Pliant Therapeutics Presents Clinical and Preclinical Data at the American Thoracic Society International Conference

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Pliant Therapeutics (PLRX) presented clinical and preclinical data at the American Thoracic Society 2025 International Conference, highlighting three key studies on their drug bexotegrast. The first study showed that bexotegrast, a dual inhibitor of αVβ6/αVβ1 integrins, reduced fibrosis-related gene expression in lung cells from non-IPF ILD patients. A second study identified biomarkers across different ILD subtypes that could help inform clinical decisions. The third study demonstrated bexotegrast's distinct antifibrotic effects, showing superior results compared to nintedanib in reducing profibrotic genes in specific cell types, both alone and in combination therapy.

Insights

Biotech Research Analyst

New data shows Pliant's bexotegrast demonstrates antifibrotic activity with distinct advantages over existing IPF treatment nintedanib.

The preclinical data presented by Pliant Therapeutics at the ATS conference provides compelling evidence for bexotegrast's unique mechanism of action and potential efficacy in treating interstitial lung diseases (ILDs). As a dual inhibitor of αVβ6/αVβ1 integrins, bexotegrast targets a specific pathway in the fibrotic process that appears complementary to existing treatments.

The oral presentation demonstrated that bexotegrast reduced expression of TGF-β signaling and fibrogenesis genes in multiple cell types from non-IPF ILD patient samples. This is significant because it suggests potential applications across various ILD subtypes, not just idiopathic pulmonary fibrosis.

Perhaps most noteworthy is the single-cell analysis showing bexotegrast and nintedanib (one of only two FDA-approved IPF treatments) have distinct pharmacodynamic profiles. Bexotegrast reduced expression of type I collagen and other profibrotic genes in key cell populations - effects not observed with nintedanib alone. Importantly, bexotegrast maintained efficacy even when combined with nintedanib, suggesting potential for combination therapy approaches.

The biomarker study identified plasma markers consistently dysregulated across multiple ILD subtypes, which could eventually facilitate patient selection and treatment monitoring in clinical settings.

While these findings represent preclinical and translational evidence rather than late-stage clinical data, they provide important scientific validation of bexotegrast's mechanism and differentiation from current standard of care. For a devastating condition like IPF, which has median survival of 3-5 years and limited treatment options, these mechanistic advantages could prove clinically meaningful if validated in ongoing human studies.

SOUTH SAN FRANCISCO, Calif., May 21, 2025 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX) today announced that the Company led oral and poster presentations of clinical and preclinical data this week as part of the American Thoracic Society (ATS) 2025 International Conference, held from May 16-21, 2025.

Characterizing the Antifibrotic Activity of Bexotegrast on Distinct Fibroblast Populations in PCLS from Multiple ILD Subtypes
In a featured oral presentation, Johanna Schaub, Ph.D., Director of Translational Sciences at Pliant Therapeutics, discussed an evaluation of the antifibrotic activity of bexotegrast in fibrotic human precision-cut lung slices (PCLS) generated from non-idiopathic pulmonary fibrosis (IPF) interstitial lung disease (ILD) patient lung explants. Results showed that bexotegrast, a dual inhibitor of αVβ6/αVβ1 integrins, reduced expression of genes related to TGF-β signaling and fibrogenesis in alveolar type 1 (AT1) cells and multiple fibroblast subpopulations.

Plasma Proteome Analysis Reveals Shared and Unique Biomarkers of ILD Subtypes
In a poster presentation, Erine Budi, Ph.D., Senior Scientist II Translational Biology at Pliant Therapeutics, reviewed a comparative analysis assessing circulating plasma biomarkers of ILD in healthy subjects and patients with idiopathic pulmonary fibrosis (IPF), rheumatoid arthritis-ILD (RA-ILD), and scleroderma associated-ILD (SSc-ILD). Results identified biomarkers consistently dysregulated across multiple ILD subtypes that could assist in informing clinical decision making in ILD.

Single-Cell Profiling Demonstrates the Antifibrotic Effects of Bexotegrast on Pathologic Lung Cell Populations in the Presence and Absence of Background Therapy
In a poster presentation, Mahru An, Ph.D., Director of Translational Sciences at Pliant Therapeutics, reviewed a single-nuclei RNAseq analysis of fibrotic human precision-cut lung slices comparing the pharmacodynamic effects of bexotegrast, a dual inhibitor of αVβ6 and αVβ1 integrins, alone, or in combination with nintedanib. Results showed that treatment with bexotegrast or nintedanib displayed distinct cell-specific pharmacodynamic profiles. In addition, bexotegrast alone, or in the presence of nintedanib, significantly reduced the expression of type I collagen and other profibrotic genes in aberrant basaloid cells (αVβ6-expressing) and fibroblasts (αVβ1-expressing), while treatment with nintedanib alone did not.

The presentation and posters presented at the 2025 ATS Conference are available by accessing the links above or on Pliant’s website under the Publications section at https://pliantrx.com/publications.

About Pliant Therapeutics, Inc.

Pliant Therapeutics is a clinical-stage biopharmaceutical company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases. Pliant's lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of α_vß₆ and α_vß₁ integrins that is undergoing evaluation for the treatment of idiopathic pulmonary fibrosis, or IPF. Bexotegrast has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and Orphan Drug Designation from the European Medicines Agency in IPF. Pliant is conducting a Phase 1 study for PLN-101095, a small molecule, dual-selective inhibitor of α_vß₈ and α_vß₁ integrins, that is being developed for the treatment of solid tumors. In addition, Pliant has received regulatory clearance for the conduct of a Phase 1 study of PLN-101325, a monoclonal antibody agonist of integrin α₇β₁ targeting muscular dystrophies.

For additional information, please visit: www.PliantRx.com. Follow us on social media X, LinkedIn, and Facebook.

Investor and Media Contact:

Christopher Keenan
Vice President, Investor Relations and Corporate Communications
Pliant Therapeutics, Inc.
ir@pliantrx.com

FAQ

What were the key findings of PLRX's bexotegrast studies presented at ATS 2025?

The studies showed that bexotegrast reduced fibrosis-related gene expression in lung cells, demonstrated distinct antifibrotic effects, and showed superior results compared to nintedanib in reducing profibrotic genes in specific cell types.

How does Pliant Therapeutics' bexotegrast compare to nintedanib in treating lung fibrosis?

According to the study, bexotegrast alone or with nintedanib significantly reduced type I collagen and profibrotic genes in specific cells, while nintedanib alone did not show these effects.

What biomarker findings did Pliant Therapeutics present for ILD subtypes?

The study identified biomarkers that were consistently dysregulated across multiple ILD subtypes (IPF, RA-ILD, and SSc-ILD), which could help inform clinical decision making in ILD.

What is the mechanism of action of PLRX's bexotegrast?

Bexotegrast is a dual inhibitor of αVβ6 and αVβ1 integrins that reduces expression of genes related to TGF-β signaling and fibrogenesis in specific lung cell populations.