffra (resmetirom); 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," inform," "intended," "intends," "may," "might," "on track," "planned," "planning," "plans," "positions," "potential," "powers," "predicts," "predictive," "projects," "seeks," "should," "will," "will achieve," "will be," "would" 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 of obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections; the challenges with the commercial launch of a new product, particularly for a company that does not have commercial experience; risks associated with meeting the objectives of Madrigal's clinical studies, 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 Madrigal's studies; any delays or failures in enrollment, and the occurrence of adverse safety events; risks related to the effects of Rezdiffra's (resmetirom's) mechanism of action; enrollment and trial conclusion uncertainties; market demand for and acceptance of our product; the potential inability to raise sufficient capital to fund ongoing operations as currently planned or to obtain financings on terms similar to those arranged in the past; the ability to service indebtedness and otherwise comply with debt covenants; outcomes or trends from competitive studies; future topline data timing or results; our ability to prevent and/or mitigate cyber attacks; the timing and outcomes of clinical studies of Rezdiffra (resmetirom); the uncertainties inherent in clinical testing; and uncertainties concerning analyses or assessments outside of a controlled clinical trial. 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, or 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 the sections appearing in Part I, Item 1A of its Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on February 28, 2024, and as updated from time to time by Madrigal's other filings with the SEC.

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Agenda

1 Introduction

Bill Sibold

Chief Executive Officer Madrigal Pharmaceuticals

2	Disease Overview and
Current Treatment Paradigm

Stephen Harrison, M.D.

Medical Director, Pinnacle Clinical Research; Visiting Professor of Hepatology, Oxford; Lead Principal Investigator of the MAESTRO studies

3 Review of Rezdiffra Label and Clinical Data

Becky Taub, M.D.

Chief Medical Officer and President of R&D Madrigal Pharmaceuticals

4 Rezdiffra Commercial Strategy

Bill Sibold

5 Q&A

Bill Sibold, Stephen Harrison, Becky Taub and Mardi Dier

Chief Financial Officer

Madrigal Pharmaceuticals

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Terri's Story

Terri is a patient leader in the NASH community

Her story illustrates the serious burden of NASH progression

• She was told: "You have fatty liver, but don't worry about it"
• NASH cirrhosis was later detected during gallbladder surgery
• Developed ascites, hepatic encephalopathy and then hepatocellular carcinoma
• Ultimately had liver transplant, but difficult post-transplant experience

NASH, nonalcoholic steatohepatitis. Ascites, excess abdominal fluid and swelling. Hepatic encephalopathy, impaired cognitive function due to the liver's inability to filter toxins from the blood.

Hepatocellular carcinoma, liver cancer.

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Key Takeaways for Today's Call

Rezdiffra approval is		First-in-class label		Set to deliver
an unprecedented		positions Rezdiffra as		successful launch and
milestone		foundational therapy		maximize potential

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Strong Label Positions Rezdiffra as Foundational Therapy

Indicated for the treatment of NASH with moderate to advanced liver fibrosis (F2/F3)

NOW APPROVED

No biopsy requirement in label

Once-daily, oral; simple dosing

No contraindications; no boxed warning; no monitoring requirements beyond SOC

Landmark label for first FDA-approved medicine for NASH

sets standard for potential future treatments

Source: Rezdiffra prescribing information. West Conshohocken, PA: Madrigal Pharmaceuticals, Inc.; 2024. SOC, standard of care

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Disease Overview

and Current

Treatment Paradigm

NASH is a Chronic and Progressive Liver Disease

NAFLD: Nonalcoholic Fatty Liver Disease:

Entire spectrum of fatty liver disease in individuals without significant alcohol consumption

	NAFL:	NASH:
Normal Liver	Nonalcoholic

NASH

Cirrhosis

Nonalcoholic Fatty Liver	Steatohepatitis

	▪ Isolated steatosis	▪ Steatosis
Fat accumulation	(fat in ≥5% of	▪ Ballooning
	hepatocytes)	▪ Inflammation

with Fibrosis

▪ F1: fibrosis stage 1 =	▪ F4: fibrosis stage 4 =
Mild	Cirrhosis

Moderate to Advanced

• F2: fibrosis stage 2
• F3: fibrosis stage 3

NASH is the more advanced form of NAFLD, which can progress to cirrhosis,

liver failure, or result in premature death1-5

Hepatocytes, liver cells. Steatosis, excess fat in liver cells. Steatohepatitis, build up of excess fat in liver cells causing inflammation and damage.

1. Sheka AC, et al. JAMA. 2020;323(12):1175-83. 2. Alkhouri N, McCullough AJ. Gastroenterol Hepatol (N Y). 2012;8(10):661-8. 3. EASL-EASD-EASO. J Hepatol. 2016;64:1388-402. 4. Diehl AM, Day C. NEJM. 2017;377:3063-72. 5. Honda et al. Int J Mol Sci. 2020;21:4039.

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The NASH Patient Journey, Diagnosis and Treatment

Initial Suspicion		Diagnosis & Risk Assessment		Treatment for Moderate to Advanced
& Referral		at Hep/GI		(F2/F3) NASH Patients

Initial	Referral to
suspicion at	a specialist
primary care	(Hep/GI)

Confirmation of NASH diagnosis

and fibrosis using NITs

• Ongoing Diet, Exercise and Co-morbidity management

Prior Approach: TODAY'S Approach:

No treatments available to halt or improve fibrosis; resolve NASH

Hep, hepatologist; GI, gastroenterologist; NITs, noninvasive tests.

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Goal: Treat Before Negative Patient Outcomes Occur

Up to 17X Higher Risk of Liver-Related Mortality in Patients with NASH with Moderate to Advanced Fibrosis1

17X

higher

risk

10X

higher

risk

1.41X

0

F0

F1

F2

F3

~22%

of patients with F3 fibrosis progress to cirrhosis within 2 years2

Goal: Treat NASH with moderate to advanced fibrosis before negative patient outcomes occur

1. Angulo P, et al. Gastroenterology. 2015;149:389-397. 2. Loomba R, Adams L. Hepatology. 2019;70(6):1885-1888.

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