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© 2025 PLIANT THERAPEUTICS Developing Novel Treatments for Fibrotic Diseases J.P. MORGAN HEALTH CARE CONFERENCE January 2025
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© 2025 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 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 theforward-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. 22
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© 2025 PLIANT THERAPEUTICS Pliant – Breaking New Ground in Fibrosis Industry-Leading Integrin/Fibrosis Platform Bexotegrast – Disease modifying Potential in IPF Well Funded into 2027 31 – Includes cash, cash equivalents and short-term investments. Blockbuster Potential in Areas of High Unmet Need • Four approved INDs • Library of 10,000+ integrin binding molecules • Bexotegrast - Ph2b/3 BEACON-IPF registrational program: ⎼ Phase 2b data expected 2Q 2026 • Pulmonary Fibrosis is a $4+ billion market reaching $6- 10 billion within 10 years • High unmet need due to tolerability/efficacy issues with approved agents • Opportunity to expand the market to new indications (i.e. progressive pulmonary fibrosis) • Bexotegrast showed improvement in FVC vs. placebo as monotherapy and in SOC combo • Favorable safety and tolerability profile • Potentially disease modifying by reversing fibrosis ⎼ Reduction in total lung collagen post 12-week treatment • Clinically meaningful reduction in cough severity • $406.5 million of cash1 as of September 30, 2024 • Operations are funded into 2027
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© 2025 PLIANT THERAPEUTICS Pliant Development Pipeline 4 Program Indication Preclinical Clinical Anticipated Milestone Timing Phase 1 Phase 2a Phase 2b / 3 Dual selective inhibitor of αvβ6 /αvβ1 Idiopathic Pulmonary Fibrosis BEACON-IPF Phase 2b enrollment complete Start Phase 3 Phase 2b data 1Q 2025 1Q 2025 2Q 2026 Progressive Pulmonary Fibrosis Initiate Phase 2b BEACON-PPF trial 2H 2025 Inhibitor of αvβ8 /αvβ1 Solid Tumors Phase 1 data 1Q 2025 Anti-integrin mAb of α7β1 DMD & Other Muscular Dystrophies Phase 1 ready (CTA active) Bexotegrast (PLN-74809) PLN-101095 PLN-101325
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© 2025 PLIANT THERAPEUTICS Bexotegrast Has Outperformed at All Stages of Development 5 Bexotegrast PC/Phase 1 Phase 2 Improvement in Lung Function (FVC) Symptomatic Improvement (Cough) Reduction in Lung Fibrosis (HRCT and PET Imaging) Additive Effect on Top of SOC (80%) Favorable Safety & Tolerability Profile Oral, Once-Daily Dosing αvβ6 Target Saturation (PET Imaging) Reduced TGF-β Signaling (pSMAD) Reduced Pro-Fibrotic Gene Expression Bexotegrast – 4 Key Differentiators • Improvement in lung fuction • Favorable safety and tolerability profile • Potential disease modifying reversal of fibrosis • Symptomatic improvement – cough severity
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© 2025 PLIANT THERAPEUTICS 140 mL 80 mL 29 mL 49 mL 107 mL NA -100 -50 0 50 100 150 200 Bexotegrast 320 mg INTEGRIS-IPF Nerandomilast 36 mg Phase 2 Admilparant 60 mg Phase 2 IPF Admilparant 60 mg Phase 2 PPF Taladegib 200 mg Phase 2a Buloxibutid 200 mg Phase 2a Change in FVC (mL) from Placebo Comparison of Approved & Select Investigational Agents in IPF / PPF Bexotegrast Shows Superior Effect on FVC with no Notable AEs1 6 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 comparisons provide 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 the other datasets represented on this slide. In larger trials of bexotegrast, the clinical activity suggested by our INTEGRIS-IPF trial may not be replicated 1 – No Head-to-head studies were conducted with bexotegrast against other drug products. Results of actual head-to-head comparisons may differ. Agents in Development No background therapy No U.S. participants 50-80% of patients on background therapy 56 mL 61 mL -26 mL 51 mL 54 mL ASCEND CAPACITY 1 CAPACITY 2 INPULSIS 1 INPULSIS 2 Approved Agent Phase 3 Studies Discontinuations Notable Adverse Events 36-wk 19% alopecia 57% dysgeusia 52% alopecia 43% muscle spasm 17-31% diarrhea 14% vs. 10% placebo 26-week 8% hypertension 7% hypotension 5% vs. 17% placebo 10% vs. 11% placebo 15% vs. 0% placebo 26% vs. 0% placebo 12-wk: 33% 36-wk: 46% None Daily Dose
