Biomarker discovery and validation are a key discipline to de-risk later stage drug discovery phases. They are defined as quantifiable biological parameters that indicate the status of a disease or the response of the body to a disease-modulating agent, and are monitored in biological fluids or tissues through a broad range of technologies.
At Evotec, we perform both unbiased biomarker discovery and hypothesis validation within a disease-relevant context. As a result, we develop and make use of disease-mimicking animal models to validate biomarkers within the context of a living organism. Most importantly, where possible, we work directly with patient material to ensure clinical translatability.
Relying on our strong drug discovery expertise, we aim to identify for our partners:
- Pharmacodynamic, efficacy and target engagement biomarkers
- Stratification biomarkers to support the identification of a target patient population
- Alternate tissue or pathway read-outs (surrogate biomarkers)
- Safety biomarkers to monitor toxicity
Evotec has a longstanding experience in applying various techniques and technologies to support biomarker studies in any type of body fluid, cell, tissue or animal model. These include, but are not limited to:
- Mass spectrometry-based proteomics and metabolomics
- Immunoassays and flow cytometry
Biomarker discovery and validation
Evotec offers a unique platform of innovative proteomics and metabolomics technologies to address key issues in translational biomarker discovery and validation in various therapeutic areas. Both the expertise and the sample and the data processing infrastructure are in place for accurate quantification across large sample cohorts, enabling integrated, large-scale projects to discover and validate diagnostic, pharmacodynamic or predictive biomarkers.
Immunoassays are an indispensable technology to assess pharmacodynamics biomarkers. Combining high sensitivity with a relatively high-throughput, immunoassays are a well suited method to measure protein levels and signalling events. Evotec’s knowledge and expertise in this area allows us to assist with the discovery of biologically and scientifically relevant biomarkers, as well as the measurement and interpretation of their changes in cellular models, animal models and ultimately patient samples across key therapeutic areas such as CNS, neurodegeneration, pain, inflammation, metabolic disease, oncology and immunology.
Evotec’s versatile immunoassay platform
Having translatability in mind, Evotec routinely develop, validate and apply ultra-sensitive protein biomarker quantification read-outs using state-of-the-art immunoassay technologies for hypothesis-driven biomarker research. Multiple technology options, such as single molecule counting Singulex technology, Mesoscale electrochemiluminescence or hTRF/TR-FRET allow for tailor-made approach to a gold-standard immunoassay.
Flow cytometry and ELISpot
Supporting primarily immunology and immuno-oncology focused projects, we apply flow cytometry approaches to evaluate drug mode of action and validate potential clinical markers. This includes the quantification of specific immune cell populations with diagnostic and/or prognostic significance using methods like FACS or ELISpot.
Evotec offers both unbiased as well as targeted gene expression profiling for the discovery of predictive, prognostic and pharmacodynamic biomarker candidates in cells, tissues and body fluids from animals and humans and the development of qRT-PCR assays for the confirmation and validation of transcriptional biomarkers.
The combination of in vivo pharmacology with imaging techniques offers a powerful tool to further analyse disease relevant biomarkers and assist in early risk assessments. Histology, immunohistochemistry (IHC) and radioligand binding are performed largely ex vivo and help to identify disease and target relevant changes. In contrast, optical and medical imaging can yield in life quantitative information amenable to statistical analysis, which adds significant value to our drug discovery efforts.
Immunohistochemistry and histology
Evotec integrates two leading ex vivo imaging platforms for biomarker studies, namely the Opera high-content imaging platform and the Ventana IHC platform. Experience includes the development of software solutions for quantification of labelling, and transfer of Ventana protocols with the clinic.
Ex vivo radioligand binding autoradiography
Functional responses using GTPγS radioligand binding and ex vivo receptor occupancy are monitored using state-of-the-art imaging technologies (Beta Imager & Phosphoimager) to determine protein localisation.
With the use of fluorescent probes and/or luciferase, we are able to monitor biological processes and track specific cell populations/markers in a living organism (specifically mouse).
In collaboration with co-localised leading small animal imaging facilities, Evotec accesses a combined functional-anatomic platform to validate clinical translation of specific biomarkers such as metabolites.