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mAb104 + DX8951

Development stage
Preclinical
Lead developer
Daiichi Sankyo
Modality
Small Molecules, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
Intravenous
01

Overview

**mAb104 + DX8951** is an antibody-drug conjugate (ADC) that combines the monoclonal antibody mAb104 (or a Fab fragment thereof) with the cytotoxic small molecule exatecan mesylate (DX8951), linked via a cleavable peptide linker (such as GGFG)[2][1]. The mAb104 component provides targeting (in published studies, this is commonly against human IgG Fc or certain tumor antigens), while the DX8951 payload is a highly potent topoisomerase I inhibitor. The linker is stable in plasma but cleaved inside lysosomes after cellular uptake, releasing DX8951 to induce DNA damage and cell death[2][1]. Preclinical data shows potent activity in trastuzumab-resistant HER2-positive breast cancer and low HER2-expressing tumors[1]. Exatecan is a derivative of camptothecin with greater solubility and potency than other topoisomerase I inhibitors like topotecan or SN-38[4][6].

Other names
Fab-αHFc-CL-DX8951
02

Targets

TOP1 (DNA Topoisomerase I)ERBB2 (Erb-b2 receptor tyrosine kinase 2)

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