Target and Technology

Vadastuximab talirine (SGN-CD33A; 33A) targets CD33, a protein expressed on most acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) blast cells. Normal tissue expression of CD33 is largely restricted to hematopoietic cells. Because treatments have not meaningfully changed in more than four decades, AML is a significant unmet need.

Vadastuximab talirine uses our proprietary antibody-drug conjugate (ADC) technology, which is composed of a novel CD33-directed antibody conjugated to two molecules of a highly potent DNA crosslinking agent called a PBD (pyrrolobenzodiazepine) dimer via a site-specific conjugation technology with engineered cysteines (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the site-specific conjugation technology allows uniform drug-loading of the cell-killing PBD agent to the CD33-directed antibody. The ADC is designed to be stable in the bloodstream and to release its potent DNA binding agent when internalized by CD33-expressing cells.

Development Status

Seattle Genetics has discontinued the phase 3 CASCADE clinical trial and suspended patient enrollment and treatment in all of its other vadastuximab talirine clinical trials.

Proposed Mechanism of Action

33A_mono_release.jpg