Company Overview

December 2017

NASDAQ: MDGL

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Any statements, other than statements of historical facts, made in this presentation regarding our future financial or business performance, conditions, plans, prospects, trends, or strategies and other financial and business matters; our ability to obtain additional financing; the estimated size of the market for our product candidates, the timing and success of our development and commercialization of our anticipated product candidates; and the availability of alternative therapies for our target market, are, or may be deemed, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “could,” “should,” “would,” “anticipate,” “believe,” “estimate,” “continue,” “design,” “expect,” “intend,” “plan,” “potential,” “predict,” “seek” or the negative of these words and similar expressions and their variants may identify forward-looking statements.

These forward-looking statements reflect management’s current expectations, are based on certain assumptions and involve certain risks and uncertainties, which change over time. Our actual results may differ materially from the results discussed in these forward-looking statements due to various factors. Important factors that may cause actual results to differ materially from the results discussed in these forward-looking statements include, but are not limited to, risks related to securing and maintaining relationships with collaborators; risks relating to our clinical trials; risks relating to the commercialization, if any, of our proposed product candidates (such as marketing, regulatory, product liability, supply, competition, and other risks); dependence on the efforts of third parties; dependence on intellectual property; and risks related to our cash resources and ability to obtain working capital to fund our proposed operations. Further information regarding on the factors that could affect our business, financial conditions and results of operations are contained our filings with the U.S. Securities and Exchange Commission, which are available at www.sec.gov. These forward-looking statements represent management’s expectations as of the date hereof only, and we specifically disclaim any duty or obligation to update forward-looking statements as a result of subsequent events or developments, except as required by law.

Forward Looking Statements

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Madrigal Investment Highlights

Multiple Possible Value-Creating Catalysts over Next 18 Months

MGL-3196: First-in-Class Thyroid Hormone Receptor (THR)-β Agonist

Large & Underserved Markets in NASH & Genetic Lipid Disorders

Seasoned Management Team

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Madrigal’s Team: Led by an Experienced Management Team with Multiple Successful NDA/MAAs and Marketed Products

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Paul Friedman, M.D.

Chairman and CEO

Former CEO of Incyte

Former President of R&D at Dupont Pharmaceuticals

Marc Schneebaum

CFO, SVP

Former CFO, SVP at Synta

Former CEO at Predictive Biosciences

Rebecca Taub, M.D.

CMO, EVP R&D

Founder of Madrigal

Aided in discover of Eliquisand MGL-3196 at Roche

Pipeline: Madrigal has Two Phase 2 Programs with Multiple Near-Term Catalysts

Compound Indication Pre-Clinical Phase 1 Phase 2 Phase 3 Upcoming Catalysts

MGL-3196Thyroid Hormone Receptor-β (THR-β) Agonist

Nonalcoholic Steatohepatitis (NASH)

Phase 2 liver biopsy data

Phase 3 initiation

Familial Hypercholesterolemia

(FH)

Topline Phase 2 data

Phase 3 initiation

MGL-3745THR-β Agonist

NASH and FH

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Madrigal is focused on the development of its pipeline of THR-β agonists for the treatment of NASH and Familial Hypercholesterolemia (FH)

Unmet Need: Madrigal Aims to Treat Patients with NASH, a Large and Underserved Population

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~3-5% of the US population has NASH

NAFLD is the most common liver disease world-wide~25% of US population

Rapid progression, <2 years 25% of NASH Stage 3 fibrosis progress to cirrhosis

NASH is the most severe form of nonalcoholic fatty liver disease (NAFLD)

Characterized by inflammation and damage caused by a buildup of fat in the liver that leads to cirrhosis, fibrosis, and cell death

Develops most often in patients with obesity/metabolic syndrome, diabetes and dyslipidemia

NASH represents an indication with significant unmet need

Estimated to affect 3-5% of the US adult population

Expected to be the leading cause of liver transplant

There are currently no approved therapies for the treatment of NASH

American Liver Foundation, Aliment Pharmacology TherapyWGO (World Gastroenterology Organization) 2012

Mechanism of Action: The Importance of Liver THR-β in NASH

The THR-β receptor mediates the beneficial effects of thyroid hormone in the liver, on LDL-cholesterol and triglycerides, fatty liver and insulin sensitivity

