Day One

• Employing a matched-pair strategy using inert payloads and non-binding antibodies, to systematically isolate and quantify the contributions of payload and target engagement to overall observed toxicity, providing a clear mechanistic attribution for dose-limiting adverse events
• Utilizing tissue microarrays with quantitative immunohistochemistry for target expression, to map the biodistribution of target antigens in critical normal organs,creating a preclinical risk assessment tool for on-target toxicity before candidate selection
• Developing computational toxicology models that partition free payload and intact ADC concentrations, to predict which component is driving clinical adverse events, informing linker design strategies to minimize systemic payload release

• 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

This informal session offers the perfect opportunity to connect with industry front-runners and key opinion leaders specializing in pathology and toxicity 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.

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

• Traditional nonclinical models often fail to predict clinical outcomes for complex ADCs, creating a need for more advanced and biologically relevant preclinical approaches.
• Novel in vitro systems can improve decision-making in drug discovery by providing better insights into key factors such as target uptake, payload characteristics, and tissue toxicity
• Integrating these systems into a broader translational strategy, along with improved species selection, biomarker use, and mechanistic data, can produce more predictive nonclinical packages and enable faster, more confident go/no-go decisions

• Developing a reproducible non-clinical monkey ILD model using repeated dosing of DXd-based ADCs to characterize pulmonary toxicities and establish translational relevance to clinical interstitial lung disease findings
• Longitudinally profiling plasma, BALF, and BALF-derived extracellular vesicles using high-dimensional proteomics to identify early biomarker candidates associated with ADC-induced lung injury progression
• Integrating single-cell RNA sequencing with extracellular vesicle proteomic signatures to map alveolar epithelial, macrophage, monocyte, and fibroblast responses, enabling mechanistic insight into DXd-ADC–associated ILD and improving translation from preclinical models to clinical outcomes

• Engineering an ADC panel with varying payload hydrophobicity to quantify how lipophilic payloads passively diffuse across cell membranes, establishing a predictive relationship between logD and off-target toxicities
• Investigating the contribution of membrane transporters to the bystander effect, including how influx and efflux mechanisms regulate intracellular payload accumulation and intercellular transfer, to determine their impact on off-target toxicity and therapeutic selectivity
• Correlating in vitro bystander killing potential in 3D spheroid co-cultures with in vivo outcomes to establish a predictive screening assay, enabling optimization of payload properties for an improved therapeutic index

The FDA’s landmark guidance to reduce and ultimately replace animal testing has sent shockwaves through the toxicology community. The central question asks how to build a compelling, regulator-friendly safety package without decades of historical precedent.

Join regulatory experts, translational scientists, and industry pioneers as they chart a practical path forward for implementing NAMs in ADC development by:

• Building confidence in in vitro models, evaluating how organoids, microphysiological systems, and iPSC-derived tissue panels can be benchmarked against historical clinical data for known ADC toxicities like ILD and ocular keratopathy to establish predictive thresholds that regulators will trust
• Constructing a weight-of-evidence framework, discussing how to integrate high-content imaging, computational modeling, and mechanistic biomarker data into a cohesive safety package that compensates for the absence of traditional animal toxicology endpoints
• Collaborating with regulators on validation, exploring how to engage the FDA early in the NAMs development process through pre-IND meetings and qualification programs, ensuring that novel testing strategies are aligned with agency expectations and positioned for successful adoption

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

• Analyzing recent regulatory feedback to interpret how the FDA’s Project Optimus guidance is being applied to dose selection and toxicity mitigation strategies, providing a clear roadmap for designing Phase I dose-finding studies
• Designing clinical dose-optimization strategies for antibody–drug conjugates that balance therapeutic exposure and tolerability, to proactively address regulatory expectations
• Applying lessons from Ligachem Bio’s ADC pipeline to integrate translational toxicology, pharmacokinetics, and early safety signals into adaptive Phase I study designs

• Applying large language models to capture and structure real-time toxicity events from clinical data sources, enabling more comprehensive and timely identification of ADC-related adverse events
• Developing a clinically annotated framework for systematic collection of patient samples across clinical trials and standard-of-care settings, supporting integrated analyses of ADC toxicity mechanisms
• Leveraging advanced analytical techniques to characterize toxicity profiles and compare them with analogous sporadic events, enabling deeper mechanistic insights and more informed strategies for toxicity prediction and management