EX-99.1 2 brhc10032676_ex99-1.htm EXHIBIT 99.1

Exhibit 99.1
Developing Novel Treatments for Fibrotic Diseases Corporate Presentation JANUARY 2022

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 to be 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, the timing and outcome of regulatory decisions, future availability of clinical trial data, our collaborations for our product candidates and the maintenance of those collaborations; 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; that many 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 patients in 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 which such 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 and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section 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 for which they are being investigated. 2

Pliant – Company Highlights Strategic Partnership with Novartis Validates PlatformLargest ($80M) upfront for a preclinical NASH programSignificant expense offset to pipeline programsBroad multi-target research collaborationNext generation anti-fibrotic molecules targeting novel integrins Industry-Leading Fibrosis PlatformBuilt on integrin-mediated inhibition of TGF-β pathway resulting in antifibrotic effect and shown to be safeProprietary drug discovery platform based on novel in-house compound library of integrin bindersLead molecule PLN-74809 is highly antifibrotic in lung and liver while well tolerated at highest doses tested Programs Targeting High Unmet Medical Need with High-Impact, Near-Term CatalystsPLN-74809 in Phase 2a development in IPF and PSCPhase 2a topline data in IPF expected mid-2022Significant clinical derisking: target engagement (PET) and TGF-β pathway inibition (pSmad)IND submissions in oncology and muscular dystrophies expected by YE 2022 Strong Financial PositionOver $385 million raised to date in four financing rounds including June 2020 IPO (Nasdaq: PLRX)$221 million cash1 balance as of September 30, 2021Company funded into 2H 2023 1 - Includes cash, cash equivalents and ST investments. 3

Recent Company Highlights 4 Positive interim data from PLN-74809 PET imaging target engagement studyPLN-74809 showed target engagement up to 98% in lungs of IPF patientsAll doses tested achieved target engagement above threshold for predicted antifibrotic activity PLN-74809 Phase 2a INTEGRIS-IPF trial enrollment completePLN-74809 has been administered to over 450 subjects to date and shown to be well toleratedINTEGRIS-IPF topline data expected mid-2022 PLN-74809 Phase 2a INTEGRIS-PSC trial on track for full enrollment by mid-2022INTEGRIS-PSC topline data expected late 2022 / early 2023 FDA authorized evaluation of long-term treatment with PLN-74809 at doses up to 320 mg in IPFNo safety concerns identified to date at doses up to 640 mgNo treatment-related effects in chronic GLP tox, NOAEL set at the highest dose testedExpected 1H 2022 initiation of 6-month Phase 2a trial of PLN-74809 at 320 mg in IPF patients Early-stage programs in Oncology and DMD advancing toward INDINDs expected in both indications by YE 2022

Pliant’s Integrin Focused Library Core Platform for Novel Pipeline and Partner Programs 5 Pliant’s proprietary library of integrin binding compoundsEmphasis on structural diversityBroad spectrum of receptor subfamilies including αV integrins, collagen and laminin binders 5,000 10,000 RGD targeted Collagen targeted Laminin targeted 2,500 7,500 IntegrinsCell surface receptors that facilitate cell-cell and cell-extracellular matrix adhesion and interactionA major path of communication between the extracellular matrix, inflammatory cells, fibroblastsClosely involved in signaling processes governing tissue fibrosis

Pliant Development Pipeline 6 Program Indication Preclinical Clinical Anticipated Milestone GlobalRights Phase I Phase II Phase III Dual selective inhibitor of aVb6/aVb1 IdiopathicPulmonary Fibrosis Phase 2aTopline DataExpected Mid-2022 Primary SclerosingCholangitis Phase 2aEnrollment Complete Expected Mid-2022 Inhibitor of aVb8 Solid Tumors IND FilingExpected YE 2022 Anti-integrin mAb DMD Other Muscular Dystrophies IND FilingExpected YE 2022 Selective inhibitor of aVb1 NASH-AssociatedLiver Fibrosis Phase 2 Initiation INTEGRIS-IPF Enrollment Complete WHOLLY OWNED PARTNERED PLN-74809 Oncology Muscular Dystrophies PLN-1474

