Identification and use of the appropriate biomarkers can make the difference between failure and success
Biomarkers are biological or biochemical indicators used to track progress of disease, effect of therapeutic interventions, and drug-induced toxicity.
Informed and data-driven use of biomarkers has proven critical to guide the pre-clinical and clinical development of a drug, select the most appropriate dosing regimen, and identify the patient population most likely to respond. Ultimately, it informs on whether or not a program should move forward or be discontinued.
Different types of biomarkers are utilized during the preclinical phase of a drug discovery program. They can be can be classified as follows:
- Target engagement (TE): these biomarkers measure the percentage of the target protein that is bound by the drug. They are extremely useful to establish a direct link between PK and efficacy. They also can determine for how long and how much a target protein must be engaged by the drug to observe efficacy and/or toxicity.
- Pharmacodynamics: these biomarkers measure how the pathways downstream of the target protein are modulated, following the binding of the drug to the protein itself. This class can be divided into proximal and distal biomarkers. Proximal biomarkers measure the modification of a molecule immediately downstream of the target, including the substrate itself. Distal biomarkers measure biological or biochemical effects that are further downstream.
- Responder Identification (ID) Biomarkers: these biomarkers identify the biological and/or biochemical characteristics that render a specific patient sub-population more sensitive or more resistant to a specific drug treatment.
The combined and timely development and validation of each type of biomarker requires a deep understanding of the drug development process and extreme familiarity with what is required to transform a novel discovery into real drugs. For each type of biomarker, the most appropriate assays must be developed and implemented: they must be robust, sensitive, rigorously validated in vivo and translatable into the clinic. Our team of experts at IRBM can work closely with you to design and implement the most successful biomarker plan for your program.
From the initiation of a program, our team will work on the identification and validation of TE assays in the target tissue or in a surrogate tissue, depending on program needs. We can run feasibility studies and reach a Go/No Go decision in a short time frame.
If the selected TE assay cannot be translated into the clinic, we can determine which is the most appropriate proximal or distal PD assay that can be used to guide the clinical development. Depending on the target, we can develop robust, analytically validated and tailored read-out tools and assays, developed with the most advanced technologies: alternatively, or in conjunction, we can have a broad-net approach and utilize -omics approaches including genomics, transcriptomics, proteomics and metabolomics. In the field of -omics, we are particularly skilled at developing LC-MS methods for metabolite and biomarker discovery.
We can generate and validate responder ID hypotheses using a comprehensive repertoire of in vitro tools and validate them in vivo using robust assays in the most appropriate rodent models.
At IRBM we take a holistic approach to biomarker development and validation, bringing together teams from different disciplines, all based under one roof, to create a carefully designed PK-PD-efficacy relationship study, and accelerate your program.