Day One

• Examine why continued reliance on tubulin and topoisomerase payloads is becoming strategically and clinically unsustainable, as hundreds of ADCs with the same mechanisms move into the clinic and patient populations become saturated and resistant
• Provide a reality‑based assessment of which novel payload classes are genuinely close to clinical readiness, separating mechanisms with real translational momentum from those that remain conceptual
• Argue why the ADC field is at an inflection point, where measured rule‑breaking and early risk‑taking on novel payloads is now required to avoid long‑term stagnation

• Examine the rationale for payloads that induce immunogenic cell death (ICD) rather than relying on conventional cytotoxic mechanisms alone
• Compare the activity of Ryvu's lead payload candidates against established ADC payloads across multiple tumor targets and models
• Understand how novel payload mechanisms can expand therapeutic opportunities, improve differentiation, and address emerging resistance in the ADC landscape

A structured opportunity for face-to-face discussions and exchange of business cards across the ADC payload community, enabling focused exchange on the latest advances in payload design, resistance mechanisms, linker strategies, and translational challenges shaping clinical success.

• Examine the scientific rationale for leveraging oncogenic pathway inhibition as an ADC payload strategy, demonstrating how targeted delivery of PI3K/mTOR inhibitors can achieve meaningful anti-tumor activity beyond traditional cytotoxic mechanisms
• Explore preclinical data supporting ADC-enabled delivery of Omipalisib to overcome the systemic toxicities that have historically limited PI3K/mTOR inhibitors, unlocking a previously inaccessible therapeutic window in pathway-addicted tumors
• Define the critical biological and engineering considerations required to optimize non-cytotoxic payloads, including linker-spacer design, conjugation strategy, and the unique pharmacology created by ADC-mediated pathway inhibition

• Review new clinical and mechanistic data from the most advanced NMT inhibitor, zelenirstat, and examine how emerging efficacy, safety, and biological activity findings are helping validate NMT inhibition as a promising ADC payload mechanism
• Explore the biology underpinning NMT inhibition, including emerging understanding of isozyme dependency in cancer cells and why NMT1 represents an attractive and potentially selective therapeutic vulnerability
• Assess why growing biological, clinical, and translational evidence is increasing interest in NMT inhibitors as ADC payloads, and discuss how the mechanism could be deployed to address resistance and enable greater payload differentiation beyond conventional cytotoxic approaches

• End-to-end case study of a DNA-targeting ADC program, from payload selection and antibody pairing through to in vitro and in vivo evaluation
• Exploration of key chemistry and biology challenges, including conjugation strategy, assay predictivity, and species-dependent translational gaps
• Deep dive into tolerability outcomes in higher-order species and the critical learnings that shaped program termination and future redesign strategies

• Collaborate with peers to identify why promising ADC payloads frequently fail in clinical development, exploring the translational challenges associated with efficacy, toxicity, exposure, and resistance
• Discuss how organoids, tissue-on-chip platforms, microfluidic systems, and other human-relevant models can improve payload selection and uncover safety liabilities earlier in development
• Exchange lessons learned and practical solutions for building more predictive preclinical strategies, before sharing key recommendations with the wider audience to help improve ADC development success rates

An interactive platform for scientists, drug developers, and industry experts to showcase the latest advances in ADC payload innovation, enabling attendees to engage directly with presenters across areas including novel payload discovery, biology-driven mechanisms of action, linker-payload design, translational evaluation, resistance biology, and next-generation ADC strategies.

• Assess whether the performance ceiling of established payloads is driven by the payload itself or by broader ADC design factors, including antibody biology, internalization dynamics, and target selection
• Explore the impact of tumor biology and cell-cycle kinetics on ADC efficacy, discussing whether reliance on traditional cytotoxic mechanisms leaves significant tumor populations untreated and how developers can address these limitations
• Examine how linker design, payload permeability, and medicinal chemistry have been used to fine-tune bystander killing, highlighting lessons from both efficacy gains and toxicity liabilities
• Debate how antibody engineering, immune-mediated mechanisms of action, and novel ADC platforms can unlock greater value from proven payload classes without requiring entirely new warheads

• Distil the most important translational and clinical lessons from the widespread adoption of topoisomerase I payloads across multiple tumor settings
• Analyze which resistance mechanisms could have been anticipated and which only emerged through large-scale clinical use, informing more effective development strategies moving forward
• Translate real-world experience into actionable guidance for designing nextgeneration topo payloads and identifying orthogonal mechanisms capable of addressing resistant patient populations