Cutting-Edge Science
Focused on the Fight
Against Fibrosis
Pliant is on a quest to break new ground in fibrosis treatment through innovative scientific discovery. Applying our extensive expertise in integrin and fibrosis biology, we have our sights set on creating groundbreaking new therapies for fibrosis and fibrosis-related diseases.
Our Path
Fibrosis is caused when cells that normally repair tissue through scar formation become dysregulated, or out of control. This dysregulation causes the cells to create and deposit excessive collagen in the affected organs, a process known as fibrosis. Fibrosis replaces healthy tissue with scar tissue in vital organs, causing irreparable damage and eventual organ failure.
Our Approach
Our initial focus is on treating fibrosis by inhibiting integrin-mediated activation of transforming growth factor beta, or TGF-β, a key driver in fibrosis. Integrins are cell surface proteins that are normally expressed at very low levels, but in certain fibrotic diseases have been shown to be upregulated and to cause the continuous activation of TGF-ß. Pliant has applied its deep understanding of fibrosis biology, medicinal chemistry and translational medicine expertise to develop a set of proprietary tools to discover candidates to inhibit this pathway.
The Role of Integrins in Fibrosis
The TGF-β Fibrosis Cascade
PLN-74809 – Pliant’s Tissue-Specific Approach to Treating Fibrosis
Our Target
Transforming growth factor beta, or TGF-β, is a key driver of fibrosis. A number of investigational therapies for fibrotic and other diseases systemically block TGF-β, risking toxicity to a patient’s unaffected organs due to TGF-β’s many important roles in healthy tissues. At Pliant, our focus is on using tissue-specific integrin targets to block TGF-β only in affected organs, with the goal of reducing side effects.
Our Advanced Integrin Library
Pliant has developed an industry-leading library of over 10,000 annotated integrin binding molecules to probe the molecular drivers of fibrotic disease. This library enables the screening of newly identified targets to create a deep well of potential drug candidates.
Currently, our proprietary capabilities include a target expression atlas, an expansive library of over 10,000 integrin binding molecules, integrin screening assay platform, live fibrotic human tissue assay program, PET ligand imaging program, and biomarker assays. We continue to expand our integrin inhibitor library and develop tools, such as additional PET ligands as well as novel disease biomarkers. In addition, we have a searchable library of over 70,000 compounds for non-integrin targets.
Our Publications
Our team has unmatched expertise in fibrosis and integrin biology and we value sharing our knowledge. We regularly publish and present our research in a variety of forums to advance the discovery of novel targeted therapies to finish fibrosis. Read our most recent publications below.
Most Recent Publications
IPF
ICALF October 2024
ERS September 2024
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Post-hoc biomarker analysis in participants with IPF receiving bexotegrast over 12-weeks in INTEGRIS-IPF
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(Oral Presentation) Safety and tolerability of bexotegrast in Phase 2 trials of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC)
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Safety and tolerability of bexotegrast in Phase 2 trials of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC)
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(Oral Presentation) Bexotegrast reduces type 1 collagen deposition in participants with idiopathic pulmonary fibrosis (IPF) after 12 weeks of therapy
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Bexotegrast reduces type 1 collagen deposition in participants with idiopathic pulmonary fibrosis (IPF) after 12 weeks of therapy
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Bexotegrast is antifibrotic in precision-cut lung slices prepared from fibrotic interstitial lung disease explants
ATS May 2024
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(Oral Presentation) Update on the safety and tolerability of bexotegrast, a dual-selective inhibitor of integrins αvβ6 and αvβ1, in development for idiopathic pulmonary fibrosis and primary sclerosing cholangitis
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(E-Poster) Update on the safety and tolerability of bexotegrast, a dual-selective inhibitor of integrins αvβ6 and αvβ1, in development for idiopathic pulmonary fibrosis and primary sclerosing cholangitis
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Evaluation of quantitative imaging in a Phase 2a study for the treatment of idiopathic pulmonary fibrosis with bexotegrast (INTEGRIS-IPF)
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Bexotegrast targets TGF-β inhibition to specific cell types in the fibrotic human lung
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Post-hoc analysis of biomarkers of interstitial lung disease progression in participants with idiopathic pulmonary fibrosis receiving bexotegrast over 12-weeks in INTEGRIS-IPF
ERS September 2023
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Safety, tolerability and antifibrotic activity of bexotegrast: Phase 2a INTEGRIS-IPF Study (NCT04396756)
