Tara Arvedson

As tumor heterogeneity and acquired resistance continue to limit the durability of single-payload ADCs, dual-payload

strategies are emerging as a powerful approach to deliver complementary mechanisms of action within a single, precisely engineered construct.

Join leading experts as they discuss how orthogonal chemistry, enzymatic precision, and innovative linker design can converge to create stable, scalable, and clinically translatable dual-payload ADC platforms by:

• Balancing combinatorial potency with molecular precision, examining how one-step multi-payload conjugation, glycan directed strategies, and orthogonal enzymatic chemistries can achieve controlled payload ratios and spatial placement to address tumor heterogeneity without compromising stability
• Redefining site-specific conjugation as the foundation for dual-payload success, debating how high-precision enzymatic platforms and EGCit-enabled linker systems can deliver homogeneous constructs with optimized DAR distribution, improved pharmacokinetics, and reduced off-target toxicity
• Designing linker architectures to strategically combat resistance, evaluating how innovative cleavable, traceless, or
• modality-specific linkers can coordinate sequential or complementary payload release, integrate novel payload classes, and maintain manufacturability while expanding the therapeutic index

• Rationally engineering linker architectures to precisely tune payload-specific release kinetics, balancing plasma stability with efficient intracellular cleavage, thereby maximizing synergistic efficacy and overcoming heterogeneous tumour resistance
• Implementing technical improvements to achieve controlled, site-specific dual loading, enabling precise drug-to-antibody ratios while preventing payload exchange, stochastic distribution, or conjugation-site competition
• Developing integrated, high-throughput screening workflows to rapidly evaluate novel payload combinations, leveraging modular linker platforms, parallel conjugation strategies, and miniaturized in vitro cytotoxicity and stability assays to identify promising synergistic warhead pairings