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TOP1i ADC
- Development stage
- Preclinical
- Lead developer
- Manhattan Biosolutions
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics
- Administration
- Intravenous
01
Overview
Manhattan BioSolutions is developing a proprietary antibody-drug conjugate (ADC) platform that utilizes legumain-cleavable linkers paired with exatecan-derived topoisomerase I (TOP1) inhibitor payloads. This technology leverages the overexpression of legumain, a cysteine protease, in the tumor microenvironment to enable tumor-selective release of the cytotoxic payload. By remaining stable in systemic circulation and undergoing rapid activation only upon exposure to lysosomal legumain following internalization, the platform aims to improve the therapeutic index of TOP1 inhibitors. In collaboration with the National Cancer Institute (NCI) through the PIVOT program and Binghamton University, Manhattan BioSolutions is applying this technology to develop treatments for pediatric cancers. Preclinical studies have demonstrated complete tumor regression and strong durability in various solid tumor xenograft models.
- Other names
- Exatecan-based TOP1i ADCLegumain-cleavable TOP1i ADCTOP1 inhibitor ADCTOP-1 inhibitor ADCTOP 1 inhibitor ADC
02
Targets
TOP1 (DNA Topoisomerase I)
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