Pliant Therapeutics, Inc. · NASDAQ:PLRX
Pliant Therapeutics — Investor Presentation (January 2023)
70 slides from Pliant Therapeutics's investor presentation, Jan 9, 2023
Slide 1: Developing Novel Treatments for Fibrotic Diseases
Exhibit 99.1 Developing Novel Treatments for Fibrotic Diseases JANUARY 2023 © 2023 PLIANT THERAPEUTICS
Slide 2: Disclaimers
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 pres
Slide 3: Pliant – Company Highlights
Pliant – Company Highlights Industry-Leading Fibrosis Platform Programs Targeting High Unmet Medical Need with High-Impact, Near-Term Catalysts • Built on integrin-mediated inhibition of TGF-β pathway resulting in antifibrotic effect and shown to be safe • Bexotegrast in Phase 2a development in IPF
Slide 4: The Pliant Team
The Pliant Team Experienced in Fibrosis and Drug Development Core Team Founders Bernard Coulie, M.D., Ph.D., M.B.A. Dean Sheppard, M.D. President, CEO, and Director Professor of Medicine, Chief of the Division of Pulmonary, Critical Care, Allergy and Sleep, and Director of the Lung Biology Center. H
Slide 5: Pliant's Integrin Focused Library
Pliant’s Integrin Focused Library Core Platform for Novel Pipeline and Partner Programs Integrins • Cell surface receptors that facilitate cell-cell and cell-extracellular matrix adhesion and interaction • A major path of communication between the extracellular matrix, inflammatory cells, fibroblast
Slide 6: Pliant Development Pipeline
Pliant Development Pipeline Clinical Anticipated Global Program Indication Preclinical Milestone Rights Phase I Phase II Phase III Phase 2a Idiopathic 320 mg 12-Week Pulmonary Data Expected Bexotegrast Fibrosis Early 1Q 2023 (PLN-74809) Primary Phase 2a Dual selective inhibitor Sclerosing Data Expec
Slide 7: Fibrosis – A Silent Killer
Fibrosis – A Silent Killer Idiopathic Pulmonary Fibrosis (IPF) is a lethal Primary Sclerosing Cholangitis (PSC) is a pathological process with limited therapeutic options progressive inflammatory liver disease resulting in scarring of bile ducts, and cirrhosis • 140k patients in the U.S.; 30k-40k ne
Slide 8: Understanding the IPF Commercial Opportunity
Bexotegrast Understanding the IPF Commercial Opportunity Current Commercial Landscape in IPF Significant Need for New Therapeutic Options ® ® • Two marketed agents – Esbriet and Ofev • Esbriet and Ofev display modest slowing of IPF progression − >$3 billion total global revenues in 2021 − Inconclusi
Slide 9: Integrins Drive Cell-Matrix Interactions in Fibrosis
α β / α β Integrins Drive Cell-Matrix Interactions in Fibrosis v 6 v 1 a b a b b / Integrins promote fibrosis by TGF- activation V 6 V 1 b • TGF- is central mediator of fibrosis • a b /a b Integrins activate latent TGF-b only in fibrotic tissue V 6 V 1 • Systemic TGF-b blockade carries toxicity risk
Slide 10: Bexotegrast Provides Profound Antifibrotic Activity Through Upstream Inhibition of TGF-β Activation
Bexotegrast Provides Profound Antifibrotic Activity Through Upstream Inhibition of TGF-β Activation bexotegrast FIBROSIS Col1a1 Col3a1 Timp1 CTGF ATX Pamrevlumab … b • Upstream inhibition of TGF- leads to reduction of multiple profibrotic genes • Competitor programs only block one of multiple profib
Slide 11: Pliant Compounds Have Not Shown Adverse Effects Typical of Systemic TGF-β Inhibition
