Developing Novel Treatments
for Fibrotic Diseases

AUGUST 2024
© 2024 PLIANT THERAPEUTICS

Disclaimers
This presentation has been prepared by Pliant Therapeutics, Inc. ("we," "us," "our," "Pliant" or the “Company”). The information set forth herein does not purport tobe complete or to contain all of the information you may desire. Statements contained herein are made as of the date of this presentation unless stated otherwise,
and this presentation shall not under any circumstances create an implication that the information contained herein is correct as of any time after such date or that
information will be updated or revised to reflect information that subsequently becomes available or changes occurring after the date hereof.
This presentation includes forward-looking statements regarding Pliant’s proprietary drug candidates, the timing of the start and conclusion of ongoing or planned
clinical trials, including the timing of, and our ability to achieve, anticipated milestones, the sufficiency of our cash, cash equivalents and short-term investments, thetiming and outcome of regulatory decisions, future availability of clinical trial data, our collaborations for our product candidates and the maintenance of thosecollaborations; business and results from operations; and other matters. Actual results could differ materially from those contained in any forward-looking statements
as a result of various factors, including without limitation: that Pliant’s drug candidates do not advance in development or result in approved products on a timely or
cost effective basis or at all; the cost, timing and results of clinical trials; our ability to manage and mitigate the impact of the ongoing COVID-19 pandemic; thatmany drug candidates that have completed early-stage trials do not become approved drugs on a timely or cost effective basis or at all; the ability to enroll patientsin clinical trials; possible safety and efficacy concerns; regulatory developments; the ability of Pliant to protect its intellectual property rights, and unexpected costs,
charges or expenses that reduce cash runway. Pliant’s pipeline programs are in various stages of pre-clinical and clinical development, and the process by whichsuch pre-clinical or clinical therapeutic candidates could potentially lead to an approved therapeutic is long and subject to significant risks and uncertainties. Pliant
undertakes no obligation to update forward-looking statements as a result of new information or otherwise. For a discussion of these and other risks anduncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see thesection entitled “Risk Factors” and elsewhere in the Company's most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q on file with the
Securities and Exchange Commission (the "SEC") and our other filings with the SEC.
This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about
our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections,assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of
uncertainty and risk.

This presentation concerns drugs that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration(the “FDA”). They are currently limited by Federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes forwhich they are being investigated.

© 2024 PLIANT THERAPEUTICS

2

Pliant – Breaking New Ground in Fibrosis
Industry-Leading Integrin/Fibrosis
Platform• Four approved INDs utilizing small-molecule integrin
inhibitors⎼ Most in the industry• Proprietary library of 10,000+ integrin binding
molecules

Bexotegrast – Disease modifying
Potential in IPF• Bexotegrast showed improvement in FVC vs. placebo
at all doses tested⎼ Effect seen as monotherapy and in combo with
SOC

Blockbuster Opportunities in Areas ofHigh Unmet Need
• IPF is currently a $4+ billion market - expected to reach$6-$10 billion in the next 10 years• High unmet need due to tolerability/efficacy issues withapproved agents• Opportunity to expand the market to additional patientsand indications (i.e. progressive pulmonary fibrosis)

Funded Through Phase 2b Data
• $438.1 million of cash1 as of June 30, 2024
• Operations are funded through 2026 – Runway wellpast Phase 2b data

• Reduction in total lung collagen seen post 12-weektreatment: potential reversal of fibrosis• Clinically meaningful reduction in cough severity

1 – Includes cash, cash equivalents and short-term investments.

© 2024 PLIANT THERAPEUTICS

3

Pliant Development Pipeline

Program

Indication

ClinicalPreclinical
Phase 1

Bexotegrast(PLN-74809)
Dual selective inhibitorof αvβ6 /αvβ1

PLN-101095

Anti-integrin mAb of α7β1

Phase 2b / 3

Idiopathic
PulmonaryFibrosis

BEACON-IPF
Phase 2b enrollment
complete 1Q 2025;
data mid-2026

Primary
Sclerosing
Cholangitis

24-Week 320 mg
data presented

Solid Tumors

Initial data 4Q 2024
or early 2025

DMD
Other Muscular
Dystrophies

Phase 1 ready

Inhibitor of αvβ8 /αvβ1

PLN-101325

Phase 2a

Anticipated Milestone

GlobalRights© 2024 PLIANT THERAPEUTICS

4

Pliant’s Integrin Focused Library
Core Platform for Novel Pipeline and Partner Programs
Integrins• Cell surface receptors that facilitate cell-cell andcell-extracellular matrix adhesion and interaction• A major path of communication between the extracellular matrix,
inflammatory cells and fibroblasts• Closely involved in signaling processes that govern tissue
fibrosisPliant’s Proprietary Library of 10,000+ Integrin Binding Compounds• Emphasis on optimal pharmacokinetic and selectivity profiles• Broad spectrum of receptor subfamilies including αV integrins,
collagen and laminin binders© 2024 PLIANT THERAPEUTICS

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Bexotegrast Reduces TGF- Signaling and Downstream
Profibrotic Pathways Through Inhibition of Integrins αvβ6 / αvβ1
V6 / V1 integrins promote fibrosis by activating TGF-

• TGF- is a central mediator of fibrosis• V /V1 Integrins activate latent TGF- in fibrotic tissue• Systemic TGF- blockade carries toxicity risks

Selectively blocking TGF- in fibrotic tissues may
provide a low risk, effective antifibrotic approach

