NN-223

NN-223 is a humanized single-domain antibody (nanobody) that targets and neutralizes tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine implicated in the pathogenesis of neuroinflammation and synaptic dysfunction. Developed by NanoNewron LLC, NN-223 (formerly designated TNFI-α) was derived from camelid antibodies and optimized through machine learning-guided humanization to reduce immunogenicity while maintaining high potency, demonstrating an IC50 of 48.84 picomolar. Although NN-223 does not cross the blood-brain barrier (BBB) independently, it serves as a foundational component of NanoNewron's therapeutic platform for Alzheimer's disease and other neurodegenerative disorders. In this platform, TNF-α inhibitory nanobodies are engineered into multi-specific molecules linked to the company's NewroBus technology—nanobodies that target the transferrin receptor 1 (TfR1) to facilitate receptor-mediated transcytosis across the BBB. As of early 2025, NN-223 is in preclinical development.

Other names

TNF-α inhibitory nanobodyTNFI-alphaNanoNewron TNF-alpha nanobody