Pliant Compounds Have Not Shown Adverse Effects Typical of 1 Systemic Inhibition of TGF-β Pathways By targeting integrins that are upregulated specifically in fibrotic tissues, Pliant’s small molecule 1 compounds may avoid toxicities associated with systemic TGF-β blockade 1 Affected organ system Sy
Slide 12: Bexotegrast Nonclinical Toxicology Studies
Bexotegrast Nonclinical Toxicology Studies No effects of concern for clinical advancement GLP Study category Studies completed Findings with Bexotegrast (PLN-74809) • 1-Month IND-enabling NHP and mouse No findings limiting clinical advancement including • 3-Month Sub-chronic NHP and mouse • No pulmo
Slide 13: Dual Inhibition Blocks COL1A1 Gene Expression in Human IPF Tissue
Fold-change (log2) Dual α β /α β Inhibition Blocks COL1A1 Gene Expression More v 6 v 1 than Single Inhibition in Human IPF Tissue • Ex-planted lungs from 5 IPF patients Profibrotic Gene Expression Panel • Sliced and cultured for 7 days Selective Dual COL1A1 COL1A1 2 SERPINE1 # MMP7 COL3A1 1 ITGB6 SN
Slide 14: Bexotegrast Phase 1a Data Summary: Pharmacokinetics
Bexotegrast Phase 1a Data Summary Pharmacokinetics Pharmacokinetics 10000 C max • Well absorbed, orally bio-available 8000 • Long T : ~50 hrs – QD dosing 1/2 6000 4000 Summary PK Curves by Cohort at Steady State 2000 Day 7 0 10000 40 80 160 320 Dose (mg) 150000 320 mg AUC 0_24 160 mg 1000 80 mg 1000
Slide 15: Bexotegrast Phase 1a Data Summary: Safety
Bexotegrast Phase 1a Data Summary Safety - Well tolerated in healthy participants Drug-Related Treatment-Emergent Adverse Events Reported in ≥2 Bexotegrast -Treated Healthy Participants from Seven Phase 1 Studies with Available Safety Data Participants, n (%) Bexotegrast, TEAE Preferred Term Placebo
Slide 16: Bexotegrast Phase 1b Proof of Biological Mechanism
BAL Cell pSmad2 (% change) Bexotegrast Phase 1b Proof of Biological Mechanism Strong PK/PD Relationship – C above IC max 50 Results in Predicted Biological Effect Phase 1b Expansion Trial Investigating Higher Data Presented June 2019 Doses Data Presented February 2022 Mean PK/PD Response in Subjects
Slide 17: Bexotegrast Demonstrated Significant pSmad2 Suppression at 24 Hours
Concentration (ng/mL) (Dashed Lines) Bexotegrast Demonstrated Significant pSmad2 Suppression Relative to Baseline at 24 Hours Alveolar pSmad2/Smad2 Percentage Change from Baseline at 24 Hours Mean PK/PD Response Alveolar pSmad2/Smad2 Mean PK/PD Response Alveolar pSmad2/Smad2 Mean PK/PD Response (Par
Slide 18: Durable pSmad2 Suppression Relative to Placebo
Bexotegrast Demonstrated Durable pSmad2 Suppression Relative to Placebo at 6 Hours and 24 Hours at All Dose Levels pSmad2/Smad2 percentage change from baseline, delta versus placebo in Part 1 and Part 2 80 mg QD 0 160 mg QD 320 mg QD -50 -100 -150 -200 6 24 6hr 24hr Time (h) (Day 7) Placebo (n=8/4)
Slide 19: Tissue pSmad Levels Correlated with Extractable Collagen Levels
Tissue pSmad Levels are Highly Significantly Correlated with Extractable Collagen Levels in normal and fibrotic lungs 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
Slide 20: Putting the Phase 1b pSmad2 Data into Perspective
Putting the Phase 1b pSmad2 Data into Perspective Durable pSmad2 suppression at all dose levels relative to placebo at 6 hours and 24 hours Dose- and plasma concentration-dependent response with up to 92% and 76% suppression of pSmad2 from baseline at 6 and 24 hours, respectively Bexotegrast well to