FIBROSIS

bexotegrast

COL1A1COL3A1
TIMP1
CCN2
ENPP2
…
© 2024 PLIANT THERAPEUTICS

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Bexotegrast Has Outperformed at All Stages of Development
Bexotegrast Has Shown Blockbuster Potential in Early and Mid-Stage Trials
Blockbuster Market Opportunity of $4+ Billion

Bexotegrast
Preclinical
Improvement in Lung
Function (FVC)

Phase 1

Phase 2• Ofev 2023 revenues of $3.9 billion• Increasing IPF incidence with aging population• Significant portion of market unserved due to tolerability/efficacy issues

Symptomatic Improvement(Cough)Reduction in Lung Fibrosis(HRCT and PET Imaging)
Additive Effect on Top of
SOC (80%)
αvβ6 Target Saturation(PET Imaging)

Potential Backbone Therapy• Favorable tolerability profile to date, as monotherapy, and incombination with SOC• Bexotegrast + SOC reduced FVC mL decline by 80% over 24 weeks
compared to SOC alone

Reduced TGF-β Signaling(pSMAD)

Reduced Pro-Fibrotic Gene
Expression
Favorable Tolerability
ProfileOral, Once-Daily Dosing

Expanding Treatable Population• Patients felt better - Clinically meaningful reduction in cough severity
seen in Phase 2a• Reduction in total lung collagen seen in Phase 2 suggests reversal offibrosis – potential disease modifying therapy© 2024 PLIANT THERAPEUTICS

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Bexotegrast Has Significant Respiratory Market Potential
US PREVALENCE OF FIBROSING ILD INDICATIONS1

73K• Fibrosing ILDs encompass over 200
indications with common disease
pathophysiology• Underdeveloped market with limited
treatment options for non-IPF
diseases including PPF, SSc-ILD,
and PH-ILD• Like in IPF, bexotegrast could
provide the only disease-modifying
antifibrotic treatment option acrossother fibrosing ILDs

Progressive pulmonary
fibrosis (PPF) 2

~400K

150K
Idiopathic pulmonary
fibrosis (IPF) 2

PATIENTS

Rheumatoid arthritisassociated interstitiallung disease (RA-ILD)

43K
18K

Other interstitial lungdiseases (ILDs)

Unclassified interstitiallung disease (ILD)

25K
Pulmonary hypertensionassociated interstitial lung disease(PH-ILD) 2
1 Estimated prevalence based on progressive fibrosing phenotype of various ILDs using Wijsenbeek M et al. Curr Med Res Opin. 2019;35(11):2015-2024.
2 Indications with available therapies

57K

28K
Scleroderma-associated interstitiallung disease (SSc-ILD) 2© 2024 PLIANT THERAPEUTICS

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INTEGRIS-IPF – Phase 2a Study of Bexotegrast
in IPF Patients© 2024 PLIANT THERAPEUTICSINTEGRIS-IPF Phase 2a Study Design and Objectives
RANDOMIZATION
Bexotegrast

3:1
Placebo

PRIMARY AND SECONDARY ENDPOINTS• Safety, tolerability, PK

Placebo (n=8)

Placebo (n=31)
Bexotegrast 40 mg (n=22)

END OF STUDYSCREENING

EXPLORATORY ENDPOINTS

Bexotegrast 80 mg (n=23)
Bexotegrast 160 mg (n=22)
Bexotegrast 320 mg (n=21)

Bexotegrast 320 mg(n=18)1• Change in forced vital capacity (FVC)over 12 weeks and 24 weeks• High resolution CT-based quantitativelung fibrosis (QLF) imaging• Patient reported cough severity• Effect on selected biomarkers

Stratified for the use of nintedanib or pirfenidone

Day -28

Baseline
Day 1

Week 12

Week 24

Up to
Week 48(Safety)

1 – Treatment duration per protocol: minimum of 24 weeks and a maximum of 48 weeks© 2024 PLIANT THERAPEUTICS

10Key Takeaways from the INTEGRIS-IPF Trial

Bexotegrast Demonstrated a Favorable Safety and Tolerability Profile up to 40 Weeks

Bexotegrast Demonstrated a Dose-dependent Treatment Effect on Registrational Endpoint• Statistically significant increases from baseline in mean FVC at Week 12• Treatment benefits were present at Week 24 across physiologic (FVC), radiographic (QLF) and symptomatic(cough) assessments versus placebo• Bexotegrast treatment effect was observed with and without use of standard-of-care agents

Data Provide Strong Support of Bexotegrast’s Antifibrotic Mechanism of Action© 2024 PLIANT THERAPEUTICS

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FVC Change from Baseline over 12 Weeks
mITT Population.0* p < 0.05 vs placebo** p < 0.01 vs placebo
FVC = forced vital capacity; mITT = modified intent to treat; 1 participant in the placebo group was identified as a statistical outlier across all treatment groups and excluded from the mITT analysis.

