Pliant Therapeutics, Inc. · NASDAQ:PLRX
Pliant Therapeutics — Investor Presentation (January 2022)
29 slides from Pliant Therapeutics's investor presentation, Jan 10, 2022
Slide 1: Developing Novel Treatments for Fibrotic Diseases
Developing Novel Treatments for Fibrotic Diseases Corporate Presentation JANUARY 2022
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 th
Slide 3: Pliant – Company Highlights
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-Le
Slide 4: Recent Company Highlights
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 tri
Slide 5: Pliant's Integrin Focused Library
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 Co
Slide 6: Pliant Development Pipeline
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 Expec
Slide 7: Fibrosis: The Silent Killer
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
Slide 8: aVb6 / aVb1 Integrins Drive Cell-Matrix Interactions in Fibrosis
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
Slide 9: PLN-74809 Provides Profound Antifibrotic Activity through Upstream Inhibition of TGF-b Activation
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 pr
Slide 10: Pliant Compounds Have Not Shown Adverse Effects of Systemic Inhibition of TGF-β Pathways
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 Keratoacantho
Slide 11: Dual avb6/avb1 Inhibition Blocks COL1A1 Gene Expression More than Single Inhibition in Human IPF Tissue
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
Slide 12: PLN-74809 – Extended Phase 1a Data Summary
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
Slide 13: PLN-74809 – Phase 1b Proof of Biological Mechanism
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
Slide 14: Reduction in Pulmonary pSMAD Appears to Be a Marker for Reduction of Fibrosis
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 Col
Slide 15: Phase 2a PET Trial – avb6 Expression Correlated with Extent of Fibrosis in IPF
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 Kimur
Slide 16: 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 acquisitionAdministration of a single dose of PLN-74809: 60 mg – 120 mg – 240 mg – 320 mgInter
Slide 17: Dose and Plasma Concentration Dependent Target Engagement
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 *
Slide 18: 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 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 do
Slide 19: INTEGRIS-IPF Phase 2a Trial in IPF
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:
Slide 20: Quantitative Lung Fibrosis (QLF): A Sensitive Measure of FVC Change Over Time in IPF
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% specifici
Slide 21: INTEGRIS-PSC Phase 2a Trial in PSC
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 endpoints
Slide 22: Pliant Development Pipeline
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 Expe
Slide 23: Pliant's Integrin-Based Oncology Program
Pliant’s Integrin-Based Oncology Program
Slide 24: Activated TGF-β Contributes to Immune Exclusion & Evasion, Tumor Metastasis and Angiogenesis
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 la
Slide 25: αVβ8 Inhibitor/Anti-PD-1 Combo Reduced Tumor Burden and Increased Survival in Preclinical Models
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
Slide 26: Selective Muscle Cell Integrin Agonism for the Treatment of Muscular Dystrophies
Selective Muscle Cell Integrin Agonism for the Treatment of Muscular Dystrophies
Slide 27: Pliant's Muscular Dystrophy Program – Overview
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
Slide 28: Pliant's mAb Demonstrated Improved Muscle Membrane Integrity and Diaphragm Function in Mouse DMD Model
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) md
Slide 29: Developing Novel Treatments for Fibrotic Diseases
Developing Novel Treatments for Fibrotic Diseases Corporate Presentation JANUARY 2022
Pliant Therapeutics — Investor Presentation (January 2022) on 6ix