Target Discovery - Case Study
One of the main challenges for bi-specific antibodies is that potential target combinations run in the millions. The best combinations need to satisfy multiple requirements. Targets need to be widely expressed across patients to make it economically viable. For selectivity, both targets need to be highly expressed on the type of tumor, while at least one of the targets must have low expression across all healthy tissues. Then a number of target specific criteria need to be evaluated in part by experts.
The key problem was how to make sure you assess all possible combinations, find the best ones and then enable an efficient detailed assessment by experts.
The customer took a project approach to the problem and created an initial list of targets which were then evaluated by hand. Creating the initial list took a lot of effort. Updating it was always difficult. The manual evaluation also took substantial amounts of time per target.
Euretos created a workflow that evaluates millions of potential target pairs for over 30 different types of cancer. It ranks those target pairs on a number of criteria, including expression across healthy and tumor tissue. Each pair can be evaluated very easily in great detail by disease experts in terms of target profile, normal & tumor expression, patents and scientific references. The underlying data is continuously updated and new selection criteria and methods are launched regularly.
The workflow is now the starting point for target discovery in this area. Candidate target pairs are discussed in regular target review sessions. The most promising targets are then selected for further in vitro and in vivo analysis. Many highly interesting combinations have been progressed into preclinical testing which would have otherwise not been considered.