Matthew Sender

• Rationally designing Auristatin S to improve the tolerability of auristatin payloads through the tuning of permeability and bystander activity
• Explaining how Auristatin S maintains key auristatin properties, including strong tubulin binding affinity and induction of immunogenic cell death
• Exploring Auristatin S improved preclinical therapeutic window

As ADC development continues to expand across increasingly diverse targets, payloads, and antibody formats, 

understanding which molecular and physicochemical properties most strongly influence safety is critical to widening the 

therapeutic window. This panel will explore which variables can be modulated to improve safety and how mechanistic insights 

can be translated into smarter candidate selection by:

• Identifying the most critical determinants of ADC safety by examining how payload characteristics, antibody properties, conjugation parameters, and overall molecular design contribute to off-target toxicity and therapeutic window
• Exploring how payload and antibody properties can be strategically modulated by assessing the impact of payload physicochemical characteristics, Fc-mediated interactions, non-specific uptake mechanisms, and other molecular features on ADC distribution, cellular uptake, and toxicity
• Debating emerging strategies to improve ADC safety by design including Fc-silencing, alternative antibody formats, bispecific and biparatopic approaches, masked antibodies, and other engineering technologies, while considering how these approaches can translate mechanistic understanding into improved candidate selection and clinical safety