© 2024 PLIANT THERAPEUTICS

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Comparison of Approved & Select Investigational Agents in IPF / PPF
Bexotegrast Shows Superior Effect on FVC with no Notable AEs
Approved Agent Phase 3 Studies

Agents in Development

Change in FVC (mL) from Placebo

200
50-80% of patients on background therapy
150

No background therapy
No U.S. participants

140 mL107 mL

100

80 mL
56 mL

49 mL

50

61 mL

51 mL

54 mL

29 mL
NA

0
26-week
8% hypertension
7% hypotension

NotableAdverse Events

None

17-31% diarrhea

Discontinuations

14% vs.
10% placebo

15% vs.
0% placebo

10% vs.
11% placebo

Daily Dose

Bexotegrast
320 mg
INTEGRIS-IPF

BI 1015550
36 mg
Phase 2

BMS986278
60 mg
Phase 2 IPF

-50
-100

57% dysgeusia
52% alopecia
43% muscle spasm

36-wk
19% alopecia

5% vs.
17% placebo

26% vs.
0% placebo

12-wk: 33%
36-wk: 46%

BMS986278
60 mg
Phase 2 PPF

Taladegib
200 mgPhase 2a

Buloxibutid
200 mgPhase 2a

-26 mLASCENDCAPACITY 1 CAPACITY 2 INPULSIS 1 INPULSIS 2

Bexotegrast, BI-1015550, BMS-986278, ENV-101 and C21 from Phase 2 trials. Graphic is not meant to represent a head-to-head study. Comparing the results from different trials may be unreliable due to different
protocol designs, trial designs, patient selection and populations, number of patients, trial endpoints, trial objectives and other parameters that may not be the same across trials. Therefore, cross-study comparisonsprovide very limited information about the efficacy of safety of a drug. Bexotegrast INTEGRIS-IPF study consisted of n-22 subjects in the 320 mg arm, a significantly smaller number of patients than reflected in theother datasets represented on this slide. In larger trials of bexotegrast, the clinical activity suggested by our INTEGRIS-IPF trial may not be replicated© 2024 PLIANT THERAPEUTICS

13

Proportion of Participants with Relative FVCpp Decline ≥ 10%
mITT Population

Proportion of Participants
FVCpp decline ≥ 10%

mITT Population at 12 Weeks

FVCpp = Forced vital capacity, percent predicted.
1- Ann Am Thorac Soc. 2017 Sep;14(9):1395-1402; 2- Am J Respir Crit Care Med. 2022 Apr 15;205(8):936-948.

© 2024 PLIANT THERAPEUTICS

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Mean (SE) Change in QLF (%)

QLF Mean Percent Change from Baseline at Week 12
Per CT protocol population

QLF = quantitative lung fibrosis© 2024 PLIANT THERAPEUTICS

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Bexotegrast Reduced Serum Fibrosis Biomarkers
Change from Baseline at 4 and 12 Weeks vs. Placebo
PRO-C3
Type III collagen synthesis neoepitope

Plasma Integrin beta-6 (ITGB6)
0.22(SEM) Change
Mean (SEM)
LS MeanChangeLSvsBaseline
fromPlacebofrom Baseline vs Placebo

1

-1
-2

**

-3
4 weeks
40 mg

80 mg

(ng/ml)

0

40 mg

0.01

(NPX units; log2 scale)

LS Mean (SEM) Change
from Baseline vs Placebo(ng/ml)2

80 mg
160 mg-0.20

320 mg

*
-0.4
-1

**
****

-0.6
-2

****

**

-0.8
-3

12 weeks
160 mg44 weeks
weeks
320 mg

40 mg

*

80 mg

12 weeks
12
weeks

160 mg

320 mg* p < 0.05 vs placebo** p < 0.01 vs placebo**** p < 0.0001 vs placebo

LS = Least Squares; SE = Standard Error

PRO-C3, a serum biomarker of type III collagen synthesis, was previously shown
to be elevated in patients with IPF and associated with progressive disease1
Elevated ITGB6 plasma levels previously shown to be associated with ILD progression, as definedby mortality, transplant, or ≥ 10% relative reduction in FVC (mL) over 12 months2
1- Respir Res. 2019 Jul 12;20(1):148.
2- Lancet Respir Med. 2022 Jun;10(6):593-602.

© 2024 PLIANT THERAPEUTICS

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FVC Change from Baseline over 24 Weeks
ITT Population vs. SoC Sub-GroupITT Population

Standard-of-Care Sub-Group

Bexotegrast reduced FVC decline
by 67% relative to placebo at Week 24

Bexotegrast + SOC reduced FVC decline
by 80% relative to SOC alone at Week 24

Participants not on SoC not shown due to small sample size, n=4 (320 mg) and n=2 (placebo)
FVC = forced vital capacity; ITT=intent to treat; SoC = standard of care (nintedanib or pirfenidone)© 2024 PLIANT THERAPEUTICS

17

Bexotegrast Demonstrated Durable Increase in FVC at Week 24
ITT Population
320 mgPlacebo
FVC increase
from baseline

FVC decline
from baseline

89% of bexotegrast-treated participants with FVC increaseat Week 12 maintained an increase at Week 24
FVC = forced vital capacity; ITT = intent to treat.
Participants with missing data not included© 2024 PLIANT THERAPEUTICS

18

QLF Mean Percent Change from Baseline at Weeks 12 and 24
Per CT Protocol Population
320 mgPlacebo

Minimal Clinically
Important Difference1

Bexotegrast group demonstrated stabilization of fibrosis, in contrast toplacebo group which showed clinically meaningful progression at Weeks 12 and 24
QLF = quantitative lung fibrosis; QLF Minimal Clinically Important Difference for whole lung: 2%; stable disease (-2%, 2%)
Per CT protocol population: Participants with both baseline and post baseline high resolution computed tomography (HRCT) scans meeting evaluability criteria per Imaging Charter
1 EU Radiology 2020 30:726-734© 2024 PLIANT THERAPEUTICS