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© 2025 PLIANT THERAPEUTICS Assessment of Late-Stage IPF Programs in Fibrotic Human PCLS 7 • Across two independent experiments, fibrotic PCLS from 4 unique human lung donors were treated for 6 to 7 days • Experiment 1 (2 IPF, 2 PPF donors): ⎼ Bexotegrast vs. Nerandomilast • Experiment 2 (4 IPF donors): ⎼ Bexotegrast vs. Admilparant • All agents tested at clinical Cmax • Minimal effect on pro-fibrogenic gene expression observed with nerandomilast and admilparant Experiment 1 Experiment 2 Vehicle Nerandomilast Bexotegrast ACTA2 COL1A1 COL1A2 COL3A1 CTGF CTHRC1 FN1 LOXL2 PDGFRB POSTN SERPINE1 SERPINH1 TGFB1 Fold Change (log2) -1.0 -0.5 0 0.5 1.0 DMSO Admilparant Bexotegrast ACTA2 COL1A1 COL1A2 COL3A1 CTGF CTHRC1 FN1 LOXL2 PDGFRB POSTN SERPINE1 SERPINH1 TGFB1 Fold Change (log2) -1.0 -0.5 0 0.5 1.0
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© 2025 PLIANT THERAPEUTICS Bexotegrast Has Significant Respiratory Market Potential 8 US PREVALENCE OF FIBROSING ILD INDICATIONS1 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 • 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 across other fibrosing ILDs ~400K 73K 150K 57K 18K 43K 25K 28K Progressive pulmonary fibrosis (PPF) 2 Idiopathic pulmonary fibrosis (IPF) 2 Rheumatoid arthritis- associated interstitial lung disease (RA-ILD) Unclassified interstitial lung disease (ILD) Other interstitial lung diseases (ILDs) Pulmonary hypertension- associated interstitial lung disease (PH-ILD) 2 Scleroderma-associated interstitial lung disease (SSc-ILD) 2 PATIENTS
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© 2025 PLIANT THERAPEUTICS ~ $4B+ Pulmonary Fibrosis Market is Underpenetrated 9 Drivers of Future Market Growth • Aging population will increase treatment eligible patient population • Earlier treatment initiation possible with improved diagnosis • Bexotegrast expected to increase treatment rate and duration on treatment WW MARKET FOR THERAPEUTICS APPROVED FOR IPF & PPF (2018-23) 2018 19 20 1.3 21 0.9 22 0.3 23 2.4 2.9 3.6 4.2 4.3 4.1 2.9 3.4 3.8 1.7 2.3 1.3 1.2 1.1 1.3 Ofev (BI) Esbriet (Roche) Source: Boehringer Ingelheim and Roche Annual Reports 2018 – 2023 ($ Billions)
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© 2025 PLIANT THERAPEUTICS Over 75% of IPF Patients are NOT Optimally Treated 0 100 200 300 Optimally Treated (dosing & persistency) Treated Prevalence THOUSANDS US EU4+UK JP 10 • Available therapies have no impact on progression of fibrosis, survival or QOL • Efficacy / safety tradeoffs result in patient refusal to receive treatment • Intolerability leads to suboptimal dosing, and permanent discontinuation Source: Data on file
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© 2025 PLIANT THERAPEUTICS Pulmonary Fibrosis Market Could More Than Double Within 10 Years 0.0 .0 .0 .0 .0 10.0 1 .0 11Source: Data on file
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© 2025 PLIANT THERAPEUTICS Bexotegrast Expected to Address Unmet Needs Across Key Patient Segments 12 Down dosing, poor adherence and low persistency impacts the real-world efficacy of current IPF treatments Active Switchers Improved safety/tolerability profile of bexotegrast shifts the risk- benefit of therapy for patients refusing existing antifibrotic options Untreated Naïve Patients progressing on an existing treatment (efficacy failure) will have a novel therapy added Add-On Source: Physician Research, Pliant analysis Monotherapy Opportunity Combination Opportunity Limited antifibrotic options result in premature discontinuation of treatment due to inadequate efficacy response and/or tolerability Untreated Discontinued