Slide 21: Phase 2a PET Trial – Receptor Occupancy
Bexotegrast Phase 2a PET Trial – α β Receptor Occupancy v 6 Measured by an α β PET Ligand v 6 TRIAL DESIGN 71-y/o ♂ left lung transplant 2yr prior to scan • Single-site open-label trial at Stanford University • Adults with IPF diagnosis (n=12) and FVC ≥ 45% of predicted • Patients receive single ora
Slide 22: Phase 2a PET Trial in IPF – Interim Analysis Methodology
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 acquisition • Administration of a single dose of bexotegrast: 60 mg – 120 mg – 240 mg – 3
Slide 23: Dose- and Plasma Concentration-Dependent Target Engagement
Dose- and Plasma Concentration-Dependent Target Engagement Dose-Dependent Target Engagement Plasma Conc-Dependent Target Engagement 98% 1 10000 100 94% 83% 80 80 75 71% 60% 60 60 52% Best-fit values 50 0 Bottom 40 40 1.11 Hillslope 25 87.4 Top 20 20 2.96 EC (nM) 50 0 0 0 60 120 240 240 320 320 0.1 1
Slide 24: Putting the Interim Phase 2a PET Data into Perspective
Putting the Interim Phase 2a PET Data into Perspective Target engagement above the threshold for predicted anti-fibrotic activity NORMAL LUNG across all doses (>50% target engagement) Dose- and plasma concentration-dependent response approaching target saturation at the two highest doses IPF LUNG •
Slide 25: INTEGRIS-IPF Study Design and Objectives
INTEGRIS-IPF Study Design and Objectives PRIMARY AND SECONDARY ENDPOINTS RANDOMIZATION • Safety, tolerability, PK bexotegrast (PLN-74809) 3:1 Placebo EXPLORATORY ENDPOINTS Placebo (n=23) • Change in Forced Vital Capacity (FVC) over 12 weeks bexotegrast 40 mg (n=22) • High Resolution CT-based Quantit
Slide 26: Executive Summary
Executive Summary Bexotegrast Well Tolerated Over 12 Weeks of Treatment • Most TEAEs were mild or moderate in severity • No discontinuations due to adverse events • No deaths or drug-related SAEs Bexotegrast-Treated Patients Experienced an 80% Reduction in FVC Decline Over 12 Weeks (-15.1 mL, Pooled
Slide 27: Participant Disposition
Participant Disposition SCREENED n=141 SCREEN FAILURE n=51 RANDOMIZED AND TREATED n=90 BEXOTEGRAST PLACEBO n=67 n=23 Discontinued Discontinued 1 n=3 (13%) n=2 (3%) Safety Analysis n=67 Safety Analysis n=23 With SoC n=18; Without SoC n=5 With SoC n=55; Without SoC n=12 Efficacy Intent-to Treat Analys
Slide 28: Baseline Demographics
Baseline Demographics bexotegrast bexotegrast bexotegrast bexotegrast Placebo Characteristic 40 mg 80 mg 160 mg All (n=23) (n=22) (n=23) (n=22) (n=67) Male sex―no. (%) 18 (81.8) 19 ( 82.6) 16 ( 72.7) 53 ( 79.1) 22 ( 95.7) Female sex-no. (%) 4 (18.2) 4 (17.4) 6 (27.3) 14 (20.9) 1 (4.3) Age―yr (SD) 69
Slide 29: Baseline Disease Characteristics
Baseline Disease Characteristics bexotegrast bexotegrast bexotegrast bexotegrast Placebo 40 mg 80 mg 160 mg All Characteristic (n=23) (n=22) (n=23) (n=22) (n=67) Time since diagnosis of IPF―yr, Mean (SD) 1.78 (0.925) 2.39 (1.422) 2.13 (1.083) 2.10 (1.176) 2.62 (1.378) Standard of Care Use 17 (77.3)
Slide 30: Safety Summary
Safety summary bexotegrast bexotegrast bexotegrast bexotegrast Placebo 40 mg 80 mg 160 mg All AE, n (%) of Participants Reporting (n=23) (n=22) (n=23) (n=22) (n=67) Any AEs 16 ( 72.7) 15 ( 65.2) 15 (68.1) 46 (68.7) 14 (60.9) 45 (67.2) 14 (60.9) TEAE 16 ( 72.7) 15 ( 65.2) 14 ( 63.6) Related to study
Slide 31: Safety Summary by SOC Use in Pooled Bexotegrast Groups
