Understanding, on the one hand, what the body does to the therapy (i.e., Pharmacokinetic, PK), and, on the other hand, what the therapy does to the body (i.e., Pharmacodynamic, PD) is essential to maximize the chances of successful development of your drug.
Linking therapy exposure to the pharmacodynamic effect in a PK/PD model is crucial for high-risk medicinal products, such as single and multi-specific antibodies, to determine the Minimum Anticipated Biological Effect Level (MABEL). MABEL approach considers data from mechanistic ex vivo/in vitro studies and in vivo pre-clinical models to select appropriate, first in human (FIH) starting doses of the biotherapeutic product (i.e., absolutely safe and biologically active).
Quantitative ligand binding assays (LBA) are commonly used to measure biotherapeutic compounds' concentration, either free or complexed with its soluble target, in biological fluids.
Pharmacodynamic changes can impact many pathways, such as the kinetics of circulating biomarkers (soluble biomarkers) or the distribution and the function of immune cell subsets (immunophenotyping). For the development of cell-targeted biotherapeutics, their binding to their single (Monoclonal abs, Fab, Fab’2, nanobodies, ADC…) or multiple molecular targets (bi- or multi-specific antibodies, BiTEs…), that is receptor occupancy (RO), is a critical pharmacodynamic readout.
Active Biomarkers relies on a comprehensive array of technological platforms for measuring circulating levels of your bioactive therapy and its impact on the body. Depending on the required sensitivity, throughput, and dynamic range, we can develop and validate LBA-based PK assays using technologies such as conventional ELISA, Gyrolab xPloreTM, MSD SQ120, Ella or Simoa™ HD1.
We can monitor pharmacodynamic changes by immunoassay (Luminex BioPlex 200, SIMOA SP-X, MSD SQ120, Ella).