For a named target with an approved drug indication, Euretos was asked to suggest alternative indications. The fundamental challenge for the customer was to take a truly unbiased approach which would not be limited by the current expertise of the company. Also they found it very challenging to take such an unbiased approach within a limited time frame.

They had tried a more literature driven approach in the past, but found it especially difficult to assess and rank indications outside of their normal area of expertise. Also having an objective and scalable approach was challenging to achieve.

“In this project we evaluated you against our internal investigations and the results of one other external provider. What really sets you apart is how you combine a fundamentally biological and data driven approach. The breadth of the indications you assess and the depth of your analysis sets you apart and is a clear value add to our internal capabilities.”

Global Head, Large European Pharma

For all major indications, Euretos has created highly detailed molecular disease models which include a (cellular) dysregulation profile. Also, detailed target profiles are already present in the platform including cell type expression and co-expression networks. To find alternative indications, we analyse the impact of target perturbation to identify which disease indications are most closely associated with the target of interest. We model, to what extent, perturbation of the target results in a correction of the gene dysregulation profile associated with each disease model. This way, at a fundamental biological level, potential indications are matched with the target’s biological profile. For selected indications target suitability is analysed in the context of the indication in terms of efficacy, druggability, drug response, toxicity and potential off-target effects.

We were able to pinpoint a number of indications that look very promising based on the expected target involvement in the indication. Further in vitro and in vivo testing is underway. Further targets expansion project are now being planned based on the same methodology.