Kazuyoshi Kumagai

The FDA’s landmark guidance to reduce and ultimately replace animal testing has sent shockwaves through the toxicology community. The central question asks how to build a compelling, regulator-friendly safety package without decades of historical precedent.

Join regulatory experts, translational scientists, and industry pioneers as they chart a practical path forward for implementing NAMs in ADC development by:

• Building confidence in in vitro models, evaluating how organoids, microphysiological systems, and iPSC-derived tissue panels can be benchmarked against historical clinical data for known ADC toxicities like ILD and ocular keratopathy to establish predictive thresholds that regulators will trust
• Constructing a weight-of-evidence framework, discussing how to integrate high-content imaging, computational modeling, and mechanistic biomarker data into a cohesive safety package that compensates for the absence of traditional animal toxicology endpoints
• Collaborating with regulators on validation, exploring how to engage the FDA early in the NAMs development process through pre-IND meetings and qualification programs, ensuring that novel testing strategies are aligned with agency expectations and positioned for successful adoption

• Developing a reproducible non-clinical monkey ILD model using repeated dosing of DXd-based ADCs to characterize pulmonary toxicities and establish translational relevance to clinical interstitial lung disease findings
• Longitudinally profiling plasma, BALF, and BALF-derived extracellular vesicles using high-dimensional proteomics to identify early biomarker candidates associated with ADC-induced lung injury progression
• Integrating single-cell RNA sequencing with extracellular vesicle proteomic signatures to map alveolar epithelial, macrophage, monocyte, and fibroblast responses, enabling mechanistic insight into DXd-ADC–associated ILD and improving translation from preclinical models to clinical outcomes