Target Validation

Drugs in development typically fail in the clinic due to lack of efficacy and/or toxicity, both of which are often attributed to inadequate pre-clinical target validation.

Target validation is the first step in discovering a new drug and can typically take 2-6 months. The process involves the application of a range of techniques that aim to demonstrate that drug effects on the target can provide a therapeutic benefit with an acceptable safety window.  Early in-depth target validation increases understanding between target manipulation and disease efficacy, leading to increased likelihood of success in the clinic.  Once a target has reached an acceptable level of validation and disease linkage, the project moves into the hit identification phase.

The spectrum of target validation techniques are summarised below:

Sygnature has an established track record for validating disease-modifying targets from different target classes and across numerous therapeutic areas. Using our experience in tailored assay development, Sygnature can offer a complementary suite of techniques to help build a strong platform of evidence for your biological targets, for example: –

Functional analysis

• Value-adding in vitro assays to measure the biological activity of the target, characterise pharmacology and assess the effects of modulating function.
• Use of ‘tool’ molecules to demonstrate desired in vitro biological effect.

Expression profile

• mRNA and protein distribution pattern to determine target expression and function in both healthy and disease states.
• Correlation of expression with disease progression or exacerbation using disease-relevant cells/tissue.

Cell-based models

• 3-dimensional (3D) cultures and co-culture models, human stem cells (iPSC) , including access to disease cells.

Biomarkers

• Biomarker identification and validation using multiple techniques to include transcriptomics (qPCR platforms), protein analyte detection (Luminex) and flow cytometry.