VIDA

The clinical phases of drug development are characterized by high failure rates of newly developed compounds and associated high costs. This can be remedied by new methods for the design of new active ingredients and for improved active ingredient analysis, which can be incorporated into more meaningful, functional preclinical tests.

Taking the development of new agents for the treatment of anxiety disorders as an example, the VIDA consortium is developing: 1) in silico methods for modeling and predicting on- and off-target binding, 2) biophysical analysis methods for characterizing on-target binding of potential drug candidates in physiological environments, 3) robust phenotypic assay systems as an indispensable precursor to successful clinical trials.

In the course of drug development, about two thirds of all synthetic drug candidates fail already in early development phases. The reasons for this are mainly insufficient selectivity towards the actual target structure (off-target effects), the resulting side effects, and the subsequent lack of treatment effects or effects that cannot be clearly assigned.

To increase the productivity of preclinical development phases, the project partners 2bind GmbH, NMI and PharmAI GmbH are developing innovative preclinical methods and tests using the example of new active substances for the treatment of anxiety disorders as part of the VIDA project funded by the BMWi. As a scientific basis, the consortium is using research results from the NMI that point to a disturbed inhibition of neurons of the central nervous system (CNS) as the cause of anxiety disorders. Initial results show that so-called mimetic peptides can be used to address cellular mechanisms that are essential for stabilizing required inhibitory circuits in the CNS. Due to their structure and binding properties, the latter peptides serve as a template in the VIDA project for the development and characterization of novel, synthetic drug candidates with pharmacokinetic properties superior to peptide structures for the treatment of anxiety disorders.

As a partner from the field of bioinformatics, PharmAI GmbH is developing an innovative in silico method for the identification of new small molecule drug candidates, which takes into account both on- and off-target interactions. Based on the structure of selected mimetic peptides, this allows the identification of new drug candidates as well as substances already available on the market and patentable (drug repositioning) with corresponding properties.

2bind GmbH contributes novel biophysical analysis methods based on MicroScale Thermophoresis (MST) and Biolayer Interferometry (BLI) to the project network. This will enable the analysis of small molecule drug candidates in terms of on-target interactions in near physiological environments (i.e. in the presence of off-targets).

Through the NMI, robust and translational preclinical assay systems based on relevant cell culture models will be made available. These multiparametric methods will allow quantitative mode-of-action as well as phenotypic analyses regarding synaptic stability after deployment of drug candidates to be tested.

After successful completion of the project, these novel and target-oriented methods will be available to pharmaceutical companies as a service and will accordingly expand the portfolios of 2bind GmbH, NMI and PharmAI GmbH.