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IMGC936 is an investigational ADAM9-targeting antibody-drug conjugate (ADC) that is comprised of a high-affinity humanized antibody site-specifically conjugated to DM21, a next-generation linker-payload that combines a maytansinoid microtubule disrupting payload with a stable peptide linker.
ADAM9 is a cell surface protein that belongs to the ADAM (a disintegrin and metalloproteinase) family of proteases, which have been implicated in cytokine and growth factor shedding and cell migration. Dysregulation of ADAM9 has been implicated in tumor progression and metastasis, as well as pathological neovascularization. It has been shown that ADAM9 is over-expressed in multiple solid tumor types and that anti-ADAM9 antibodies are efficiently internalized and degraded by tumor cell lines, making ADAM9 an attractive target for ADC development.
In preclinical studies, IMGC936 showed cytotoxic activity against a broad panel of ADAM9-positive tumor cell lines. Consistent with the in vitro activity, IMGC936 has shown compelling anti-tumor activity in ADAM9-positive xenograft models. Importantly, IMGC936 showed favorable safety and toxicokinetic profiles in a repeat dose toxicology study in cynomolgus monkeys.
IMGC936 is being evaluated in a Phase 1 dose escalation study in solid tumors, including non-small cell lung, colorectal, pancreatic, gastric and triple negative breast cancers.
MacroGenics and ImmunoGen are co-developing IMGC936 in a 50/50 collaboration.
Relevant publications and presentations can be found at https://dev.macrogenics.com/publications/.
The safety and efficacy of investigational agents and/or investigational uses of approved products have not been established.