Much of the oncogenic signalling that matters takes place at protein-protein interfaces inside the cell. Antibodies cannot reach those targets. Small molecules tend to struggle with interfaces that are large, flat or dynamic. Our mIB platform uses mRNA to put a designed blocking peptide exactly where those interactions happen.
Drug discovery has been good at the outside of the cell and less good at the inside. Receptors and secreted proteins can be reached with antibodies. Intracellular protein-protein interactions have been harder, and for good reason: the interface is often large, the contact surfaces are flat, and the complex may assemble and disassemble continuously. Beta-catenin, a central node in WNT signalling, is the best-known example of a target that has resisted conventional approaches.
mIB stands for mRNA Interactome Blockers. A blocking peptide is encoded as mRNA and delivered in a lipid nanoparticle:
mRNA-LNP → cytosolic mRNA → translation → blocking peptide → binds the interface → complex does not form
Encoding the blocker rather than manufacturing it as a peptide changes what is possible. Sequence, length, binding architecture and intracellular localisation can all be engineered. Expression is transient, with no genomic integration. Several independently optimised mRNAs can be co-formulated in a single lipid nanoparticle, so more than one interaction can be blocked at once, with the ratio tuned. For tumours that route around a single blockade, that is a different proposition from combining separately developed drugs.
Our lead programme addresses hepatocellular carcinoma with active WNT signalling, a substantial subgroup with limited treatment options. The blocker targets the beta-catenin/TCF4/BCL9L complex and is delivered intravenously in a liver-directed lipid nanoparticle. The programme is designed to reach in-vivo proof of concept and development candidate nomination.
Head and neck squamous cell carcinoma depends heavily on DNA repair, which is part of why it responds poorly to radiotherapy and cisplatin. Our second programme blocks FANCD2, a central node in the DNA repair pathway, using mRNA delivered directly into the tumour as a sensitiser alongside standard radiotherapy and cisplatin.
We are explicit about the stage we are at. Our evidence is cell-based. In a p53/MDM2 benchmark, changing the blocker architecture and adding a nuclear localisation signal produced measurable changes in p53 expression compared with controls. For WNT, we screened 23 candidate blocker designs against the beta-catenin/TCF4/BCL9L complex, with VEGFA and c-Myc measured by qPCR. We have also designed a three-mRNA lipid nanoparticle cocktail for intratumoural administration. There are no in-vivo data yet; in-vivo proof of concept is the next milestone.
Our mIB work is protected by patent family WO2025104494, with a priority date of 13 November 2023 and national phase entries in the United States, Europe, India and the UAE. Examination is pending.
ScirosBio is based in Abu Dhabi. Madhu Subramani is Chief Executive Officer. Nigel Horscroft is Chief Scientific Officer, with 25 years in mRNA therapeutics, virology and antiviral drug discovery across CureVac, Pfizer and Ethris. The mIB concept was invented with Professor Friedrich Metzger and Dr Justin S Antony, who continue to advise the company.
For scientific and partnering enquiries: info@scirosbio.com