Fibrosis: The Silent Killer https://www.lungsandyou.com/ipf www.jhmicall.org Idiopathic Pulmonary Fibrosis (IPF) is a lethal pathological process with limited therapeutic options Primary Sclerosing Cholangitis (PSC) is a progressive inflammatory liver disease resulting in scarring of bile ducts, and cirrhosis Currently no FDA approved therapeutics30k-45k patients in the U.S.Median survival: 10-12 years without intervention 140k patients in the U.S.; 30k-40k new cases/year; 40k deaths/yearMedian survival: 3–5 years - Worse than some common cancers2 FDA approved therapeutics generate annual revenues >$3.6 billion despite significant remaining unmet medical need 7

aVb6 / aVb1 Integrins Drive Cell-Matrix Interactions in Fibrosis TGF-b is central mediator of fibrosisaVb6 /aVb1 Integrins activate latent TGF-b only in fibrotic tissueSystemic TGF-b blockade carries toxicity risks aVb6 / aVb1 Integrins promote fibrosis by TGF-b activation Selectively blocking TGF-b in fibrotic tissues may provide a low risk, effective antifibrotic approach Col1a1Col3a1Timp1CTGFATX… FIBROSIS 8

PLN-74809 Provides Profound Antifibrotic Activity through Upstream Inhibition of TGF-b Activation 9 Col1a1Col3a1Timp1CTGFATX… FIBROSIS PLN-74809 Pamrevlumab Upstream inhibition of TGF-b leads to reduction of multiple profibrotic genesCompetitor programs only block one of multiple profibrotic gene products

Pliant Compounds Have Not Shown Adverse Effects of Systemic Inhibition of TGF-β Pathways1 Affected Organ System Systemic TGF-β Blockade Observed with Pliant Compounds?1 Cardiovascular System Cardiotoxicity Immune System Autoimmunity/Inflammation GI System Autoimmunity/Inflammation Skin Keratoacanthomas/SCC Hematology Thrombocytopenia/Anemia By targeting integrins that are upregulated specifically in fibrotic tissues, Pliant’s small molecule compounds may avoid toxicities associated with systemic TGF-β blockade1 1 - Based on preclinical GLP tox studies as well as clinical trials to date. No No No No No 10

Dual avb6/avb1 Inhibition Blocks COL1A1 Gene Expression More than Single Inhibition in Human IPF Tissue 11 Ex-planted lungs from 5 IPF patients Sliced and cultured for 7 days Profibrotic Gene Expression Panel Decaris et al. Respir Res (2021) 22:265

Administered to over 450 subjects to date including healthy volunteers and patientsGenerally well toleratedMost frequently reported AEs were headache and constipation with no drug-related severe AEs reported PLN-74809 – Extended Phase 1a Data Summary Well absorbed, orally bio-availableLong T1/2: ~50 hrs – QD dosing Safety Summary (Participants with drug-related TEAEs) Summary PK Curves by Cohort at Steady State PK sampling up to 144h; only 0-24hr plotted.Doses 10mg to 40mg from Study PLN-74809-P1-01, Day 14.Doses 80mg, 160mg and 320mg from Study PLN-74809-104, Day 7. Multiple Ascending QD Doses MAD 10 mg(N=9) 20 mg(N=9) 40 mg(N=9) 80 mg(N=8) 160 mg(N=16) 320 mg(N=8) AE Severity Mild -- 11% -- 13% 19% 25% Moderate -- -- -- 25% 6% -- Severe -- -- -- -- -- -- Pharmacokinetics Safety Data presented as box plots (max to min) with line at median and + at mean. 12 CONFIDENTIAL

PLN-74809 – Phase 1b Proof of Biological Mechanism 13 Strong PK/PD Relationship – Cmax above IC50 Results in Predicted Biological Effect Alveolar pSMAD2/SMAD2(all time points) * = p < 0.05 vs placebo and Cmax < 700 ng/mL group Mean PK/PD Response in Subjects with Cmax > 700ng/mL Data Presented June 2019 Phase 1b Study Investigating Higher Doses – Data Expected in 1Q2022 Data from this study and the PET target engagement trial evaluate 80, 160 or 320 mg to demonstrate the relationship between: Antifibrotic activity TGF-β signaling inhibition PLN-74809 target engagement PLN-74809 plasma exposure

14 Reduction in Pulmonary pSMAD Appears to Be a Marker for Reduction of Fibrosis Diagnostic open lung biopsies from 10 patients with ILD and suspected IPF 2-3 distinct lung regions sampled from each patient 5 controls (non-transplanted lungs) Total pSMAD3 had a strong correlation vs. extractable Collagen I (Western Blot) Adapted from Chapman HA et al. March 12, 2020; 382:1068-1070 Tissue pSMAD Levels Are Highly Significantly Correlated with Extractable Collagen Levels in Normal and Fibrotic Lungs

