Compared with traditional anti-tumor drugs, ADC has long circulation time in serum, strong therapeutic efficacy, high tumor cell specificity, weak non-target cytotoxicity and significantly reduced systemic toxicity. However, the complex structure confers unique toxicological characteristics to ADCs. Due to the existence of macromolecular monoclonal antibody structure, ADC is mainly distributed in plasma, extracellular fluid and lymphoid tissue, which shows similar pharmacokinetic characteristics to macromolecular antibodies, such as low clearance rate, long half-life, low surface distribution volume and poor oral bioavailability. However, due to the presence of small molecules and linkers, ADC has more diverse degradation modes and toxicity than macromolecular drugs. Therefore, the challenges of ADC development strategies and analytical method development, establishment, and validation, as well as preclinical in vitro and in vivo research issues must be well understood. BOC Sciences is committed to providing a one-stop solution for in vivo evaluation of ADC development. Our evaluation data can provide customers with information about the efficacy and safety of ADC and provide guidance for clinical trial design.
BOC Sciences has established a comprehensive bioanalysis and detection platform to evaluate the metabolism, distribution, elimination and immunogenicity of ADC. Our in vivo assays cover various cell lines from various animal models, including mice, rats, rabbits, monkeys, etc.
ADC in vivo decomposition/metabolism process includes antibody decomposition/metabolism and small molecule drug metabolism. ADCs release effector molecules in the cell or circulatory system before reaching tumor cells. And unbound antibodies and antibody fragments follow the metabolic pathway of antibodies to produce amino acids by enzymatic hydrolysis and are reused by the body. The identification and detection of metabolites in animals such as circulatory system, excreta and important tissues such as liver metabolites will help to further evaluate the safety of ADC and provide further basis for the selection of animal species for preclinical safety.
The distribution of ADC molecules and their released free effector molecules in various tissues is different due to the the binding to the target and the physicochemical properties of the drug. The liver, lung, kidney and skin are the more common distribution organs of ADC. It is necessary for the safety and efficacy of ADC to evaluate the distribution characteristics of ADC in vivo through safety evaluation and pharmacodynamics animal species.
In vivo PK assays investigated the PK profile of each analyte after administration. Integrating PK parameters, drug efficacy and safety data can meet the needs of ADC drug development at different stages, such as target selection, antibody affinity, linker stability, animal-to-human extrapolation, and dose selection and adjustments, E-R correlation studies (exposure-response relationships) and DDI studies, etc.
Immunogenicity is one of the major factors determining the circulating half-life of ADCs, increasing ADC clearance and reducing its exposure. Immunogenicity of ADCs can be caused by antibody moieties, effector molecules, or neo-epitopes generated. BOC Sciences has launched a comprehensive in vivo assay service to assess the potential immunogenicity of ADCs.
In order to quickly respond to customers' ADC R&D needs, we have established a one-stop platform to handle laboratory and commercial-scale ADC development and production. Our services include ADC pre-development, cGMP ADC manufacturing capabilities and comprehensive ADC analytical support.
BOC Sciences has rich experience in preclinical ADC development, and has undertaken dozens of projects in the preclinical development and bioanalysis of ADC drugs. We can help customers quickly complete the establishment and validation of preclinical ADC in vivo analysis methods to meet the FDA/NMPA/TGA IND declaration requirements for pharmacokinetics. If you are interested in our ADC in vivo analysis services, please contact us for more information and a detailed quotation.
BOC Sciences provides comprehensive support services for your ADC quality studies, including drug-to-antibody ratio (DAR), drug distribution, chromatographic drug distribution, size exclusion chromatography drug conjugate, charge variant separation and free small molecule analysis and so on.