Home MGD013 (PD-1 x LAG-3)


Monoclonal antibodies that target the immune checkpoints Lymphocyte-activation gene 3 (LAG-3) and PD-1 have shown enhanced clinical antitumor activity when given in combination. Recognizing the therapeutic potential of dual checkpoint blockade, we have engineered MGD013, a IgG4κ bispecific DART® molecule, to bind PD-1 and LAG-3 concomitantly or independently and disrupt these non-redundant inhibitory pathways to further restore exhausted T-cell function.

We anticipate that MGD013 could be used for the treatment of a wide range of cancers, including both solid tumors and hematological malignancies. MGD013 is the first in a series of product candidates that recognize multiple immune regulator targets. MGD013 has demonstrated a favorable preclinical safety and toxicological profile and is currently being evaluated in a Phase 1 dose escalation study.

Pre-Clinical Development

At the 2017 SITC Annual Meeting, MacroGenics highlighted pre-clinical data showing MGD013 bound with high affinity to human and cynomolgus monkey PD-1- and LAG-3-expressing cells and blocked PD-1/PD-L1, PD-1/PD-L2 and LAG-3/HLA (MHC-II) interactions, with resultant signaling blockade. Functional characterization revealed enhanced cytokine secretion in response to antigen stimulation that was greater than that of the combination of individual equimolar amounts of PD-1 and LAG-3 mAbs. MGD013 was well tolerated in a repeated-dose (Q1Wx4) cynomolgus monkey toxicology study. (Learn More: 2017 SITC Poster).

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