Red arrows: IPF lungWhite arrows: transplant lung 0 SUV 5.5 71-y/o ♂ left lung transplant 2yr prior to scan Phase 2a PET Trial – avb6 Expression Measured by a PET Ligand is Correlated with Extent of Fibrosis in IPF 15 PET Ligand Uptake Confined to IPF Lung in Unilateral Lung Transplant Patient Kimura et al., Nature Com. 2019 Single-site open-label trial at Stanford UniversityAdults with IPF diagnosis (n=12) and FVC ≥ 45% of predictedPatients receive single oral dose of PLN-74809 with PET scans prior to dosing and at Tmax post doseDose cohorts being evaluated: 60 mg, 120 mg, 240 mg, and 320 mg TRIAL DESIGN ENDPOINTS Primary: Evaluation of αvβ6 target engagement by PLN-74809 assessed by change in PET tracer uptake following a single oral doseSecondary: Assessment of safety and tolerability of PLN-74809 in IPF patients Exploratory: Relationship between PLN-74809 systemic exposure and positron emission tomography (PET) imaging and biomarkers in IPF participants

Phase 2a PET Trial in IPF – Interim Analysis Methodology PET scan acquisitions at baseline (no drug) and after drug administration (4 hours post-dose)1 week interval between baseline and post-dose PET scan acquisitionAdministration of a single dose of PLN-74809: 60 mg – 120 mg – 240 mg – 320 mgInterim PK and target engagement data from 6 dose administrations in 4 patients 2 out of 4 patients received one single dose 2 out of 4 patients received two single doses with at least a 2-week washout interval between dosesAll patients on standard of care therapy (nintedanib)Image analysis for target engagement in highly fibrotic regions of the lungs 16 60 mg 120 mg 240 mg 320 mg Patient 1 x Patient 2 x x Patient 3 x x Patient 4 x

Dose and Plasma Concentration Dependent Target Engagement 17 52% 60% 98% 83% 94% 71% Best-fit values Bottom 0 Hillslope 1.11 Top 87.4 EC50 (nM) 2.96 Dose-Dependent Target Engagement Plasma Conc-Dependent Target Engagement * Free plasma concentration *

Putting the Interim Phase 2a PET Data into Perspective Target engagement above the threshold for predicted anti-fibrotic activity across all doses (>50% target engagement) PLN-74809 penetrates highly fibrotic areas of the lung Potential anti-fibrotic activity of PLN-74809 at clinical dosesInforms dose selection in Phase 2b trials and beyondProvides robust PK/PD model to predict exposure-response relationship Normal lung IPF lung Dose- and plasma concentration-dependent response approaching target saturation at the two highest doses 18

ScreeningDay -28 Last doseWeek 12 BaselineDay 1 End of StudyWeek 14 PLN-74809-IPF-202 [INTEGRIS-IPF]Phase 2a Global Safety-PK-Exploratory Efficacy Trial in IPF Key inclusion/exclusion criteriaAdults with IPF diagnosisFVC ≥ 45% of predictedStratified for pirfenidone or nintedanib use Randomization 3:1 (PLN-74809:placebo) Primary and secondary endpointsSafety, tolerability, PK Exploratory endpointsChange in FVC over 12 weeksHigh Resolution CT-based Quantitative Lung Fibrosis (QLF) imaging Effect on selected biomarkers Placebo (n=21) PLN-74809 40 mg (n=21) PLN-74809 80 mg (n=21) PLN-74809 160 mg (n=21) 19 Enrollment Complete with Topline Data Expected Mid-2022

Quantitative Lung Fibrosis (QLF): A Sensitive Measure of FVC Change Over Time in IPF QLF: a computed tomography (CT) biomarker Assessment via high resolution CT imaging Standardized and centralized image analysisQLF is an automated quantification of lung fibrosis94.4% sensitivity and 94.7% specificityFibrosis presence/ absence detected at threshold level of 1%1QLF is a sensitive measure of change over time in IPF A change of 2% in QLF from baseline correlates with a clinically meaningful worsening or improvement of FVCMoreover, clinically meaningful changes in FVC are associated with statistically significant changes in QLF2,3Inverse correlation with:Percent predicted FVC at 6 & 12 months3,4Percent predicted DLCOProgression Free Survival (PFS) 20 1 H.Kim and J Goldin et al. Acad Radiol;22:70-80; 20152 Kafaja et al. AJRCCM;197:644–652, 20183 Kim et al.Ther Adv Respir Dis; 15: 1–11, 20214 Richeldi et al. Lancet Respir Med 2020; 8: 25–33 Screening Week 26 ΔFVC= -24%; ΔQLF= 7.8%; ΔSOBQ= 30 CONFIDENTIAL Representative coronal and axial HRCT images from a placebo arm participant in the BMS-986020 P2a study at screening and week 26. Change over 26 weeks: FVC: −24%; QLF score: 7.8%. Classification overlay for QLF score is in blue and red.3DLCO – diffusion capacity for carbon monoxide; FVC, forced vital capacity

