Day One

• Evaluating orthogonal versus linear linker architectures to demonstrate superior in vivo efficacy and therapeutic index enabled by controlled, multi-stage drug release at the tumor site
• Comparing traditional PEGylated linkers with novel Polysarcosine (PSAR)-based shielding technologies to optimize the hydrophilicity-masking balance, minimizing offtarget interactions while maintaining favorable pharmacokinetics
• Presenting proof-of-concept data for a tumor-selective linker design, where enzymatic cleavage within the microenvironment precisely exposes the cytotoxic payload, enhancing therapeutic specificity and safety

• Using peptide-based affinity tags and native transglutaminase to achieve chemoselective, covalent conjugation exclusively at engineered glutamine residues enabling homogeneous, site-specific bioconjugation
• Leveraging innate specificity of enzymatic catalysis for peptide substrates, to drive the conjugation reaction with high fidelity and efficiency, ensuring a homogeneous DAR product with minimal by-products
• Using Therano-Sticktm to conjugate antibody fragments and improve the therapeutic index

• Understanding the advantages of the Veraxa hydrophilic click chemistry technology for enhancing ADC stability and pharmacokinetics while minimizing non-specific tissue uptake
• Showcasing reduction of off-target toxicity via charged payloads and tumor selective linkers to improve the therapeutic index and broaden the safety window for nextgeneration ADC therapies
• Increasing ADC selectivity by dual targeting bispecific ADCs via an End-Gate Approach to overcome tumor heterogeneity and mitigate on-target off-tumor toxicity for more precise cancer cell killing

• This informal session offers the perfect opportunity to connect with industry front-runners and key opinion leaders specializing in linker and conjugation chemistry within the ADC field. This is your chance to build meaningful connections to carry through the rest of the conference, while gaining exclusive, first-hand insights into the latest research and developments.

• Introducing the site-specific conjugation platform process to understand the advantages of having multi payloads on native antibodies
• Demonstrating the efficacy of Dual ADCs in comparison to single-payload ADCs to overcome intra-tumoral heterogeneity
• Validating native antibody-like pharmacokinetics and safety profiles to showcase the benefits of hydrophilic peptide linkers in mitigating aggregation

As linker innovation rapidly evolves from incremental chemistry optimization to multifunctional control over stability, selectivity, and biodistribution, the field faces a defining challenge: how do we systematically reduce systemic toxicity while preserving potency in increasingly complex tumor environments?

Join leading experts as they exolore how to harmonize conjugation precision, linker stability, and tumor-selective release mechanisms into integrated design frameworks by:

• Reconciling stability with selective activation, examining how charge-shielding, hydrophobicity-masking, and hydrophilic click chemistries can be strategically combined with orthogonal linker architectures to prevent premature systemic cleavage while preserving efficient tumor-site payload release
• Redefining conjugation precision as a determinant of safety, debating the extent to which homogeneous, site-specific enzymatic attachment and controlled DAR distribution can improve pharmacokinetics, reduce off-target toxicity, and enhance the predictability of biomarker-driven efficacy
• Designing linkers to modulate biomarker dependence and bystander effects, evaluating whether next-generation architectures should enforce strict antigen-density reliance or enable controlled payload diffusion to address tumor heterogeneity while maintaining an optimized therapeutic window

• Leveraging the next‑generation EGCit linker to achieve enhanced plasma stability, reduced off‑target uptake, and rapid intracellular release, ensuring controlled delivery of multiple payloads with minimal systemic toxicity
• Employing microbial transglutaminase–based site‑specific conjugation and modular click‑chemistry assembly to achieve uniform DAR, high homogeneity, and orthogonal installation of distinct payloads without cross‑reactivity
• Advancing dual‑payload ADCs, including the branched‑linker TROP‑2 candidate CBB‑120, to simultaneously target tumor heterogeneity and resistance pathways through synergistic mechanisms of action

• Leveraging conserved Fc N-glycans and orthogonal conjugation chemistries to create spatially defined attachment sites for dual payload incorporation, enabling homogeneous, structurally stable ADCs Fc integrity, and pharmacokinetic performance
• Integrating highly stable, irreversible linker technologies with controlled DAR to independently modulate two mechanistically distinct payloads, minimizing premature release, reducing systemic toxicity, and maintaining payload balance
• Applying Biohaven’s MATE™ platform and advanced conjugation strategy to nextgeneration programs such as BHV-1510 and BHV-1530, supporting dual-payload designs that combine synergistic cytotoxic mechanisms, improved safety margins, and enhanced anti-tumor durability

• 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

• Connect with peers in a relaxed atmosphere and continue building new and existing relationships while exploring the latest advancements in ADC linker and conjugation chemistry research..
• To submit a poster, please contact info@hansonwade.com

• Mitigating systemic toxicity through highly stable, site‑specific enzymatic conjugation that maintains linker integrity and minimizes premature payload release
• Enhancing anti‑tumor activity with hydrophilic, next‑generation linker architectures designed to improve solubility, reduce aggregation, and support dual‑payload loading
• Streamlining bioconjugation workflows with modular, enzyme‑driven manufacturing that enables reproducible DAR control, orthogonality, and scalability for complex ADC formats

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