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© 2025 PLIANT THERAPEUTICS Progressive Pulmonary Fibrosis (PPF) Market Opportunity 13 PPF Has High Unmet Medical Need, Comparable to IPF • Patients follow a similar disease course to IPF with significant symptoms and mortality rates • There is no difference in the approach to the treatment and management of PPF patients compared to IPF patients • Majority of PPF patients remain untreated; one approved treatment option with safety and tolerability challenges PPF Significantly Expands the Commercial Potential of Bexotegrast Beyond IPF • PPF increases the addressable patient population by approximately 100,000 in the U.S. • Ofev net sales grew with PPF approval while Esbriet net sales remained flat with a single indication of IPF • PPF lowers prescribing barrier by simplifying payer authorization process (progression without definitive diagnosis)
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© 2025 PLIANT THERAPEUTICS Bexotegrast Decreased Fibrotic Gene Expression in PPF Explant Tissue 14 DMSO Bexo ALK5i COL1A1 SERPINE1 COL1A2 COL3A1 ACTA2 MMP2 TIMP1 CTGF log2 fold change -1 0 1 HP (3), RA-ILD (2), Scleroderma (2), NSIP (1) N = 2 IPF, 1 HP, 1 NSIP DMSO IPF Non-IPF 0.0 0.5 1.0 1.5 COL1A1 Relative Expression ✱✱✱ ✱✱✱✱ [c] = 200 nM # p = 0.053 vs DSMO * p < 0.05 vs DSMO ** p < 0.01 vs DSMO *** < 0.001 vs DSMO **** < 0.0001 vs DSMO DMSO 200 pm 2 nM 60 nM 200 nM 0.0 0.5 1.0 1.5 COL1A1 Bexotegrast [c] Relative Expression * ** p=0.053 In precision-cut lung slices from 7 lungs exhibiting different forms of lung fibrosis, bexotegrast decreased pro- fibrotic gene expression strongly and in a dose-dependent manner after 7 days of culture
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© 2025 PLIANT THERAPEUTICS Phase 2b Enrollment Phase 2b Treatment BEACON-IPF Phase 2b/3 Study On track for Enrollment Completion (1Q25) and Topline Data (2Q26) 15 START OF STUDY END OF STUDY Bexotegrast 160 mg dose Randomization 1:1:1 Randomization 1:1 KEY PRIMARY ENDPOINT • Change from baseline in absolute FVC (mL) at Week 52 KEY SECONDARY ENDPOINTS • Time to disease progression (≥ 10% absolute decline from baseline in FVCpp, respiratory- related 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 Randomization 1:1:1 Placebo once daily for 52 weeks Bexotegrast 320 mg dose Phase 3 2-Dose Enrollment Phase 3 Single Dose Enrollment Phase 3 Treatment Phase 2b Phase 3 Phase 2b Enrollment Complete Phase 3 Data Phase 3 Enrollment Complete Bexotegrast selected dose(s) once daily for 52 weeks Placebo once daily for 52 weeks (n=120) Bexotegrast 160 mg dose once daily for 52 weeks (n=120) Bexotegrast 320 mg dose once daily for 52 weeks (n=120) Phase 2b Data and Phase 3 Dose Selection
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© 2025 PLIANT THERAPEUTICS Phase 2a Collagen PET Study – Design and Objectives Quantification of Type 1 Collagen in the Lung using PET Imaging PRIMARY AND SECONDARY ENDPOINTS • Quantification of type 1 collagen in the lung as assessed by changes from baseline in standardized uptake value (SUV) of 68GA-CBP8 (type-1 collagen probe) • Safety and tolerability EXPLORATORY ENDPOINTS • Changes in FVC and FVCpp • Change in VAS for cough severity • Changes in fibrosis biomarkers INCLUSION CRITERIA • Diagnosis of IPF (within 8 years) • FVC percent predicted ≥ 5% • DLCO ≥ 30% • Estimated glomerular filtration rate ≥ 50mL/min Placebo (n=3) RANDOMIZATION 2:1 Bexotegrast Placebo SCREENING END OF STUDY Week 14 Stratified for the use of SoC (nintedanib or pirfenidone) Day -28 Last dose Week 12 Baseline Day 1 Bexotegrast 160 mg (n=7) 16 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
