Kazuyoshi Kumagai

• 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

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