THR-β agonists reduce liver fat through breakdown of fatty acids, and stimulate mitochondrial biogenesis in the NASH liver, thus, we believe, reducing lipotoxicity and improving liver function

We believe MGL-3196 has pleiotropic effects characteristic of an “ideal” NASH drug, with potential for addressing the underlying metabolic syndrome and hallmark features of NASH: steatosis/lipotoxicity, inflammation, ballooning, fibrosis (both directly and indirectly)

We believe treating NASH, rather than fibrosis, is key to addressing the disease

—Resolution of NASH, without reducing fibrosis, is an approvable endpoint —Recognition that liver fibrosis will decrease with time after NASH resolves (similar to reduction

of fibrosis as the liver regenerates after cure of HCV)

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We believe that MGL-3196, a selective THR-β agonist, will treat the underlying disease in NASH patients

Clinical Gastroenterology,2003;37(4):340-343 J Clin Endocrinol Metab.2016; 101(8:3204-3211

Hepatology. 2015;61:1547-54, Gastroenterology, 2015;149:389-97 Cell Biosci (2016) 6:46

Safety: Addressing Safety is Critical; Highly Selective THR-βAgonist Avoids Off-target Effects

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*** ******

***

p<.05*p<.01**P<.001***

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*** *** *****

T3

MGL-3196

High selectivety for THR- β may reduce toxicity, which is mediated through the systemic THR-α receptor

Very high protein binding, low penetration of tissues outside the liver including brain, heart and bone also expected to limit toxicity

MGL-3196 treated healthy volunteers and patients show normal central thyroid axis and vital signs

Unlike thyroid hormone (T3), MGL-3196 decreases cholesterol without impact on bone or cartilage in preclinical studies

Adverse Events (AEs) mostly mild, similar to control without safety or tolerability issues in Phase 1 and twelve week interim NASH Phase 2 readout

24d study in 40 week old diet-induced obese (DIO) mice on High Fat Diet (HFD) for 38 weeksIllustrative comparison of MGL-3196 to other molecules

Selective Mechanism of Action Strong Preclinical and Clinical Safety Data

J Med Chem. 2014;57(10):3912-3923 BMJ 2011;342:d2238

Preclinical: MGL-3196 Proof-of-Concept Well Established in Animal Models

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Reduced Hepatic TGs Improved Insulin Sensitivity

Reduced Liver Enzymes Improved Liver Histology All NASH Components

Liver Triglycerides

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* p<0.05

*

Insulin Tolerance Test (0.5 U/kg insulin)

ALT

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Liver Fat (Histology)

MGL-3196Control

Upper panels: 24d study in 17 wk old DIO mice (po, qd) on high fat diet (HFD) 13 wks; lower panels: 24d study in 40 wk old DIO mice on HFD 35 wks

Phase 1: Robust LDL and Triglyceride Lowering Established in 14 Day Multiple Ascending Dose Study

Once daily oral treatment led to highly statistically significant and dose-dependent up to ~30% reduction of apolipoprotein B (ApoB), total, LDL, non-HDL cholesterol; Strong trends in triglyceride reduction up to 60%; Near maximal effect at 80 mg dose

Change from Baseline (CFB) by mean % CFB calculated for each individual subject 24h after 14th dose; baseline value obtained just prior to first dose; ApoB, apolipoprotein B; Chol, total cholesterol; LDL-C, LDL cholesterol directly measured; Non-HDL-C, non-HDL cholesterol; TG, triglycerides (median %CFB)

*** p<0.001 ** p<0.01 * p≤0.05 “p≤0.1

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****

* *

*

*

“

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10Atherosclerosis 230 (2013) 373-380

Six dose cohorts, 36 total healthy volunteers dosed daily with MGL-3196 (5, 20, 50, 80, 100, or 200 mg) and 12 with placebo for 14 days

Healthy volunteers with slightly elevated LDL cholesterol (> 110 mg/dL)

Well-tolerated, appeared safe at all doses tested

No effect on vital signs, heart rate, central thyroid axis, or liver enzymes

Phase 2: MGL-3196 Trial Design is Targeted at Highly Relevant Primary and Secondary Endpoints

