MGD007 (gpA33 x CD3)

Background

MGD007 is a humanized, Dual-Affinity Re-Targeting, or DART^®, molecule that recognizes both the glycoprotein A33 antigen, or gpA33, and CD3 and was our first clinical DART molecule designed to target solid tumors. MGD007 is an Fc domain-bearing DART molecule engineered to have prolonged circulating serum half-life. The gpA33 antigen is found on over 95% of primary and metastatic human colorectal cancers, including cancer stem cells, which are thought to be responsible for tumor recurrence and metastasis. The primary mechanism of action of MGD007 is its ability to redirect T cells, via their CD3 component, to kill gpA33-expressing cells.

Clinical Development

In 2014, we initiated a Phase 1 dose-escalation study with MGD007. This study is designed to characterize the safety and tolerability of MGD007 and establish the maximum tolerated dose (MTD) of MGD007 administered on either weekly or every three week schedules of administration among patients with metastatic colorectal carcinoma. Pharmacokinetics, pharmacodynamics, and the anti-tumor activity of MGD007 will also be assessed.

We continue to enroll patients in the Phase 1 study.

Pre-Clinical Development

In April 2014, we presented data from a pre-clinical study of MGD007 at the American Association for Cancer Research (AACR) Annual Meeting. We showed that MGD007 has robust activity against human colorectal cancer in murine xenograft models and a favorable pharmacokinetic profile in non-human primates. Key findings included:

MGD007 mediates potent lysis of gpA33-positive colorectal cancer cell lines in vitro,
Tumor growth inhibition in vivo was observed at doses as low as 4 µg/kg and
In non-human primates, four weekly doses of up to 200 µg/kg were well-tolerated with prolonged pharmacokinetics, consistent with that of an Fc-containing molecule (Learn More: 2014 AACR Presentation)

Our Rights

Under the terms of a collaboration, MacroGenics retains full development and commercialization rights to MGD007 in the U.S., Canada, Mexico, Japan, South Korea and India. MacroGenics’ partner, Servier, has an option to obtain rights to MGD007 in all other countries. (Learn More: Servier DART Collaboration)