On April 21, 2026 Promatix Biosciences Ltd (Promatix), an emerging UK-based biotechnology company developing innovative new classes of cancer therapies using cis-bispecific antibodies, reported new data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026. The data demonstrate how the Company’s proprietary integrated proteomics-driven discovery platform addresses a fundamental limitation in antibody-drug conjugate (ADC) development – the scarcity of truly tumour-selective targets – by systematically identifying complementary antigen pairs and significantly expanding the target landscape for next-generation bispecific ADCs.
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The data are being presented in a poster titled, "Overcoming the Limited Monospecific Target Landscape in Cancer via Discovery of Tumor-Selective AND- and OR-Gate Bispecifics". The poster outlines Promatix’s integrated discovery strategy, combining large-scale proteomic profiling (TxPro) with computational modelling (CipherPro) to identify complementary antigen pairs suitable for tumour-selective bispecific targeting. By exploiting hybrid avidity utilizing an AND-Gate, where both antigens are required for binding, Promatix aims to improve tumour selectivity, enhance efficacy and reduce toxicity.
While advances in payloads, linkers, and conjugation technologies have improved ADC performance, target selection remains a key determinant of therapeutic index and continues to limit innovation in the field. This challenge has driven increasing interest in bispecific ADCs and logic-gated targeting strategies designed to improve selectivity and enable safer, more effective therapies.
"Across the ADC field, target selection is increasingly recognized as the critical bottleneck for achieving meaningful improvements in efficacy and safety," said Dr. Michael Hunter, CEO and Co-Founder of Promatix. "Our integrated platform is designed to overcome this limitation through a systematic, data-driven approach to identifying complementary antigen pairs. It greatly expands the universe of viable tumour-selective targets beyond what conventional monospecific approaches can achieve and provides a scalable foundation for advancing next-generation ADC performance. In ADC development, we believe success will be determined by better targets, which will ultimately lead to better drugs."
Limited Availability of Tumour-Selective Monospecific Targets Highlights Need for Next-Generation Strategies
Using Promatix’s oncology-focused proteomics database, TxPro, comprehensive profiling of surface protein expression across tumours and normal tissues revealed that truly tumour-selective monospecific targets are rare across tumour types, highlighting fundamental biological constraints of conventional single-target ADC strategies. Of the 2,768 surface proteins evaluated, only 575 showed high cancer expression (above 10,000 copies per cell), and, ultimately, just a small subset of 24 proteins demonstrated strong differential expression (DE) on tumour versus normal tissue.
Notably, targets currently used in approved ADCs for solid tumours do not display strong DE profiles, underscoring the limited availability of highly tumour-specific antigens and the inherent safety challenges associated with single-target approaches. In contrast, several of the high-selectivity targets identified by TxPro correspond to antigens with emerging clinical relevance, including CLDN6, for which encouraging early clinical activity has been reported in ovarian cancer.
Current Bispecific Landscape Shows Limited Target Novelty
The current bispecific landscape continues to rely on a limited number of established antigens, with EGFR and MET dominating many existing programs. Overall, target novelty remains low, with only 15.3% of constructs including at least one unique target and just 2.5% incorporating two novel targets. Among explored programs, EGFR × MET demonstrated the most robust complementary expression, reinforcing its role as a reference benchmark.
Promatix Logic-Gated Bispecific Modelling Substantially Expands Target Opportunities
Using the CipherPro logic-gated modelling framework to predict complementary expression patterns, Promatix evaluated 165,025 possible bispecific combinations derived from the 575 tumour-expressed surface proteins identified in TxPro. Logic-gated modelling uses simple Boolean rules like AND or OR to combine multiple inputs and control the final output.
Application of the integrated TxPro + CipherPro platform revealed a marked increase in predicted tumour-selective opportunities across multiple selection criteria. Using a DE threshold greater than 10-fold with AND-gated modelling, 2,164 bispecific combinations were identified compared to only 24 monospecific targets. Even under more stringent expression and normal-tissue filters, the bispecific number remained substantial. Both AND- and OR-gated binding modes were shown to dramatically improve the number of selective targeting opportunities: AND-gated designs delivered the strongest predicted gains in tumour selectivity, while OR-gated strategies supported broader tumour coverage, particularly in heterogeneous disease settings.
Experimental Validation Supports Predictive Power of the Promatix Platform
The TxPro + CipherPro platform identified EGFR × EphA2 as a compelling AND-gated bispecific candidate based on expression patterns across tumour and normal tissues. Minimal overlap of the two targets was observed in normal tissues, while strong tumour co-expression was confirmed experimentally using immunofluorescence staining on a patient colorectal tumour biopsy as well as flow cytometry in colon cancer patient-derived xenograft lines. These results demonstrate the feasibility of selective dual-target engagement and show how computational prediction can be translated into biologically validated bispecific target selection. The EGFR × EphA2 programme, PBS293, is in development for metastatic colorectal cancer and is designed to address a broader patient population, independent of RAS/BRAF mutation status and including right-sided colorectal tumours, for which current treatments, including monoclonal antibodies targeting EGFR, such as cetuximab, are ineffective.
"As the ADC field continues to evolve, expanding the universe of tumour-selective targets will be essential to sustaining innovation," said Dr. Roy Pettipher, Chief Scientific Officer of Promatix. "Our data demonstrate that logic-gated bispecific discovery provides a viable and scalable path toward safer and more effective therapies across many cancer indications. The platform doesn’t just predict new bispecific targets; it identifies combinations that work biologically and can be validated experimentally. Importantly, this approach has already been used to identify a promising ADC candidate, our lead programme, PBS293, targeting EGFR and EphA2 for the treatment of colorectal cancer, demonstrating how predictive discovery can translate into actionable therapeutic programmes."
(Press release, Promatix Biosciences, APR 21, 2026, View Source [SID1234664671])