bexotegrast (PLN-74809) / Pliant Therapeutics - LARVOL DELTA

Randomized, Double-blind Study of Efficacy and Safety of Bexotegrast (PLN-74809) for Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2/3 | N=320 | Terminated | Sponsor: Pliant Therapeutics, Inc. | Phase classification: P=N/A ➔ P2/3

Phase classification • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

The Matrix Reloaded: The Hepatic Matrisome as a Therapeutic Opportunity to Fight Liver Fibrosis. (PubMed, Biomolecules) - "The antifibrotic potency of drugs that interfere with the matrisome at different levels has been demonstrated in preclinical studies, but translation to clinical trials remains still limited. So far, simtuzumab (LOXL2 inhibitor antibody), imatinib (small-molecule inhibitor against discoidin domain receptors-DDRs), bexotegrast (integrin inhibitor), GR-MD-02 (galectin 3 inhibitor), and BMS-986263 (siRNA-targeting HSP47) have been or are being evaluated in clinical trials related to CLD, and some of them have shown promising results."

Journal • Review • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • SERPINH1

The dual integrin inhibitor Bexotegrast, indicated for idiopathic pulmonary fibrosis, shows a anti-fibrotic phenotype in human MASH liver spheroids (EASL 2026) - "Human-derived 3D spheroid models serve as cost-effective and predictive tools for identifying successful anti-fibrotic drug candidates. Bexotegrast (PLN-74809) and PLN-1474, repurposed from ongoing idiopathic pulmonary fibrosis (IPF) trials, demonstrated promising anti-fibrotic effects in human MASH liver spheroids."

Fibrosis • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Pulmonary Disease • Respiratory Diseases • TGFB1 • TIMP1

Beyond attenuation: a translational review of curative-intent pharmacological targets in idiopathic pulmonary fibrosis. (PubMed, Front Med (Lausanne)) - "The current standard-of-care agents, pirfenidone and nintedanib, merely slow disease progression and are burdened by significant toxicity...Analysis reveals that targeting broad-spectrum enzymes (e.g., autotaxin via ziritaxestat) or downstream effectors (e.g., Connective Tissue Growth Factor (CTGF) via pamrevlumab) has failed, likely due to mechanistic redundancy or insufficient target engagement. In contrast, highly specific, next-generation inhibitors targeting upstream signal initiation points such as the lysophosphatidic acid receptor 1 (LPAR1) (admilparant) and local αvβ6 integrin-mediated activation of transforming growth factor-beta (TGF-β) (bexotegrast) have yielded promising Phase 2 data, demonstrating a sophisticated translational learning loop. Furthermore, the geroscience approach targeting cellular senescence (dasatinib/quercetin) has introduced a controversial new paradigm, while the recent approval of nerandomilast (a phosphodiesterase 4B (PDE4B)..."

Journal • Review • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CTGF • TGFB1

Bexotegrast for treatment of idiopathic pulmonary fibrosis (BEACON-IPF): study protocol for a multinational, phase 2b/3, double-blind, randomised, multicentre, controlled trial. (PubMed, BMJ Open Respir Res) - P2 | "Background therapy with pirfenidone or nintedanib is permitted in ≤70% of the study population. Study results will be disseminated in peer-reviewed journals and international conferences targeted to medical, academic and patient communities. NCT06097260."

Journal • P2/3 data • P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Phase 2 Clinical Trials in Primary Sclerosing Cholangitis: Making the Most of Every Opportunity? (PubMed, J Hepatol) - No abstract available

Journal • P2 data

Phase II INTEGRIS-PSC trial of bexotegrast, an αvβ6/αvβ1 integrin inhibitor, in primary sclerosing cholangitis. (PubMed, J Hepatol) - P2 | "Bexotegrast was well tolerated in participants with PSC and liver fibrosis for up to 40 weeks with numerically less progression observed in exploratory pharmacodynamic markers."

