Public Funding for Oxford Biotherapeutics Ltd

Pancreatic cancer is an agressive cancer with c.260,000 deaths per year globally and a 5% 5-yr survival rate. Current therapies have limited efficiacy and are asscociated with severe side-effects.Thus there remains a clear need for a drug that cures or significantly extends survival. Antibody drug conjugates (ADCs) are class of cancer drugs combining the specificity of antibodies with the potency of chemotherapy drugs. Oxford BioTherapeutics (OBT) has identified a novel cancer-associated target upregulated in pancreatic cancer. In collaboration with Spirogen, OBT is developing an ADC directed to the target comprising a specific, high affintiy antibody combined with a novel DNA binding toxin. The objective of this project is to complete preclinical development of the ADC, including demonstration of preclinical safety and efficacy, in addition to formal GMP manufacture, having the potential to provide an effective new treatment for cancer patients with high unmet medical need.

To establish a hepatotoxicity biomarker database in zebrafish embryos (ZFEs) using compounds with known toxicities. To use this database in parallel with OGeS''s existing OGAP database to select and validate potential drug safety protein biomarkers in both ZFEs and rodents (and ultimately, man). To develop highthroughput Ordered Peptide Array (OPA) screens initially, followed by antibody (Ab) based platform technologies. Biomarkers will be selected on the basis of quantitative changes correlating to characteristic morphologic and/or phenotypic observations in ZFE. Commercialised OPA and/or Ab screens (applicable to zebrafish, rat and human samples) will be offered to pharma industry in parallel to phenotypic zebrafish screens to improve drug discovery efficiency in preclinical safety asessment initially, with potential clinical applications explored subsequently. and hepatotoxicity.