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Inclusion/Exclusion

NASH on liver biopsy: NAS≥4 with fibrosis

≥10% liver fat on MRI-PDFF

Include diabetics, statin therapy

Comparator/Arms

MGL-3196 or Placebo, once daily

Primary Endpoint

Reduction of liver fat (MRI-PDFF) at 12 weeks

Secondary Endpoints

NASH biomarkers and lipids at 12, 36 weeks

Repeat MRI-PDFF at 36 weeks

Liver biopsy at 36 weeks - reduction/resolution of NASH in patients on drug; reduction of fibrosis

Design

Stage

Drug MGL-3196

Blinded 2:1

Phase 2

Number of Patients

Centers

Treatment Duration

125, Fully Enrolled

~30, USA

36 Weeks

Study Overview Study Details

Phase 2: MGL-3196 Study Achieved Primary Endpoint in Interim Readout

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ALL MGL-3196

HIGH MGL-3196¹

Placebo

Number of patients 78 44 38

Primary Endpoint:Relative change in MRI-PDFF (% change from baseline, median)Significance relative to placebo

-36.3%

p<0.0001

-42.0%

p<0.0001

-9.6%

Percentage of patients attaining ≥30% liver fat reductionSignificance relative to placebo

60.3%

p<0.0001

75.0%

p<0.0001

18.4%

Statistically significant improvements in low-density lipoprotein cholesterol (LDL-C), triglycerides and lipoprotein (a) Lp(a)²

Statistically significant improvements in liver enzymes in drug-treatment group²

Very good all subject tolerability: mostly mild and a few moderate AEs, the numbers of which are balanced between placebo and drug-treated groups; 3 reported SAEs all considered unrelated to drug

Two regularly scheduled DSMB meetings held May 2017 and September 2017 to review data from the Madrigal NASH Phase 2 trial. DSMB recommended to continue the trial with no changes to the protocol

¹ Prespecified group of patients (44/78) with relatively higher MGL-3196 drug levels² These beneficial effects are more pronounced in the group of pre-specified patients with

higher levels of MGL-3196Ther. Adv. Gastroenterol. 2016; 9:692-701

Excellent correlation between decline in fat content on MRI-PDFF and NAS score, steatosis and ballooning on biopsy

Competitive Position: MGL-3196 Well-Positioned in the NASH Landscape

Pleiotropic and cardio-beneficial actions position MGL-3196 as potential best-in-class NASH therapeutic

Opportunities for differentiation from other NASH agents

Efficacy on NASH and cardiovascular endpoints position MGL-3196 to be used in combination with anti-fibrotic and/or anti-inflammatory agents

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Targetcompound

NAS Score

FibrosisScore Liver Lipids

NASH Prevention

Insulin Sensitivity LDL TGs

CV Risk Side Effects

FXR ✔ ✔ ✔ ✔ ✔ — LDL-C Pruritus

Anti-fibrotic ? ✔ — ✖ — — — ? Unknown

PPARαδ ✔ ✖ — ? ✔ PPARα/δ Well-tolerated

Anti-inflam ✔ ? — — — — — ? Well-tolerated

Pioglitazone ✔ ✔ ✔ ✔ ✔ PPAR CHF,bone,weight

MGL-3196 ✔ ✔ ✔ ✔ ✔ CV Benefit Well-tolerated

Lancet 385:956-65; 2015; Gastroenterology Feb 11 2016; pii:S0016-5085(10)00140-2Tobira press release July 25, 2016; Ann Intern Med. doi:10.7326/M15-1774 2016

FH: In addition to NASH, Madrigal also Targeting Familial Hypercholesterolemia in Phase 2 Trials

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HeFH and HoFH caused primarily by inactivating mutations in LDL receptor

Early onset cardiovascular disease, HoFH < age 20

Associated with several of potentially severe cardiovascular diseases including coronary heart disease, carotid artery disease, and chronic kidney disease

Severe Debilitating

Dyslipidemia

Novel Therapeutic Approaches

Needed

1/200-1/500 HeFH; 1/250,000-1/1,000,000 HoFH

Higher frequency in certain genetically homogeneous populations

High prevalence for a genetic disease

High Genetic Prevalence

Despite current and newer therapies, HoFH and most HeFH not achieving treatment goals on standard care

