Headquarters: Tokyo, Japan
Founded: 2022 (University of Tokyo spin-out)
Focus: Targeted protein degradation for neurodegenerative disease proteins
Website: https://www.toyo-biotech.com
Toyo Biotechnology is a University of Tokyo spin-out company developing targeted protein degradation (TPD) technologies for the treatment of Alzheimer's disease, Parkinson's disease, and related neurodegenerative conditions. The company leverages a novel TPD platform that combines small molecule degraders with brain-penetrant delivery systems, enabling the elimination of disease-driving proteins that are currently considered "undruggable" by conventional approaches[1].
Targeted protein degradation represents a paradigm shift in drug discovery — instead of simply inhibiting a protein's function, TPD compounds recruit the cell's own protein disposal machinery (the ubiquitin-proteasome system) to selectively destroy the target protein. This approach is particularly valuable for neurodegenerative diseases because many of the key pathogenic proteins — including tau, alpha-synuclein, huntingtin, and TDP-43 — have been difficult to drug with traditional small molecule inhibitors due to their complex structures and lack of well-defined active sites[2].
TPD technologies work by engaging two key mechanisms:
PROTACs are bifunctional molecules with two key domains: a ligand that binds to the target protein of interest (POI) and a ligand that recruits an E3 ubiquitin ligase. When a PROTAC simultaneously binds to both the target and the ligase, it brings them into proximity, leading to ubiquitination of the target protein and its subsequent degradation by the proteasome[3].
Key advantages of PROTACs:
Molecular glue degraders are monovalent molecules that promote protein-protein interactions between the target protein and a substrate receptor (typically an E3 ligase complex)[4]. Unlike PROTACs, molecular glues do not require high-affinity binding to the target — they work by stabilizing interactions that lead to target ubiquitination and degradation. Several molecular glue degraders have received regulatory approval for cancer, validating the therapeutic approach.
Despite the promise of TPD for neurodegeneration, significant challenges have limited progress:
Toyo Biotechnology has developed proprietary chemistry to address the brain penetration challenge, creating a library of CNS-penetrant PROTAC and molecular glue scaffolds.
Target: Tau protein (all isoforms including 3R and 4R tau)
Stage: Lead optimization
Indication: Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy
TB-301 recruits the CRBN E3 ligase to target tau for proteasomal degradation. The compound has demonstrated:
Target: Alpha-synuclein
Stage: Preclinical (hit-to-lead)
Indication: Parkinson's disease, Dementia with Lewy bodies
TB-302 targets alpha-synuclein using a brain-penetrant molecular glue approach. The compound has shown reduction of alpha-synuclein aggregates in cellular models of Parkinson's disease[5].
Toyo Biotechnology's platform consists of:
Toyo Biotechnology collaborates with:
Toyo Biotechnology's work intersects with key mechanisms and topics in NeuroWiki:
Toyo Biotechnology. Company Profile - Targeted Protein Degradation for Neurodegeneration. 2024. ↩︎ ↩︎
Lai AC, et al. Targeted protein degradation: modular degraders for CNS diseases. Nature Chemical Biology. 2023. ↩︎
Tong Q, et al. Huntingtin degradation using PROTAC technology in Huntington's disease models. Journal of Clinical Investigation. 2022. ↩︎
Lu M, et al. Molecular glue degraders: beyond PROTACs for CNS targets. Trends in Pharmacological Sciences. 2022. ↩︎
Yang B, et al. Alpha-synuclein targeted degradation in Parkinson's disease models. NPJ Parkinson's Disease. 2023. ↩︎