Slide 1: Characterizing the Antifibrotic Activity of Bexotegrast on Distinct Fibroblast Populations in PCLS
Characterizing the Antifibrotic Activity of Bexotegrast on Distinct Fibroblast Populations in PCLS from Multiple ILD Subtypes Johanna Schaub, Mahru An, Richard Ahn, Steve Ho, Vikram Rao, Hanieh Farhadi, Chris Her, Selorm Tamakloe, Jennifer Yuzon, Paul Wolters, Martin Decaris © 2025 PLIANT THERAPEUTI
Slide 2: Disclosures
Disclosures Pliant Therapeutics • Employee and shareholder © 2025 PLIANT THERAPEUTICS 2
Slide 3: Progressive Pulmonary Fibrosis
Progressive Pulmonary Fibrosis • PPF is interstitial lung disease (ILD) with radiological signs of fibrosis and progression over time (Rajan, et al. 2023) Fibrosing ILD Explants at Transplant SSc RA-ILD IPF Collagen (PSR) NSIP HP Rajan, et al. 2023 © 2025 PLIANT THERAPEUTICS 3
Slide 4: Transcriptomic Analysis of Precision-Cut Lung Slices
Transcriptomic Analysis of Precision-Cut Lung Slices: A Novel Approach to Investigate Drug MOA in Fibrotic Lung Explants Bulk mRNA expression © 2025 PLIANT THERAPEUTICS 4
Slide 5: αvβ6/αvβ1 Integrins Drive TGF-β Activation in Lung Fibrosis
αvβ6/αvβ1 Integrins Drive TGF-β Activation in Lung Fibrosis αVβ6/αVβ1 integrins promote fibrosis • TGF-β is a central mediator of fibrosis by activating TGF-β • αVβ6/αVβ1 integrins activate latent TGF-β in fibrotic tissue • Systemic TGF-β blockade carries toxicity risks FIBROSIS COL1A1 COL3A1 TIMP1
Slide 6: Bexotegrast Reduces TGF-β Signaling and Downstream Profibrotic Pathways
Bexotegrast Reduces TGF-β Signaling and Downstream Profibrotic Pathways through Inhibition of Integrins αvβ6/αvβ1 αVβ6/αVβ1 integrins promote fibrosis • TGF-β is a central mediator of fibrosis by activating TGF-β • αVβ6/αVβ1 integrins activate latent TGF-β in fibrotic tissue • Systemic TGF-β blockad
Slide 7: Integrin αvβ6 Expression Is Elevated in Fibrotic ILD Explants
Integrin αvβ6 Expression Is Elevated in Fibrotic ILD Explants • PPF is interstitial lung disease (ILD) with radiological signs of fibrosis and progression over time (Rajan, et al. 2023) • Integrin β6 (ITGB6) expression is elevated in IPF and in PPF Normal SSc RA-ILD Integrin β6 IPF NSIP HP Rajan, et
Slide 8: snRNA-seq of Non-IPF Fibrotic PCLS Identified Target Cell Populations
snRNA-seq of Non-IPF Fibrotic PCLS Identified Target Cell Populations • 3 Non-IPF fibrotic ILD donors Stromal ⎼ 2 RA-ILD, 1 HP • PCLS treated for 7 days with bexotegrast Myeloid • >150,000 nuclei isolated • Annotations based on published fibrotic lung single cell RNAseq datasets Arterial Goblet AT1
Slide 9: Bexotegrast Reduced Markers of TGF-β Signaling in AT1 Cells
Bexotegrast Reduced Markers of TGF-β Signaling in AT1 Cells ITGB6 • ITGB6 is expressed most highly in AT1, AT2, and basal cells AT1 AT2 DC Mast Basal Goblet T cell B cell Capillary Lymphatic Pericyte Plasma B Unassigned Myofibroblast Monocyte Fibroblast inflammatory Myeloid undefined Stromal undefin
Slide 10: Bexotegrast Significantly Reduced Fibrogenic Gene Expression in Multiple Fibroblast Populations
Bexotegrast Significantly Reduced Fibrogenic Gene Expression in Multiple Fibroblast Populations Top Downregulated BP GO Terms in Stromal Cells • Across all stromal cells, bexotegrast ID Description Adj. p value significantly reduced the expression of GO:0030198 extracellular matrix organization 2E-2
Slide 11: Bexotegrast Significantly Reduced Fibrogenic Gene Expression in Profibrotic Fibroblasts
Bexotegrast Significantly Reduced Fibrogenic Gene Expression in Profibrotic Fibroblasts Top Downregulated BP GO Terms in Profibrotic Fibroblasts • CTHRC1Hi/COL1A1Hi population of profibrotic ID Description Adj. p value fibroblasts were identified GO:0030198 extracellular matrix organization 1.1E-13
Slide 12: Summary and Conclusions
Summary and Conclusions snRNA-seq of PCLS can be used to evaluate the effects of novel therapeutics on specific cell populations within fibrosing ILD explants Integrin αVβ6 expression is increased in lungs of patients with multiple fibrotic ILD subtypes Bexotegrast, a dual αVβ6/αVβ1 inhibitor, reduc
Slide 13: Thank You!
Thank You! Please use the QR code shown PLIANT THERAPEUTICS UCSF to link to the ePoster Martin Decaris Paul Wolters Steve Ho Vikram Rao Chris Her Selorm Tamakloe Mahru An Richard Ahn Jennifer Yuzon Hanieh Farhadi © 2025 PLIANT THERAPEUTICS