Main Conference Day 1Wednesday, 27 May 2026 - European Time GMT+1

Antibody Drug Conjugates (ADCs) are rapidly changing the clinical treatment of cancer, and these sophisticated therapeutics have multiple interactions within the tumor microenvironment (TME) that are important for drug design. In this talk, I will share our experimental and computational results highlighting the impact of the TME on the ADC, including macrophage and protease effects, and the impact of the ADC on the TME, such as immune activation.

Conditional logic-gated bispecific ADCs can be optimised to enable precise tumour targeting while delivering deeper and broader efficacy by integrating dual-antigen recognition. This approach enhances potency, mitigates on-target/off-tumour toxicities, and addresses intratumoural heterogeneity. The talk will highlight engineering principles, preclinical validation, and translational insights advancing this next-generation ADC modality.

To address critical challenges in ADC discovery, such as elucidating mechanisms of resistance and systematically identifying synergistic payload combinations, Turbine integrates transcriptomic, genomic, and protein–protein interaction data into computational “virtual cell” models. These models are trained on perturbation-response profiles to accurately recapitulate cellular behavior. In this presentation, we highlight the application of our virtual-cell–based screening framework for prioritizing synergistic payload partners, complemented by automated in vitro validation and mechanistic simulations that enable detailed interrogation of resistance pathways.

As the field increasingly recognizes the limitations of traditional cytotoxic payloads, differentiation through novel mechanisms of action has become essential. Amanitin-based ADCs, with their unique inhibition of RNA polymerase II, exemplify this next wave of innovation, designed to overcome resistance mechanisms. The Phase I/IIa experience with HDP 101, an anti-BCMA ADC with amanitin as novel payload, provides a clear view of the translational path associated with developing a first in class ADC payload. During dose escalation and at doses below the MTD, HDP‑101 has demonstrated objective responses, including complete remissions, in patients refractory to currently available therapies, including prior treatments directed at the same target.