Significant commercial opportunity for MGL-3196 in HoFH, refractory HeFH

European Heart Journal doi:10.1093/eurheartj/ehu274; 2014

FH: Phase 2 HeFH Clinical Trial with Anticipated Readout in 1Q 2018

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Inclusion/Exclusion

HeFH on maximally tolerated statins (typically high dose), ezetimibe

Comparator/Arms

MGL-3196 or Placebo, once daily

Primary Endpoint

LDL cholesterol lowering

Secondary Endpoints

TGs, Lp(a), ApoB lowering

Safety

Design

Stage

Drug MGL-3196

2:1

Phase 2

Number of Patients

Centers

Treatment Duration

116, fully enrolled

13, Europe

12 weeks

Study Overview Study Details

Catalysts: Our Expectations for Development Timing

Completion of long-term toxicology studies for MGL-3196

Completion of Phase 1 trial of MGL-3196 dosed with statins for NASH

Initiation of Phase 2 trial of MGL-3196 for NASH

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Initiation of 12-week Phase 2 trial of MGL-3196 for HeFH

Positive topline 12-week data from Phase 2 trial of MGL-3196 for NASH

Upcoming Catalysts:

36-week topline liver biopsy data from Phase 2 trial of MGL-3196 for NASH

Topline data from Phase 2 trial of MGL-3196 for HeFH

Phase 3 NASH

Phase 3 HeFH

Completed Milestones:

2018+20172016

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Madrigal Investment Highlights

Multiple Possible Value-Creating Catalysts over Next 18 Months

MGL-3196: First-in-Class Thyroid Hormone Receptor (THR)-β Agonist

Large & Underserved Markets in NASH & Genetic Lipid Disorders

Seasoned Management Team

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Appendix:

Additional Material

THR-β Agonism: Expected Direct Anti-Fibrotic Actions

• Fat deposition, lipotoxicity and resultant local inflammation are seen in NASH

• Hepatocyte dysregulation and damage ensue up to and including apoptosis. These perturbations lead to a profibrotic environment through:

• Ongoing inflammation;• Production by the dysregulated / damaged / dying hepatocytes of profibrotic factors,

with TGF-β among the most important

• Thyroid hormone receptor agonism has been shown to dampen inflammation in vivo and to inhibit TGF-β signaling in cell culture and in vivo

• In animal models of liver fibrosis, the extent of fibrosis is decreased by thyroid hormone administration and increased if thyroid hormone receptors are knocked out (PNAS 113: 3451, 2016)

• THR-β is the operative receptor in hepatocytes

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THR-β: Decreased Liver Fibrosis and Apoptosis

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• THR-β knockout and hypothyroid mice have delayed liver regeneration, increased apoptosis (PLoS ONE 5(1): e8710, 2010)

• THR-β -/- mice have increased liver fibrosis with age

• Treatment with thyroid hormone reduces fibrosis in animal models of liver fibrosis (PNAS 113: 3451, 2016)

MGL-3196, a First-in-Class Liver-Directed THR- β Agonist

• We believe MGL-3196 is the first bona fide THR-β selective molecule with key advantages over previous companies’ analogues• Discovery of MGL-3196 and backups at Roche utilized a novel functional assay that went beyond what previous companies

had done (simple receptor binding assay)• Earlier compounds from other companies, purported to be THR-β selective, show no functional selectivity in this

assay and, like thyroid hormone, activate the THR-α receptor equally well as the β receptor• in vivo data confirm MGL-3196’s high liver uptake and preclinical safety: no heart, bone/cartilage, or brain uptake; safe in

long-term animal toxicology studies• Avoids activity at the systemic THR-α receptor (increased heart rate, osteoporosis) • Unlike other company’s earlier thyroid receptor agonists, no cartilage findings in chronic toxicology or liver enzyme

increases in human studies

Thyroid Gland

Liver T4 T3

T4 T3

Nuc T

hyro

id H

orm

one

Rece

ptor

α o

r β

TSH

Thyroid Hormone Pathway

T4

T4, prohormoneT3, active hormoneTSH, thyroid stimulating hormone

less α potent

m

ore ß selective

α-potency (nM)

β/α relative to T3

-5

0

5

10

15

20

25

30

35

-500 500 1500 2500 3500 4500

Thyroid Hormone (T3) MB07811 (GC1)MGL-3196 EprotiromeKB

GC-1

21J Med Chem. 2014;57(10):3912-3923

MGL-3196 Agonism of Hepatic THR-β

• In livers of euthyroid individuals T3 induces about half the maximal transcriptional activity of THR-beta

• MGL-3196 can further beneficially increase this transcriptional activity as we have shown in euthyroid animal models and humans.

