Sara Wichner

As the field expands beyond traditional cytotoxic payloads toward degraders and other complex, hydrophobic modalities, linker and conjugation chemistry must evolve to solve escalating biophysical challenges. From high-DAR constructs to degrader-antibody conjugates, the central question emerges: how do we push payload complexity and loading capacity without compromising stability, manufacturability, or in vivo performance?

Join leading experts as they discuss how novel linker architectures, advanced analytical precision, and site-selective

conjugation strategies can be integrated into cohesive platforms by:

• Balancing high payload loading with biophysical stability, examining how innovative linker architectures and hydrophobicity mitigating designs can enable DAR 8 and greater while preserving solubility, structural integrity, and favorable pharmacokinetics
• Redefining conjugation control as a platform enabler, debating how pyridazinedione-based site-selective strategies and advanced analytical tools can deliver precise, homogeneous DAR control to unlock reproducible, scalable next-generation constructs
• Harnessing traceless and site-specific linker strategies to enable emerging modalities, evaluating how degrader-compatible, hydrophobicity-masking, and cleavable designs can expand the ADC paradigm to include degrader-antibody conjugates and other novel payload classes without sacrificing developability or therapeutic index

• Screening a diverse linker-drug library incorporating variations in payload potency, release triggers and conjugation handles to identify optimal combinations, enabling fine-tuned control over pharmacokinetics and on-target activity
• Validating conjugate solubility and aggregation states through physiochemical analytical methods to provide definitive, accessible monomer quantification
• Demonstrating in vitro cytotoxicity and selectivity for high-DAR (DAR ≥8) conjugates engineered with optimized linker-drug designs that overcome hydrophobicity-driven aggregation