Journal • P2 data • Cholestasis • Fibrosis • Immunology • Liver Cirrhosis

BEACON-PPF: a phase 2b study of bexotegrast for treatment of progressive pulmonary fibrosis (PPF) [WITHDRAWN] (ERS 2025) - No abstract available

P2b data • Immunology • Pulmonary Disease • Respiratory Diseases

Characterizing the antifibrotic activity of bexotegrast on pathologic cell populations in multiple ILD subtypes (ERS 2025) - "In ATI cells, bexotegrast also significantly reduced expression of genes related to TGF-β signaling (e.g. ITGB6 and SMAD7), actin binding and focal adhesions. These findings demonstrate the antifibrotic activity of bexotegrast in fibrotic human lung tissue and support further investigation of bexotegrast in ILD-associated progressive pulmonary fibrosis."

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Pneumonia • Rheumatoid Arthritis • Rheumatology • COL1A1 • ITGB6 • SMAD7 • SULF1 • TGFB1

Evaluation of the antifibrotic effect of a dual αvβ6/αvβ1 integrin inhibitor in a mouse model of rheumatoid arthritis-associated interstitial lung disease (ERS 2025) - "These changes in fibrosis were accompanied by significant reductions in the number of PDGFRα + lung fibroblasts (54%, p<0.001). These findings indicate that dual inhibition of α V β 6 /α V β 1 integrins is antifibrotic in a mouse model of RA-ILD and support further investigation into the potential antifibrotic activity of bexotegrast in non-IPF fibrosing ILDs."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammatory Arthritis • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • PDGFRA • TGFB1

Bexotegrast improves markers and symptoms of cholestasis and stabilizes markers of liver fibrosis in participants with primary sclerosing cholangitis (BSG 2025) - P2 | "This study supports the targeting of integrin-mediated TGF-β activation as a potential therapeutic approach for PSC. Further studies on the use of BEXO in PSC are warranted"

Cholestasis • Dermatology • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Pruritus • TGFB1

Randomized, Double-blind Study of Efficacy and Safety of Bexotegrast (PLN-74809) for Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=320 | Terminated | Sponsor: Pliant Therapeutics, Inc. | Trial completion date: Sep 2025 ➔ Apr 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2025 ➔ Apr 2025; DSMB recommendation

Trial completion date • Trial primary completion date • Trial termination • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Pliant Therapeutics Provides Update on BEACON-IPF (GlobeNewswire) - P2b/3 | N=360 | BEACON-IPF (NCT06097260) | Sponsor: Pliant Therapeutics, Inc. | "In March of this year, Pliant announced the voluntary discontinuation of BEACON-IPF following a prespecified data review and recommendation by the trial’s independent...DSMB, as well as a secondary review and recommendation...citing an imbalance in IPF-related adverse events. Following an analysis of the full safety and efficacy data from the BEACON-IPF trial, the Company is discontinuing development of bexotegrast in IPF....At Week 12, bexotegrast 160 mg and 320 mg treatment groups demonstrated improvements in forced vital capacity (FVC) decline of 72 mL (p0.05), respectively, compared to placebo. At Week 24, bexotegrast 160 mg and 320 mg treatment groups demonstrated improvements in FVC decline of 58 mL (p>0.05) and 8 mL (p>0.05), respectively, compared to placebo. The full results from BEACON-IPF will be submitted for future publication."

Discontinued • P2/3 data • Idiopathic Pulmonary Fibrosis

Single-cell Profiling Demonstrates the Antifibrotic Effects of Bexotegrast on Pathologic Lung Cell Populations in the Presence and Absence of Background Therapy (ATS 2025) - "CONCLUSION Treatment of fibrotic human PCLS with bexotegrast or nintedanib showed distinct cell-specific pharmacodynamic profiles, with bexotegrast found to significantly reduce TGF-β-regulated gene expression (e.g. COL1A1) in αVβ6 and αVβ1-expressing pathologic lung cell populations. These findings demonstrate the potential for bexotegrast to provide antifibrotic benefit alone or in combination with currently approved treatments for IPF."

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • COL1A1 • CTHRC1 • FLT1 • KDR • PDGFRB • TGFB1 • TIMP1

Characterizing the Antifibrotic Activity of Bexotegrast on Distinct Fibroblast Populations in PCLS From Multiple ILD Subtypes (ATS 2025) - "In PCLS from fibrotic non-IPF ILD explants, inhibition of integrins αVβ6 and αVβ1 with bexotegrast reduced fibrogenic gene expression across multiple fibroblast subpopulations. These data are consistent with our previous observations in IPF explants and support further investigation of the antifibrotic activity of bexotegrast in ILD-associated progressive pulmonary fibrosis. 1Tsukui, T. et al."

