ADC (Antibody-Drug Conjugate) DMPK Services

The stability of ADCs in the blood matrix can help assess the stability of ADCs in the circulatory system, assess the off-target risk and species differences. WuXi AppTec DMPK has established various in vitro systems for evaluating the stability of ADCs, including whole blood, plasma, and serum, and also has the capability to detect a variety of analytes, such as free payload, ADC, total antibody, DAR value and identification of payload-related metabolites, etc. These capabilities enable us to provide comprehensive evaluations of the in vitro stability of ADCs, thereby assisting in the early evaluation of ADC candidates.

In vitro assessment of payload release of ADC is helpful to understand the cleavage mode of ADC and identify the payload-related species after cleavage, which provides data support for the detection or evaluation of pharmacokinetic/toxokinetic studies. WuXi AppTec DMPK has established various systems to evaluate payload release in lysosome, liver S9, liver homogenate or tumor cells. Detection of known free small molecules, as well as metabolite identification studies on payload-related species can be performed to fully evaluate payload release of ADC.

Not only large molecules (total antibody and conjugated antibody) but also small molecules (free payload and related species) are quantified for ADC project. Quantitative bioanalysis of total antibody, conjugated antibodies, payload, and relevant metabolites is run throughout all stages of ADC project development. In order to correctly evaluate the ADME characteristics of ADCs, comprehensive bioanalytical methods are required. The ADC integrated bioanalysis platform, established by WuXi AppTec DMPK, provides various analysis services, including ligand binding analysis (LBA), liquid chromatography mass spectrometry, liquid chromatography high-resolution mass spectrometry, and Hybrid LBA-LC/MS. The integrated bioanalysis platform enables the detection of total antibody, conjugated antibody, immunogenicity, payload and payload-related species, DAR value, etc. and facilitates metabolite identification and biotransformation analysis. 

If new paylaod-related species is genearated as main payload-release product after in vivo cleavage of ADC, it is necessary to evaluate the plasma protein binding, tissue distribution, metabolism, excretion/mass balance, drug metabolizing enzymes and transporter effects. In vivo ADME of the payload is normally carried out by using radioisotope labeling trace technology, including specific tissue distribution studies to elucidate the targeting characteristics.

WuXi AppTec DMPK has established the platform of ¹⁴C/³H labeled ADC synthesis, mass balance, tissue distribution (including tumor-bearing mice), and metabolite identification studies in small and large animals, to comprehensively evaluate the ADME characteristics of ADC in animals.