Philip Moquist
Seminars
Join this interactive roundtable to explore how non-specific ADC uptake into healthy tissues contributes to dose-limiting toxicities and what the industry can do to predict better, characterize, and mitigate these mechanisms early in development.
Join this discussion to examine how emerging mechanistic insights can be translated into safer ADC design strategies and improved therapeutic window by:
- Investigating non-specific ADC uptake pathways beyond macropinocytosis by leveraging CRISPR-Cas9 screening and healthy cell models to identify the receptors and endocytic mechanisms driving off-target toxicities
- Understanding how ADC physicochemical properties such as surface charge, hydrophobicity, linker stability, and DAR influence non-specific uptake into healthy tissues, and debating which design parameters offer the greatest opportunity for toxicity mitigation
- Translating mechanistic insights from fluorescent imaging, spatial biology, and clinically validated ADC safety data into predictive screening strategies that enable earlier candidate prioritization and improved therapeutic windows
As the ADC field rapidly expands beyond the established topoisomerase-I paradigm into dual-payload constructs, bispecific formats, and entirely novel toxin classes, the safety assessment playbook must evolve. With no historical safety data to rely on and toxicity mechanisms that may be fundamentally different from traditional ADCs, developers face an urgent need to establish new frameworks for predicting and mitigating risk.
Join preclinical safety leaders from biotech and large pharma as they share strategies for de-risking the next generation of ADC innovation by:
- Designing fit-for-purpose toxicology packages for dual-payload ADCs, debating whether standard NHP studies are sufficient to detect additive or synergistic toxicities, and exploring how staggered-dosing studies and payload-selective biomarkers can deconvolute the contribution of each warhead to the overall safety profile
- Assessing the unique liabilities of bispecific and biparatopic formats, discussing how altered binding avidity, internalization kinetics, and tissue distribution create novel safety challenges that require bespoke in vitro and in vivo models to accurately predict clinical risk
- Prioritizing novel payload classes by mechanistic profiling, evaluating how a standardized preclinical safety screening cascade, encompassing human primary cell panels, tissue organoids, and computational modelling, can rapidly identify the most promising payloads with differentiated toxicity profiles before committing to costly IND-enabling studies
- 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