19

Cough Severity Visual Analog Scale (VAS) Change from Baseline
ITT Population
320 mgPlacebo

Chronic cough
cough inin IPFIPF isis an
an independent
independent predictor
predictor ofof diseasedisease progression
progression andand mortality
mortality11
Chronic
1 - Respirology 2011; 16: 969–975.
Cough VAS measures patient reported cough severity over last 2 weeks on scale of 0-100 mm© 2024 PLIANT THERAPEUTICS

20

PLN-74809-205 – Phase 2a Collagen PET Study
Topline Results© 2024 PLIANT THERAPEUTICS

Design and Objectives
Quantification of Type 1 Collagen in the Lung using PET Imaging
PRIMARY AND SECONDARY ENDPOINTSRANDOMIZATION
Bexotegrast• Change in whole lung standardized uptake value(SUV) of 68GA-CBP8 (type-1 collagen probe)

Placebo• Safety and tolerability

2:1

END OF STUDYSCREENING

EXPLORATORY ENDPOINTS

Placebo (n=3)

Bexotegrast 160 mg (n=7)

Baseline
Day 1• Change in VAS for cough severity• Changes in fibrosis biomarkers
INCLUSION CRITERIA• Diagnosis of IPF (within 8 years)• FVC percent predicted ≥ 45%• DLCO ≥ 30%• Estimated glomerular filtration rate ≥ 50mL/min

Stratified for the use of SoC (nintedanib or pirfenidone)

Day -28• Changes in FVC and FVCpp

Last dose
Week 12

Week 14

FVC: forced vital capacity, FVCpp: forced vital capacity percent predicted; SoC = Standard of care; VAS: visual analog scale
68GA-CBP8: peptide-based collagen binding probe 8 tagged with Gallium-68 radioisotope© 2024 PLIANT THERAPEUTICS

22

Quantification of Collagen in the Lung using PET Imaging• 68Ga-CBP8 is a PET probe that binds type I
collagen with high specificity1

Healthy Control

IPF Patient• The probe binds to both freshly synthesized
and mature collagen• IPF patients have higher standardized uptake
values (SUV) compared to healthy volunteers2,
indicating higher amounts of total lung collagenNote: Uptake in the heart and vasculature as well as in the liver is to be expected based on the probe’s half-life andbiodistribution• 68Ga-CBP8 previously detected treatment
response to anti-fibrotic therapy in a mousemodel of pulmonary fibrosis1

68GA-CBP8: peptide-based collagen binding probe 8 tagged with Gallium-68 radioisotope

SUV: standardized uptake value; SUV measures the ratio of the uptake of a radiotracer in tissue
1Désogere et al, Sci Trans Med. 2017; 2Montessi Am J Respir Crit Care Med 200:2 2019
© 2024 PLIANT THERAPEUTICS

23

Key Findings
Bexotegrast cohort showed reduced PET ligand standardized uptake values (SUV) compared to placebo• Reduction in SUV post-treatment indicates less total lung collagen, suggesting potential reversal of fibrosis• Additional support of bexotegrast’s antifibrotic mechanism of action
No safety concerns identified over 12 weeks of treatment• Most adverse events were mild with no study discontinuations observed• No SAEs observed
Bexotegrast cohort showed improved lung function and decreased cough severity across all timepoints• Positive FVC change compared to decline in placebo across all time points• Decrease in cough severity observed at all time points compared to worsening seen on placebo
Biomarker results further support bexotegrast’s antifibrotic mechanism• Bexotegrast cohort showed reduced circulating PRO-C3 and Integrin Beta-6 levels at Weeks 4 and 12
compared to placebo© 2024 PLIANT THERAPEUTICS

24

Bexotegrast Showed Reduced PET Tracer SUV Compared to Placebo
ITT Population
PET SUV at Week 12

Reduction in post-treatment SUV indicates a reduction in total lung collagen
Reduced post-treatment total lung collagen suggests potential reversal of fibrosis
2 Montessi AJRCCM 200:2 2019

SUV = Standardized Uptake Value; SE = Standard Error; 68GA-CBP8: peptide-based collagen binding probe 8 tagged with Gallium-68 radioisotope
SUV measures the ratio of the uptake of a radiotracer in tissue; Top quartile SUV is the mean of SUVs within the top quartile for each lung section; Whole lung is the average of the left and right lungs© 2024 PLIANT THERAPEUTICS

25

PET Imaging Study – Clearly Visible Reduction of Total Lung Collagen
Baseline

Week 12
Participant A

SUVHigh Collagen

1.3• Bexotegrast 160 mg for 12 weeks• Decrease in SUVQ4, -0.17 (-15.5%)• Improvement in FVC, 130 mL

Participant B
Low Collagen• Placebo for 12 weeks• Increase in SUVQ4, 0.21 (18.4%)• Decline in FVC, -180 mL
0
SUV = Standardized Uptake Value; SUVQ4: top quartile SUV; 68GA-CBP8: peptide-based collagen binding probe 8 tagged with Gallium-68 radioisotope
FVC: forced vital capacity; VAS; visual assessment scale for cough severity (0-100)
SUV measures the ratio of the uptake of a radiotracer in tissue and quantifies the amount of type I collagen detected© 2024 PLIANT THERAPEUTICS

