Teratogenicity Assessment

• The evaluation of potential teratogenic liability of drug candidates is typically performed late in the drug discovery processes. Standard testing relies solely on animal models, which are both cost- and time-intensive and do not always fully predict the teratogenic effects observed in humans.
• Evotec’s in vitro human iPSC-derived platform enables teratogenicity assessment with direct human relevance. The assay is optimized for 384-well plate format and is compatible with high throughput workflows. This setup enables de-risking of drug candidates in the early stages of drug discovery programs and can inform chemistry campaigns to dial out potential teratogenic hazards.
• The teratogenicity platform consists of four hiPSC-based models that demonstrate over 80% accuracy in classification of compounds with known teratogenic and non-teratogenic profiles.
• To contextualize hiPSC assay data, Evotec offers additional general cytotoxicity evaluation. This includes an assessment of cellular metabolic activity (Presto Blue assay) and investigation of transcription and translation inhibition (luciferase-based) in an unrelated cancer cell line. These assays can be implemented flexibly depending on individual project needs.

Teratogenicity assessment is performed in four hiPSC-derived cellular models. The impact of experimental compounds on these systems is evaluated based on automated image analysis. Specifically, parallel examination of cell count and alternations in differentiation efficiency (model-specific readouts, see Figure 1 for an example). The applicability of hiPSC-derived models for identifying teratogenic compounds was validated by screening 140 substances of known teratogenic and non-teratogenic profiles. The collective results from all four hiPSC-based systems demonstrated high predictive capabilities of the platform with accuracy exceeding 80% (Figure 2).