Main Conference Day 2Tuesday, 15 December 2026 - PT (Pacific Time, GMT-08:00)

How T cells integrate signals from multiple receptors is poorly understood. We will show that sub-micrometre microvillar “close contacts” formed by T cells interacting with their targets are sites of early signal integration, using the T-cell receptor and PD-1 as exemplars. A PD-1 blocking antibody induced inhibitory signaling when Fc receptor engagement enhanced PD-1 trapping at these contacts. Engineering the antibody to avoid trapping eliminated this effect, improving blockade efficacy.

CD19 is the primary amplifying co-receptor on B cells and is an important target for antibody-based therapeutics for the treatment of B cell malignancies and autoimmune disorders. Here, we report the engineering and characterization of two novel anti-CD19 clones with novel epitopes and functional properties to modulate B cell signaling.

I will present SureTAC™, a novel platform that selectively degrades disease-driving membrane proteins via the endo-lysosomal pathway. Unlike conventional blockers, SureTACs offer deeper inhibition and access to previously undruggable targets. Using PD-L1 proof-of-concept data in vitro and in vivo, I will highlight the therapeutic potential across oncology and inflammation to advance first-in-class therapies for improved patient outcomes.

Current ADCs face limitations from poor target internalization and healthy tissue expression. Tacalyx addresses this by developing antibodies against tumor-associated carbohydrate antigens (TACAs). Because TACAs are densely displayed across most cell-surface proteins, their engagement triggers rapid, robust crosslinking and internalization via multiple endocytic pathways, driving highly efficient cell killing and potentially mitigating payload resistance. Preclinical data demonstrate this platform’s strong therapeutic efficacy. The lead candidate is undergoing CMC development ahead of Phase I trials next year.

This presentation will highlight E-688/HLX316, a sialidase-armed anti-B7-H3 nanobody that leverages targeting-induced proximity to drive deep and sustained tumor desialylation. E-688 achieved >1,000-fold enhanced desialylation potency and robust single-agent antitumor activity across multiple mouse models, with a favorable safety profile in NHPs, demonstrating the potential of targeted desialylation as a new immuno-oncology approach.