• Interestingly, systemic hypothyroidism, at the level of the thyroid gland itself, leads to increases in plasma lipids (LDL-C and triglycerides) and increases the risk of nonalcoholic fatty liver disease.

• In fact, actual NASH is at least twice as common in hypothyroid individuals as in the general population.

• Further, liver-specific hypothyroidism is present in human NASH, caused by degradation of thyroid hormone (increased deiodinase 3 produced by stellate and inflammatory cells) in the NASH liver.

• In a vicious cycle this liver-specific hypothyroidism increases as NASH progresses. • Thus, MGL-3196, which is not affected by deiodinases, can increase transcriptional activity

over an even broader range than in the non-NASH euthyroid state.• With MGL-3196-induced resolution of NASH, with the concomitant decrease in numbers and

level of activation of stellate cells, normalization of hepatic thyroid function should occur.

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MGL-3196: Reduction of Key NASH, Fibrosis Pathway Genes at Human Comparable Drug Levels

TIMP1 tissue inhibitor metalloproteinaseCTGF connective tissue growth factorSMA smooth muscle actinSAA serum amyloid ACRP C-reactive protein

“HFD”, lane 1 mean HFD gene expression normalized to mean Lean; Lanes (2-7) mean gene expression normalized to mean of DIO; “Rosi” (rosiglitazone, 3 mg/kg, 24 wks) Red, higher expression; blue decreased expression

Inflammation HFD Lean 0.1 0.3 1 3 RosiMCP-1/CCL2MIP-2α/CXCL2MIP-2ß/CXLCL3A20/TNFaip3CRPAnnexin 2SAA1FibrosisCollagen 1Galectin-3TIMP1Collagen 4a2SMACollagen 4a1CTGFKeratin 18Collagen 3Galectin-1

25 week study in lean control mice and HFD mice treated with Vehicle, 0.1 to 3 mg/kg MGL-3196 or Rosiglitazone (3mg/kg)

Bad Good

1 2 3 4 5 6 7

MGL-3196 (mg/kg)

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MGL-3196: Radiographic Tissue Distribution22

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• MGL-3196 is highly protein bound (>99%) and is taken up into the liver by hepatic transporters• The primary route of elimination after an oral dose of [14C]MGL-3196 in rats and dogs was the

feces via biliary excretion• Uptake was low to undetectable heart, bone and brain, further supporting the safety of MGL-

3196

MGL-3196: Long-term Dosing in Humans is Enabled

• Single Ascending Dose (SAD) study

• Multiple Ascending Dose (MAD) study • Six dose cohorts, 36 total HV dosed daily with MGL-3196 (5, 20, 50, 80, 100, or 200 mg) and 12

with placebo for 14 days• Healthy volunteers with slightly elevated LDL cholesterol (> 110 mg/dL)

• Well-tolerated, appeared safe at all doses tested• No effect on vital signs, heart rate, central thyroid axis, or liver enzymes

• Phase 1 studies dosing MGL-3196 with statins

• Series of GLP toxicology and CMC studies support all indications• Manufacturing and product formulation• Chronic toxicology package• Phase 2-enabling

Completed:

25Atherosclerosis 230 (2013) 373-380

Lipid Lowering in Additional Phase 1 Studies

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Baseline (BL); triglycerides (TG) (all) or >150 mg/dL at BL; Lp(a) shown only for subjects with measurable BL Lp(a)

p<.003p <.0001

• In Phase 1 studies, 38 healthy volunteers were dosed with one-two days of a statin and multiple daily doses (9-11) of MGL-3196 (100 or 200 mg)

• Robust lipid lowering was observed (up to 60% LDL-C), subjects reaching an average LDL-C of 70 mg/dL, ApoB of 59 mg/dL

• Consistent with MAD data, subjects with higher MGL-3196 exposures did not demonstrate more lipid lowering.