26

Bexotegrast Showed Improved Lung Function Compared to Placebo
ITT Population
FVC

FVCpp at Week 12

4%
106 mL

Bexotegrast cohort maintained a clear separation from placebo at all time points

Note: One placebo subject did not have FVC that meet quality standards per ATS guidelines at Weeks 4, 8 and 12
LS = Least Squares; SE = Standard Error; FVC = Forced Vital Capacity; FVCpp = Forced Vital Capacity Percent Predicted© 2024 PLIANT THERAPEUTICS

27

Bexotegrast Showed Decreased Cough Severity Compared to Placebo
ITT Population
Cough Severity Over 12 Weeks of Treatment

Bexotegrast cohort experienced decreased cough severity across all timepoints
compared to increased severity on placebo

EOT: end of treatment; SE: standard error; VAS = Visual Analog Scale
Cough VAS measures patient reported cough severity over last 2 weeks on scale of 0-100 mm© 2024 PLIANT THERAPEUTICS

28

Bexotegrast Showed Reduced Fibrosis Biomarkers Compared to Placebo
ITT Population
ITGB6

PRO-C3* p < 0.05 vs placebo

PRO-C3 has been shown to be elevated in patients with IPF and associated with progressive disease3
PRO-C3 and PRO-C6, serum biomarkers of type III and VI collagen synthesis, were previously shown
4
1
Elevated
ITGB6
plasmalevels haveshown
to be associatedwith ILD diseaseprogression
to beelevatedin patients
withbeen
IPF andassociatedwith progressive
3Respir Res. 2019 Jul 12;20(1):148. doi: 10.1186/s12931-019-1118-7; 4Lancet Respir Med. 2022 Jun;10(6):593-602. doi: 10.1016/S2213-2600(21)00503-8. Epub 2022 Jan 18

ITGB6: Integrin Beta 6; LS = Least Squares; PRO-C3 = Type III Collagen Synthesis Neoepitope; SE = Standard Error© 2024 PLIANT THERAPEUTICS

29

BEACON-IPF – Seamless Adaptive Phase 2b/3
Trial of Bexotegrast in IPF© 2024 PLIANT THERAPEUTICS

BEACON-IPF Phase 2b/3 Study Design – Currently Enrolling
Phase 2b Enrollment

Phase 2b Treatment

Phase 2b

Randomization 1:1:1

KEY PRIMARY ENDPOINT•

Placebo once daily for 52 weeks (n=120)

Change from baseline in absolute FVC (mL)at Week 52

END OF STUDYSTART OF STUDY

Bexotegrast 160 mg dose once daily for 52 weeks (n=120)
Bexotegrast 320 mg dose once daily for 52 weeks (n=120)

Phase 32-Dose Enrollment

Phase 3 Single
Dose Enrollment

Phase 3

Randomization 1:1:1

Phase 3 Treatment

Randomization 1:1

Placebo once daily for 52 weeks
Bexotegrast 160 mg dose
Bexotegrast selected dose(s) once daily for 52 weeks

KEY SECONDARY ENDPOINTS•Time to disease progression (≥ 10% absolutedecline from baseline in FVCpp, respiratoryrelated hospitalization, or all cause mortality
through week 52)•

Change from baseline in absolute FVC (mL)at Week 52 in those ON and NOT on
background therapy•

Change from baseline in Living with
Pulmonary Fibrosis Dyspnea and Cough
Domain scores at Week 52•

Safety and tolerability over 52 weeks

Bexotegrast 320 mg dose

Phase 2b
Enrollment
Complete

Phase 2b Data
and Phase 3
Dose Selection

Phase 3
Enrollment
Complete

Phase 3Data

© 2024 PLIANT THERAPEUTICS

31

INTEGRIS-PSC – Phase 2a Study ofBexotegrast in PSC Patients© 2024 PLIANT THERAPEUTICSINTEGRIS-PSC Study Design and Objectives
First PSC Trial Enriched with Participants with Suspected Liver Fibrosis
RANDOMIZATIONPRIMARY AND SECONDARY ENDPOINTS

Bexotegrast• Safety, tolerability, PK

3:1
Placebo

EXPLORATORY ENDPOINTS

Placebo• Changes in liver fibrosis markers, ELF scoreand PRO-C3

Bexotegrast 40 mg (n=24)

END OF STUDYSCREENING

Placebo (n=30)

Bexotegrast 80 mg (n=20)
Bexotegrast 160 mg (n=20)
Bexotegrast 320 mg (n=27)

Bexotegrast 320 mg*

Stratified for the use of UDCA

Day -42

Baseline
Day 1

Week 12

Week 24• Changes in liver biochemistry• Changes in liver imaging
INCLUSION CRITERIA• Suspected moderate/severe fibrosis definedby at least one criterion:– ELF ≥ 7.7– TE ≥ 8 but ≤ 14.4 kPa– MRE ≥ 2.4 but ≤ 4.9 kPa– Historical biopsy

Up to
Week 48*(Safety)

UDCA = Ursodeoxycholic acid; ELF = enhanced liver fibrosis*Trial will complete once the last trial participant enrolled reaches 24 weeks of treatment© 2024 PLIANT THERAPEUTICS

33

INTEGRIS-PSC – Key Findings at Week 12
Bexotegrast was Well Tolerated in Participants with PSC• No safety concerns identified across all dose groups, including the 320 mg dose group• The most common AEs were observed at lower rates in bexotegrast-treated patients vs. placebo• No treatment-related SAEs on bexotegrast
Bexotegrast Demonstrated Antifibrotic Activity in a PSC Population with Suspected Liver Fibrosis• Reduced liver fibrosis markers ELF and PRO-C3 at all doses relative to placebo over short-term treatment• Contrast MRI suggested improved hepatocyte function and bile flow at all doses relative to placebo
Additional Findings• Statistically significant reductions in itch relative to placebo for the 160 mg and 320 mg doses• ALP remained stable at all doses relative to increases on placebo© 2024 PLIANT THERAPEUTICS

34

Itch Numerical Rating Scale – Change from Baseline at Week 12
Safety Population* p < 0.05 vs placebo

Bexotegrast showed statistically significant reductions in itch relative to placebo
for the 160 mg and 320 doses
NRS: Numerical Rating scale; Itch NRS is a patient reported outcome which assesses severity of itch, over the last 24 hours, on a scale of 0 (no itch) to 10 (Worst imaginable itching).

