Therapeutic area

P17

P17 is an inhibitor peptide of the transforming growth factor beta 1 (TGF-b1), a potent modulator of a number of genes involved in organogenesis, tissue regeneration, immune response, and fibrosis, including genes for the extracellular matrix (ECM). TGF-b1 has been implicated in the excess production of collagen in many disorders characterized by the excessive and deranged accumulation of ECM proteins as hepatic, lung, heart and kidney fibrosis. Approaches that have the potential to minimize the accumulation of collagen in these organs have being studying. One of these approaches include the blocking the biological activities of TGF-b1.
Effectiveness of P17 has been evaluated in rats and mice models where hepatic fibrosis was induced by carbon tetrachloride.

Antifibrogenic effect of P17 is being studied in a lung fibrosis model in vivo induced by bleomycin as a preclinical assessment of possible therapeutic benefits against lung fibrosis in humans. Lung fibrosis is the end stage of a heterogeneous group of disorders characterized by the excessive accumulation of collagen. It is a potentially lethal and chronic response of the lung to injury resulting from different causes as bacterial infection inhalation of organic and inorganic dusts, radiation, systemic diseases or drugs. An initial injury of the lung provokes an unresolved inflammation or alveolar epithelial cell activation. Inflammatory and epithelial cells release cytokines and growth factors like PDGF, IGF1 and TGFb1 inducing fibroblast migration and proliferation, and changes in cell phenotype. In the microenvironment of the injured lung, myofibroblasts may induce epithelial cell apoptosis, basement membrane disruption and an increase in lung collagen content.

Pharmacological agents currently in use to treat lung fibrosis in animal models are either ineffective or too toxic in humans. Thus, effectiveness of P17 in experimental models of lung fibrosis is considered one of the main objectives for Digna Biotech. The results from these studies in lung fibrosis animal models and the development of a strategy for the administration of aerosolized P17 in humans will both afford a preclinical phase before starting a clinical Phase I study.

Preliminary studies have revealed P17 has a significantly antifibrogenic effect in a mice lung fibrosis model induced by bleomycin.