p=.001

MGL-3196 Phase 2 NASH Study: Likelihood of Success

• Excellent correlation between decline in fat content on MRI-PDFF and NAS score, steatosis and ballooning on biopsy (Ther. Adv. Gastroenterol. 2016; 9:692-701)

• Rapid liver fat changes detectable with MRI-PDFF after caloric restriction and weight loss: easily detectable and near maximal by 6 weeks (PLoS One.2016; 11(4):E0153595)

• Two regularly scheduled DSMB meetings held May 2017 and September 2017 to review data from the Madrigal NASH Phase 2 trial

• DSMB recommended to continue the trial with no changes to the protocol

• Positive 12-week primary (MRI-PDFF) and secondary endpoint data provides significant additional confidence

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We believe that the impressive preclinical NASH animal and human lipid lowering effects, positive 12-week data, and the excellent safety profile point to a high probability of success

NASH Phase 2 Demographics

Baseline Demographics

n 125

Mean age 50.4

Gender - n (%)

Female 63 ( 50.4)

Male 62 ( 49.6)

Ethnicity - n (%)

Not Hispanic or Latino 66 ( 52.8)

Hispanic or Latino 59 ( 47.2)

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NASH Baseline Characteristics

Baseline

BMI (kg/m²) 35.07 (mean)

Type 2 diabetes n (%) 44 ( 35.2)

Hypertension n (%) 37 ( 29.6)

Triglycerides 172.0 (mean)

MRI-PDFF 20.17% FF (mean)

NAS at Screening 4.9 (mean)

Fibrosis score - (%)

1A, B 56%

2/3 43%

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NAS score of at least 4, range 4-8 and fibrosis 1-3

Current Challenges in Treatment of FH

HoFH• Most patients still not reaching LDL-C goal • Newer agents, Lomitapide (Juxtapid, MTPi) and

Mipomersen (Kynamro, anti-ApoB) may have safety issues

• Both carry FDA label warning*, hepatotoxicity• Increased ALT and hepatic fat

• Elevated Lp(a) remains an issue

HeFH• In HeFH, standard care (statins, ezetimibe) most HeFH

still not achieving goal• Even with PCSK9 inh 40% not at target

• Further treatment opportunities include relative statin intolerance in some and elevated Lp(a)

HoFHLipid Lowering Therapy

LDL decrease

Conventional

Statins Up to 28%

Ezetimibe <10%

LDL apheresis 20-40%

New Treatment Options

Lomitapide Up to 50%

Mipomersen 25%

PCSK9 inh 23%

30Drugs. 2015; 75(15): 1715–1724*Kynamro, Juxtapid FDA label, prescribing information

MGL-3196: Unique and Complementary Lipid Lowering Profile

• Thyroid pathway clinically validated and differentiated in FH

• Both LDL receptor-dependent and –independent cholesterol lowering:• Stimulates cholesterol breakdown and elimination• Lowers ApoB and Lp(a)• Decreases levels of PCSK9 (human data) and angiopoietin-like protein 3 ANGPTL3

(gene expression)• MGL-3196 lowers LDL in concert with statins in clinical & preclinical studies• Thyroid agonists lower cholesterol in LDL receptor knockout mice*• In Phase 3 trials in HeFH, an earlier THR agonist lowered LDL cholesterol and Lp(a)**• MGL-3196 acts through a mechanism that potentially lowers Lp(a), a severely

atherogenic particle that is elevated in FH

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In FH, we believe MGL-3196 will deliver additional LDL-C and Lp(a) lowering on top of conventional treatment

* Endocrinology 2012 Nov;153(11):5143-9** Lancet Diabetes Endocrinol2014; 2: 455–63

Proposed Phase 2a HoFH Clinical Trial Protocol

Study Study Details

Drug MGL-3196 Inclusion/Exclusion• HoFH on standard care, may include PCSK9ab, statins,

ezetimibe

Comparator/Arms• Patient is his own control• MGL-3196 may be titrated

Primary Endpoint• LDL cholesterol lowering

Secondary Endpoint• TGs, Lp(a), ApoB lowering• Safety

Design Open label

Stage Ph2

# Patients 6-8

Centers 6

Treatment duration

12 weeks

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