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Circulating ITGB6 levels are elevated in patients with idiopathic pulmonary fibrosis and reduced following lung transplant
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Dual αvβ6/αvβ1 integrin inhibitor bexotegrast reduces fibrogenesis in pathological cell populations present in the fibrotic human lung
Gordon Research Conference August 2023
ATS June 2023
ATS May 2022
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Combining dual αVβ6/αVβ1 integrin inhibitor, PLN-74809, with standard-of-care therapies has a synergistic effect on reducing fibrogenic gene expression in fibrotic human lung slices
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PLN-74809, a dual-selective inhibitor of integrins αvβ6 and αvβ1 shows dose-dependent target engagement in the lungs of patients with idiopathic pulmonary fibrosis (IPF)
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PLN-74809, an oral, dual-selective αvβ6/αvβ1 inhibitor in Phase 2 clinical trials for idiopathic pulmonary fibrosis (IPF), sustainably reduces transforming growth factor-beta (TGF-β) activity in the lungs of healthy participants with once-daily dosing
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PLN-74809, a dual-selective inhibitor of αvβ6 and αvβ1, is well tolerated in over 280 healthy participants
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Therapeutic biomarker discovery in idiopathic pulmonary fibrosis (IPF) through proteomic analysis of precision-cut lung slice (PCLS) supernatants
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Pharmacological inhibitors of integrin αvβ6 that differentially modulate protein conformation are similarly effective at inhibiting TGF-β signaling in the fibrotic lung
ATS May 2020
ERS September–October 2019
PSC
ERS September 2024
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(Oral Presentation) Safety and tolerability of bexotegrast in Phase 2 trials of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC)
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Safety and tolerability of bexotegrast in Phase 2 trials of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC)
EASL June 2024
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Dual alpha-v/beta-6 and alpha-v/beta-1 integrin inhibitor bexotegrast targets TGF-beta inhibition to specific cell types in human liver explant tissue with biliary fibrosis
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Oral alpha-v/beta-6 and alpha-v/beta-1 integrin inhibitor bexotegrast in primary sclerosing cholangitis: Updated 12-week interim safety and efficacy analysis of the INTEGRIS-PSC Phase 2a trial
ATS May 2024
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(Oral Presentation) Update on the safety and tolerability of bexotegrast, a dual-selective inhibitor of integrins αvβ6 and αvβ1, in development for idiopathic pulmonary fibrosis and primary sclerosing cholangitis
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(E-Poster) Update on the safety and tolerability of bexotegrast, a dual-selective inhibitor of integrins αvβ6 and αvβ1, in development for idiopathic pulmonary fibrosis and primary sclerosing cholangitis
AASLD November 2023
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Oral αvβ6/αvβ1 integrin inhibition in primary sclerosing cholangitis: 12-week interim safety and efficacy analysis of INTEGRIS-PSC, a Phase 2a trial of bexotegrast
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Inhibition of integrin αVβ1 attenuates profibrogenic gene expression by myofibroblasts in fibrotic human liver explants
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Dual αVβ6/αVβ1 integrin inhibitor bexotegrast attenuates profibrogenic gene expression across multiple pathologic cell types in human liver explant tissue with biliary fibrosis
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Oral αVβ6/αVβ1 integrin inhibition in primary sclerosing cholangitis: 12-week interim safety and efficacy analysis of INTEGRIS-PSC, a phase 2a trial of bexotegrast
Gordon Research Conference August 2023
EASL June 2023
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INTEGRIS-PSC Phase 2a study: Evaluating the safety, tolerability, and pharmacokinetics of bexotegrast (PLN-74809) in participants with primary sclerosing cholangitis
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Dual alpha-v/beta-6 and alpha-v/beta-1 integrin inhibitor bexotegrast attenuates profibrogenic gene expression of myofibroblasts in human liver explant tissue with biliary fibrosis
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Non-invasive imaging method demonstrates anti-fibrotic efficacy of a dual integrin alpha-v/beta-6 and alpha-v/beta-1 inhibitor in a rat model of biliary fibrosis
AASLD November 2019
Oncology
SITC November 2023
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Phase 1a trial of PLN-101095, an integrin αvβ8 and αvβ1 inhibitor, as monotherapy and in combination with pembrolizumab, in treatment-resistant patients with advanced or metastatic solid tumors
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Integrin αvβ1 is expressed in multiple solid tumors and drives the adhesion of cancer-associated fibroblasts to latent TGF-β
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Selective targeting of integrins αVß8 and αVß1 within the dynamic ecosystem of pancreatic cancer to improve overall anti-tumor response
