Main Conference Day 3Thursday, 12 June 2025 - BST (British Summer Time, GMT+1)

SAIL66, a next-generation tri-specific T-cell engager targeting CLDN6, CD3, and CD137, was developed using proprietary Dual-Ig® technology. Dual-Ig® enables unique ability to CD3 and CD137, but not simultaneously. SAIL66 demonstrates remarkable selectivity, avoiding cross-reactivity with related CLDN family. In vitro and in vivo studies reveal SAIL66's superior T cell activation and enhanced anti-tumor efficacy compared to conventional TCEs.

T cell-engaging (TCE) multispecific antibodies demonstrate great clinical efficacy, though their molecular complexity is a challenge for drug manufacturability, developability, and obtaining desirable PK/PD properties. Here, we showcase the discovery and engineering of novel anti-CD3 heavy chain-only antibodies (HCAbs), which demonstrate T cell cytotoxicity comparable to clinically validated TCEs when paired with IgG or TCR modalities. This work introduces a flexible new tool for enabling this important class of biologics.

Bispecifics and multispecifics that use only one light chain are a preferred format in view of manufacturability. We have established straightforward procedures to generate common light chain multispecifics from existing monospecific therapeutic antibodies, and we have also implemented an approach to obtain 2-in-1 symmetric antibodies where the light and heavy chain bind to different targets. We demonstrate that for bispecific multivalent T cell engagers the placement geometry of the binding modules is pivotal in controlling potency and mitigating cytokine release.