Promatix’s lead asset ADC for colorectal cancer has positive preclinical data

UK-based biotechnology company Promatix Biosciences has presented positive preclinical data on its lead asset, PBS293-MMAE, at the 16th World ADC London Summit, according to the company’s press release.

PBS293-MMAE is described as a first-in-class cis-bispecific antibody-drug conjugate (ADC) targeting colorectal cancer, a space where treatment options remain limited despite advances in targeted therapy and immuno-oncology.

According to Promatix, the molecule was developed using its proprietary proteomics-based discovery platform, designed to systematically analyse tumour and normal tissue surface proteins to identify differentiated antigen pairs.

Unlike conventional ADCs that target a single antigen, PBS293-MMAE uses what the company describes as cis-bispecific “AND-gate” targeting. The therapy binds strongly only when two target antigens — EGFR and EphA2 — are co-expressed on the same tumour cell. This dual engagement mechanism, referred to as hybrid avidity, is intended to enhance tumour selectivity while reducing off-target toxicity.

The approach addresses one of the core limitations of ADC development: balancing potency with safety.

“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, according to the press release.

EGFR still matters, and it’s not enough

EGFR is a clinically validated oncology target, particularly in colorectal cancer. However, EGFR-targeting antibodies such as cetuximab are effective only in a subset of patients and are associated with toxicity due to EGFR expression in healthy tissues.

This therapeutic window problem has limited broader use.

By pairing EGFR with EphA2 — another antigen expressed in colorectal tumours — Promatix aims to restrict binding to cancer cells that co-express both targets. According to the company, this may expand the therapeutic window and improve efficacy compared with mono-specific ADCs or antibody therapies.

Positioned within the expanding ADC landscape

The timing is notable. The global ADC field has seen significant momentum over the past 24 months, with large pharmaceutical companies aggressively investing in next-generation payloads and bispecific formats.

Major deals — including multibillion-dollar licensing agreements in oncology ADCs — have intensified competition in the solid tumour space. However, most next-generation innovation has focused on linker chemistry and payload optimization rather than fundamentally new targeting logic.

Promatix’s cis-bispecific approach attempts to shift innovation from chemistry toward biological selectivity.

The broader colorectal cancer context

Colorectal cancer remains one of the leading causes of cancer-related death globally. While immunotherapies have reshaped treatment in MSI-high tumours, the majority of patients with microsatellite-stable disease still rely on chemotherapy backbones with targeted add-ons such as EGFR inhibitors.

If the company’s preclinical findings translate clinically, dual-antigen targeting strategies could represent a meaningful advancement in solid tumour precision therapy.

Development stage

PBS293-MMAE remains in preclinical development. According to the company, the data presented at the summit provide early evidence supporting further advancement toward IND-enabling studies.

Clinical validation will be critical in determining whether the hybrid avidity mechanism translates into improved therapeutic index in patients.

Investor takeaway

• Promatix is positioning itself within the high-growth ADC segment.

• The company is targeting a known limitation in EGFR-based therapies — toxicity.

• Dual-antigen “AND-gate” logic represents mechanistic differentiation.

• Clinical proof-of-concept will determine commercial viability.

If successful, cis-bispecific ADCs could represent a next-wave evolution in solid tumour targeting rather than incremental chemistry upgrades.