Safety Summary by SOC use in Pooled Bexotegrast Groups Without Background SOC (N=17) With Background SOC (N=73) bexotegrast Placebo bexotegrast Placebo AE, n (%) of Participants Reporting (n=12) (n=5) (n=55) (n=18) Any AEs 8 ( 66.7) 3 ( 60.0) 38 ( 69.1) 11 ( 61.1) TEAE 8 ( 66.7) 3 ( 60.0) 37 ( 67.3)
Slide 32: Most Frequent TEAEs – Any Causality
Most Frequent TEAEs – Any Causality bexotegrast bexotegrast bexotegrast bexotegrast Placebo AE, n (%) of Participants Reporting 40 mg 80 mg 160 mg All (n=23) (n=22) (n=23) (n=22) (n=67) Most frequent TEAEs (≥ 10% in at least one arm) Diarrhea 2 (9.1) 5 (21.7) 5 (22.7) 12 (17.9) 1 (4.3) – Related to
Slide 33: Incidence of Diarrhea in IPF Randomized Clinical Trials
Incidence of Diarrhea in IPF Randomized Clinical Trials 70% 62% 60% 50% 40% 31% 30% 26% 24% 18% 20% 17% 10% 0% 0% 1 2 3 3 4 ESBRIET OFEV BI 1015550 BI 1015550 + SoC BG00011 Bexotegrast Bexotegrast + SoC Mono 1 2 3 4 ESBRIET USPI, OFEV USPI, Richeldi et al, 2022, Raghu et al, 2022 © 2023 PLIANT THERA
Slide 34: No Treatment-Emergent SAEs were Related to Study Drug
No Treatment-Emergent SAEs were Related to Study Drug Standard toxicity Any alternative cause or Treatment Group Preferred term Action taken Outcome grade confounding factors? Grade 3 Recovered / Acute respiratory failure No Dose not changed (Severe) Resolved bexotegrast 40 mg Grade 2 Removed carpet
Slide 35: Incidence of Acute Exacerbations in Recent Phase IPF Randomized Clinical Trials
Incidence of Acute Exacerbations in Recent Phase 2 IPF Randomized Clinical Trials Proportion of participants with Investigational agent Trial phase Trial duration acute exacerbation of IPF Active, 1.5% (n=1/67) Bexotegrast 2a 12 weeks Placebo, 0% (n=0/23) 52 weeks Active, 17% (n=9/54) 1 BG00011 2b (
Slide 36: Safety Evaluation – Conclusions
Safety Evaluation – Conclusions Bexotegrast was well tolerated with no dose relationship for adverse events No deaths or treatment related SAEs No participants discontinued bexotegrast due to TEAE Most frequent TEAE seen was diarrhea, but only seen in patients on standard of care © 2023 PLIANT THERA
Slide 37: Pharmacokinetic Evaluation
Pharmacokinetic Evaluation Based on sparse sampling, overall, bexotegrast pharmacokinetics and % unbound in IPF consistent with that of previous studies Concentrations in IPF participants increased approximately proportionally with dose Overall % unbound was ~0.3 to 0.5% Full PK curve will be predic
Slide 38: Change in FVC from Baseline to Week 12
Change in FVC from Baseline to Week 12 MMRM analysis - ITT population 100 50 24.6 0 -25.1 -50 -46.1 -74.1 -100 -150 40mg 80mg 160mg Placebo (n=22) (n=23) (n=22) (n=23) Treatment Change from baseline analyzed using a mixed model for repeated measures with terms for treatment group, SOC (Y/N), visit,
Slide 39: Change in FVC over Weeks in INTEGRIS-IPF
Change in FVC over 12 weeks in INTEGRIS-IPF MMRM analysis - ITT population Bexotegrast 40 mg Bexotegrast Pooled Doses 50 50 0 0 -5.6 -14.2 -14.9 -15.1 -27.3 -50 -50 -44.3 -46.1 -44.3 -50.5 -50.5 -74.1 -74.1 40mg All Bexotegrast (PLN-74809) -100 -100 (n=22) (n=67) Placebo Placebo (n=23) (n=23) -150 -
Slide 40: Change in FVC in On SoC Subgroup
Change in FVC from Baseline to Week 12 in On SoC Subgroup MMRM analysis - ITT population 50 0 -11.9 -50 -47.5 -58.3 -100 -95.2 -150 -200 40 mg 80 mg 160 mg Placebo (n=17) (n=19) (n=19) (n=18) Treatment Change from baseline analyzed using a mixed model for repeated measures with terms for treatment g
