Promatix Biosciences has reported preclinical data showing its cis-bispecific ADC PBS293-MMAE was 50-fold more potent than cetuximab-MMAE in colorectal cancer cells, with improved tumour selectivity and reduced skin toxicity.

The UK-based biotech presented the data at the 16th World ADC London Summit, highlighting tumour growth inhibition and hybrid avidity-driven selectivity in colorectal cancer models.

In HCT116 colorectal cancer cells, PBS293-MMAE demonstrated low-nanomolar potency more than 50 times greater than cetuximab-MMAE. In xenograft models using the same cell line, the candidate achieved significantly stronger, dose-dependent tumour growth inhibition and sustained tumour suppression.

The company also reported substantially lower cytotoxicity in normal human keratinocytes compared with cetuximab-MMAE, supporting the tumour-selective design of the molecule.

PBS293-MMAE targets EGFR and EphA2, which are co-expressed in colorectal cancer cells. While EGFR is a clinically validated target, therapies such as cetuximab are limited by toxicity due to EGFR expression in healthy tissue. Promatix’s approach uses cis-bispecific “AND-gate” targeting through hybrid avidity, designed to trigger strong binding only when both antigens are present on the same tumour cell.

Proteomic and FACS analysis of patient-derived colorectal xenograft tissue confirmed high membrane co-localisation of EGFR and EphA2, supporting the biological rationale for dual-target engagement. Hybrid avidity-dependent binding was confirmed across cell binding, internalisation and cytotoxicity studies.

“The ADC field has made significant progress in payload, linker and conjugation chemistry, yet true tumour-selective targeting remains a major challenge,” said Dr Michael Hunter, ceo and co-founder of Promatix. “Many of the most validated oncology targets, such as EGFR, are also expressed in healthy tissue, which can constrain the therapeutic window and limit efficacy. By utilising our unique capability to identify differentiated antigen pairings and engineering ADCs that depend on dual engagement, we aim to improve selectivity, enhancing both efficacy and safety across novel and validated targets.”

He added that the initial focus is in solid tumours where current standards of care remain inadequate for many patients.

Promatix said the data support the potential of its proteomics-based platform to optimise cis-bispecific ADC discovery and design, with PBS293-MMAE positioned as its lead colorectal cancer programme. Detailed results were presented in a poster at the 16th World ADC London Summit.