ScreeningDay -28 Last doseWeek 12 BaselineDay 1 End of StudyWeek 14 Key inclusion/exclusion criteriaAdults with large duct PSCPre-cirrhotic/no hepatic impairmentStratified for UDCA use Randomization 3:1 (PLN-74809:placebo) Primary and secondary endpointsSafety, tolerability, PK Exploratory endpointsEffect on fibrosis biomarkers (e.g., Pro-C3, ELF)Change in ALP over 12 weeksImaging Placebo (n=21) PLN-74809 40 mg (n=21) PLN-74809 80 mg (n=21) PLN-74809 160 mg (n=21) PLN-74809-PSC-203 [INTEGRIS-PSC]Phase 2a Global Safety-PK-Fibrosis and Cholestasis Biomarker Trial in PSC 21 Enrollment Expected to be Completed by Mid-2022

Pliant Development Pipeline 22 Program Indication Preclinical Clinical Anticipated Milestone GlobalRights Phase I Phase II Phase III Dual selective inhibitor of aVb6/aVb1 IdiopathicPulmonary Fibrosis Phase 2aTopline DataExpected Mid-2022 Primary SclerosingCholangitis Phase 2aEnrollment Complete Expected Mid-2022 Inhibitor of aVb8 Solid Tumors IND FilingExpected YE 2022 Anti-integrin mAb DMD Other Muscular Dystrophies IND FilingExpected YE 2022 Selective inhibitor of aVb1 NASH-AssociatedLiver Fibrosis Phase 2 Initiation INTEGRIS-IPF Enrollment Complete WHOLLY OWNED PARTNERED PLN-74809 Oncology Muscular Dystrophies PLN-1474

Pliant’s Integrin-Based Oncology Program

Activated TGF-β Contributes to Immune Exclusion & Evasion, Tumor Metastasis and Angiogenesis 24 Integrins activate TGF-β on cancer cells and multiple cell types in the tumor micro-environmentThis leads to immune suppression and resistance to I/O therapiesSelectively inhibiting integrin binding to latent TGF-β complex has potential to:Safely block TGF-β activationEnhance efficacy of multiple checkpoint inhibition pathways Integrin Activation of TGF-β Oncogenic Effects of TGF-β Activation

αVβ8 Inhibitor/ Anti-PD-1 Combo Reduced Tumor Burden and Increased Survival in Preclinical Models vs. Anti-PD-1 Alone 25 EMT6 Model, N=20 per arm Pliant’s lead oral αVβ8 inhibitor matched the maximal therapeutic effect of αVβ8 antibody in vivo TGI (%) 74% 80% **** p<0.0001

Selective Muscle Cell Integrin Agonism for the Treatment of Muscular Dystrophies

Pliant’s Muscular Dystrophy Program – Overview Targeting an integrin receptor on the muscle cell surfaceIntegrin target is upregulated as a compensatory mechanism in different types of muscular dystrophyActs as a substitute for dystrophin, helping to stabilize the muscle membrane, decreasing muscle damageMutations in the target result in human congenital myopathyAllosteric agonistic monoclonal antibodyActivates the target to augment the compensatory mechanismPotential to combine across multiple muscular dystrophy indicationsTarget is upregulated across different forms of muscular dystrophyMechanism is unrelated to underlying gene mutationMay be combined with existing therapies as well as new modalities (CRISPR, gene therapy,…) 27

Pliant’s mAb Demonstrated Improved Muscle Membrane Integrity and Diaphragm Function in Mouse DMD Model 28 Antibody treatment protected against muscle damage Mean +/- SD n=10/group Duchenne muscular dystrophy (DMD) causes progressive wasting of cardiac and respiratory muscles (main cause of death) mdx/Agonist Ab (low dose) mdx/Agonist Ab (high dose) Reduction of clinical biomarkers including serum creatine kinase and skeletal troponin Improvement in diaphragm function is expected to significantly improve patient pulmonary function

Developing Novel Treatments for Fibrotic Diseases Corporate Presentation JANUARY 2022