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Research and Clinical Trial Disease Areas

Oasis Pharmaceuticals has developed a portfolio of pepducin treatments for Nonalcoholic Steatohepatitis (NASH),  Atopic Dermatitis (AD), IPF/PAH, IBD, and other PAR2-related diseases.

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Nonalcoholic Steatohepatitis

The target, PAR2, is a cell surface receptor that is highly upregulated in NASH progression in multiple liver cell types including hepatocytes, stellate cells and macrophages. PAR2 activates fibrosis, inflammation, steatosis and insulin resistance in NASH.  Phase 1 clinical trials (SAD/MAD) are underway with the PAR2 inhibitor OA-235i in NASH patients.


Atopic Dermatitis and Pruritus

PAR2 is a well-validated target in skin that triggers and perpetuates the vicious cycle of itch and inflammation in adults and children suffering from AD and related allergic skin conditions. Skin barrier deficits further enhance the activity of dust mite and epidermal PAR2 protease agonists like kallikrein-5 and -14, cathepsins, and mast cell tryptase. Cleavage of PAR2 stimulates IL-4, IL-13, and thymic stromal lymphopoietin (TSLP), to trigger AD lesion formation and directly activates the itch response via C-fibers. Phase 1 studies (SAD, MAD) with topical OA-3 in AD patients are currently enrolling.


Idiopathic Pulmonary Fibrosis

PAR2 is upregulated in lung epithelium, fibroblasts, and inflammatory cells in IPF patients, and subjects with high expression of lung PAR2 have worse over-all survival and honeycomb lesions. Increased pro-coagulant protease (factors VIIa/Xa/TF) activity in the lung and local inflammatory proteases such as mast cell tryptase trigger an overexuberant PAR2 fibrotic response. Pepducin blockade of PAR2 activity significantly suppresses fibrosis, TGF-beta and ERK1/2 pathways and collagen deposition in IPF.

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