Slide 41: Change in FVC in Not on SoC Subgroup
Change in FVC from Baseline to Week 12 in not on SoC Subgroup MMRM analysis - ITT population 200 138.1 150 100 50 25.8 0 -50 -43.1 -44.4 -100 40 mg 80 mg 160 mg Placebo (n=5) (n=4) (n=3) (n=5) Treatment Change from baseline analyzed using a mixed model for repeated measures with terms for treatment
Slide 42: Proportion of Participants with FVCpp Decline ≥ 10%
Proportion of Participants with FVCpp Decline ≥ 10% ITT population 20 18.2% 17.4% 15 10 8.7% 4.5% 5 0 40 mg 80 mg 160 mg Placebo (N=22) (N=23) (N=22) (N=23) FVCpp ≥ 10% Decline 1 FVCpp ≥ 10%: strong predictor of disease progression and mortality FVCpp = Forced vital capacity, percent predicted 1 Ann
Slide 43: Forced Vital Capacity Evaluation – Conclusions
Forced Vital Capacity (FVC) Evaluation – Conclusions Bexotegrast -treated participants experienced a benefit in FVC change from Baseline to 1 Week 12 (-15.1 mL for pooled bexotegrast group) compared to those on placebo (-74.1 mL) Bexotegrast treatment effect was evident with and without use of stand
Slide 44: Mean Percent Change in QLF Extent from Baseline to Week 12
Mean Percent Change in QLF Extent from Baseline to Week 12 CT protocol population within screening window 8 6 4 3.15% 2 1.15% 0.70% 0.00% 0 40 mg 80 mg 160 mg Placebo (N=15) (N=18) (N=14) (N=17) © 2023 PLIANT THERAPEUTICS 44 QLF = quantitative lung fibrosis Mean Percent Change in QLF (SD)
Slide 45: Mean Percent Change in QLF Extent: Improved, Stable or Worse
Mean Percent Change in QLF Extent from Baseline to Week 12 CT protocol population Proportion of Participants with “Improved”, “Stable” Drop Line Plot of Change in Individual QLF Scores at or “Worse” QLF Score at 12 Weeks Week 12 for Bexotegrast and Placebo Groups 100 46.7% 16.7% 21.4% 29.4% 72.2% 75
Slide 46: Quantitative Lung Fibrosis Evaluation – Conclusions
Quantitative Lung Fibrosis Evaluation – Conclusions Dose-dependent antifibrotic effect as evidenced by QLF Imaging No progression in 160 mg group at Week 12 based on mean change from baseline Higher proportion of participants remained stable or improved in the 80 mg and 160 mg groups versus placebo
Slide 47: Serum Biomarkers of Collagen Synthesis were Reduced
Serum Biomarkers of Collagen Synthesis were Reduced in Participants Receiving Bexotegrast (Change from Baseline after 4- and 12-weeks vs Placebo) PRO-C3 PRO-C6 Type III collagen synthesis neoepitope Type VI collagen synthesis neoepitope 40 mg 2 2 80 mg 40 mg 1 160 mg 80 mg All 160 mg 0 0 All -1 -2 -
Slide 48: Conclusion and Next Steps
Conclusion and Next Steps Results from the INTEGRIS-IPF trial exceeded our expectations showing a favorable safety and tolerability profile and a treatment effect on FVC and QLF Importantly, the fact the treatment effect was also observed on top of standard of care therapy gives us confidence that b
Slide 49: Bexotegrast 320 mg Phase 2a Trial in IPF
Bexotegrast Phase 2a 320 mg Dose Global Safety-PK-Exploratory Efficacy Trial in IPF Enrollment Complete; 12-Week Interim Data Expected in Early First Quarter 2023 Randomization 3:1 (bexotegrast :placebo) KEY INCLUSION/EXCLUSION CRITERIA Placebo (n=7) PRIMARY AND SECONDARY ENDPOINTS • Adults with IPF
