Indication selection, patient stratification, and IND preparation for STX-002: the first-in-class LRG1 inhibitor for treatment of chronic kidney disease and immunotherapy-resistant tumours.

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LRG1 is a secreted glycoprotein that plays a key role in a range of highly prevalent chronic diseases by promoting vascular dysfunction, fibrosis and uncontrolled cell proliferation. Mounting evidence shows its involvement in diseases such as chronic kidney disease (CKD) which affects over 800 million people globally with significant morbidity and mortality, and several solid cancers of enormous unmet need, in which uncontrolled cell proliferation and vascular and immune dysfunction contribute to substantially worse outcomes.LRG1 LTD, trading as **Senya Therapeutics**, is developing proprietary biologics targeting LRG1 to provide therapeutic interventions in these key disease populations. To date, the company has developed a lead molecule, STX-002, that inhibits the activity of LRG1 and has successfully demonstrated its efficacy and safety in a range of translational preclinical models including non-human primates. These results have shown that the compound is safe and well-tolerated, and that our approach can be used to treat disease through vascular normalisation, deceleration of fibrosis, and an improved homeostatic microenvironment.This project focuses on STX-002, a humanised hinge-stabilised IgG4 function-blocking antibody. The project aims to confirm the nephrology indications for STX-002 and generate patient selection criteria for the chosen indications. For oncology, the project aims to gain data to support initiation of a basket trial for patients with high risk of immune evasion and high levels of LRG1 and for the use of STX-002 in neoadjuvant settings. The project also plans to deliver GMP development and IND plans. The work will be conducted at clinical and biomedical research centres in London (Imperial), Edinburgh (University) and Amsterdam (Netherlands Cancer Institute (NKI)) with thought-leader clinician collaborators who will access archival biopsy material and analyse the samples and related patient data. The CMC development and pre-IND plan will be co-developed with a UK-based vendor with expertise in CMC and IND-enabling work. Finally, the project also includes health economic assessment of STX-002-based treatment, result of which will help guide clinical development strategy and support future investment decisions.The results of these work packages are crucial for refining the therapeutic hypothesis of STX-002 and developing a clear path to the clinical stage. The output from this program therefore will significantly enhance the readiness for Series A raise. Senya envisages that treatment of CKD and immunotherapy-resistant solid tumours with STX-002 will address substantial unmet needs in these disease areas.