This webinar will provide a general overview of the regulatory guidelines required for developmental and reproductive toxicity (DART) testing. In order to initiate clinical trials for women of child-bearing potential (WOCBP), the FDA requires initiation of preclinical DART studies using mammalian research models. These regulated studies provide important information regarding the effects of drug exposures prior to and during parental mating, as well as evaluating maternal and fetal changes during gestation, and identifying any alterations in the development of the offspring following birth.

Frontage develops a full validation of the XTMAB-16 NAb (neutralizing antibody) assay with acceptable drug and target tolerances to guide future clinical trials.

Accurate determination of the drug-to-antibody ratio (DAR) of interchain cysteine-linked antibody–drug conjugates (ADCs) is challenging. High-resolution mass spectrometry (HRMS) analysis of the ADCs at the intact or subunit level provides a feasible way to measure the DAR. However, the measured DAR is usually lower than the true DAR because of the variation in ionization efficiency between different DAR species. In this work, we developed a novel standard-free HRMS method involving isotope-labeled payload conjugation, protease digestion, and liquid chromatography–HRMS (LC-HRMS) analysis for accurate determination of the DAR of the interchain cysteine-linked ADCs with cleavable or non-cleavable linkers. Isotope-labeled payload conjugations eliminated the structural and chemical differences between different DAR species and ensured that the drugs or payload-containing peptides could be separated from each other in the mass spectrometer. A papain digestion strategy for ADCs with cleavable linkers showed a DAR of 3.79, with a relative standard deviation (RSD) of 0.48 (n = 3). Similarly, the trypsin and chymotrypsin digestion strategy that is applicable to ADCs with non-cleavable linkers showed a DAR of 3.77 and an RSD of 0.86 (n = 3). The DAR determined by this method was consistent with the DAR of the ADCs that was measured by the UV/Vis method. This method will be very useful to researchers working in the field of ADC discovery and development.