Slide 50: Bexotegrast INTEGRIS-PSC Phase 2a Trial in PSC
Bexotegrast INTEGRIS-PSC – Phase 2a Global Safety-PK-Fibrosis and Cholestasis Biomarker Trial in PSC Data Expected in the Third Quarter of 2023 Randomization 3:1 (bexotegrast :placebo) Placebo (n=21) KEY INCLUSION/EXCLUSION CRITERIA PRIMARY AND SECONDARY ENDPOINTS • Adults with large duct PSC • Safe
Slide 51: PLN-101095 Dual Selective Integrin Inhibitor
PLN-101095 Dual Selective α β / α β V 8 V 1 Integrin Inhibitor Reprograming the Immunosuppressive Tumor Micro-Environment of Solid Tumors © 2023 PLIANT THERAPEUTICS
Slide 52: Potential First-in-Class Small Molecule Dual Inhibitor
Potential First-in-Class Small Molecule Dual α β / α β Inhibitor V 8 V 1 α β Biology Pharmacology Differentiation Development Status V 8 Highly selective No major findings in inhibitor of α β & α β V 8 V 1 28D GLP rat & dog Supports human dose α β regulates TGFβ Dual mode of action toxicology studie
Slide 53: Pliant's Approach to Addressing Immune Checkpoint Inhibitor Resistance
Pliant’s Approach to Addressing Immune Checkpoint Inhibitor Resistance Common Mechanisms of I-O Resistance Pliant’s Approach Potently inhibit general immunosuppressive Tumor-specific IFNγ levels at baseline predict immune checkpoint to restore CD8 T cell IFNy [4,5] pembrolizumab responses secretion
Slide 54: High ITGB8 on Tumor or T cells Has Poor Prognosis
High ITGB8 on Tumor or T cells Has Poor Prognosis Ovarian Cancer Breast Cancer Lung Cancer High ITGB8 expression on tumor cells has a worse clinical prognosis Takasaka N. et al. JCI Insight 2018;3 doi 10.1172/jci.insight.122591 Melanoma Non-Small Cell Lung Cancer High ITGB8 score on infiltrating T c
Slide 55: PLN-101095 Inhibited Tumor Growth in the EMT6 Model
PLN-101095 Inhibited Tumor Growth and Promoted T cell Infiltration in the EMT6 Model + + Tumor Growth Inhibition in EMT6 Tumors CD8 T Cells CD8 T Cells SITC 2022 Poster #1352 © 2023 PLIANT THERAPEUTICS 55
Slide 56: Single Agent PLN-101095 Promoted T Cell Infiltration
Single Agent PLN-101095 Promoted T Cell Infiltration Reduced TGF-β Signaling Increased Expression of IFNγ-Regulated Genes TGFβ Activity Granzyme B IFNγ CXCL9 PDL1 SITC 2022 Poster #1352 © 2023 PLIANT THERAPEUTICS 56
Slide 57: PLN-101095 Plus αPD-1 in EMT6 Syngeneic Mouse Model
PLN-101095 Plus αPD-1 Demonstrated High Tumor Growth Inhibition in EMT6 Syngeneic Mouse Model Tumor Growth Inhibition in EMT6 Tumors Survival SITC 2022 Poster #1352 © 2023 PLIANT THERAPEUTICS 57
Slide 58: PLN-101095 Inhibited Pan02 Tumor Growth
PLN-101095 Inhibited Pan02 Tumor Growth & Increases T cell Infiltration + + CD8 T cells Tumor Growth Inhibition in Pan02 Tumors TGFβ Signaling CD8 T Cells ✱✱✱ ✱✱✱✱ 0.5 1500 1000 Rat IgG2a + Vehicle ✱ ✱✱✱ Anti-mPD1 + Vehicle 0.4 800 Anti-mPD1 + PLN-101095 1000 0.3 600 * 0.2 400 500 0.1 200 0 0 0.0 0
Slide 59: PLN-101095 Increased IFNγ Signature & Reduced TGFβ Gene Signatures
PLN-101095 Potently Increased IFNγ Signature & Reduces TGFβ Gene Signatures Anti-PD-(L)1 Non-Responsive Baseline Gene Signature Vehicle + PLN-101095 + αPD-1 αPD-1 High TGFβ Cxcl9 Signature H2-Ab1 2 H2-DMa Low IFNγ Gzma - 0 Signature Prf1 Gzmb Cxcl10 -2 Ifng PLN-101095 Promotes ICI Responsiveness POS
Slide 60: PLN-101095 Nonclinical Safety Studies