© 2024 PLIANT THERAPEUTICS

35

ELF Score – Change from Baseline at Week 12
Safety Population

ELF: enhanced liver fibrosis.

Bexotegrast reduced ELF score relative to placebo at all doses© 2024 PLIANT THERAPEUTICS

36

PRO-C3 – Percent Change from Baseline
Safety Population* p < 0.05 vs placebo** p < 0.01 vs placebo

All doses reduced collagen synthesis (PRO-C3) relative to placebo withstatistical significance at Week 12 for 40 mg and 160 mg doses
PROC-C3: neo-epitope pro-peptide of type III collagen formation.
Only participates with both a baseline and post baseline are summarized.

© 2024 PLIANT THERAPEUTICS

37

MRI Parameters – Change from Baseline at Week 12
Sub-Study Safety Population
Relative Enhancement

Time of Arrival to Common Bile Duct

* p < 0.05 vs placebo** p < 0.01 vs placebo

All doses showed increased relative enhancement compared to placebo,suggesting improved hepatocyte function
All doses reduced time of arrival to the common bile duct compared to placebo,suggesting improved bile flow
Relative enhancement (RE), using the contrast agent gadoxetate, is a measure of hepatocyte function. Time of arrival of gadoxetate to bile duct is a measure of excretory function.
MRI was an optional sub study to main study.

© 2024 PLIANT THERAPEUTICS

38

ALP – Change from Baseline at Week 12
Safety Population – Participants with ALP > ULN at Baseline* p < 0.05 vs placebo

Bexotegrast improved ALP relative to placebo at all doses in subgroupwith elevated ALP at baseline

ALP -Alkaline phosphatase.

© 2024 PLIANT THERAPEUTICS

39

INTEGRIS-PSC Part 3 Study Design and Objectives
First PSC Trial Enriched for Participants with Suspected Liver Fibrosis
PRIMARY AND SECONDARY ENDPOINTSRANDOMIZATION• Safety, tolerability, PK
Bexotegrast

3:1

EXPLORATORY ENDPOINTS
Placebo

END OF STUDYSCREENING

Placebo (n=9)

Bexotegrast 320 mg (n=27)

Stratified for the use of UDCA

Day -28

Baseline
Day 1

Week 12

Week 24

Up to
Week 48(Safety)• Changes in transient elastography at Week 24• Changes in liver fibrosis markers, ELF scoreand PRO-C3• Changes in liver imaging• Changes in liver biochemistry
INCLUSION CRITERIA• At-risk for moderate/severe fibrosis defined byat least one criterion:– ELF ≥ 7.7– TE ≥ 8 but ≤ 14.4 kPa– MRE ≥ 2.4 but ≤ 4.9 kPa– Historical biopsy

Due to trial design and enrollment trajectory, longest treatment duration was 40 weeks

UDCA = Ursodeoxycholic acid ; TE = Transient elastography; ELF = enhanced liver fibrosis© 2024 PLIANT THERAPEUTICS

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INTEGRIS-PSC – Key Findings at Week 24 for 320 mg Cohort
Bexotegrast 320 mg was well tolerated in participants with PSC over longer term dosing• Favorable safety and tolerability profile maintained up to 40 weeks• No treatment-related severe or serious adverse events on bexotegrast
Bexotegrast continued to demonstrate antifibrotic activity• Improvement in liver stiffness compared to placebo by transient elastography at Week 24• Reduction in ELF score at Week 24 observed relative to an increase on placebo in high-risk subpopulation• Stable ELF score observed from Week 12 to 24 in the overall bexotegrast-treated population
Bexotegrast improved markers and symptoms of cholestasis• Statistically significant improvement in ALP levels at Week 24 compared to placebo• Contrast MRI suggests continued improvement in hepatocyte function and bile flow from Week 12 to 24• Stable score on the Itch NRS compared to an increase on placebo over 24 weeks• Pruritis and cholangitis AEs reported in lower proportions of bexotegrast treated patients than placebo© 2024 PLIANT THERAPEUTICS

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INTEGRIS-PSC – Participant Disposition – 320 mg Cohort
SCREENED
n=52

SCREEN FAILURE
n=49
RANDOMIZED AND TREATED
n=36

BEXOTEGRAST 320 mg

PLACEBO

Safety Population n=27

Safety Population3 n=9With UDCA n=18 (66.7%)

With UDCA n=6 (66.7%)

Discontinued Treatment

Discontinued Treatmentn=41 (14.8%)

n=0

1 – Adverse Event (n=1), Withdrawal by subject (n=2) other (n=1); One discontinuation occurred post Week 12.
UDCA = Ursodeoxycholic acid© 2024 PLIANT THERAPEUTICS

