Nucleome Therapeutics (Oxford, UK) has announced the nomination of its first preclinical development candidate. NTP464 is part of a first-in-class monoclonal antibody agonist program designed to promote the resolution of inflammation, with potential applicability across a broad range of autoimmune and inflammatory conditions.
The announcement follows a period of scientific and technological progress for the company, which applies 3D human genetics to uncover the molecular mechanisms that drive disease. Central to this approach is the company’s proprietary Micro Capture-C (MCC) platform, a lab-based technology that maps physical interactions within the genome at unprecedented resolution. When combined with machine learning and advanced computational analysis, MCC enables Nucleome to decipher how non-coding genetic variation influences gene regulation in human disease.
According to Nucleome’s chief executive officer, Dr. Mark Bodmer, these advances have transformed the way genetic data can be used for drug discovery and patient stratification. He explained, “We have created the most comprehensive physical map of molecular mechanisms in inflammatory disease and continue to enhance this with emerging data. This means we can now uncover causal drivers of disease in humans, in areas of the greatest unmet patient need.”
NTP464 targets a previously unrecognized inflammation checkpoint identified using Nucleome’s proprietary genetic methods. By analyzing how genetic variants associated with autoimmune disease alter three-dimensional interactions between regulatory elements and protein-coding genes, the company uncovered a key multi-cellular regulator of inflammation resolution. In healthy individuals, this mechanism helps restore immune balance, but it becomes dysregulated in diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease.
The nominated monoclonal antibody agonist has shown strong potency, selectivity, and developability in preclinical testing. In multiple in vitro assays, NTP464 demonstrated the ability to inhibit activation of B cells, T cells, and macrophages, while also promoting the suppressive activity of regulatory T cells. Together, these effects support a novel therapeutic principle focused on actively resolving inflammation rather than simply suppressing immune responses. The program will now progress towards investigational new drug (IND)-enabling studies.
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