Can a Two-Key Lock Crack Colorectal Cancer?

Promatix's AND-gate molecule demonstrated 50-fold potency gains over standard therapy in early colorectal cancer models

20 Mar 2026

A UK biotech has reported striking preclinical results from an antibody-drug conjugate that fires only when a cancer cell carries two specific proteins at once, a design intended to improve both efficacy and tolerability in colorectal cancer.

Promatix Biosciences presented data in February 2026 on PBS293-MMAE, a cis-bispecific ADC that targets EGFR and EphA2 simultaneously. The molecule internalises its toxic payload only when both proteins appear together on the same cell surface. Because healthy tissue rarely carries both markers at high levels, the mechanism is designed to kill tumour cells while leaving normal cells largely intact.

The early numbers are notable. In KRAS-mutant colorectal cancer models, the compound was more than 50 times more potent than a standard EGFR-targeting comparator, while causing substantially less toxicity in normal skin cells. The findings were presented at the 16th World ADC London Summit in London.

The molecule draws on TxPro, Promatix's proprietary tumour surface proteomics database, which maps membrane proteins across tumour and healthy tissue to identify antigen pairings that are highly co-expressed in cancer but not in normal cells. The platform has so far identified over 2,000 potential dual-target combinations across multiple cancer types. Promatix plans to advance a first clinical development candidate this year.

The clinical rationale is straightforward. Standard EGFR-targeting antibodies benefit only around 15% of colorectal cancer patients, constrained by toxicity and genetic exclusions tied to RAS and BRAF mutations. PBS293-MMAE is designed to work regardless of mutation status and to include right-sided tumours, where treatment options are currently limited.

ADCs have attracted significant investment across oncology in recent years, but single-antigen approaches remain vulnerable to off-tumour toxicity. Dual-antigen gating is an attempt to widen the therapeutic window, though translating preclinical selectivity into clinical safety and efficacy remains the field's central challenge.

Whether this selectivity holds in human trials will determine whether the AND-gate approach can meaningfully expand the addressable patient population for ADC-based therapies in solid tumour oncology.