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Pneumonia • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Sclerosis • COL1A1 • COL5A1 • CTHRC1 • ITGAV • ITGB6 • POSTN • SMAD7 • TGFB1

Characterizing the Antifibrotic Activity of Bexotegrast on Distinct Fibroblast Populations in PCLS from Multiple ILD Subtypes (GlobeNewswire) - "Pliant Therapeutics presents...data at the American Thoracic Society International Conference....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."

Preclinical • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

Plasma Proteome Analysis Reveals Shared and Unique Biomarkers of ILD Subtypes (GlobeNewswire) - "Pliant Therapeutics presents...data at the American Thoracic Society International Conference....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."

Biomarker • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

Single-Cell Profiling Demonstrates the Antifibrotic Effects of Bexotegrast on Pathologic Lung Cell Populations in the Presence and Absence of Background Therapy (GlobeNewswire) - "Pliant Therapeutics presents...data at the American Thoracic Society International Conference....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."

Preclinical • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

Pliant Therapeutics Announces Strategic Realignment of Workforce and Operations (GlobeNewswire) - "The restructuring aims to minimize costs and preserve cash reserves as the Company awaits topline data from the BEACON-IPF Phase 2b/3 trial of bexotegrast in patients with idiopathic pulmonary fibrosis (IPF). Pliant expects topline data from the BEACON-IPF trial to be available in the second quarter of 2025. Once available, the Company will evaluate the final dataset and determine next steps for bexotegrast’s development."

P2/3 data • Idiopathic Pulmonary Fibrosis

A Comparative Study With ING-006, Nintedanib, Nerandomilast and Bexotegrast Using the In Vivo CAM-Patient-Derived IPF Model (ATS 2025) - "ING-006 also demonstrates superior inhibitory activity over fezagepras (formerly PBI-4050) in ZQ-16 stimulated-pErK lung fibroblasts as well as through inhibition of fibrotic gene expression. CAM-IPF is an efficient method to predict antifibrotic activity. Among other compounds currently used or under investigation for IPF treatment, ING-006 shows superior antifibrotic activity in fibroblasts and lung tissue xenografts from IPF patients, making it a promising candidate for IPF treatment."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • ACTA2 • COL1A1 • COL3A1 • CTGF • SERPINE1 • TGFB1

Evaluation of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of PLN-74809 (ANZCTR) - P1 | N=80 | Completed | Sponsor: Pliant Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Pliant Therapeutics Announces Upcoming Presentations at the 2025 American Thoracic Society International Conference (GlobeNewswire) - "Pliant Therapeutics, Inc...today announced that the Company will present three scientific posters at the upcoming 2025 American Thoracic Society (ATS) International Conference, taking place in San Francisco, California from May 16-21, 2025."

Clinical data • Fibrosis • Interstitial Lung Disease

Bexotegrast, an α V β 6 and α V β 1 Integrin Inhibitor, Is Associated With Dose-Dependent α V β 6 Target Engagement in the Lungs of Participants With Idiopathic Pulmonary Fibrosis (ATS 2025) - No abstract available

Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

BEACON-IPF, an Adaptive, Randomized, Placebo-Controlled, Global, Phase 2b/3 Study of Bexotegrast for Treatment of Idiopathic Pulmonary Fibrosis: Baseline Characteristics of Participants Enrolled to Date (ATS 2025) - No abstract available

Clinical • P2/3 data • P2b data • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Dual αvβ6 and αvβ1 Inhibition Over 12 Weeks Reduces Active Type 1 Collagen Deposition in Individuals with Idiopathic Pulmonary Fibrosis: A Phase 2, Double-Blind, Placebo-controlled Clinical Trial. (PubMed, Am J Respir Crit Care Med) - P2 | "Bexotegrast treatment resulted in numerical improvements in FVC, cough severity, and biomarker levels. The reduced uptake of 68Ga-CBP8 in the lungs of participants with IPF indicates an antifibrotic effect of bexotegrast, suggesting the potential for favorable lung remodeling."

Clinical • Journal • P2 data • Cough • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases