Panel Discussion: Architecting Dual-Payload ADCs Through Orthogonal Conjugation Chemistry to Overcome Tumor Resistance

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