The Phenotypic BioMAP® Platform for Drug Repurposing and Repositioning

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d8896998e85">The BioMAP® phenotypic profiling platform provides an unbiased, target-agnostic and data-driven approach to understanding the effects of new therapies on human tissue biology. This is accomplished through use of human primary cells from different tissues in complex (often co-) culture conditions stimulated to recapitulate specific tissue and disease states. These models or systems include endothelial and epithelial cells, fibroblasts, PBMCs, and other cell types under experimental conditions that accurately represent inflammation, fibrosis, immune responses, respiratory, dermal, and cardiovascular biology, and have been qualified using clinical agents where their effects are already known. When novel test agents are evaluated against twelve such systems, the measurement of 148 translational protein biomarkers that are relevant to the tissue biology being modelled generates a phenotypic “fingerprint” profile. Enhanced data analytics and bioinformatics-based approaches allow statistical correlation of a new profile with those generated from the testing of over 4500 substances, allowing mechanism of action identification and clustering, benchmarking with standard of care drugs, and predictive efficacy and potential safety/toxicity determinations. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d8896998e87">Nintedanib was originally developed to treat Idiopathic Pulmonary Fibrosis (IPF) but has also been approved to treat various proliferative diseases, including cancer, and is under review as a treatment option for cardiac fibrosis. We will show how anti-fibrotic aspects of nintedanib’s BioMAP profile are similar to those of pirfenidone, a drug that is also approved for treating IPF. However, nintedanib’s additional activities support its efficacy as an anti-cancer drug, which is further underlined by demonstrated similarities to other approved anti-cancer drugs. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d8896998e89">Another prominent example is aspirin: originally developed for pain and inflammation, BioMAP data also support its use as an anti-coagulant and show potential for treating cancer, which represent other possible applications for this well-known drug. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d8896998e91">Taken together, these examples highlight the suitability of BioMAP for drug repurposing.