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Baseline Disease Activity Markers – 320 mg Cohort Participants
Bexotegrast
320mg(n=27)

Placebo190.6 (91.29)

318.6 (282.73)

22 (81.5)

6 (66.7)

Alanine aminotransferase (ALT) (U/L)

60.4 (37.76)

85.8 (70.79)

Aspartate aminotransferase (AST) (U/L)

44.6 (24.69)

58.2 (50.91)

Total Bilirubin (mg/dL)

0.53 (0.208)

0.76 (0.424)

Direct bilirubin (mg/dL)

0.16 (0.062)

0.33 (0.341)

9.0 (0.84)

9.5 (0.93)

46.48 (19.536)

60.18 (39.630)

8.7 (3.14)

8.6 (2.85)(n=9)

Liver Biochemistry, mean (SD)
Alkaline phosphatase (ALP) (U/L)> ULN, n (%)

Markers of Fibrosis, mean (SD)ELF Score

PRO-C3 (ng/mL)Transient Elastography (kPa)

ELF: Enhanced Liver Fibrosis; PROC-C3: neo-epitope pro-peptide of type III collagen formation.
PRO-C3 quantified using Roche COBAS platform (assay reports approximately 2x higher concentrations than previous generation PRO-C3 ELISA)© 2024 PLIANT THERAPEUTICS

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Improvement in Liver Stiffness with Bexotegrast Compared to Placebo
Safety Population – 320 mg Cohort
Week 24

Reduced liver stiffness by transient elastographysuggests stabilization of liver fibrosis© 2024 PLIANT THERAPEUTICS

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Reduction in ELF Observed with Bexotegrast in High-Risk Patients
Safety Population – 320 mg Cohort
Participants at High Risk of Progression 1

All Participants(Baseline ELF > 9.8)
320 mgPlacebo

320 mgPlacebo2

Reduction in ELF score at Week 24 observed, compared to an increaseon placebo in patients at high risk for disease progression
ELF: enhanced liver fibrosis.
1 – ELF score >9.8 is associated with increased risk for advanced liver fibrosis and disease progression.
2 – Includes one patient who was not included in 12-week interim analysis due to sample unavailability at the time of interim analysis.

© 2024 PLIANT THERAPEUTICS

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Bexotegrast Reduced ALP over 24 Weeks
Safety Population – 320 mg Cohort
All Participants
320 mgElevated ALP at Baseline
Placebo

320 mgPlacebo

Statistically significant ALP reductions observed in bexotegrast
participants compared to increased ALP on placebo
ALP - alkaline phosphatase* p < 0.05 vs placebo© 2024 PLIANT THERAPEUTICS

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Continued Improvement in MRI Parameters Observed from Week 12 to 24
Safety Population – Sub Study - 320 mg Cohort
Relative Enhancement

Time to Arrival to Common Bile Duct

320 mg

320 mgRelative Enhancement and time to arrival continued to improve at Week 24
suggesting further improvement in hepatocyte function and bile flow
Placebo not shown due to small n. n=1 placebo for relative enhancement; n=2 placebo for time to arrival to common bile duct.
Relative enhancement (RE), using the contrast agent gadoxetate, is a measure of hepatocyte function. Time of arrival of gadoxetate to bile duct is a measure of bile flow/excretory function.
MRI was an optional sub study to main study.

© 2024 PLIANT THERAPEUTICS

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Stable Itch NRS Observed with Bexotegrast Compared to Increase on Placebo
Safety Population – 320 mg Cohort
320 mgPlacebo

Mean Itch NRS score did not increase over 24 weeks of treatment with bexotegrast
compared to an increase on placebo
NRS: Numerical Rating scale; Itch NRS is a patient reported outcome which assesses severity of itch, over the last 24 hours, on a scale of 0 (no itch) to 10 (Worst imaginable itching)© 2024 PLIANT THERAPEUTICS

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Bexotegrast – Conclusions and Next Steps

Bexotegrast continues to be well tolerated across multiple patient populations• Well tolerated in over 700 trial participants treated with bexotegrast to date

• No treatment-related SAEs observed in patient studies to date
Bexotegrast continues to demonstrate broad antifibrotic activity across multiple indications• Strong evidence for antifibrotic activity across pulmonary and hepatic fibrosis indications• Evidence to date suggests potential disease modification in both IPF and PSC• Totality of evidence provide strong confidence in ongoing BEACON-IPF Phase 2b/3 trial
Path forward for bexotegrast• Pliant remains focused on execution of the ongoing BEACON-IPF• Pliant will continue to evaluate the best path forward in PSC

49© 2024 PLIANT THERAPEUTICS

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PLN-101095
Dual Selective αVβ8 / αVβ1
Integrin Inhibitor

Reprograming the Immunosuppressive Tumor Micro-Environment of Solid Tumors© 2024 PLIANT THERAPEUTICS

Activated TGF-β Contributes to Immune Exclusion & Evasion, Tumor
Metastasis and Angiogenesis
Integrin Activation of TGF-β

Oncogenic Effects of TGF-β Activation• Integrins activate TGF-β oncancer cells and multiple cell
types in the tumor microenvironment• This leads to immune
suppression and resistance to I/Otherapies• Selectively inhibiting integrinbinding to latent TGF-β complex
has potential to:─ Safely block TGF-β activation
─ Enhance efficacy of multiple
checkpoint inhibition pathways© 2024 PLIANT THERAPEUTICS