PLN-101095 Nonclinical Safety Studies No Effects of Concern for Clinical Advancement Study Studies Completed Findings with PLN-101095 Category • No adverse findings in rat or dog DRF • 14-day DRF in rat Repeat Dose • 7-day DRF in dog Toxicology • All doses tolerated • GLP 1-Month IND-enabling rat •
Slide 61: Key Program Highlights
Key Program Highlights Oral route of administration of small molecule α β inhibitor V 8 Highly potent dual inhibitor of α β / α β inhibitor V 8 V 1 Activity demonstrated in multiple PD-1 resistant tumor models Greater reduction in TGF-β signaling than either α β or TGF-β mAb V 8 1,2 Significant redu
Slide 62: Selective Muscle Cell Integrin Agonism for Muscular Dystrophies
Selective Muscle Cell Integrin Agonism for the Treatment of Muscular Dystrophies © 2023 PLIANT THERAPEUTICS
Slide 63: α7β1: A Drug Target in Muscular Dystrophies
α β : A Drug Target in Muscular Dystrophies 7 1 • Predominantly expressed in skeletal, heart and smooth muscle • α β strong genetic modifier in MDX mice 7 1 – Lack of α β worsens disease phenotype 7 1 – Over expression increases survival and improves function • Pharmacological agents that increase e
Slide 64: Integrin α7β1 Agonist Antibody Promoted Muscle Maturation
Integrin α β Agonist Antibody Promoted Muscle Maturation 7 1 TREATMENT REGIME AB1071 hMMTs treated with 1 ug/ml or 10 ug/ml Pliant antibody contain myotubes with substantially improved sarcomere organization that can withstand tetanic stimulation compared to IgG4 control (+) “Exercise” IgG4 α7β1 ago
Slide 65: Effect of PLN-101325 in Ca2+ Homeostasis of B10-mdx Myotubes
Effect of PLN-101325 in Ca2+ Homeostasis and Resting Membrane Potential of B10-mdx Myotubes Reduced intracellular resting calcium and hyperpolarization of the membrane potentially support improved plasmalemmal integrity by PLN-101325 2+ Intracellular resting Ca Resting membrane potential p, one-way
Slide 66: Body Weight Improvement at 4 and 12 Weeks of Treatment
Body Weight Improvement at 4 and 12 Weeks of Treatment • PLN-101325 3x/ wk IP • 5-6 wk old D2-MDX mice 8 ± 3% Increase in 9 ± 1% Increase in Weight Increase 12-week 4-week Body Weight Body Weight 9 ± 1% Running test © 2023 PLIANT THERAPEUTICS 66
Slide 67: Improved Response to Post Eccentric Injury
Improved Response to Post Eccentric Injury at 4 and 12 Weeks of Treatment Plantar flexion test • Gastrocnemius (GC): Premier mover muscle for plantar flexion. • GC only muscle to join both ankle and knee. Eccentric muscle injury protocol: A series of 20 tetanic stimulations (80Hz, 0.2ms pulse, 500ms
Slide 68: Diaphragm Force Significantly Improved
Diaphragm Force Significantly Improved at 4 Weeks of Treatment © 2023 PLIANT THERAPEUTICS 68
Slide 69: Pliant's α7β1 mAb Improved Muscle Membrane Integrity and Diaphragm Function
Pliant’s α β mAb Demonstrated Improved Muscle Membrane 7 1 Integrity and Diaphragm Function in Mouse DMD Model Antibody treatment protected against Duchenne muscular dystrophy (DMD) causes muscle damage progressive wasting of cardiac and respiratory muscles (main cause of death) Serum Creatine Kinas
Slide 70: Pliant Development Pipeline
Pliant Development Pipeline Clinical Anticipated Global Program Indication Preclinical Milestone Rights Phase I Phase II Phase III Phase 2a Idiopathic 320 mg 12-Week Pulmonary Data Expected Bexotegrast Fibrosis Early 1Q 2023 (PLN-74809) Primary Phase 2a Dual selective inhibitor Sclerosing Data Expec
Pliant Therapeutics — Investor Presentation (January 2023) on 6ix