Kwasi Amofa

• Engineering an ADC panel with varying payload hydrophobicity to quantify how lipophilic payloads passively diffuse across cell membranes, establishing a predictive relationship between logD and off-target toxicities
• Investigating the contribution of membrane transporters to the bystander effect, including how influx and efflux mechanisms regulate intracellular payload accumulation and intercellular transfer, to determine their impact on off-target toxicity and therapeutic selectivity
• Correlating in vitro bystander killing potential in 3D spheroid co-cultures with in vivo outcomes to establish a predictive screening assay, enabling optimization of payload properties for an improved therapeutic index

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