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DSTA4637S
- Development stage
- Phase 1
- Lead developer
- Genentech
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous
01
Overview
DSTA4637S is a novel antibody-antibiotic conjugate (AAC) designed to target and eliminate intracellular Staphylococcus aureus, including methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains, which are not adequately addressed by current standard-of-care antibiotics. The drug consists of a humanized monoclonal THIOMAB IgG1 antibody that specifically recognizes S. aureus, linked via a protease-cleavable linker to a rifamycin-class antibiotic payload known as dmDNA31 (4-dimethylaminopiperidino-hydroxybenzoxazino rifamycin). Upon binding to S. aureus, the complex is phagocytosed by immune cells; inside the cell, cathepsins cleave the linker and release dmDNA31 to kill intracellular bacteria[2][4][6]. DSTA4637S has demonstrated safety and tolerability in phase 1 studies in healthy volunteers and patients with S. aureus bacteremia when administered intravenously alongside standard-of-care antibiotics[2][5][9].
- Other names
- Anti-S. aureus TAC
02
Targets
RpoC (Bacterial DNA-directed RNA polymerase beta' subunit)SpA (Staphylococcal protein A)RNAP (Bacterial dna-dependent RNA polymerase)
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