MGC028 (ADAM9 ADC)

Background

MGC028 is an investigational, preclinical ADC incorporating an ADAM9-targeting antibody and a novel topoisomerase I inhibitor-based linker-payload, SYNtecan E™. This cleavable linker payload is based on exatecan, a clinically-validated and potent camptothecin that readily combines with Synaffix’s HydraSpace™ technology.

We believe Synaffix’s approach potentially provides advantages vis-à-vis other topoisomerase I inhibitor-based ADCs. In fact, Exatecan appears to be more potent and less susceptible to multi-drug resistance (MDR) mechanisms than other TOP1 inhibitors, such as SN38 and deruxtecan. Additionally, site-specific conjugation of SYNtecan to the normally glycosylated amino acid in the Fc domain abolishes FcGamma receptor and mannose receptor binding, which contribute to non-targeted uptake of ADCs in alveolar macrophages and reported to be associated with lung toxicity, and therefore may provide a safety benefit for patients.

ADAM9, or “a disintegrin and metalloprotease domain 9”, is a member of the ADAM family of multifunctional type 1 transmembrane proteins that play a role in tumorigenesis and cancer progression and is overexpressed in multiple cancers, making it an attractive target for cancer treatment.

MGC028 is the second ADAM9-targeted ADC that we have pursued. The first was IMGC936, a molecule with a maytansinoid payload that was advanced under a co-development arrangement with Immunogen, Inc. (now part of AbbVie). Under the 50/50 collaboration, Immunogen led clinical development of IMGC936. Neither MacroGenics nor AbbVie intends to further pursue development of IMGC936 as the molecule did not achieve our pre-established clinical safety and efficacy benchmarks.

Note that ocular toxicities that are typically seen with maytansinoid payloads – and which were observed in our IMGC936 cynomolgus toxicology study – were not observed in the MGC028 pilot toxicology study.

Pre-Clinical Development

Please refer to our most recent corporate deck on our Events & Presentations page for the latest pre-clinical information available on MGC028.

Our Rights

MacroGenics retains global rights to MGC028.

Presentations & Publications

Relevant Publications and Presentations can be found at https://macrogenics.com/publications/.

The safety and efficacy of investigational agents and/or investigational uses of approved products have not been established.