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. Vadastuximab talirine is being broadly evaluated in myeloid malignancies, including MDS and AML. 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

  • Vadastuximab talirine is being evaluated in the global pivotal phase 3 CASCADE clinical trial in older patients who are newly diagnosed with AML.
  • We plan to initiate a phase 2 trial in younger AML in 2017, and a phase 1/2 trial is ongoing in MDS.
  • Vadastuximab talirine was granted Orphan Drug Designation by both the U.S. Food and Drug Administration (FDA) and the European Commission for the treatment of AML. FDA orphan drug designation is intended to encourage companies to develop therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States.

Proposed Mechanism of Action