Conventional T cell engagers are constrained by on-target, off-tumour toxicity due to limited tumour-specific antigens. Plectonic’s logic-gated, multispecific T cell engagers (Logibodies) integrate dual-antigen recognition to achieve conditional T cell activation. This architecture drives potent and durable tumour cell killing in vitro and in vivo while minimising off-tumour toxicity. Plectonic advances a proprietary Logibody pipeline and welcomes collaborations to co-develop, safe and effective, next-generation T cell therapies.

T cell engagers (TCEs) have shown promising clinical efficacy, but are still associated with significant toxicities, such as cytokine release syndrome (CRS). To address this, we have developed novel affinity attenuated and CD8-biased TCEs. Case studies will be presented on the discovery and engineering of clinical lead candidates for CLDN18.2, CD20 and GPC-3, focusing the presentation on how the binders were generated and how the TCEs engage their receptors.

LGTX-101, a next-generation, ML-derived, selectivity-enhanced Nectin-4 x CD3 T-cell engager identified via the EVA™ platform, which screened >270,000 designs. Its novel 3+1 architecture drives targeted T-cell cytotoxicity with >78,000-fold selectivity for tumours over healthy cells. In humanised BT-474 xenograft models, LGTX-101 shows robust efficacy, achieving up to 98% tumour growth inhibition, including at low doses, supporting a promising therapeutic window for Nectin-4–expressing cancers. LGTX-101 is in IND enabling studies with a clinical trial anticipated to commence in H1 2027.