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© 2025 PLIANT THERAPEUTICS Quantification of Collagen in the Lung using PET Imaging • 68Ga-CBP8 is a PET probe that binds type I collagen with high specificity1 • 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 collagen • 68Ga-CBP8 previously detected treatment response to anti-fibrotic therapy in a mouse model of pulmonary fibrosis1 17 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 Healthy Control IPF Patient Note: Uptake in the heart and vasculature as well as in the liver is to be expected based on the probe’s half-life and biodistribution
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© 2025 PLIANT THERAPEUTICS Bexotegrast Showed Reduced PET Tracer SUV Compared to Placebo ITT Population 18 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 2 Montessi AJRCCM 200:2 2019 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
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© 2025 PLIANT THERAPEUTICS Bexotegrast Blocks New Collagen Deposition Over 12-Weeks 68GA-CBP8 Collagen PET Scans from Representative Trial Participants 19 Baseline Week 12 BexotegrastPlacebo 1.3 SUV 0 Low Collagen High Collagen Participant A: bexotegrast 160 mg • Decrease in SUVQ4: -0.17 (-15.5%) • Improvement in FVC: 130 mL Participant B: placebo • Increase in SUVQ4: 0.21 (18.4%) • Decline in FVC: -180 mL 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
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© 2025 PLIANT THERAPEUTICS Bexotegrast Improved Lung Function and Cough Severity Improvements correlated with PET Tracer SUV 20 -200 -150 -100 -50 0 50 100 150 0 4 8 12 LS Mean (SE) Change From Baseline in FVC (mL) Week Bexotegrast 160 mg (n=7) Placebo (n=2) +14.5 −91.5 FVC 106 mL FVC, forced vital capacity; LS, least squares; ρ, correlation; PET, positron emission tomography; SUV, standardized uptake value; VAS, visual analog scale. Note: One placebo subject did not have FVC that meet quality standards per ATS guidelines at Weeks 4, 8 and 12 -40 -20 0 20 40 60 0 4 8 12 Mean (SE) Change From Baseline in VAS Score Week +40.3 −25.1 Cough Severity Treatment with bexotegrast improved FVC over 12 weeks, maintaining a clear separation from placebo at all time points Correlation between change in 68Ga-CBP8 PET SUV and change in FVC (ρ=− ) Participants in the bexotegrast group reported decreased cough severity across all on-treatment time points compared with placebo Change in cough severity is predicted by change in FVC (R2=0.77)
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© 2025 PLIANT THERAPEUTICS PLN-101095 Dual Selective αVβ8 / αVβ1 Integrin Inhibitor Reprograming the Immunosuppressive Tumor Micro-Environment of Solid Tumors
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© 2025 PLIANT THERAPEUTICS PLN-101095 – Potential First-in-Class SMI Dual αVβ8/αVβ1 Inhibitor H g y d b f αVβ8 d αVβ1 • Tumors that overexpress αVβ8 have a poor prognosis Activity demonstrated in multiple PD-1 resistant tumor models • Increased T-cell infiltration and high tumor growth inhibition Greater reduction in TGF-β g g αVβ8 or TGF-β , b • TGF-β is a central mediator of immune suppression in the tumor microenvironment Small molecule with oral administration • Ease of administration compared to mAb programs 22 Significant reduction in tumor fibrogenesis • Inhibition of αVβ1 on fibroblasts may aid immune infiltration of fibrotic tumors
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© 2025 PLIANT THERAPEUTICS PLN-101095 – Ongoing Phase 1 Study in Patients Resistant to ICIs 23 250mg BID, n=1 500mg BID, n=1 g ID, ≥ g ID, ≥ g ID, ≥ PLN-101095 Monotherapy PLN-101095 Combination with α-PD-1 Day 15: Add α-PD-1 Day 1: Start PLN-101095 Week 10: Assess tumor response Day 35: DLT window STUDY POPULATION • Advanced or metastatic solid tumors for which pembrolizumab is indicated & have received at least 2 doses pembrolizumab • Pembrolizumab relapsed or refractory 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 Enrollment Completed Enrollment Initiated