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PLN-101095 – Potential First-in-Class SMI Dual αVβ8/αVβ1 Inhibitor
Highly potent dual inhibitor of αVβ8 and αVβ1
• Tumors that overexpress αVβ8 have a poor prognosis

Small molecule with oral administration• Ease of administration compared to mAb programs

Activity demonstrated in multiple PD-1 resistant tumor models• Increased T-cell infiltration and high tumor growth inhibition

Greater reduction in TGF-β signaling than either αVβ8 or TGF-β1,2 mAb• TGF-β is a central mediator of immune suppression in the tumor microenvironment

Significant reduction in tumor fibrogenesis• Inhibition of αVβ1 on fibroblasts may aid immune infiltration of fibrotic tumors© 2024 PLIANT THERAPEUTICS

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PLN-101095 – Approach to Immune Checkpoint Inhibitor ResistanceCommon Mechanisms of I-O Resistance

PLN-101095 Approach

Tumor-specific IFNγ levels at baseline predict
pembrolizumab responses [4,5]Potently inhibit general immunosuppressive
immune checkpoint to restore CD8 T cell IFNγ
secretion

Immunosuppressive stroma / myeloid compartment associatedwith active TGF-β signaling predicts atezolizumab responses [3]Prevent both free and latent TGF-β signaling frommajor integrin sources found in solid tumors

Tumor infiltrating lymphocytes highly sensitive to TGF-βimmunosuppression [e.g.1,2]

Dual mechanism significantly increases quantity
of TILs and increases resistance to exhaustion

Dual inhibition of αVβ8 & PD-1 exploit unexpected synergistic pathways leading to enhanced tumor killing6
1- Thomas DA, et al. Cancer Cell. 2005 Nov;8(5):369-80. 2- Yang, ZZ. et al. Leukemia. 2014 28, 1872–1884. 3- Mariathasan, S. et al. 2018 Nature 554, 544–548.

4- Ayers, M et al. J Clin Invest. 2017 127(8):2930-2940. 5- Cindy Yang, S.Y. et al. Nat Commun. 2021 12, 5137. 6- Larrick J et al., DOI: https://doi.org/10.21203/rs.3.rs-1778271/v1© 2024 PLIANT THERAPEUTICS

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PLN-101095 – Ongoing Phase 1 Study in Patients Resistant to ICIs
PLN-101095
Monotherapy
Day 1:Start PLN-101095

PLN-101095
Combination with α-PD-1

Day 15:
Add α-PD-1

Day 35:
DLT window

Week 10:
Assess tumor response

STUDY POPULATION• Advanced or metastatic solid tumors for which
pembrolizumab is indicated & have received at least
2 doses pembrolizumab• Pembrolizumab relapsed or refractory

2000mg BID, n ≥ 3

1500mg BID, n ≥ 3

1000mg BID, n ≥ 3

500mg BID, n=1250mg BID, n=1

ENDPOINTS• Primary: safety & tolerability• Secondary: mono- and combination therapy PK• Exploratory:• PK & PD• Antitumor activity: ORR, TTR, DOR, PFS & OS

Safety Review Committee (SCR) Meetings will review safety data within the
DLT windowed 35 days, including AEs, lab values, and DLTs for all participants
enrolled in a dose cohort© 2024 PLIANT THERAPEUTICS

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PLN-101325 – Selective Muscle Cell Integrin
Agonist for the Treatment of Muscular
Dystrophies© 2024 PLIANT THERAPEUTICS

α7β1: A Drug Target in Muscular Dystrophies•

Predominantly expressed in skeletal, heartand smooth muscle•

α7β1 strong genetic modifier in MDX mice–

Lack of α7β1 worsens disease phenotype–

Over expression increases survival andimproves function•

Pharmacological agents that increase
expression show similar effects•

Human mutations in α7β1 result in congenitalMD•

ITGA7 frameshift (heterozygous,
nonfunctional mutation is associated with leanmuscle volume reduction (UK Biobank)

J Cell Bio 2001, Human Gen Ther 2015, Molecular Therapy 2017

© 2024 PLIANT THERAPEUTICS

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PLN-101325 – Pliant’s Muscular Dystrophy Program – Overview
Targeting α7β1,an integrin receptor on the muscle cell surface• α7β1 is upregulated as a compensatory mechanism in different types ofmuscular dystrophy• Acts as a substitute for dystrophin, helping to stabilize the muscle membrane,
decreasing muscle damage• Mutations in the target result in human congenital myopathy
Allosteric agonistic monoclonal antibody• Activates the target to augment the compensatory mechanism
Potential to combine across multiple muscular dystrophy indications• Target is upregulated across different forms of muscular dystrophy• Mechanism is unrelated to underlying gene mutation• May be combined with existing therapies as well as new modalities(CRISPR, gene therapy,…)© 2024 PLIANT THERAPEUTICS

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PLN-101325 – Data from MDX Knockout Suggest High Potential in DMD
Improved Muscle Cell Membrane Integrity• Reduced intracellular resting calcium• Reduced hyperpolarization of muscle cell membrane
Increased Diaphragm Force• Dose dependent increase in both diaphragm weight and force• Highest dose of PLN-101325 approaches wild-type diaphragm force
Increased Body Weight• Dose-dependent increase in body weight over 12 weeks of treatment• 9% total increase in body weight at 12 weeks of treatment at high dose
Improved Response to Muscle Injury• Dose-dependent improvement in contractile force over 12 weeks of treatment post-injury compared toplacebo© 2024 PLIANT THERAPEUTICS

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