UK-based Promatix Biosciences has received a non-dilutive Innovate UK Biomedical Catalyst grant to advance PBS293-exatecan, its lead EGFR × EphA2 cis-bispecific antibody-drug conjugate, toward development candidate nomination. The award, under the Biomedical Catalyst 2025 Industry-led R&D small projects competition, will fund manufacturing scale-up, preclinical proof-of-concept studies in cell-line-derived and patient-derived xenograft models, and IND-enabling safety studies. No specific monetary value was disclosed.
PBS293-exatecan pairs an exatecan payload with a full IgG1 cis-bispecific antibody targeting EGFR and EphA2, two antigens co-expressed on colorectal tumour cells. The design relies on an "AND-gate" mechanism in which productive binding and payload delivery require simultaneous engagement of both antigens on the same cell — intended to spare normal tissue that expresses only one target. In preclinical studies, the conjugate demonstrated potent killing of colorectal cancer cell lines while substantially sparing normal keratinocytes and endothelial cells. Existing EGFR-targeted therapies, including Eli Lilly's cetuximab (Erbitux), are primarily used in RAS/BRAF wild-type colorectal cancer and are associated with class-related skin toxicities. Promatix reports its approach is designed to function independently of RAS/BRAF mutation status, potentially broadening eligible patient populations.
The grant also supports expansion into oesophageal cancer and non-small cell lung cancer, applying the same cis-bispecific logic to additional solid tumour indications. Work will be conducted with UK contract research organisations Abzena, Crown Bioscience, and Labcorp UK.
The ADC field has grown crowded at the EGFR axis, with agents including patritumab deruxtecan and amivantamab-based combinations advancing in lung cancer. Promatix's differentiation rests on the dual-antigen selectivity mechanism rather than a novel payload class, using an exatecan payload — a topoisomerase I inhibitor with an established clinical safety profile seen in other approved ADCs.